plants
Systematic Review
The Genus Diospyros: A Review of Novel Insights into the
Biological Activity and Species of Mozambican Flora
Adriana Ribeiro, Rita Serrano
, Isabel B. Moreira da Silva, Elsa T. Gomes, João F. Pinto
and Olga Silva *
Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa,
1649-003 Lisboa, Portugal; ribeiroadriana@edu.ulisboa.pt (A.R.); rserrano@edu.ulisboa.pt (R.S.);
isabelsilva@edu.ulisboa.pt (I.B.M.d.S.); eteixeiragomes@sapo.pt (E.T.G.); jfpinto@ff.ul.pt (J.F.P.)
* Correspondence: osilva@edu.ulisboa.pt; Tel.: +351-217-946-400
Abstract: Species of the Diospyros L. genus (Ebenaceae family) have been largely used in traditional
medicine for the treatment of several diseases, especially infectious ones. To date, active major
compounds such as naphthoquinones, triterpenoids, and tannins have been isolated and pharmacologically validated from Diospyros species. The present study summarizes the information available
in the literature on the species described in the Flora of Mozambique. To do so, scientific databases
(e.g., PubMed, Scopus, Web of Science, and Google Scholar) were searched using various keywords
and Boolean connectors to gather and summarize the information. Of the 31 native and naturalized
species in the Flora of Mozambique, 17 are used in different regions of Africa and were described for
their traditional uses. They were reported to treat more than 20 diseases, mostly infectious, in the
gastrointestinal and oral cavity compartments. This work provides an overview of the therapeutical
potential of Diospyros species and explores novel insights on the antimicrobial potential of extracts
and/or isolated compounds of these Mozambican species.
Keywords: antimicrobial activity; anti-inflammatory activity; cytotoxicity; Diospyros; ethnomedicinal
practice; herbal medicine; infectious diseases
Citation: Ribeiro, A.; Serrano, R.;
da Silva, I.B.M.; Gomes, E.T.;
Pinto, J.F.; Silva, O. The Genus
1. Introduction
Diospyros: A Review of Novel
The genus Diospyros L. (Ebenaceae family) contains species that have been recognized
and used in traditional medicine (extended ethnomedical use) and have potential new
health benefits supported by in vitro biological, in vivo pharmacological, and clinical
tests [1–4]. Furthermore, within certain cultures or communities, various traditional systems have used all plant parts of this botanical genus (leaf, fruit, bark, twig, hardwood, and
root) as herbal medicines [1,4].
Beyond their pharmacological value, Diospyros spp. have distinct and complementary
important qualities, namely valuable wood, and edible fruits, which provide significant
economic benefits and are recognized and utilized in various industrial and commercial
sectors [1,4].
Generally, Diospyros spp. are tree shrubs or subshrubs with entire alternate leaves, solitary flowers, and fleshy fruits (berries) with usually two or more seeds. The characteristics
of the leaves and flowers of these species are often used to identify fossil casts [5–7].
Diospyros species are predominantly distributed between the tropics, and the most
notable diversity of this botanical genus occurs in Africa [5,6,8]. As confirmed in The Plant
List [9], the WFO Plant List currently contains 1575 species related to the genus Diospyros,
of which 734 have accepted scientific names [10]. Regarding the Mozambican flora, the
genus is represented by 31 species (Table 1), corresponding to 18 accepted scientific name
species, seven accepted subspecies (subsp.), three species that are considered synonyms,
and three species that are not yet in the WFO plant list as of 12 February 2022 [10–12].
Insights into the Biological Activity
and Species of Mozambican Flora.
Plants 2023, 12, 2833. https://
doi.org/10.3390/plants12152833
Academic Editor: Adeyemi Oladapo
Aremu
Received: 26 June 2023
Revised: 21 July 2023
Accepted: 29 July 2023
Published: 31 July 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Plants 2023, 12, 2833. https://doi.org/10.3390/plants12152833
https://www.mdpi.com/journal/plants
Plants 2023, 12, 2833
2 of 34
Table 1. Species of the genus Diospyros L. present in Mozambican Flora.
First
Discription
Year
1980
Scientific Name
Author
Common Name
English/Local
MD 1
N
Z
T
MS
GI
M
CD
Np
IUCN 2
D. anitae
F.White
malawi star apple/-
LC
1911
D. bussei
Gürke
coral star-berry/-
NT
1935
D. consolatae
Chiov.
-/novolo
LC
1963
D. dichrophylla
(Gand.) De Winter
poison star-apple/-
LC
1933
D. ferrea
(Willd.) Bakh.
-/-
A
coastal
jackal-berry/dodo
LC
1962
D. inhacaensis
F.White
1988
D. kabuyeana
F.White
-/-
LC
large-leaved
jackal-berry/
cula, fuma, jacualala,
mucula, murriba,
tendje
LC
NT
1873
D. kirkii
Hiern
1980
D. mafiensis
F.White
-/-
1844
D. mespiliformis
Hochst. ex A.DC.
african ebony,
jackal-berry/
muribariba, mucula,
muquéué,
murriparipa,
mutona, mussuma
1956
D. quiloensis
(Hiern) F.White
crocodile-bark
jackal-berry/
midodo, murodo
1873
D. rotundifolia
Hiern
dune star-apple/
impapa, mapiti,
munhentze
1861
D. senensis
Klotzsch
spiny jackal-berry/
matamba,
mudalima,
tombatica
LC
LC
∇
LC
LC
∆
NE
1861
D. squarrosa
Klotzsch
rigid starberry/cachenz’ere,
mpomopo,
senzasicana, sicana
1980
D. truncatifolia
Caveney
square-leaved star
apple/
impope, mpope
LC
LC
1873
D. verrucosa
Hiern
warty
star-apple/djacola,
mkonhomo,
nkalanongo,
riparipa
1961
D. whyteana
(Hiern) P.White
bladder-nut/-
LC
1963
D. zombensis
(B.L.Burtt) F.White
malawi star-apple/-
LC
1891
D. abyssinica subsp.
abyssinica
(Hiern) F.White
giant diospyros/-
LC
1988
D. abyssinica subsp.
attenuata *
(Hiern) F.White
giant diospyros/-
LC
1980
D. abyssinica subsp.
chapmaniorum
(Hiern) F.White
giant diospyros/-
LC
1837
D. loureiriana subsp.
loureiriana a
G.Don
dye star-apple, sand
starapple/chipongoti,
nhandima
LC
1805
D. lycioides Desf.
subsp. sericea
(Bernh.) De Winter
eastern blue-bush,
red star-apple/
chitomatomana,
m’dima
LC
Plants 2023, 12, 2833
3 of 34
Table 1. Cont.
First
Discription
Year
Scientific Name
Author
Common Name
English/Local
1968
D. natalensis subsp.
natalensis *
(Harv.) Brenan
acorn jackal-berry/-
A
2009
D. natalensis subsp.
nummularia
(Harv.) Brenan
Jordaan
acorn diospyros,
acorn jackal-berry,
granite jackal-berry
**/-
A
F.White
-/aboba, kidanko,
mpome,
nhamudima, popa
LC
A
b
D. usambarensis subsp.
usambarensis /rufescens
MD 1
N
Z
T
MS
GI
M
CD
Np
IUCN 2
c
D. villosa (L.) var. villosa
De Winter
hairy starapple/nhachibabane,
nhaurratane,
chicanela,
chicumbela,
chibabane
c
D. villosa var. parvifolia
(De Winter) De
Winter
hairy star-apple/-
A
-
-
A
d
D. consolatae-rotundifolia
intermediates
d
D. kirkii-mespiliformis intermediates
-
-
A
d
D. sp. no. 1 sensu FZ
-
-
A
1
Distribution in Mozambique (blue, MD) [10,11]; Common name local (green, MD) [12]: N—Niassa; Z—Zambezia;
T—Tete; MS—Manica and Sofala; GI—Gaza–Inhambane; M—Maputo; CD—Cabo Delgado; Np—Nampula;
* Not identified; ** Other names—small-leaved jackal berry, Tickey tree; ∇: Gaza; ∆: Sofala. 2 International
Union for the Conservation of Nature: LC—least concern; NE—not evaluated; NT—near threatened [B2ab(iii)];
A—absent. WFO Plant List: a D. loureiroana G.Don subsp. loureiriana; b Synonym of D. loureiroana subsp.
rufescens (Caveney) Verdc.; c Synonym of D. villosa (L.) De Winter; d not included in the WFO Plant List [10,11];
(-)—not available.
Concerning primary health care (PHC), herbal medicines are used by 80% of the
African population, and more than 70% of the population of Mozambique uses such
medicines for treating all diseases [13–15]. For instance, several Diospyros species with antimicrobial potential have been reported [4,16–18]. Worldwide, the magnitude of infectious
diseases (ID), encompassing antimicrobial resistance (AMR), represents a major health
problem (approximately 700,000 people die every year) [19,20]. Infectious diseases have a
high impact in Africa, particularly in Mozambique [21].
Most of the native and naturalized Diospyros species of Mozambique’s flora are generally recognized as traditionally used in different regions of Africa to treat different diseases,
with a particular focus on infections affecting the gastrointestinal tract and oral cavity. This
work will present a comprehensive overview of the therapeutic potential of Mozambican Diospyros species based on chemical, biological, and toxicological experimental data,
particularly addressing its antimicrobial properties and including comparative elements
concerning the biological activity of other Diospyros species.
2. Results
2.1. Ethnomedical Use of Diospyros Species of Mozambican Flora
Table 2 shows the results of the collected ethnomedical data from seventeen Mozambican species, namely D. abyssinica, D. anitae, D. ferrea, D. kabuyeana, D. loureiriana subsp.
loureiriana, D. lycioides subsp. sericea, D. mafiensis, D. mespiliformis, D. rotundifolia, D. mafiensis, D. mespiliformis, D. quiloensis, D. rotundifolia, D. squarrosa, D. usambarensis, D. verrucosa,
D. villosa, D. villosa var. parvifolia, D. whyteana, and D. zombensis. In addition, information
is given on the part of the plant used as medicine, the manufacturing process of the traditional formulation, the main traditional therapeutic use, and the country from which the
information originates.
Plants 2023, 12, 2833
4 of 34
The results show that 54.8% of the total Diospyros species from Mozambique are
referred to for their traditional use (Table 2). Among these, D. rotundifolia (Figure 1),
traditionally used to treat diarrhea [22], is a prevailing species of dense undergrowth in the
coastal area of the Marracuene District [23].
Figure 1. Diospyros rotundifolia: (a) aspect in its natural habitat; (b,c) details of leaf and fruit;
(d) transverse view of the fruit with the seeds. Photography by Elsa Gomes.
Furthermore, among the Diospyros species present in the Mozambican flora, D. villosa
(Figure 2) is a species with a well-established traditional use of both leaf [24] and root [25];
the latter mainly used as a toothbrush for hygiene purposes [26].
Plants 2023, 12, 2833
5 of 34
tt
Figure 2. Diospyros villosa: (a) Aspect in the natural habitat; (b) cross-section of the root. Photography
by Elsa Gomes (a) and Adriana Ribeiro (b).
Diospyros species have been reported to be used to treat the signals and symptoms
of over 20 diseases. Two of these species (D. abyssinica and D. mespiliformis) have been
mentioned most frequently and are used in two to fiveffdifferent countries in Africa (Table 2).
ff
Based on the diverse description in the literature for the human use of the different
parts of Diospyros, the results are grouped into infectious diseases (antibacterial, antifungal,
anthelminthic, and antiviral); gastrointestinal (diarrhea, dysentery, emetic, flatulence, and
other gastrointestinal disorders), oral cavity (oral hygiene, healing of oral wounds, and
toothaches); urogenital (anti-hemorrhagic, dysmenorrhea, and infertility); skin diseases
(dermatitis, fresh wounds, bedsores, and rashes); musculoskeletal (body pain, bruises,
painful fractures, and rheumatism); and others conditions (diabetes, internal injuries,
antidotes, hemostatic agents, and snake bites).
tt
Among all the different
Diospyros plant parts used in traditional medicine (Figure 3),
ff
ff
the root is the most-used part (82%, Figure 3a) and is most used to treat infectious diseases.
In the treatment of gastrointestinal disorders, it corresponds to 59%, for oral cavity infections, 41%, and for skin diseases, 18%, as well as for the management of other conditions,
comprising 12% (Figure 3b).
Figure 3. Traditional use of Diospyros species: (a) plant part used; (b) type of disease.
Plants 2023, 12, 2833
6 of 34
The leaf is the second-most used part of the Diospyros species, but it is used in a
similar percentage (18%) to the root to treat skin conditions and more commonly (24%) for
musculoskeletal bruises, painful fractures, body aches, and rheumatism (Figure 3a,b).
Table 2. Reported ethnomedical use of Mozambican Diospyros species.
Species
Part Used
Preparation
Method
leaf
decoction
fruit (dry)
decoction
bark
unspecified
root
decoction
leaf
bark
juice
bark
decoction
leaf
seed
squeeze
and apply
leaf
juice
tuber
decoction
root
unspecified
fruit
unspecified
root
Traditional Use
Country
Ref.
Mali
[4,27]
Mali, Guinea
Zimbabwe
[28]
Kenya
[29]
D. abyssinica
malaria
wound healing
astringent and cholagogue
gastrointestinal disorders
astringent and antipyretic
antihelminthic
abdominal pain, dysentery, and
diarrhea
snake bite
astringent
internal injuries
laxative
rash
malaria and ringworm
ringworm
wound healing
tropical ulcer (skin and soft tissue
polymicrobial infection, feet, or lower
legs localized)
upset stomach
[30]
Uganda
[31]
[32]
D. anitae
dental hygiene
healing of oral wounds
Mozambique
[33]
India
[34]
unspecified
diarrhea and sore throats
internal bleeding
renal lithiasis
anti-hemorrhagic
infertility
oral hygiene
skin diseases
unspecified
antiviral
Tanzania
[37]
chewing stick
oral hygiene
South Africa
East Africa
[4]
decoction
bloody feces
South Africa
South Central
Zimbabwe
[38–40]
Namibia
Zambia
[41]
D. ferrea
bark
[35,36]
D. kabuyeana
root
D. loureiroana subsp. loureiroana
root
D. lycioides subsp. sericea
root bark
dysentery
headache
root
chewing stick
infertility
Plants 2023, 12, 2833
7 of 34
Table 2. Cont.
Species
Part Used
Preparation
Method
Traditional Use
Country
Ref.
root
unspecified
diarrhea
Mozambique
Tanzania
[42]
Central
Southern
Eastern
Western
Africa
[27,43–47]
Burkina Faso
[48]
Ghana
[27]
Nigeria
[49–51]
Zambia
[44,52]
D. mafiensis
leprosy
skin diseases (including fungal
infections)
D. mespiliformis
leaf and bark
decoction
leaf
decoction
root
leaf, bark
and root
chewing stick
analgesic and antipyretic
antihelminthic
dermatomycosis
fungal infections
induction of childbirth
hemostatic agent
malaria, pneumonia, and
trypanosomiasis
sexually transmitted diseases
diarrhea and dysentery
leprosy
oral infections
whooping cough
bruises, bedsores, rash, and wounds
ringworm
oral hygiene
decoction
toothache
leaf
decoction
antipyretic
dermatitis
diarrhea and dysentery
malaria
headache
pneumonia
rheumatism
malaria and pneumonia
infection with fever
antipyretic
antidote for a variety of poisonous
substances
diarrhea and dysentery
haemostatic agent
oral infections
wound healing
malaria and oral candida infection
(used as mouthwash, management of
HIV/AIDS opportunistic diseases)
leaf
decoction
fruit
decoction
stem bark
root
leaf
decoction
decoction
decoction
root
decoction
root
infusion
abdominal pain, body and heart pain
seed
unspecified
antibacterial
stem bark
decoction
malaria
sexually transmitted diseases
Zambia
[44]
root
not report
diarrhea
South African
[22]
root
not report
sexually transmitted diseases
Tanzania
[37]
South Central
Zimbabwe
Guinea
[53]
[4]
D. quiloensis
D. rotundifolia
D. squarrosa
Plants 2023, 12, 2833
8 of 34
Table 2. Cont.
Species
Part Used
Preparation
Method
root bark
root
unspecified
chewing stick
Traditional Use
Country
Ref.
schistosomiasis
oral hygiene
fungal infections and overt
symptoms of type 2 diabetes (i.e.,
polyuria, polydipsia, excessive thirst,
and sweating)
Malawi
Tanzania
[54]
[55,56]
leprosy
Tanzania
[4,57]
South African
[24]
Mozambique
[4,25,58]
South Africa
[59]
D. usambarensis
decoction
D. verrucosa
root
unspecified
leaf
unspecified
D. villosa
decoction
root
toothbrush
decoction
D. villosa var. parvifolia
leaf
gastrointestinal disorders
painful fractures
gastrointestinal disorders
laxative
musculoskeletal system
oral hygiene
wounds (skin/subcutaneous tissue)
emetic
antihelminthic
emetic and flatulence
gastrointestinal disorders
infusion
root
D. whyteana
root
unspecified
antibacterial
dysmenorrhea
rash
South Africa
[60]
root bark
unspecified
schistosomiasis
Malawi
[4,61]
D. zombensis
The majority of documented medicinal uses of Diospyros species are attributed to their
effectiveness in treating microbial infections, encompassing bacterial, fungal, and parasitic
infections. These include conditions such as diarrhea, dysentery, and various skin and oral
cavity infections.
2.2. Chemical Composition of Mozambican Diospyros Species
The main classes of chemical constituents identified in Diospyros species from the
Mozambican flora are listed in Table 3.
The presence of phenolic acid derivatives, like flavonoids and naphthoquinones
(NQs), particularly 1,4-naphthoquinones (1,4-NQs), and terpenoids, mainly triterpenoids
(especially lupan, ursane, oleanane derivatives) [3,4,17,62,63] and tetraterpenoids
(carotenoids), have been reported [4]. Other chemical constituents in these Diospyros
species include hydrocarbons, lipids, amino acids, and sugars [1,4,5,62].
Table 3. Chemical compounds identified in Mozambican Diospyros species.
Species
Part
Used
Chemical Class
root bark
naphthoquinone
stem bark
leaf
naphthoquinone
triterpenoid
Compounds
Extract
Ref.
plumbagin
(2-methyl-5-hydroxy-1,4-naphthoquinone)
diospyrin, isodiospyrin
betulinic acid, betulin and lupeol
P. ether, CF,
DCM, MeOH,
H2 O, EtOH 80%
MeOH
[28]
D. abyssinica
[64,65]
Plants 2023, 12, 2833
9 of 34
Table 3. Cont.
Species
Part
Used
Chemical Class
Compounds
Extract
Ref.
n.r
n.r
triterpenoid
naphthoquinone
betulinic acid, betulin and lupeol
diosindigo A
n.r
n.r
[4]
[4]
seed
naphthoquinone
isodiospyrin
Hex
[66]
MeOH
n.r
MeOH
MeOH
EtOAc
[67]
[4]
[67]
EtOAc
[67]
n-Hex
[68]
n-Hex
[68]
CF, n-Hex
[68,69]
EtOH
[70]
EtOH
[4]
n.r
[4]
D. consolatae
D. dichrophylla
D. ferrea
leaf
n.r
leaf
leaf
diterpenoid
leaf
triterpenoid
fruit
triterpenoid
fruit
root
fruit
root
triterpenoid
naphthoquinone
leaf
triterpenoid
n.r
triterpenoid
pregnenolone and androstan-6-one
β-sitosterol
citronellol
phytol
thunbergol
betulin, α-amyrin,
friedelan-3-one and olen-12-ene
friedelin, epifriedelinol, lupeol, lupenone,
and betulin
β-sitosterol and stigmasterol
7-methyljuglone, isodiospyrin, diosindigo A
and 8-hydroxyisodiospyrin
gallic acid
friedelin, friedelin-3-ol, taraxerol and
taraxerone
ursolic acid
stem
naphthoquinone
7-methyljuglone and diospyrin
n.r
[71]
n.r
n.r
n.r
triterpenoid
bauerenol, betulin and lupeol
β-sitosterol
diosindigo A
n.r
n.r
n.r
[4]
[4]
[4]
branche
fruit
root, stem
naphthalene
naphthoquinone
triterpenoid
naphthoquinone
naphthoquinone
MeOH
MeOH
n.r
n.r
CF
[72]
[41]
[53]
[71]
[71]
n.r
naphthoquinone
Diospyroside A, B, C and D
7-methyljuglone and juglone
lupeol and ursolic acid
isodiospyrin and bisisodiospyrin
7-methyljuglone and isodiospyrin
mamegakinone, methylnaphthazarin
and 8-hydroxyisodiospyrin
n.r
[4]
root bark
naphthoquinone
CF, DCM,
MeOH
[42,73,74]
stem bark
leaf
bark
naphthoquinone
triterpenoid
naphthoquinone
stem bark
triterpenoid
diosquinone, diosindigo A, 7-methyljuglone,
3-hydroxiquinone, and 6,8-bisdiosquinone
7-methyljuglone and diosindigo A
α-amyrin, lupeol and betulinic acid
diosquinone, isodiospyrin, and plumbagin
lupeol, betulin, betulinic acid, α-amyrin,
and bauerenol
triterpenoid
monoterpenoid
phenol
[67]
D. inhacaensis
D. kirkii
naphthoquinone
D. lycioides
D. mafiensis
CF, MeOH
Ee
[73]
[75]
[4,52]
CF
[4,76]
Plants 2023, 12, 2833
10 of 34
Table 3. Cont.
Species
Part
Used
Chemical Class
Compounds
Extract
Ref.
stem
bark,
leaf, bark
triterpenoid
betulinic acid, betulin, lupeol, bauerenol, and
α-amyrin
CF,
MeOH
[4,76]
n.r
[77]
P. ether
MeOH
MeOH
[78]
[79]
[79]
D. mespiliformis
leaf
flavonoid
root
root, bark
fruit
naphthoquinone
naphthoquinone
naphthoquinone
7-O-(4′′′ -O-acetyl)-allopyranosyl(1′′′ → 2′′ )β-glucopyranoside, along with eight
flavonoid metabolites—luteolin
3′ ,4′ ,6,8-tetramethyl ether, luteolin
4′ -O-β-neohesperidoside, luteolin
7-O-β-glucoside, luteolin, quercetin,
quercetin 3-O-β-glucoside, quercetin
3-O-α-rhamnoside, and rutin
diosquinone, and plumbagin
diospyrin
plumbagin
root, stem
n.r
n.r
naphthoquinone
triterpenoid
fatty acid
7-methyljuglone, and diospyrin
betulinic acid, α-amyrin, and lupeol
heptacosanoic acid
n.r
n.r
n.r
[4]
[4]
[4]
n.r
naphthalene
4,5,6,8-tetramethoxy naphthaldhyde,
5-hydroxy-4,6,8-trimethoxy naphthaldehyde,
4,5,6-trimethoxynaphthalehyde,
4,5-dimethoxynaphthaldehyde, and
5-hydroxy-4-methoxy-2-naphthaldehyde
MeOH
[4]
n.r
triterpenoid
root
naphthoquinone
stem
D. natalensis
D. quiloensis
D. rotundifolia
n.r
[4]
n.r
[71]
naphthoquinone
betulin and lupeol
7-methyljuglone, neodiospyrin and
rotundiquinone
7-methyljuglone and diospyrin
n.r
[71]
n.r
naphthoquinone
7-methyljuglone
n.r
[4]
root
naphthoquinone
MeOH
[54,80]
stem bark
naphthoquinone
MeOH
[54]
root bark
naphthoquinone
n.r
[57]
root bark
triterpenoid
stem bark
naphthoquinone
n.r
[57]
stem bark
triterpenoid
diosindigo A, 7-methyljuglone, diosquinone
and isodiospyrin
betulinic acid and betulin
diosindigo A, 7-methyljuglone, diosquinone
and isodiospyrin
betulinic acid and betulin
n.r
[57]
n.r
naphthoquinone
7-methyljuglone
n.r
[4]
bark
triterpenoid
MeOH
[4]
root bark
naphthoquinone
oleanolic acid
7-methyljuglone, diosquinone, isodiospyrin
and mamegakinona
P. ether, MeOH
[4,61]
D. squarrosa
D. usambarensis
7-methyljuglone, isodiospyrin, diosindigo A
and B, bis-isodiospyrin and mamegakinone
7-methyljuglone and diosindigo A
D. verrucosa
D. whyteana
D. zombensis
Extract: Ace—acetone; CF—chloroform; DCM—dichloromethane; Ee—ether; EtOAc—ethyl acetate;
EtOH—ethanol; H2 O—water; Hex—hexane; MeOH—methanol; P. ether—petroleum ether; n.r—not reported.
Plants 2023, 12, 2833
11 of 34
Among the NQs (Figure 4), 80% are 1,4-NQs, either as monomers such as plumbagin
(1) and 7-methyljuglone (2) or as dimers such as diospyrin (3) and isodiospyrin (4), while
trimers and tetramers are less represented in this genus [4,81].
Figure 4. Diospyros representatives identified 1,4-naphthoquinones.
In the Mozambican Diospyros species, plumbagin (1) and 7-methyljuglone (2) are the
most prominent 1,4-NQs identified [3,4]. The presence of 7-methyljuglone has been reported
in diethyl ether, dichloromethane, chloroform, methanol, and hydroethanol extracts of the
root, stem, and bark of most species [1,5] and in the ether extract of D. lycioides branches [41].
Plumbagin has been identified on the root bark of D. abyssinica [28], and isodiospyrin
(4), a dimeric 7-methyljuglone derivative [3], has been reported in a hexane extract of
D. dichrophylla seeds [66] and in the diethyl ether extract of bark and phylum of almost all
Mozambican Diospyros species [4].
D. mespiliformis has been one of the best-studied Mozambican Diospyros species, having
NQs identified in different plant parts [4,79] and triterpenoids in leaf, bark, and stem
bark [4,76,82].
ff
Triterpenoids (lupane, ursane, oleanane, taraxerane, and friedelane) are present in
more than 90% of Diospyros species. Lupane-type compounds (Figure 5), such as betulinic
acid (1, Figure 5), betulin (2, Figure 5), and lupeol (3, Figure 5), are the most active substances present in Diospyros African species [4,64,83,84]. These compounds were detected
in different types of extracts (petroleum ether, dichloromethane, chloroform, methanol, hydroethanol, and aqueous extracts) and their fractions [1,5,28,41]. Several biological activities
ff
have been demonstrated for them, mainly for betulinic acid and its derivatives [83,85–88].
Condensed tannins (proanthocyanidins and oligopolymeric complex tannins), and particularly hydrolysable tannins (gallotannins, ellagitannins), and have also been identified
in Mozambican Diospyros species such as D. villosa [4,25,58] and D. mespiliformis [82,89].
In addition, from the methanolic extract derived from D. lycioides twigs, three naphthalene glycosides were identified [72], and carotenoids were identified in the fruit of
this species [90]. The presence of galactiol and vitamin E in the D. ferrea leaf was also
reported [67].
Plants 2023, 12, 2833
12 of 34
Figure 5. Diospyros identified representative lupan-type triterpenoids.
So far, the biologically active marker secondary metabolites isolated and studied from
several species of the genus Diospyros have mainly been naphthoquinones, triterpenoids,
and tannins. Compounds belonging to these chemical classes have been isolated from the
twigs, bark, roots, leaves, stems, and fruits of Mozambican species of this genus. Examples
include plumbagin, 7-methyljuglone, diospyrin, and isodiospyrin, which have been isolated
from the root of several Diospyros species.
2.3. In Vitro and In Vivo Biological Activity of Mozambican Diospyros Species and
Marker Compounds
In Tables 4–6, the different in vitro and in vivo biological activities and toxicological
tests performed on Mozambican Diospyros species, and their isolated marker secondary
metabolites are summarized. A total of thirteen species (41.9%), namely D. abyssinica,
D. bussei, D. ferrea, D. kabuyeana, D. lycioides, D. loureiriana, D. mafiensis, D. mespiliformis,
D. natalensis, D. squarrosa, D. usambarensis, D. verrucosa, and D. villosa, were evaluated for
biological activities other than antibacterial activities (Table 4).
2.3.1. Anti-Inflammatory and Analgesic Activity
Aqueous extract of D. abyssinica root bark has shown stronger anti-inflammatory
activity (enzyme 15-lipoxygenase (LOX) inhibition) than quercetin [27].
ff
that the hexane fraction of D. mespiliformis leaves has antiIn vivo assays have shown
inflammatory properties (inhibits stronger the LOX), and that the methanolic extracts of
different plant parts showed wound healing effects. On the other hand, the butanol and
ethyl acetate fractions activate LOX activity. These results show that D. mespiliformis extract
can have pro-inflammatory and anti-inflammatory effects [51].
Lupeol isolated from D. mespiliformis stem bark has shown analgesic activity in both
pain inhibition (neurological-first phase) and origin (inflammatory-second phase) in biphasic tests (in vivo) [76].
2.3.2. Antihyperglycemic Activity
Another finding has revealed that the oral administration of a methanolic extract
obtained from the leaves of D. ferrea (400 mg/kg) for a duration of 21 days in diabetic
rats ffshowed significant antihyperglycemic activity
ff [91]. The root of this species is rich
in phenolic acids, especially gallic acid, and is therefore traditionally used as a potent
antioxidant [70].
ff
2.3.3. Antifungal Activity
Several studies have reported the potential antifungal activity of the root and root
bark of most Diospyros species [42,54,92]. However, the antifungal activity of a leaf extract
of D. mespiliformis has also been confirmed [47,93].
Various Diospyros medicinal plants are also effective against Candida spp. [1]. The
methanolic extract of the D. abyssinica root is active against this microorganism [94]; how-
Plants 2023, 12, 2833
13 of 34
ever, in another study, it was only moderately active against the same microorganism [95].
Another medicinal plant, D. mespiliformis, is more active against C. neoformans than against
C. albicans. A leaf extract showed anti-C. albicans activity, while a bark extract showed
in vitro activity against C. neoformans-isolated strains from South African AIDS patients [96].
D. mespiliformis, traditionally used to treat ringworm, shows remarkable antimicrobial
activity against Trichophyton mentagrophytes and Microsporum canis. This result supports
the traditional use of this species against dermatophytosis [47]. Aqueous and ethanolic
extracts of the leaf and bark of D. mespiliformis showed significant antifungal activity against
Aspergillus niger, Aspergillus flavus, and Microsporum gypseum [97].
2.3.4. Antiparasitic Activity
Diospyros species have antiparasitic activity, especially against both chloroquinesensitive (3D7) and chloroquine-resistant (FcB1) strains of Plasmodium falciparum [31,94].
The decoction of the stem of D. mespiliformis was tested against Plasmodium bergheiinfected mice and demonstrated potent activity, including the inhibition of beta-hematin in
an in vitro study [98].
In vitro studies from methanolic extracts of D. abyssinica leaves have provided confirmation of its antiparasitic activity against Leishmania donovani [65,94], Trypanosoma cruzi,
Trypanosoma brucei [99], Culex, and Anopheles larvae [94].
The isolated compound 7-methyljuglone obtained from the methanolic extract of D.
usambarensis root bark has significant schistosomicidal activity [54,92].
2.3.5. Antioxidant Activity
The scavenging activity of crude extract and fractions of four Diospyros species, namely
D. abyssinica, D. lycioides, D. mespiliformis, and D. villosa, present in the Mozambican Flora
was evaluated spectrophotometrically using the DPPH (1,1-diphenyl-2-picrylhydrazyl)
radical assay.
An estimation of the concentration of antioxidant vitamins (i.e., A, C, and E) from
crude methanolic extracts obtained from the leaf, bark, and root of D. mespiliformis was also
determined using the DPPH [51].
Table 4. In vitro and in vivo non-antibacterial tests of biological activity in Mozambican species of
Diospyros and marker compounds.
Biological Activity/
Species
PU
Extract/
Compound
Results
Microorganism/
Assay
Control
Ref.
Biphasic, Wistar rats
acetylsalicylic acid (asa),
100 mg/kg, p.o.
[76]
Tail flick method, adult
Wistar albino rats
ibuprofen
[100]
Tail flick method, adult
Wistar albino rats
ibuprofen
[101]
Analgesic
D. mespiliformis
SB
D. ferrea
L
D. ferrea
R
CF/lupeol
25 mg/kg, p.o
CF
MeOH
CF
MeOH
Pi1 2.2 ± 0.2/ asa =1.0 ± 0.3
Pi2 1.98 ± 0.1/ asa =1.15 ± 0.1
100–300 mg/Kg
significant activity
100–200 mg/Kg
significant activity
Anti-inflammatory
D. abyssinica
Rb
D. ferrea
L
D. ferrea
R
D. mespiliformis
H2 O (1)
MeOH (2)
CF
MeOH
CF
MeOH
1—IC50 = 16 ± 1 µg/mL
2—IC50 = 86 ± 7 µg/mL
100–300 mg/Kg = 26.2–28.2%
100–300 mg/Kg = 29.6–37.6%
100–200 mg/Kg = 37%
Sb
DCM Fraction
maximally
at 400 mg/kg
Modulation of serum
concentrations of Tumour
Necrosis Factor alpha and
Interleukin 1 beta and 6
L
Hex Fraction
5 µg/mL(1)
10 µg/mL (2)
1—IC50 = 31.21 ± 0.84 µg/mL
2—IC50 = 32.05 ± 2.79 µg/mL
LOX, using soybean
lipoxygenase type 1-B
PIPE, adult male
Wistar rats
PIPE, adult Wistar
albino rats
quercetin, IC50 value
11.5 ± 0.6 µg/mL
ibuprofen
41.1%
[27]
[100]
ibuprofen
[101]
Cytokine inhibition,
Plasmodium
berghei-infected mice
artemetherlumefantrine
[98]
LOX, Wistar rats
quercetin, IC50 value
1–46.02 ± 5.46 µg/mL
2–32.05 ± 2.79 µg/mL
[51]
Plants 2023, 12, 2833
14 of 34
Table 4. Cont.
Biological Activity/
Species
PU
Extract/
Compound
Results
Microorganism/
Assay
Control
Ref.
L
MeOH
21 days
400 mg/kg, i.p, significant
antihyperglycemic activity
Streptozotocin induced
diabetic Wistar rats
glibenclamide,
0.5 mg/Kg, p.o.
[91]
D. abyssinica
R
MeOH
Actives in test controlled by
conidial suspension
BA, C. albicans
C. cucumerinum
methylthiazolyltetrazolium
[94]
chloride (MTT)
D. ferrea
W
1-isodiospyrin
2-plumbagin
1—active against three fungi
2—active against eight fungi
HMBC
Phomopsis sp.
reference spectrum for
both H1 and C13
[102]
D. mafiensis
Rb
3-hydroxydiosquinone
3-hydroxydiosquinone
MIC50 = 14.9 µg/mL
MIC50 = 39.1 µg/mL
Reduced total aflatoxin,
1.145 to 32 ng/plac
A. parasiticus B62
[42]
A. parasiticus B62
[42]
Rb
diosquinone
MIC50 > 100 µg/mL
A. parasiticus B62
[42]
Rb
diosquinone
Reduced total aflatoxin
1.145 to 45 ng/plac
A. parasiticus B62
[42]
Rb
P. ether, DCM
(E) Fraction (F)
E = 5 mg/disc IZ: 7–20 mm
F = 0.2 mg/disc IZ: 19–20 mm
DD, C. albicans
miconazole
20 µg/disc
IZ: 29 mm
[103]
Rb
L
Ace
MIC = 0.16 µg/mL
BD, C. albicans, M. canis
amphotericin B
MIC = 0.02 µg/mL
[93]
L
DCM:MeOH
MIC = 0.10–0.50 mg/mL
BD, M. canis, T.
mentagrophytes
tetrazolium violet
[47]
[93]
[96]
Antihyperglycemic
D. ferrea
Antifungal
Rb
D. mespiliformis
CCA, A. f lavus,
A. parasiticus
ELISA, A. parasiticus,
A. flavus
CCA, A. flavus,
A. parasiticus
ELISA, A. flavus,
A. parasiticus
H2 O
MIC = 0.08 µg/mL
BD, M. canis
amphotericin B
MIC = 0.02 µg/mL
B
Ace
IZ: 7 mm (1)
IZ: 12 mm (2)
ADD, 1-C. albicans,
2-C. neoformans
nystatin
Rb
7methyljuglone
MIC = 0.025 µg/mL
Rb
isodiospyrin
MIC = 10 µg/mL
D. villosa
R
EtOH 70%
Fraction
MIC = 312.5 µg/mL
MIC = 62.5–312.5 µg/mL
BD, C. albicans
not reported
[104]
Antiparasitic
D. abyssinica
L
EtOAc
IC50 = 51.3 ± 8.8 µg/mL
IC50 = 1.5 µg/mL
IC50 = 5.6 µg/mL
BD, P. falciparum (FcB1)
L. donovani
P. falciparum
chloroquine
pentamidine
chloroquine
pentamidine
IC50 = 7 µM
chloroquine
IC50 = 0.1 µM
[31]
L
D. usambarensis
B
B
B
R
EtOAc
BA, C. cucumerinum
BA, C. cucumerinum
miconazole
MIC = 0.001 µg/mL
miconazole
MIC = 0.001 µg/mL
[92]
[54]
[65]
diospyrin
isodiospyrin
diospyrin
isodiospyrin
DCM
MeOH
IC50 = 0.5 µM
L. donovani
IC50 = 1.5 µM
P. falciparum (FcB1)
MIC = 500 mg/L
Culex, Anopheles larvae
not identified
[94]
[94]
[94]
D. bussei
R
MeOH
IC50 = 65.7 ± 2.7 µg/mL
T. brucei (Lister 427)
pentamidine
IC50 = 0.000509 µM
[99]
D. kabuyeana
L
MeOH
IC50 = 3.32 µg/mL
T. brucei (Lister 427)
pentamidine
IC50 = 0.000509 µM
[99]
D. loureiriana
Rb
Sb
L
MeOH
IC50 = 1.68 ± 0.77 µg/mL
IC50 = 11.53 ± 1.99 µg/mL
IC50 = 19.10 ± 4.41 µg/mL
P. falciparum (3D7)
chloroquine
IC50 = 0. 0045 µM
[105]
[105]
[105]
D. mespiliformis
S
EtoAC (1)
DCM (2)
MeOHfraction
(3)
1—IC50 = 3.18 µg/mL
2—IC50 = 0.78 µg/mL
3—IC50 = 0.55 µg/mL
Plasmodium
berghei-infected mice
artesunate and
chloroquine
diphosphate
[98]
D. natalensis
Sb
MeOH
IC50 = 2.85 µg/mL
T. brucei (Lister 427)
pentamidine
IC50 = 0.000509 µM
[99]
D. squarrosa
Rb
MeOH
IC50 = 5.38 µg/mL
T. brucei (Lister 427)
pentamidine
IC50 = 0.000509 µM
[99]
Plants 2023, 12, 2833
15 of 34
Table 4. Cont.
Biological Activity/
Species
PU
Extract/
Compound
Results
Microorganism/
Assay
Control
Ref.
Sb
R
L
MeOH
MeOH
MeOH
IC50 = 1.28 µg/mL
IC50 = 2.23 µg/mL
IC50 = 2.99 µg/mL
T. brucei (Lister 427)
T. brucei (Lister 427)
T. brucei (Lister 427)
pentamidine
IC50 = 0.000509 µM
[99]
Rb
7methyljuglone
Efficiency schistosomiasis
MIC = 5 ppm
Biomphalaria glabrata
not identified
[54]
D. abyssinica
Rb
EtOH (1)
MeOH (2)
H2 O (3)
1-EC50 = 16.0 ± 2 µg/mL
2-EC50 = 16.6 ± 0.4 µg/mL
3-EC50 = 21 and 29 ± 2 µg/mL
DPPH
quercetin
EC50 value
3.4 ± 0.3 µg/mL
[27]
D. lycioides
L
Ace
Rf = 0.54; 0.60; 0.83; 0.89
DPPH on TLC plates
phenolic
compounds
[38]
D. mespiliformis
F
R
F
MeOH
MeOH
MeOH
87.36% at 1 mg/mL
IC50 = 3.47 ± 0.05 µg/mL
IC50 = 6.94 ± 0.49 µg/mL
DPPH
DPPH
DPPH
B
MeOH
IC50 = 7.82 ± 0.76 µg/mL
DPPH
L
EtOAc Fraction
IC50 = 1.08 ± 0.04 µg/ml
DPPH
Sb
MeOH
IC50 = 9.53 µg/mL
DPPH
L
CF (1)
Hex (2)
1-IC50 = 10.7 µg/mL
2-IC50 = 11.8 µg/mL
DPPH
D. verrucosa
D. usambarensis
Antioxidant
D. villosa
vitamin E
ascorbic acid
2.36 ± 0.30 µg/mL
trolox
3.43 ± 0.78 µg/mL
ascorbic acid
5.08 ± 0.12 µg/mL
ascorbic acid
10.3 µg/mL
ascorbic acid
10.3 µg/mL
[106]
[51]
[51]
[51]
[51]
[107]
[107]
Part used (PU): L—leaf; B—bark; F—fruit; R—root; Rb—root bark; Sb—stem bark. Extract: Ace—acetone;
ADD—agar disc diffusion; CF—chloroform; DCM—dichloromethane; EtOAc—ethyl acetate; EtOH—ethanol;
H2 O—water; Hex—hexane; MeOH—methanol; P. ether—petroleum ether. Test: BA—TLC bioautography;
BD—broth dilution; CCA—cell culture in agar; DD: disco diffusion method; DPPH—2,2-diphenyl-1picrylhydrazyl; ELISA—enzyme-linked immunosorbent assay; HMBC—heteronuclear multiple-bond correlation
method; PIPE—percent inhibition of paw edema. Abbreviations: LOX-15-lipoxygenase; Pi1 —pain inhibition
(neurological-first phase); Pi2 —pain inhibition (inflammatory-second phase); EC50—half maximal effective
concentration; IC50—half maximal inhibitory concentration; MIC—minimum inhibitory concentration.
2.3.6. Cytotoxicity, Genotoxicity, and Toxicity of Mozambican Diospyros Species
The results of in vitro cytotoxicity tests using normal and tumorous human cells and
Artemia salina, as well as in vitro genotoxicity and in vivo acute and sub-chronic toxicity
assessment of Diospyros species, are summarized in Table 5.
Table 5. In vitro cytotoxicity and genotoxicity studies as well as in vivo toxicity studies in Mozambican Diospyros species.
Species
Parts Used
Extract
leaf
EtOAc
Toxicity Assay
Results
Ref.
IC50 = 6.0 ± 5.0 µg/mL
[31]
D. abyssinica
leaf
EtOAc
bark
EtOAc
seed
DCM:MeOH (1)
isodiospyrin (2)
Cytotoxicity against
MRC-5 human diploid embryonic
cells, Taxotere® as standard
Cytotoxicity against KB human
tumor cell lines (squamous cell
carcinoma
of the mouth), Taxotere® as standard
Cytotoxicity against human KB cell
(1) and Rhabditis pseudoelongata (2)
>85% cell inhibition
IC50 = 1.0 ± 2.0 µg/mL
[31]
(1) LD50 = 10 µg/mL
(2) LD50 = 1 µg/mL
[65]
Cytotoxicity using Brine shrimp test
(Artemia salina)
1-(LC50 = 29 µg/mL)
2-(LC50 = 0.13 µg/mL)
[66]
D. dichhropylla
Plants 2023, 12, 2833
16 of 34
Table 5. Cont.
Species
Parts Used
Extract
Toxicity Assay
Results
Ref.
leaf
MeOH
In vivo—acute oral toxicity using
male Wistar albino rats
LD50 = 2000 mg/kg
[91]
fruit
isodiospyrin (1)
8′ -hydroxyisodiospyrin (2)
Cytotoxicity strong against
Hep-3B, KB, COLO-205, and HeLa
cancer cells
1(ED50 = 0.17, 1.72, 0.16 and
0.21 µg/mL)
2(ED50 = 1.31, 1.75, 1.96 and
1.79 µg/mL)
[68]
IC50 = 500 and 1000 µg/mL
[38]
Nontoxic to the normal
cell at 300 µg/mL
[38]
IC50 = 100.34 ± 9.85 µg/mL
[105]
IC50 = 57.26 ± 0.53 µg/mL
[105]
[103]
D. ferrea
D. lycioides
leaf
Ace
leaf
Ace
Cytotoxicity against BUD-8 cell
(human
fibroblast cells) in real-time
xCELLigence system and 7.4 µg/mL
curcumin (control)
Cytotoxicity against HeLa cells
mobility assayed using the wound
healing assay and 7.4 µg/mL
curcumin (control)
D. loureiriana
root bark
MeOH
stem bark
Cytotoxicity against
human embryonic kidney cells
(HEK293),
estimated growth inhibition at
400 µg/ml
D. mafiensis
root bark
P. ether (1)
DCM (2)
EtOH (3)
fraction P. ether (4)
fraction DCM (5)
Cytotoxicity using
brine shrimp larvae test
(Artemia salina)
Standard cyclophosphamide
LC50 value of 17.78 µg/mL
1-LC50
2-LC50
3-LC50
4-LC50
5-LC50
EtOH
In vivo—acute oral toxicity
using Wistar rats of both sexes
in vivo—acute oral
administration using rats
In vivo—sub-chronic toxicity using
rats
Cytotoxicity against human
glioblastoma cell lines (1) and
hormone-dependent human prostate
cancer (2)
LD50 = 570 mg/kg
Acute toxicity is moderate
[49]
LD50 ≥ 5 g/kg
[108,109]
LD50 = 750 g/kg
LD50 = 500 g/kg
[108]
1-ED50 = 0.18 µg/mL
2-ED50 = 4.50 µg/mL
[84]
= 25.12 µg/mL
= 69.18 µg/mL
= 120.23 µg/mL
≤ 8–45.71 µg/mL
= 5.08 µg/mL
D. mespiliformis
stem bark
root bark
leaf
stem bark
leaf
stem bark
EtOAc fraction
root
diosquinone
twigs
DCM
Genotoxicity against
mutagens mitomycin C (MMC)
using the Ames test (Salmonella
typhimurium TA98)
protective effect
non-genotoxic at
500–2500 µg/mL
[60]
leaf
DCM
HydroMeOH 90%
Genotoxicity using the Ames test
(Salmonella typhimurium TA98)
shift mutations of
lowest dose is 0.50 µg/mL
higher doses are toxic
[110]
root
HydroEtOH 70%
In vivo—acute toxicity using mice
possible renal
dysfunction development
[58]
root bark
7-methyljuglone (1)
isodiospyrin (2)
Cytotoxicity against
human colon carcinoma cells
1-LD50 of
7.0 × 10−2 µg/mL
2-LD50 of
3.8 × 10−2 µg/mL
[61]
MeOH
D. whyteana
D. villosa
D. zombensis
Extracts: Ace—acetone; DCM—dichloromethane; EtOAc—ethyl acetate; EtOH—ethanol; H2 O—water;
Hex—hexane; HydroEtOH—ethanol; HydroMeOH—methanol; MeOH—methanol; P. ether—petroleum ether.
Concentration: ED50 —median effective dose; IC50 —half maximal inhibitory concentration; LC50 —lethal concentration 50%, LD50 —lethal dose 50%.
Plants 2023, 12, 2833
17 of 34
Most commonly, studies were found to be related to the in vitro assessment of cytotoxicity. For example, the extract of D. lycioides showed cytotoxicity to HeLa cells but
was non-toxic to normal cells [38]. The compound diosquinone has been shown to be
toxic against most cancer cell lines (human glioblastoma) and hormone-dependent human
prostate cancer [84]. In contrast, 7-methyljuglone and isodiospyrin compounds are active
against human colon carcinoma cells [61].
The organic extract of the inner seed of D. dichrophylla (Figure 6) is reported as
highly cytotoxic (LC50 = 29 µg/mL), particularly the isodiospyrin isolated from it
(LC50 = 0.13 µg/mL) [66].
Figure 6. Diospyros dichrophylla (Gand.) De Winter: Detail of fruits in nature, Mandevo, Namaacha
district, Maputo, 2010. Photography by Elsa Gomes.
Preclinical safety assessments of Diospyros species are of paramount importance;
however, few studies related to Mozambican Diospyros species have been conducted to
date. Cantrell et al. (2003) reported that D. dichrophylla is a potent phytotoxicant due to
the presence of isodiospyrin (from the inner seed) at a lethal dose of 0.13 g/mL [66]. In
another study, a hydroethanolic root extract of D. villosa showed possible development of
renal dysfunction using an acute toxicity test in mice [111].
2.3.7. Antibacterial Activity
In vitro antibacterial activity data collected from eleven Diospyros species (representing
35.5% of the total) are summarized in Table 6. Of the 11 species examined, 47 extracts
(including AgNPs) showed antimicrobial activity against multiple bacterial strains. The
methanolic extract
was the most tested. In some of the studies mentioned, biodirected
/
fractionation was also performed, and the antibacterial activity of the obtained fractions
and isolated compounds was determined. The results obtained are also shown in Table 6.
Plants 2023, 12, 2833
18 of 34
Table 6. In vitro antibacterial activity of Mozambican Diospyros and marker compounds.
Species
Parts Used
Test
Extract/
Compound
MIC (µg/mL)
Microorganism
Control (MIC)
µg/mL
Ref.
bark
BD
EtOAc
12
S. aureus ATCC 6538
DMSO
[65]
leaf
stem bark
BD
MeOH
125
E. coli ATCC 8740
ciprofloxacin 0.63
leaf
BD
MeOH
8000
root bark
BD
MeOH
500
S. aureus ATCC 25923
B. cereus ATCC 11775
E. coli ATCC 8740
ciprofloxacin 2.5
ciprofloxacin 0.08
ciprofloxacin 0.63
leaf
leaf
stem bark
leaf
stem bark
BD
BD
BD
MeOH
MeOH
MeOH
8000
4000
1000
BD
MeOH
125
branche
BD
MeOH
1250
branche
BD
Diospyroside A
branche
BD
Diospyroside B
branche
BD
Diospyroside C
branche
BD
Diospyroside D
branche
BD
juglone
branche
BD
7-methyljuglone
leaf
BA
leaf
BA
leaf
BA
EtOAc
Ace
EtOAc
Ace
MeOH
EtOAc
Ace
MeOH
D. abyssinica
D. bussei
[99]
D. kabuyeana
S. aureus ATCC 25923
ciprofloxacin 2.5
B. cereus ATCC 11775
ciprofloxacin 0.08
E. coli ATCC 8740
ciprofloxacin 0.63
[99]
D. lycioides
39
78–1250
39–78
156–625
39–156
312–625
156–312
19–78
39
39–156
78
0.10–0.16 *
0.12–0.17 *
0.16–0.36 *
0.20–0.45 *
0.16–0.27 *
0.05–0.45 *
0.05–0.45 *
0.05–0.45 *
S. sanguis, P. gingivalis,
S. mutans, P. intermedia
S. sanguis, P. intermedia
P. gingivalis, S. mutans
S. sanguis, P. gingivalis
P. intermedia, S. mutans
P. intermedia, S. mutans
P. gingivalis, S, sanguis
S. mutans, P. intermedia,
P. gingivalis, S. sanguis
P. intermedia, S. mutans,
S. sanguis, P. gingivalis
P. gingivalis, S. mutans
S. sanguis, P. intermedia
P. aeruginosa
ATCC 27853
S. aureus
ATCC 29213
p-iodonitrotetrazolium
chloride
E. faecalis
ATCC 29212
p-iodonitrotetrazolium
chloride
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
alkaloid sanguinarine
[41]
p-iodonitrotetrazolium
chloride
[38]
[38]
[38]
D. mafiensis
root bark
DCM
S. aureus
B. anthracis
IZ: 12 mm
root bark
P. ether-Fraction
IZ: 10–15 mm
S. typhi, S. boydii,
E. coli, K. pneumoniae
S. aureus, V. cholerae
Proteus sp., B. anthracis
S. typhi, S. boydii,
E. coli, K. pneumoniae
S. aureus, V. cholerae
Proteus sp., B. anthracis
gentamycin ampicillin
(20 µg/disc)
[103]
gentamycin ampicillin
(20 µg/disc)
[103]
isoniazid 5.0
isoniazid 5.0
[50]
[50]
ciprofloxacin, cefixime,
and gentamicin
[95]
D. mespiliformis
leaf
root
ADD
ADD
MeOH
MeOH
167
250
leaf
BD
EtOH
12,500–25,000
BD
Hex (F1)
nBOH (F2)
EtOAc (F3)
H2 O (F4)
leaf
leaf
root
(1)78.125–312.5
(2)156.25
(3)78.125–
156.25
(4)625–2500
625
625 (1)
>2500 (2 to 4)
S. aureus
S. aureus
Salmonella spp.,
Shigella spp.,
Campylobacter spp.
1-P. aeroginosa
2-S. aureus
3-E. coli
4-S. typhimurium
gentamicin 19.53
gentamicin 19.53
gentamicin 19.53
gentamicin 19.53
[97]
Plants 2023, 12, 2833
19 of 34
Table 6. Cont.
Species
Parts Used
leaf
leaf
root
Test
AD
BD
AD
Extract/
Compound
H2 O
HydroMeOH
10%
H2 O
HydroMeOH
10%
H2 O
HydroMeOH
10%
H2 O
HydroMeOH
10%
H2 O
HydroMeOH
10%
flavonol
O-rhamnoside
MIC (µg/mL)
Microorganism
Control (MIC)
µg/mL
250–500
125–500
H. influenzae (6 ci)
ampicillin 0.12–15.6
125–250
62.5–125
S. aureus (5 ci)
ampicillin 0.06–0.12
250–250
125–125
S. pneumoniae (3 ci)
ampicillin 0.015–0.12
250–250
125–125
S. pyogenes (8 ci)
ampicillin 0.015–0.06
250–500
125–250
M. catarrhalis (5 ci)
ampicillin 0.12–1.9
9770
S. aureus
not identified
diosquinone
3–30
diosquinone
15–16
S. aureus NCT 6571
S. aureus E3T
E. coli KL16
P. aeruginosa NCT 6750
ampicillin 5
Ref.
[112]
[77]
[78]
gentamicin 2
leaf
DD
methylated
flavone
IZ: 34 mm
E. coli
not identified
[78]
leaf
AWD
EtOH-Fraction
IZ: 20 mm
IZ: 18 mm
IZ: 16 mm
S. aureus, Shigella spp.
P. aeruginosa
septrin 15 mm
spetrin 16 mm
spetrin 15 mm
[113]
BD
MeOH
MeOH
MeOH
MeOH
MeOH
250
1000
500
1000
250
S. aureus ATCC 25923
B. cereus ATCC 11775
E. coli ATCC 8740
E. coli ATCC 8740
E. coli ATCC 8740
ciprofloxacin 0.08
ciprofloxacin 2.5
ciprofloxacin 0.63
ciprofloxacin 0.63
ciprofloxacin 0.63
[99]
Ace
230–1770
S. aureus, E. faecalis,
E. coli and P. aeruginosa
not reported
[22]
MeOH
MeOH
MeOH
MeOH
MeOH
4000
250
1000
4000
500
B. cereus ATCC 11775
E. coli ATCC 8740
S. aureus ATCC 25923
B. cereus ATCC 11775
E. coli ATCC 8740
ciprofloxacin 2.5
ciprofloxacin 0.63
ciprofloxacin 0.08
ciprofloxacin 2.5
ciprofloxacin 0.63
[99]
D. natalensis
leaf
leaf
leaf
root bark
stem bark
D. rotundifolia
not
reported
D. squarrosa
leaf
BD
root bark
BD
stem bark
BD
leaf
BD
MeOH
MeOH
MeOH
1000
2000
500
S. aureus ATCC 25923
B. cereus ATCC 11775
E. coli ATCC 8740
ciprofloxacin 0.08
ciprofloxacin 2.5
ciprofloxacin 0.63
[99]
root bark
stem bark
BD
MeOH
<6.25
E. coli ATCC 8740
ciprofloxacin 0.63
[82]
D. verrucosa
Plants 2023, 12, 2833
20 of 34
Table 6. Cont.
Species
Test
Extract/
Compound
MIC (µg/mL)
Microorganism
root
BD
HydroEtOH 70%
Ee
Fractions
62.5–312.5
15.6–62.5
31.2–62.5
E. faecalis ATCC 435628
E. coli ATCC 25922
M. luteus ATCC 10240
S. aureus ATCC 25923
leaf
DD
AgNPs
IZ: 15 mm
E. coli ATCC 25922
AgNPs 80 ◦ C
IZ: 18 mm
S. aureus ATCC 700698
AgNPs
IZ: 16 mm
AgNPs
IZ: 16 mm
Ace
MeOH
0.05–0.45 *
0.05–0.45 *
Parts Used
Control (MIC)
µg/mL
Ref.
D. villosa
S. epidermidis
ATCC 12228
not reported
not reported
not reported
not reported
ciprofloxacin 37 mm
gentamicin 20 mm
ciprofloxacin 6 mm
gentamicin 11 mm
[104]
[107]
ciprofloxacin 28 mm
gentamicin 20
Test: BD—broth dilution; DD—disc diffusion; ADD—agar disc diffusion; AWD—agar well diffusion. Extract: Ace—acetone; DCM—dichloromethane; Ee—ether; EtOAc—ethyl acetate; EtOH—ethanol; H2 O—water;
Hex—hexane; HydroMeOH—methanol; nBOH—n-butanol; P. ether—petroleum ether. Strains: B. anthracis—
Bacillus anthracis; B. cereus—Bacillus cereus; E. faecalis—Enterococcus faecalis; H. influenzae—Haemophilus influenzae;
K. pneumoniae—Klebsiella pneumoniae; M. catarrhalis—Moraxella catarrhalis; M. luteus—Micrococcus luteus;
P. gingivalis—Porphyromonas gingivalis; P. intermedia—Prevotella intermedia; S. typhi—Salmonella typhi;
S. typhimurium—Salmonella typhimurium; S. boydii—Shigella boydii; S. epidermis—Staphylococcus epidermidis;
S. sanguis—Streptococcus sanguinis; S. mutans—Streptococcus mutans; S. pyogenes—Streptococcus pyogenes;
V. cholerae—Vibrio cholerae. Abbreviations: ATCC—American type culture collection, BA—TLC bioautography,
ci—clinical isolate; IZ—zone of inhibition; MIC—minimum inhibitory concentration; AgNPs—silver nanoparticles;
* Rf—retardation factor.
According to the WHO, oral diseases are the most common non-communicable diseases, affecting people throughout life and causing pain, discomfort, disfigurement, and
even death [114]. The Global Burden of Disease Study reports that oral diseases are among
the leading causes of health problems, estimating that half of the world’s population is
affected by these diseases [114,115]. The same study provided a comprehensive assessment, and among the results evaluated, permanent tooth decay was the most common
cause, representing a major public health problem in many countries [116]. Therefore,
preventing and controlling the spread of this health problem is a global challenge, requiring
greater efforts and potentially innovative approaches to achieve it. The branches of several
Diospyros (particularly D. lycioides, D mespiliformis, and D. villosa) are used as toothbrushes
for oral care [41,44,52,104,117], and their plant extracts have been shown to be effective
against common oral pathogens, including Streptococcus mutans, S. sanguis, periodontal
pathogens (Porphyromonas gingivalis and Prevotella intermedia), Lactobacillus spp., and several
strains of Candida spp. [41,44,52,104,117]. In fact, over the past few decades, the scientific
community has become increasingly interested in understanding the versatility of medicinal plants from traditional herbal medicine and their guaranteed availability to improve
clinical approaches to infectious diseases with the intention of reducing antimicrobial
resistance [4].
2.4. Secondary Metabolites of Mozambican Diospyros Species as Potential Antimicrobial Agents
2.4.1. Naphtoquinones
Antibacterial Activity
Plumbagin (1, Figure 4) is recognized as an effective antibacterial agent against both
Gram-positive and Gram-negative strains of bacteria. This compound has also shown significant inhibitory activity (MIC < 12.5 µg/mL) against the resistant strain of Mycobacterium
tuberculosis H37Rv [3,78,118]. Plumbagin isolated from the bark extract of D. maritima and
showed activity against S. aureus and Aeromonas hydrophila (MIC = 0.625 and 5 µg/mL,
respectively) [119]. In addition, it has also been obtained from the root of D. mespiliformis
and has been described as one of the active marker compounds as well as an effective
antibacterial agent against Gram-positive and Gram-negative bacterial strains [50,77,112].
Plants 2023, 12, 2833
21 of 34
Another important compound isolated from D. hebecarpa, 7-methyljuglone
(2, Figure 4), also present in the root of Euclea natalensis (Ebenaceae), is potentially active
against Mycobacterium tuberculosis (H37Rv) [18].
Isodiospyrin (4, Figure 4), a dimeric 7-methyljuglone-derivative, has been reported to
be more active than diospyrin (3, Figure 4) against various Gram-positive strains, including
Streptococcus pyogenes, S. pneumoniae, Corynebacterium diphtheriae, Bacillus subtilis, Listeria
monocytogenes, Mycobacterium chelonae, and Micrococcus luteus. Isodiospyrin demonstrates
MIC values ranging from (0.78 to 50 µg/mL), while diospyrin shows MIC values ranging
from (1.56 to 100 µg/mL) [17].
Extensive research has unveiled the mechanism of action of diospyrin and 7-methyljuglone
against M. tuberculosis, highlighting their crucial role as non-competitive ATPase inhibitors
in key enzymatic reactions [120]. Additionally, emerging evidence has demonstrated the
anti-tuberculosis potential of other compounds, such as crassiflorone and plumbagin from
D. crassiflora, as well as diospyrone and plumbagin from D. canaliculata, both derived from
the stem bark [121].
In a study conducted by Kuete et al. (2010), it was demonstrated that isobavacalcone
and diospirone, derived from D. canaliculata, show promise as potential drugs against
multidrug-resistant Gram-negative strains. These compounds exhibited enhanced activity
when used in combination with efflux pump inhibitors, resulting in MIC values decreased
to <10 µg/mL [122,123].
Antifungal and Antiviral Activities
The NQs have been well established, particularly against several species of Candida,
infectious fungi of the mucosa, deep tissues, and the most common fungal diseases in
HIV/AIDS patients [124]. Plumbagin inhibits the growth of C. albicans, C. tropicalis, and
other fungi. In addition, fractions derived from plumbagin of Diospyros extracts are active
against C. albicans [1]. In comparison with ketoconazole, a standard antifungal compound, plumbagin is considered a promising antifungal agent and has been used against
C. albicans, C. glabrata, C. krusei, C. tropicalis, Cryptococcus neoformans, Aspergillus niger,
A. flavus, Alternaria sp., Cladosporium sp., Geotrichum candidum, Fusarium sp., Helminthosporum sp., M. gypseum, and Penicillium sp. [125–127]. This compound, isolated from the stem
bark of D. bipindensis, also exhibits significant activity against C. albicans [128–130].
Isolated from the root of D. virginiana, 7-methyljuglone and isodiospyrin have significant antifungal activity against Phomopsis obscurans (leaf blight), with 97.0% and 81.4%
growth inhibition at 30 µM, respectively. These compounds also demonstrate activity
against the pathogen Phomopsis viticola, with growth inhibition rates of 53.4% and 57.7%,
respectively [131].
The antiaflatoxigenic activity of D. mafiensis root, another Mozambican medicinal
plant, has been linked to the presence of diosquione and 3-hydroxydioquinone, making
this herbal drug also an important natural antifungal for preventing fungal growth and
aflatoxin accumulation in food [42]. In addition, this species has also been found to have
analgesic, antidiabetic, anti-inflammatory, and antioxidant effects, likely correlated with
the presence of these kind of constituents.
Antiparasitic Activity
NQs are highly active against pathogens in neglected tropical diseases, including
malaria, leishmaniasis, and trypanosomiasis (sleeping sickness). Studies examining
Plasmodium sp. have shown that isodiospyrin-derived isodiospyrol A exhibits antimalarial
activity (IC50 = 2.7 µg/mL) [132]. Anti-plasmodial activity has also been reported in the
ethanolic extract of leafs of D. monbuttensis (IC50 = 3.2 nM) [133]. Studies on malaria have
proposed a redox cycling mechanism (described for the novel antimalarial–antiparasitic
drug atovaquone) to support the in vitro activity of diospyrin and its analogues isolated
from D. montana against L. donovani [134].
Plants 2023, 12, 2833
22 of 34
Plumbagin and its derivative was shown to be active against Leishmania spp., while
diospyrin was active against Leishmania donovani [87]. Semisynthetic crassiflorone derivatives display trypanocidal activity against T. brucei and T. cruzi [135]. Antiplasmodial
activities with IC50 values of 16.5 to 29.4 g/mL against chloroquine-sensitive (3D7) and
chloroquine-resistant (K1) strains of P. falciparum were observed for the juglone-based
1,4-NQs present in D. sylvatica [136].
Concerning the assessment of anthelmintic activity, it was demonstrated in vitro that
D. oocarpa, D. nigrisence, D. candolleana, and D. montana are active on adult earthworms of
Pheritima posthuma [137]. Similarly, NQ derivatives, including diospyrin from D. oocarpa,
D. nigrisence, and D. candolleana, are antiprotozoal in addition to possessing anthelmintic
constituents [138].
2.4.2. Triterpenoids
Antibacterial and Antifungal Activities
Betulinic acid isolated from the root of D. lotus presents a broad spectrum against
several Gram-positive and Gram-negative bacteria [85,139–141]. Betulin isolated from
D. rubra is an active agent against Streptococcus pyogenes, with a MIC of 85 µg/mL, and
Corynebacterium diphtheriae, with a MIC range of 64 to 256 µg/mL [88].
Methanolic extract obtained from D. peregrina bark and seed containing triterpenoids
has been studied for its antidiarrheal properties [142]. Similarly, the methanolic extract
of D. peregrina fruit showed high activity against E. coli (12.6 mm zone of inhibition) and
against fungi C. albicans (10.7 mm zone of inhibition) and Penicillium spp. (7.33 mm) [143].
Betulin present in the hexane fraction isolated from the bark of D. paniculata is very
efficient against S. dysenteriae, which is responsible for diarrhea (MIC = 30 µg/mL) [144].
However, a study of a reductive green synthesis of nano-sized Ag particles using methanolic
root extracts of D. paniculata showed that the maximum activity was displayed against
Gram-positive bacteria compared to Gram-negative bacteria. The maximum activity was
observed against Penicillium notatum, A. flavus, and Saccharomyces cerevisiae, with moderate
activity towards C. albicans and A. niger [145].
In another study of ursane-type triterpenoids obtained from the leaf of D. dendo
Welw. Ex Hiern [EtOH−EtOAc (50:50) extract], antimicrobial activity (62% at 10 µg/mL)
against Pseudomonas aeruginosa was observed. This Gram-negative bacterium is considered
one of the three main causes of human opportunistic infections and has recently been
a useful model for the study of biofilm formation, implying antimicrobial resistance to
antibiotics [146].
Antiviral Activity
Structure–activity relationships between betulinic acid and its synthetic derivatives
inhibiting HIV-1 replication, HIV-1 entry, and HIV-protease or reverse transcriptase (RT)
have been verified [147,148]. Betulinic acid was identified as a highly promising antiviral
(anti-dengue) present in high proportions in most extracts of distinct species of Diospyros,
particularly from the bark of D. glans [83]. Aridanin, isolated from methanol extracts
obtained from the leaf, stem, and root of D. conocarpa, presents anti-HIV-1IN activity [149].
In a recent study, the antiviral activity of D. anisandra was demonstrated against the
influenza virus AH1N1pdm09. The n-hexane fruit extract exhibited HA inhibitory (HAI)
activity, and a fraction of it inhibited the hemagglutination from 12.5 up to 100 µg/mL,
which was attributed to the synergistic effect of the different compounds present [150].
Previously, possible antiviral activity against influenza A and B viruses has been attributed
to a redox effect of isolated zeylanone epoxide [151].
Antiparasitic Activity
Using in vitro antimalarial assays, betulinic acid 3-caffeate isolated from the dried leaf,
twig, and branch of D. quaesita was shown to be moderately active against both chloroquinesensitive and chloroquine-resistant P. falciparum clones [86]. Lupeol and lupenone, isolated
Plants 2023, 12, 2833
23 of 34
from the dichloromethane and ethyl acetate extracts of D. rubra stem, have shown moderate antimalarial activity against P. falciparum [88]. On the other hand, hydroethanolic
extracts from the trunk of D. gracilescens and the hexane fraction showed higher activity against promastigote and amastigote forms of L. donovani (IC50 = 5.84 µg/mL and
IC50 = 0.79 µg/mL, respectively) [87]. Aridanin isolated from methanol extracts of the leaf,
stem, and root of D. conocarpa can be sources of new antitrypanosomal active principles [149].
2.4.3. Tannins
Tannins isolated from Mozambican Diospyros species represent an important class of
secondary metabolites with remarkable antimicrobial potential against fungi, bacteria, and
yeast [152]. Their mechanism of action involves the disruption of microbial enzymes and
cell membranes, although their activities are diverse [153]. In addition, recent research has
suggested the ability of tannins to generate hydrogen peroxide, which contributes to their
important antibacterial properties [154].
Antibacterial and Antifungal Activities
D. melanoxylon bark is another medicinal plant considered to be active against Grampositive and Gram-negative bacteria, which is traditionally used for diarrhea, urinary, and
skin troubles and has confirmed claims against E. coli, S. aureus, S. epidermidis, Shigella
flexneri, Bacillus licheniformis, Bacillus brevis, Vibrio cholerae, P. aeruginosa, Streptococcus aureus,
Candida kruesi, and Bacillus subtilis [155]. Furthermore, it shows promise in the treatment of
candidiasis caused by different Candida species (C. viz, C. albicans, C. krusei, C. parapsilosis,
and C. tropicalis), with MIC values ranging from 0.375 to 6.0 mg/mL [156]. Extracts derived
from the bark of D. melanoxylon are rich in tannins and possess significant potential as
antimicrobial agents. In a recent study using strains isolated from humans, it was effective
against both Gram-positive and Gram-negative bacteria, suggesting the presence of a
broad spectrum of antibiotic compounds or simply general metabolic toxins in the plant
methanolic extract [157,158]. In another study conducted in India, acetone ethyl acetate
and methanol extracts of D. melanoxylon showed a MIC < 30 µg/mL against Aeromonas
hydrophila, Enterobacter aerogenes, E. coli, and Klebsiella pneumoniae [159].
Methanol extract obtained from the bark or seed of D. peregrina, which is rich in tannins
and other phenols, was evaluated for its antibacterial potential against the pathogenic
bacteria associated with diarrhea. The bark extract demonstrated inhibitory effects against
S. aureus, Shigella dysenteriae, E. coli, and P. aeruginosa, while the seed extract inhibited all
tested strains except for P. aeruginosa [160]. Similarly, the methanol extract of D. tricolor
leaves, known for its abundance of tannins and other phenols, exhibited antibacterial
activity against both Gram-positive bacteria (Bacillus cereus and S. aureus) and Gramnegative bacteria (Salmonella typhii and Escherichia coli) [161].
Diospyros kaki Thunb., known as the persimmon tree, is originally from Asia, but
it is cultivated in various parts of the world, including Mozambique. Different plant
parts are well-known and useful as medicinal plants, and the fruit is known as persimmon. This species has been extensively studied, particularly regarding the antimicrobial
activity of the tannins isolated from it. In a study conducted by Liu et al. (2019), the
antimicrobial effects of persimmon tannins (PTs) extracted from the fruit of D. kaki against
methicillin-resistant Staphylococcus aureus (MRSA) were investigated. The persimmon
tannins (MIC = 1000 µg/mL) displayed potential mechanisms of inhibitory activity (i.e.,
the tannins can change the normal morphology of MRSA and cause severe damage to
the cell wall and cell membrane) [152]. In addition, the hydrolysate of condensed tannins
(composed of a polymer of flavan-3-ols, such as catechin groups) exhibited high bacteriostatic activity in vitro against the M. avium complex (nontuberculous mycobacteria) that
causes opportunistic chronic pulmonary infections [63]. Aqueous extract from the D. kaki
fruit was tested in vivo, showing interesting antibacterial activities against Gram-negative
strains compared to Gram-positive bacteria, justifying its use in traditional medicine for the
treatment and/or management of disorders of the digestive system such as diarrhea [162].
Plants 2023, 12, 2833
24 of 34
The results of another study showed that the condensed tannins extracted from the unripened fruit of D. kaki displayed antibacterial activity against biofilms containing multiple
bacteria. It is estimated that intraoral cavity biofilms consist of at least 800 types of bacteria.
Therefore, it is suggested that this medicinal plant has a high potential for preventing
dental disease and aspiration pneumonitis in geriatric patients and recovering patients
when it is added to mouthwash and toothpaste [163].
The in vitro antibacterial potential of D. blancoi was also found against biofilm formation by S. mutans. Both extracts containing tannins and other phenols showed inhibition
ranges of 96% for methanol and 95% for ethyl acetate [164].
Recently, Diospyros species rich in tannins have been applied in the development of
nanoparticles. For instance, titanium dioxide (TiO2 ) nanoparticles containing D. ebenum leaf
extract exhibit excellent antibacterial activity and potential against Gram-negative bacteria
E. coli [165]. Silver nanoparticles (AgNPs) containing aqueous extract from the fruit of
D. malabarica have demonstrated antibacterial activity against S. aureus at 500 µg/mL and
against E. coli at 1000 ug/mL, with an average zone of inhibition size of 8.4 ± 0.3 mm and
12.1 ± 0.5 mm and 6.1 ± 0.7 mm and 13.1 ± 0.5 mm, respectively [166]. Similarly, biogenic
silver nanoparticles demonstrated excellent antibacterial activity against a broad range of
bacteria, with the highest antibacterial activity observed against E. faecalis (17.77 mm) and
B. subtilis (20 mm), also demonstrating good hemocompatibility against humans and rat
red blood cells [167].
Antiviral Activity
No studies were found on the specific activity of tannins isolated from the native
Diospyros species in Mozambique. However, a tannin isolated from D. kaki has been demonstrated to have in vitro antiviral activity against the influenza virus, vesicular stomatitis
virus, poliovirus, coxsackievirus, adenovirus, rotavirus, feline calicivirus, mouse norovirus,
Sendai virus, and Newcastle disease virus [168]. The results of another study involving
D. kaki extracts with tannin contents ranging from 0.08 to ≥0.11 mg/mL demonstrated their
capacity to inactivate human noroviruses and bacteriophage MS2, both of which are the
cause of gastroenteritis and foodborne illnesses worldwide (i.e., the results suggest that
the antiviral effect and astringent effects of tannins are likely related to noroviral genome
reduction and MS2 inactivation) [169].
Antiparasitic Activity
Species of the genus Diospyros contain a broad spectrum of antimicrobial agents identified using in vitro and/or in vivo methods against strains capable of causing opportunistic
infections as well as neglected parasitic diseases. The anthelmintic activity of a D. peregrina
fruit extract containing tannins was compared to the standard drug albendazole. The
extract was found to be more potent than the selected standard drug at a concentration of
10 mg/mL [170].
According to the WHO, malaria is one of the most widespread neglected diseases
in Africa, caused by the parasite Plasmodium and responsible for severe immune complications and deaths. The anti-Plasmodium activity of extracts from various species of the
Mozambican Diospyros species has been reported in the literature. Ethyl acetate extract from
D. abyssinica leaves showed moderate activity against chloroquine-resistant Plasmodium
falciparum (FcB1), while D. mespiliformis, traditionally used to treat malaria, showed potent
antimalarial activity in mice infected with Plasmodium berghei and significant inhibition of
beta-hematin using an in vitro assay [98].
The antiparasitic activity against Leishmania donovani, Trypanosoma cruzi, and
Trypanosoma brucei was confirmed in several studies on Diospyros species [99]. For example, an acetate leaf extract of D. abyssinica and the isodiospyrin and diospyrin marker
compounds isolated from the bark by bioguided fractionation showed high anti-L. donovani
activity (IC50 = 1.5 g/mL, extract, and IC50 = 0.5 g/mL, isolated compounds) [65].
Plants 2023, 12, 2833
25 of 34
3. Materials and Methods
This review was conducted according to the criteria described in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement (http:
//www.prisma-statement.org/; accessed on 16 January 2023). For this purpose, the scientific literature data were considered until 10 December 2022.
3.1. Search Strategy
The scientific data were collected using the search engines PubMed, Scopus, Web of
Science, and Google Scholar, identifying all scientific papers published between 1 January
1970, and 10 December 2022 using the keywords Diospyros AND antibacterial, Diospyros
AND antifungal, Diospyros AND antiparasitic, Diospyros AND antiviral, Diospyros AND
medicine, Diospyros AND chemical compounds, Diospyros AND biological activity, and
Diospyros AND toxicity.
3.2. Study Selection
As described in Figure 7, a total of 5528 scientific studies were included in the search
and initial data collection based on their title and abstract. After eliminating the duplicates,
2071 studies remained, of which 1852 could not be selected due to a lack of information relevant to this work. After the screening, 279 studies reporting on Diospyros were considered
eligible for inclusion in this review.
Figure 7. PRISMA flowchart of the screening process in the different
databases.
ff
Plants 2023, 12, 2833
26 of 34
ff
3.2.1. Criteria for Inclusion and Exclusion of Data
Inclusion Criteria
ff
ff
Related to the Diospyros genus, in particular species of the genus Diospyros present in
Mozambican Flora;
ff
Abstract or full text in English;
ff
Studies on Diospyros species concerning their medicinal
importance.
ff
Exclusion Criteria
Duplicate scientific publications;
Not directly related to medicinal issues and others related but not with species of
Mozambican Flora;
Containing irrelevant or incomplete information.
4. Conclusions
Species of the genus Diospyros have been studied worldwide, with a significant number
exhibiting pharmacological activity. One referenced example, D. kaki, native to East Asia,
NaoXinQing, is part of a patented and officially
ffi approved traditional Chinese medicine
formula for the treatment of stroke. However, there are no studies integrating data on all
Diospyros species present in the flora of Mozambique.
ffi
More than 70% of Mozambique’s population
ffi uses medicinal plants for primary health
care,
and
a
total
of
54.8%
of
the
Diospyros
species
used in the country’s ethnomedicine are
also used in other regions of Africa; however, the biological potential of most of them is still
largely unknown. For example, 64.5% of these species were not tested for their antibacterial
ffi
properties, namely D. abyssinica subsp. attenuata, D. abyssinica subsp. Chapmaniorum,
ffi
D. anitae, D. consolatae, D. consolatae-rotundifolia intermediates, D. dichrophylla, D. ferrea,
D. inhacaensis, D. kirkii, D. kirkii-mespiliformis intermediates, D. loureiriana subsp. Loureiriana,
ffi
D. natalensis subsp. Numulária, D. quiloensis, D. senensis, D. truncatifolia, D. usambarensis
subsp. Usambarensis/rufescens, D. villosa var. parvifolia, D. villosa var. villosa, D. whyteana,
D. zombensis, and Diospyros sp. no. 1 sensu FZ. On the other hand, several isolated
compounds of these species (particularly naphthoquinones and triterpenoids) have also
been isolated from other species of the genus Diospyros, showing different biological
activities including antiviral activity. However, no antiviral studies were found on the
Mozambican species.
Studies on the antifungal potential of Diospyros are still scarce. In fact, the antifungal
activity of 98.14% of the species (D. abyssinica subsp. attenuata, D. abyssinica subsp. chapmaniorum, D. anitae, D. bussei, D. consolatae, D. consolatae-rotundifolia intermediates, D. dichrophylla,
D. inhacaensis, D. kabuyeana, D. kirkii, D. kirkii-mespiliformis intermediates, D. loureiriana subsp.
loureiriana, D. lycioides Desf. subsp. sericea, D. natalensis subsp. natalensis, D. natalensis subsp.
numulária, D. quiloensis, D. rotundifolia, D. senensis, D. squarrosa, D. truncatifolia, D. verrucosa,
D. villosa var. parvifolia, D. whyteana, D. zombensis, and Diospyros sp. No. 1 sensu FZ) need
to be evaluated, as they are traditionally used to treat skin diseases and diseases of the
oral cavity, as well as other diseases where opportunistic fungal infections can co-occur. In
addition, antiparasitic activities have been studied in other species of the genus Diospyros,
however, 97.21% of Mozambican species (D. abyssinica subsp. attenuata, D. abyssinica subsp.
chapmaniorum, D. anitae, D. consolatae, D. consolatae-rotundifolia intermediates, D. dichrophylla,
D. ferrea, D. inhacaensis, D. kirkii, D. kirkii-mespiliformis intermediates, D. lycioides Desf. subsp.
sericea, D. mafiensis, D. natalensis subsp. numularia, D. quiloensis, D. rotundifolia, D. senensis,
D. squarrosa, D. truncatifolia, D. villosa var. villosa, D. villosa var. parvifolia, D. whyteana,
D. zombensis, and Diospyros. sp. no. 1 sensu FZ) have not yet had their antiparasitic
activities studied.
In summary, out of the 31 native and naturalized species in the flora of Mozambique
that are used in different regions of Africa, a total of 17 species have not been studied
as antimicrobial agents, of which three species, namely D. dichrophylla, D. whyteana, and
D. zombensis, have only been studied at the toxicological level. Of the 14 species that have
Plants 2023, 12, 2833
27 of 34
already been the subject of antimicrobial studies, D. abyssinica and D. mespiliformis are the
best studied.
This work provides comprehensive information on the chemical, biological, and
toxicological studies of the Diospyros species present in the flora of Mozambique, examining
their pharmacological potential in detail. Of the Diospyros plant parts, the root is the bestresearched and documented. The identified studies confirmed ongoing efforts to improve
the understanding of the mechanism of action underlying the biological activity, and in
particular, the antimicrobial activity of these species, drawing on their traditional use. In
addition, several secondary metabolites of Diospyros are currently being investigated for
their potential pharmacological applications. However, it is important to emphasize that
most of the available data are in vitro assessments of biological activity. Therefore, further
efforts are needed to obtain more comprehensive evidence aimed at strengthening the
validity and applicability of the results and ultimately contributing to public health benefits,
especially in the face of global antimicrobial resistance.
Author Contributions: Conceptualization, A.R., R.S., J.F.P. and O.S.; investigation, methodology, and
data collection, A.R., R.S., J.F.P. and O.S.; data analysis, A.R., R.S., J.F.P., I.B.M.d.S., E.T.G. and O.S.;
writing—original draft preparation, A.R., R.S., J.F.P. and O.S.; writing—review and editing, A.R., R.S.,
J.F.P., I.B.M.d.S., E.T.G. and O.S.; supervision—O.S.; project administration, O.S.; funding acquisition,
O.S. All authors have read and agreed to the published version of the manuscript.
Funding: This research was funded by the Foundation for Science and Technology (FCT, Portugal)
through the national funds FCT/MCTES to iMed.ULisboa (UIDP/04138/2020).
Data Availability Statement: Not applicable.
Conflicts of Interest: The authors declare no conflict of interest.
References
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
16.
17.
Rauf, A.; Uddin, G.; Patel, S.; Khan, A.; Halim, S.A.; Bawazeer, S.; Ahmad, K.; Muhammad, N.; Mubarak, M.S. Diospyros, an
under-Utilized, Multi-Purpose Plant Genus: A Review. Biomed. Pharmacother. 2017, 91, 714–730. [CrossRef] [PubMed]
Fareed, N.; El-Kersh, D.M.; Youssef, F.S.; Labib, R.M. Unveiling Major Ethnopharmacological Aspects of Genus Diospyros in
Context to Its Chemical Diversity: A Comprehensive Overview. J. Food Biochem. 2022, 46, e14413. [CrossRef]
Nematollahi, A.; Aminimoghadamfarouj, N.; Wiart, C. Reviews on 1,4-Naphthoquinones from Diospyros L. J. Asian Nat. Prod. Res.
2012, 14, 80–88. [CrossRef] [PubMed]
Mallavadhani, U.V.; Panda, A.K.; Rao, Y.R. Review Article Number 134 Pharmacology and Chemotaxonomy of Diospyros.
Phytochemistry 1998, 49, 901–951. [CrossRef] [PubMed]
Wallnöfer, B. The Biology and Systematics of Ebenaceae: A Review. Ann. Naturhist. Mus. Wien 2001, 103 Bd, 485–512.
White, F. Ebenaceae . Flora Zambesiaca 1983, 7, 269–271.
Denk, T.; Bouchal, J.M. Dispersed Pollen and Calyx Remains of Diospyros (Ebenaceae) from the Middle Miocene “Plant Beds” of
Søby, Denmark. GFF 2021, 143, 292–304. [CrossRef]
Burrows, J.E.; Burrows, S.M.; Lötter, M.C.; Schmidt, E. Trees and Shrubs of Mozambique; Print Matters Heritage: Cape Town, South
Africa, 2018; pp. 757–1114.
The Plant List (2013). Version 1.1. Published on the Internet. Available online: http://www.theplantlist.org/1.1/cite/ (accessed
on 27 January 2021).
The WFO Plant List|World Flora Online. Available online: https://wfoplantlist.org/plant-list (accessed on 1 December 2022).
Flora of Mozambique: Home Page. Available online: https://www.mozambiqueflora.com/ (accessed on 1 December 2022).
Da Silva, M.C.; Izidine, S.; Amude, A.B. A Preliminary Checklist of the Vascular Plants of Mozambique. In Southern Africa
Botanical Diversity Network 30; SABONET: Pretoria, South Africa, 2004; pp. 1–192.
World Health Organization. WHO Global Report on Traditional and Complementary Medicine 2019; World Health Organization:
Geneva, Switzerland, 2019.
WHO Traditional Medicine Strategy: 2014–2023. Available online: https://www.who.int/publications/i/item/9789241506096
(accessed on 1 December 2022).
Bandeira, S.O.; Gaspar, F.; Pagula, F.P. African Ethnobotany and Healthcare: Emphasis on Mozambique. Pharm. Biol. 2011,
39, 70–73. [CrossRef]
Babula, P.; Adam, V.; Havel, L.; Kizek, R. Noteworthy Secondary Metabolites naphthoquinones—Their Occurrence, Pharmacological Properties and Analysis. Curr. Pharm. Anal. 2009, 5, 47–68. [CrossRef]
Adeniyi, B.A.; Fong, H.H.S.; Pezzuto, J.M.; Luyengi, L.; Odelola, H.A. Antibacterial Activity of diospyrin, isodiospyrin and
bisisodiospyrin from the root of Diospyros piscatoria (Gurke) (Ebenaceae). Phytother. Res. 2000, 14, 112–117. [CrossRef]
Plants 2023, 12, 2833
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
28 of 34
Mahapatra, A.; Mativandlela, S.P.N.; Binneman, B.; Fourie, P.B.; Hamilton, C.J.; Meyer, J.J.M.; van der Kooy, F.; Houghton, P.;
Lall, N. Activity of 7-methyljuglone Derivatives against Mycobacterium tuberculosis and as Subversive Substrates for Mycothiol
Disulfide Reductase. Bioorg. Med. Chem. 2007, 15, 7638–7646. [CrossRef] [PubMed]
World Health Organization. WHO Library Cataloguing-in-Publication Data Global Action Plan on Antimicrobial Resistance.
Microbe Mag. 2015, 10, 354–355.
Antimicrobial Resistance: A Global Threat|UNEP—UN Environment Programme. Available online: https://www.unep.
org/explore-topics/chemicals-waste/what-we-do/emerging-issues/antimicrobial-resistance-global-threat (accessed on
14 January 2023).
WHO World Health Statistics 2022: Monitoring Health for the SDGs, Sustainable Development Goals. Available online:
https://www.who.int/publications/i/item/9789240051157 (accessed on 14 January 2023).
Kaikabo, A.A.; Suleiman, M.M.; Samuel, B.B.; Eloff, J.N. Antibacterial Activity of Eleven South African Plants Use in Treatment of
Diarrhoea in Folkloric Medicine. Afr. J. Tradit. Complement. Altern. Med. 2009, 6, 315–316.
Bandeira, S.; Senkoro, A.; Barbosa, F.; Mualassace, D.; Figueiredo, E. The Terrestrial Environment Adjacent to Maputo Bay. In The
Maputo Bay Ecosystem; Bandeira Salomão, P.J., Ed.; Western Indian Ocean Marine Science Association: Zanzibar Town, Tanzania,
2014; pp. 239–254.
Iwalewa, E.O.; McGaw, L.J.; Naidoo, V.; Eloff, J.N. Inflammation: The Foundation of Diseases and Disorders. A Review of
Phytomedicines of South African Origin Used to Treat Pain and Inflammatory Conditions. Afr. J. Biotechnol. 2007, 6, 2868–2885.
[CrossRef]
Conde, P.; Figueira, R.; Saraiva, S.; Catarino, L.; Romeiras, M.; Duarte, M.C. The Botanic Mission to Mozambique (1942–1948):
Contributions to Knowledge of the Medicinal Flora of Mozambique. Hist. Cienc. Saude Manguinhos 2014, 21, 539–585. [CrossRef]
Ribeiro, A.; Serrano, R.; Silva, I.B.M.D.; Gomes, E.T.; Pinto, J.F.; Silva, O. Silva Botanical Markers of Diospyros villosa Dried Root
for Pharmacognostic Characterization. In Proceedings of the iMed.Ulisboa Meeting, Lisbon, Portugal, 15 May 2021; Book of
Abstract: Lisbon, Portugal, 2021; pp. 57–191.
Maiga, A.; Malterud, K.E.; Diallo, D.; Paulsen, B.S. Antioxidant and 15-Lipoxygenase Inhibitory Activities of the Malian Medicinal
Plants Diospyros abyssinica (Hiern) F. White (Ebenaceae), Lannea velutina A. Rich (Anacardiaceae) and Crossopteryx febrifuga (Afzel)
Benth. (Rubiaceae). J. Ethnopharmacol. 2006, 104, 132–137. [CrossRef]
Nafiu, M.O.; Salawu, M.O.; Kazeem, M.I. Antioxidant Activity of African Medicinal Plants. In Medicinal Plant Research in Africa;
Elsevier: Amsterdam, The Netherlands, 2013; pp. 787–803.
Okello, S.V.; Nyunja, R.O.; Netondo, G.W.; Onyango, J.C. Ethnobotanical Study of Medicinal Plants Used by Sabaots of Mt. Elgon
Kenya. Afr. J. Tradit. Complement. Altern. Med. 2010, 7, 1–10. [CrossRef]
Namukobe, J.; Kasenene, J.M.; Kiremire, B.T.; Byamukama, R.; Kamatenesi-Mugisha, M.; Krief, S.; Dumontet, V.; Kabasa, J.D.
Traditional Plants Used for Medicinal Purposes by Local Communities around the Northern Sector of Kibale National Park,
Uganda. J. Ethnopharmacol. 2011, 136, 236–245. [CrossRef]
Lacroix, D.; Prado, S.; Kamoga, D.; Kasenene, J.; Namukobe, J.; Krief, S.; Dumontet, V.; Mouray, E.; Bodo, B.; Brunois, F. Antiplasmodial and Cytotoxic Activities of Medicinal Plants Traditionally Used in the Village of Kiohima, Uganda. J. Ethnopharmacol.
2011, 133, 850–855. [CrossRef]
Tugume, P.; Kakudidi, E.K.; Buyinza, M.; Namaalwa, J.; Kamatenesi, M.; Mucunguzi, P.; Kalema, J. Ethnobotanical Survey of
Medicinal Plant Species Used by Communities around Mabira Central Forest Reserve, Uganda. J. Ethnobiol. Ethnomed. 2016, 12, 5.
[CrossRef]
Timberlake, J.; Golding, J.; Clarke, P. Niassa Botanical Expedition—June 2003. Prep. Soc. Para A Gestão E Desenvolv. Da Reserva Do
Niassa Moçambique Biodivers. Found. Afr. 2004, 43, 3–20.
Kadavul, K.; Dixit, A.K. Ethnomedicinal Studies of the Woody Species of Kalrayan & Shervarayan Hills, Eastern Chats, Tamil
Nadu. Indian J. Tradit. Knowl. 2009, 8, 592–597.
Vijayalakshmi, R.; Ravindhran, R. Pharmacognostical Studies on Root of Diospyros ferrea (Willd.) Bakh and Aerva lanata Linn., a
Potent Indian Medicinal Plants. Asian J. Pharm. Clin. Res. 2013, 6, 323–327.
Vijayalakshmi, R.; Ravindhran, R. HPTLC Method for Quantitative Determination of gallic acid in Ethanolic Root Academic
Sciences Asian Journal of Pharmaceutical and Clinical Research. Asian J. Pharm. Clin. Res. 2012, 5, 170–174.
Choi, C.W.; Song, S.B.; Oh, J.S.; Kim, Y.H. Antiproliferation Effects of Selected Tanzania Plants. Afr. J. Tradit. Complement. Altern.
Med. 2015, 12, 96–102. [CrossRef]
Bagla, V.P.; Lubisi, V.Z.; Ndiitwani, T.; Mokgotho, M.P.; Mampuru, L.; Mbazima, V. Antibacterial and Antimetastatic Potential
of Diospyros lycioides Extract on Cervical Cancer Cells and Associated Pathogens. Evid.-Based Complement. Altern. Med. 2016,
2016, 1–10. [CrossRef]
Miller, J.S. Zulu Medicinal Plants: An Inventory By A. Hutchings with A. H. Scott, G. Lewis, and A. B. Cunningham (University
of Zululand). J. Nat. Prod. 1997, 60, 955. [CrossRef]
Semenya, S.S.; Maroyi, A. Ethnobotanical Survey of Plants Used by Bapedi Traditional Healers to Treat Tuberculosis and Its
Opportunistic Infections in the Limpopo Province, South Africa. S. Afr. J. Bot. 2019, 122, 401–421. [CrossRef]
Cai, L.; Wei, G.-X.; van der Bijl, P.; Wu, C.D. Namibian Chewing Stick, Diospyros lycioides, Contains Antibacterial Compounds
against Oral Pathogens. J. Agric. Food Chem. 2000, 48, 909–914. [CrossRef]
Plants 2023, 12, 2833
42.
43.
44.
45.
46.
47.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
29 of 34
Mmongoyo, J.A.; Nair, M.G.; Linz, J.E.; Wu, F.; Mugula, J.K.; Dissanayake, A.A.; Zhang, C.; Day, D.M.; Wee, J.M.; Strasburg, G.M.
Bioactive Compounds in Diospyros mafiensis Roots Inhibit Growth, Sporulation and Aflatoxin Production by Aspergillus flavus and
Aspergillus parasiticus. World Mycotoxin. J. 2017, 10, 237–248. [CrossRef]
Adzu, B.; Amos, S.; Muazzam, I.; Inyang, U.S.; Gamaniel, K.S. Neuropharmacological Screening of Diospyros mespiliformis in Mice.
J. Ethnopharmacol. 2002, 83, 139–143. [CrossRef] [PubMed]
Chinsembu, K.C. Ethnobotanical Study of Plants Used in the Management of HIV/AIDS-Related Diseases in Livingstone,
Southern Province, Zambia. Evid.-Based Complement. Altern. Med. 2016, 2016, 1–14. [CrossRef] [PubMed]
Adzu, B.; Amos, S.; Dzarma, S.; Muazzam, I.; Gamaniel, K.S. Pharmacological Evidence Favouring the Folkloric Use of Diospyros
mespiliformis Hochst in the Relief of Pain and Fever. J. Ethnopharmacol. 2002, 82, 191–195. [CrossRef] [PubMed]
Belemtougri, R.G.; Constantin, B.; Cognard, C.; Raymond, G.; Sawadogo, L. Effects of Two Medicinal Plants Psidium guajava L.
(Myrtaceae) and Diospyros mespiliformis L. (Ebenaceae) Leaf Extracts on Rat Skeletal Muscle Cells in Primary Culture. J. Zhejiang
Univ. Sci. B 2006, 7, 56–63. [CrossRef] [PubMed]
Mabona, U.; Viljoen, A.; Shikanga, E.; Marston, A.; Van Vuuren, S. Antimicrobial Activity of Southern African Medicinal Plants
with Dermatological Relevance: From an Ethnopharmacological Screening Approach, to Combination Studies and the Isolation
of a Bioactive Compound. J. Ethnopharmacol. 2013, 148, 45–55. [CrossRef]
Tapsoba, H.; Deschamps, J.-P. Use of Medicinal Plants for the Treatment of Oral Diseases in Burkina Faso. J. Ethnopharmacol. 2006,
104, 68–78. [CrossRef] [PubMed]
Luka, J.; Badau, S.J.; Mbaya, A.W.; Gadzama, J.J.; Kumshe, H.A. Acute Toxicity Study and Effect of Prolonged Administration
(28 Days) of Crude Ethanolic Root Extract of Diospyros mespiliformis Hochst (Ebenaceae) on Clinical, Haematological and Biochemical Parameters of Albino Rats. J. Ethnopharmacol. 2014, 153, 268–273. [CrossRef]
Nworu, C.; Onuigbo, E.; Omeje, J.; Nsirim, K.; Ogbu, J.; Ngwu, M.; Chah, K.; Esimone, C. Anti-Mycobacterial Activity of Root
and Leaf Extracts of Anthocleista djalonensis (Loganiaceae) and Diospyros mespiliformis (Ebenaceae). Int. J. Green Pharm. 2009, 3, 201.
[CrossRef]
Ebbo, A.A.; Sani, D.; Suleiman, M.M.; Ahmad, A.; Hassan, A.Z. Assessment of Antioxidant and Wound Healing Activity of the
Crude Methanolic Extract of Diospyros mespiliformis Hochst. Ex A. DC. (Ebenaceae) and Its Fractions in Wistar Rats. South Afr. J.
Bot. 2022, 150, 305–312. [CrossRef]
Chinsembu, K.C. Plants and Other Natural Products Used in the Management of Oral Infections and Improvement of Oral Health.
Acta Trop. 2016, 154, 6–18. [CrossRef]
Maroyi, A. Traditional Use of Medicinal Plants in South-Central Zimbabwe: Review and Perspectives. J. Ethnobiol. Ethnomed.
2013, 9, 31. [CrossRef] [PubMed]
Marston, A.; Msonthi, J.; Hostettmann, K. Naphthoquinones of Diospyros usambarensis Their Molluscicidal and Fungicidal
Activities. Planta Med. 1984, 50, 279–280. [CrossRef] [PubMed]
Hamza, O.J.M.; van den Bout-van den Beukel, C.J.P.; Matee, M.I.N.; Moshi, M.J.; Mikx, F.H.M.; Selemani, H.O.; Mbwambo, Z.H.;
van der Ven, A.J.A.M.; Verweij, P.E. Antifungal Activity of Some Tanzanian Plants Used Traditionally for the Treatment of Fungal
Infections. J. Ethnopharmacol. 2006, 108, 124–132. [CrossRef] [PubMed]
Moshi, M.J.; Mbwambo, Z.H. Experience of Tanzanian Traditional Healers in the Management of Non-Insulin Dependent Diabetes
Mellitus. Pharm. Biol. 2002, 40, 552–560. [CrossRef]
Khan, M.; Kishimba, M.; Locksley, H. Extractives from Ebenaceae: Constituents of the Root and Stem Barks of Diospyros verrucosa.
Planta Med. 1987, 53, 498. [CrossRef]
Ribeiro, A.; Serrano, R.; da Silva, I.B.M.; Gomes, E.T.; Pinto, J.F.; Silva, O. Diospyros villosa Root Monographic Quality Studies.
Plants 2022, 11, 3506. [CrossRef]
Aston Philander, L. An Ethnobotany of Western Cape Rasta Bush Medicine. J. Ethnopharmacol. 2011, 138, 578–594. [CrossRef]
Verschaeve, L.; Kestens, V.; Taylor, J.L.S.; Elgorashi, E.E.; Maes, A.; van Puyvelde, L.; de Kimpe, N.; van Staden, J. Investigation of
the Antimutagenic Effects of Selected South African Medicinal Plant Extracts. Toxicol. Vitr. 2004, 18, 29–35. [CrossRef]
Gafner, F.; Chapuis, J.-C.; Msonthi, J.D.; Hostettmann, K. Cytotoxic Naphthoquinones, Molluscicidal Saponins and Flavonols
from Diospyros zombensis. Phytochemistry 1987, 26, 2501–2503. [CrossRef]
Yoshihira, K.; Tezuka, M.; Takahashi, C.; Natori, S. Four New Naphthoquinone Derivatives from Diospyros spp. Chem. Pharm. Bull
1971, 19, 851–854. [CrossRef]
Matsumura, Y.; Kitabatake, M.; Ouji-Sageshima, N.; Yasui, S.; Mochida, N.; Nakano, R.; Kasahara, K.; Tomoda, K.;
Yano, H.; Kayano, S.; et al. Persimmon-Derived Tannin Has Bacteriostatic and Anti-Inflammatory Activity in a Murine Model of
Mycobacterium avium Complex (MAC) Disease. PLoS ONE 2017, 12, e0183489. [CrossRef] [PubMed]
Zhong, S.-M.; Waterman, P.G.; Jeffreys, J.A.D. Naphthoquinones and Triterpenes from African Diospyros Species. Phytochemistry
1984, 23, 1067–1072. [CrossRef]
Krief, S.; Huffman, M.A.; Sévenet, T.; Hladik, C.-M.; Grellier, P.; Loiseau, P.M.; Wrangham, R.W. Bioactive Properties of Plant
Species Ingested by Chimpanzees (Pan Troglodytes Schweinfurthii) in the Kibale National Park, Uganda. Am. J. Primatol. 2006,
68, 51–71. [CrossRef] [PubMed]
Cantrell, C.L.; Berhow, M.A.; Phillips, B.S.; Duval, S.M.; Weisleder, D.; Vaughn, S.F. Bioactive Crude Plant Seed Extracts from the
NCAUR Oilseed Repository. Phytomedicine 2003, 10, 325–333. [CrossRef] [PubMed]
Plants 2023, 12, 2833
67.
68.
69.
70.
71.
72.
73.
74.
75.
76.
77.
78.
79.
80.
81.
82.
83.
84.
85.
86.
87.
88.
89.
90.
91.
92.
93.
94.
30 of 34
Prada, N.J.; Vishnauvardhan, Z.; Baratha, J. Gc-Ms Identification of Bioactive Compounds from Solvent Ex-Tracts of Diospyros
ferrea (Willd.) Bakh, Leaf. Eur. J. Pharm. Sci. Off. J. Eur. Fed. Pharm. Sci. 2019, 6, 93–98.
Kuo, Y.H.; Li, S.Y.; Shen, C.C.; Yang, L.M.; Huang, H.C.; Liao, W.B.; Chang, C.I.; Kuo, Y.H.; Chen, C.F. Cytotoxic Constituents
from the Fruit of Diospyros ferrea. Chin. Pharm. J. 1997, 49, 207–216.
Tezuka, M.; Takahashi, C.; Kuroyanagi, M.; Satake, M.; Yoshihira, K.; Natori, S. New Naphthoquinones from Diospyros. Phytochemistry 1973, 12, 175–183. [CrossRef]
Vijayalakshmi, R.; Ravindhran, R. Comparative Fingerprint and Extraction Yield of Diospyros ferrea (Willd.) Bakh. Root with
Phenol Compounds (gallic acid), as Determined by Uv–Vis and Ft–Ir Spectroscopy. Asian Pac. J. Trop. Biomed. 2012, 2, S1367–S1371.
[CrossRef]
Van der Vijver, L.M.; Gerritsma, K.W. Naphthoquinones of Euclea and Diospyros Species. Phytochemistry 1974, 13, 2322–2323.
[CrossRef]
Théophile, O.; Christian, K.T.R.; Alain, Y.; Pascal, A.D.C.; Reine, B.G.S.; Diane, B.F.T.; Félicien, A.; Dominique, S.C.K. Natural
Chemical Compounds from Plants Extract for Prevention and Treatment of Oral Infections: A Review. Int. J. Biosci. (IJB) 2022,
20, 21–38. [CrossRef]
Khan, R.M.; Rwekika, E. 6′′ ,8’-Bisdiosquinone from Diospyros mafiensis. Phytochemistry 1999, 50, 143–146. [CrossRef]
Khan, M.R.; Rwekika, E. Naphthoquinones from the Barks of Three Species of the Genus Diospyros. Fitoterapia 1993, 64, 375.
Khan, M.R.; Rwekika, E. Triterpenoids from the Leaves of Four Species of Family Ebenaceae. Fitoterapia 1992, 63, 375–376.
Bulus, A.; Ben, A.C.; Florence, D.T.; Oluwakanyinsola, A.S.; Ogbaji, J.I. Isolation and Analgesic Property of Lupeol from Diospyros
mespiliformis Stem Bark. J. Med. Plants Res. 2015, 9, 813–819. [CrossRef]
Hawas, U.W.; El-Ansari, M.A.; El-Hagrassi, A.M. A New Acylated Flavone Glycoside, in vitro Antioxidant and Antimicrobial
Activities from Saudi Diospyros mespiliformis Hochst. Ex A. DC (Ebenaceae) Leaves. Z. Für Naturforschung C 2022, 77, 387–393.
[CrossRef] [PubMed]
Lajubutu, B.A.; Pinney, R.J.; Roberts, M.F.; Odelola, H.A.; Oso, B.A. Antibacterial Activity of Diosquinone and Plumbagin from
the Root of Diospyros mespiliformis (Hostch) (Ebenaceae). Phytother. Res. 1995, 9, 346–350. [CrossRef]
Sharma, V. Brief Review on the Genus Diospyros: A Rich Source of Naphthoquinones. Asian J. Adv. Basic Sci. 2017, 5, 34–53.
Khan, M.; Kishimba, M.; Locksley, H. Naphthoquinones from the Root and Stem Barks of Diospyros usambarensis. Planta Med.
1989, 55, 581. [CrossRef]
Hook, I.; Mills, C.; Sheridan, H. Bioactive naphthoquinones from Higher Plants. Stud. Nat. Prod. Chem. 2014, 41, 119–160.
[CrossRef]
Ebbo, A.A.; Mammam, M.; Suleiman, M.M.; Ahmed, A.; Bello, A. Preliminary Phytochemical Screening of Diospyros mespiliformis.
Anat. Physiol. 2014, 4, 156–158. [CrossRef]
Peyrat, L.-A.; Eparvier, V.; Eydoux, C.; Guillemot, J.-C.; Stien, D.; Litaudon, M. Chemical Diversity and Antiviral Potential in the
Pantropical Diospyros Genus. Fitoterapia 2016, 112, 9–15. [CrossRef]
Adeniyi, B.A.; Robert, M.F.; Chai, H.; Fong, H.H.S. In vitro Cytotoxicity Activity of diosquinone, a naphthoquinone epoxide.
Phytother. Res. 2003, 17, 282–284. [CrossRef] [PubMed]
Rauf, A.; Uddin, G.; Khan, H.; Arfan, M.; Siddiqui, B.S. Bioassay-Guided Isolation of Antibacterial Constituents from Diospyros
lotus Roots. Nat. Prod. Res. 2016, 30, 426–428. [CrossRef]
Ma, C.-Y.; Musoke, S.F.; Tan, G.T.; Sydara, K.; Bouamanivong, S.; Southavong, B.; Soejarto, D.D.; Fong, H.H.S.; Zhang, H.-J.
Study of Antimalarial Activity of Chemical Constituents from Diospyros quaesita. Chem. Biodivers 2008, 5, 2442–2448. [CrossRef]
[PubMed]
Njanpa, C.A.N.; Wouamba, S.C.N.; Yamthe, L.R.T.; Dize, D.; Tchatat, B.M.T.; Tsouh, P.V.F.; Pouofo, M.N.; Jouda, J.B.; Ndjakou,
B.L.; Sewald, N.; et al. Bio-Guided Isolation of Anti-Leishmanial Natural Products from Diospyros gracilescens L. (Ebenaceae). BMC
Complement. Med. Ther. 2021, 21, 1–12. [CrossRef]
Prachayasittikul, S.; Saraban, P.; Cherdtrakulkiat, R.; Ruchirawat, S.; Prachayasittikul, V. New Bioactive Triterpenoids and
Antimalarial Activity of Diospyros rubra Lec. EXCLI J. 2010, 9, 1–10. [PubMed]
Maitera, O.; Louis, H.; Oyebanji, O.; Anumah, A. Investigation of Tannin Content in Diospyros mespiliformis Extract Using Various
Extraction Solvents. J. Anal. Pharm. Res. 2018, 7, 00200. [CrossRef]
Maroyi, A. Diospyros lycioides Desf.: Review of Its Botany, Medicinal Uses, Pharmacological Activities and Phytochemistry. Asian
Pac. J. Trop. Biomed. 2018, 8, 130. [CrossRef]
Prada, N.J.; Vardhan, V.; Reddy, S. Antidiabetic Activity of Methanolic Leaf Extract of Diospyros ferrea (Willd) Bakh. in Streptozotocin Induced Diabetic Rats. Glob. J. Res. Anal. 2017, 6, 323–327. [CrossRef]
Marston, A.; Maillard, M.; Hostettmann, K. Search for Antifungal, Molluscicidal and Larvicidal Compounds from African
Medicinal Plants. J. Ethnopharmacol. 1993, 38, 209–214. [CrossRef]
Shikwambana, N.; Mahlo, S.M. A Survey of Antifungal Activity of Selected South African Plant Species Used for the Treatment of
Skin Infections. Nat. Prod. Commun. 2020, 15, 1934578X2092318. [CrossRef]
Diallo, D.; Marston, A.; Terreaux, C.; Touré, Y.; Smestad Paulsen, B.; Hostettmann, K. Screening of Malian Medicinal Plants for
Antifungal, Larvicidal, Molluscicidal, Antioxidant and Radical Scavenging Activities. Phytother. Res. 2001, 15, 401–406. [CrossRef]
[PubMed]
Plants 2023, 12, 2833
95.
96.
97.
98.
99.
100.
101.
102.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
115.
116.
117.
118.
31 of 34
Dougnon, V.; Hounsa, E.; Agbodjento, E.; Keilah, L.P.; Legba, B.B.; Sintondji, K.; Afaton, A.; Klotoe, J.R.; Baba-Moussa, L.;
Bankole, H. Percentage Destabilization Effect of Some West African Medicinal Plants on the Outer Membrane of Various Bacteria
Involved in Infectious Diarrhea. Biomed. Res. Int. 2021, 2021, 1–12. [CrossRef] [PubMed]
Samie, A.; Tambani, T.; Harshfield, E.; Green, E.; Ramalivhana, J.N.; Bessong, P.O. Antifungal Activities of Selected Venda
Medicinal Plants against Candida albicans, Candida krusei and Cryptococcus neoformans Isolated from South African AIDS Patients.
Afr. J. Biotechnol. 2010, 9, 2965–2976.
Ebbo, A.A.; Sani, D.; Suleiman, M.M.; Ahmed, A.; Hassan, A.Z. Phytochemical Composition, Proximate Analysis and Antimicrobial Screening of the Methanolic Extract of Diospyros mespiliformis Hochst Ex a. Dc (Ebenaceae). Pharmacogn. J. 2019, 11, 362–368.
[CrossRef]
Olanlokun, J.O.; Adetutu, J.A.; Olorunsogo, O.O. In vitro Inhibition of Beta-Hematin Formation and in vivo Effects of Diospyros
mespiliformis and Mondia Whitei Methanol Extracts on Chloroquine-Susceptible Plasmodium berghei-Induced Malaria in Mice.
Interv. Med. Appl. Sci. 2021, 11, 197–206. [CrossRef]
Christopher, R.; Mgani, Q.; Nyandoro, S.; Rousseau, A.; Vuuren, S.; Isaacs, M.; Hoppe, H. Antitrypanosomal, Antiplasmodial,
and Antibacterial Activities of Extracts from Selected Diospyros and Annonaceae Species. J. Complement. Med. Res. 2018, 7, 161.
[CrossRef]
Rani, V.S.; Ramana, K.V. Evaluation of Anti-Inflammatory and Analgesic Activities of Diospyros ferrea Leaves. Res. J. Pharm. Biol.
Chem. Sci. 2011, 2, 584–588.
Ramana, K.V.; Rambabu, P.S.G. Evaluation of Anti-Inflammatory and Analgesic Activities of Diospyros ferrea Root. Adv. Pharmacol.
Toxicol. 2010, 11, 37–40.
Ito, Y. Antifungal Compounds from Trees of the Genus Diospyros with Complete Assignment of Nuclear Magnetic Resonance
Data. Mokuzai Gakkaishi 1995, 41, 694–698.
Munissi, J.J.E. Cytotoxic and Antimicrobial Activities of the Constituents of Ten Plant Species from Tanzania. Tanzan. J. Sci. 2019,
45, 44–52.
Cirera, J.; da Silva, G.; Serrano, R.; Gomes, E.; Duarte, A.; Silva, O. Antimicrobial Activity of Diospyros villosa Root. Planta Med.
2010, 76, P454. [CrossRef]
Begum, S.; Munissi, J.J.E.; Buriyo, A.S.; Makangara, J.J.; Lucantoni, L.; Avery, V.M.; Erdelyi, M.; Nyandoro, S.S. Antiplasmodial,
Antimicrobial and Cytotoxic Activities of Extracts from Selected Medicinal Plants Growing in Tanzania. J. Biol. Act. Prod. Nat.
2020, 10, 165–176. [CrossRef]
Hegazy, A.K.; Mohamed, A.A.; Ali, S.I.; Alghamdi, N.M.; Abdel-Rahman, A.M.; Al-Sobeai, S. Chemical Ingredients and
Antioxidant Activities of Underutilized Wild Fruits. Heliyon 2019, 5, e01874. [CrossRef]
Adu, O.T.; Naidoo, Y.; Lin, J.; Adu, T.S.; Sivaram, V.; Dewir, Y.H.; El-Banna, A.N. Phytochemical Screening and Biological
Activities of Diospyros villosa (L.) De Winter Leaf and Stem-Bark Extracts. Horticulturae 2022, 8, 945. [CrossRef]
Ebbo, A.A.; Sani, D.; Suleiman, M.M.; Ahmad, A.; Hassan, A.Z. Acute and Sub-Chronic Toxicity Evaluation of the Crude
Methanolic Extract of Diospyros mespiliformis Hochst Ex a. Dc (Ebenaceae) and Its Fractions. Toxicol. Rep. 2020, 7, 1138–1144.
[CrossRef] [PubMed]
Mukhtar, Y.; Aliyu, B.S.; Zakari, S.M.; Aliko, A.A.; Habib, A.S.; Zubairu, S.M.; Bashir, R.A.; Tukur, S.; Jalingo, A.S.;
Abubakar, F.S.; et al. Phytochemical, Pharmacognostic and Acute Toxicity Study of Diospyros mespiliformis (African Ebony) Stem
Bark. Biosci. J. 2022, 10, 28–40.
Elgorashi, E. Screening of Medicinal Plants Used in South African Traditional Medicine for Genotoxic Effects. Toxicol. Lett. 2003,
143, 195–207. [CrossRef]
Cirera, J. Contribution to the Pharmacognostic Characterization of Diospyros villosa Root. Master’s Thesis, Universidade de Lisboa,
Lisboa, Portugal, 2012.
Sanogo, R.; Crisafi, G.; Germanò, M.P.; de Pasquale, R.; Bisignano, G. Evaluation of Malian Traditional Medicines: Screening for
Antimicrobial Activity. Ltd. Phytother. Res. 1998, 12, 154–156. [CrossRef]
Dangoggo, S.M.; Hassan, L.; Shina, I.S.; Manga, S. Phytochemical Analysis and Antibacterial Screening of Leaves of Diospyros
mespiliformis and Ziziphus spina-christi. J. Chem. 2012, 1, 31–37.
Peres, M.A.; Macpherson, L.M.D.; Weyant, R.J.; Daly, B.; Venturelli, R.; Mathur, M.R.; Listl, S.; Celeste, R.K.; Guarnizo-Herreño, C.C.;
Kearns, C.; et al. Oral diseases: A global public health challenge. Lancet. 2019, 394, 249–260. [CrossRef] [PubMed]
James, S.L.; Abate, D.; Abate, K.H.; Abay, S.M.; Abbafati, C.; Abbasi, N.; Abbastabar, H.; Abd-Allah, F.; Abdela, J.;
Abdelalim, A.; et al. Global, Regional, and National Incidence, Prevalence, and Years Lived with Disability for 354 Diseases and
Injuries for 195 Countries and Territories, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017. Lancet
2018, 392, 1789–1858. [CrossRef]
Douglas, K. Ethnobotanical Medicinal Plants Used as Chewing Sticks among the Kenyan Communities. Br. J. Pharm. Res. 2016,
13, 1–8. [CrossRef]
Mbaveng, A.T.; Kuete, V. Review of the Chemistry and Pharmacology of 7-Methyljugulone. Afr. Health Sci. 2014, 14, 201.
[CrossRef]
Padhye, S.; Dandawate, P.; Yusufi, M.; Ahmad, A.; Sarkar, F.H. Perspectives on Medicinal Properties of Plumbagin and Its
Analogs. Med. Res. Rev. 2012, 32, 1131–1158. [CrossRef]
Plants 2023, 12, 2833
32 of 34
119. Isnansetyo, A.; Putri Handayani, D.; Istiqomah, I.; Arif, A.; Kaneko, T. An Antibacterial Compound Purified from a Tropical
Coastal Plant, Diospyros maritima. Biodiversitas 2021, 23, 135–142. [CrossRef]
120. Karkare, S.; Chung, T.T.H.; Collin, F.; Mitchenall, L.A.; McKay, A.R.; Greive, S.J.; Meyer, J.J.M.; Lall, N.; Maxwell, A. The
Naphthoquinone diospyrin Is an Inhibitor of DNA Gyrase with a Novel Mechanism of Action. J. Biol. Chem. 2013, 288, 5149–5156.
[CrossRef] [PubMed]
121. Kuete, V.; Tangmouo, J.G.; Marion Meyer, J.J.; Lall, N. Diospyrone, crassiflorone and plumbagin: Three Antimycobacterial
and Antigonorrhoeal Naphthoquinones from Two Retrieved from Diospyros spp. Int. J. Antimicrob. Agents 2009, 34, 322–325.
[CrossRef]
122. Kuete, V.; Ngameni, B.; Tangmouo, J.G.; Bolla, J.-M.; Alibert-Franco, S.; Ngadjui, B.T.; Pagès, J.-M. Efflux Pumps Are Involved
in the Defense of Gram-Negative Bacteria against the Natural Products Isobavachalcone and Diospyrone. Antimicrob. Agents
Chemother. 2010, 54, 1749–1752. [CrossRef]
123. Tangmouo, J.G.; Lontsi, D.; Ngounou, F.N.; Kuete, V.; Meli, A.L.; Manfouo, R.N.; Kamdem W., H.; Tane, P.; Beng, V.P.;
Sondengam, B.L.; et al. Diospyrone, a new coumarinylbinaphthoquinone from Diospyros canaliculata (Ebenaceae): Structure
and Antimicrobial Activity. Bull. Chem. Soc. Ethiop. 2005, 19, 81–88.
124. Janeczko, M.; Kubiński, K.; Martyna, A.; Muzyczka, A.; Boguszewska-Czubara, A.; Czernik, S.; Tokarska-Rodak, M.;
Chwedczuk, M.; Demchuk, O.M.; Golczyk, H.; et al. 1,4-Naphthoquinone Derivatives Potently Suppress Candida albicans Growth,
Inhibit Formation of Hyphae and Show No Toxicity toward Zebrafish Embryos. J. Med. Microbiol. 2018, 67, 598–609. [CrossRef]
125. Dzoyem, J.P.; Tangmouo, J.G.; Lontsi, D.; Etoa, F.X.; Lohoue, P.J. In vitro Antifungal Activity of Extract and Plumbagin from the
Stem Bark of Diospyros crassiflora Hiern (Ebenaceae). Phytother. Res. 2007, 21, 671–674. [CrossRef] [PubMed]
126. Dzoyem, J.P.; Kechia, F.A.; Kuete, V.; Pieme, A.C.; Akak, C.M.; Tangmouo, J.G.; Lohoue, P.J. Phytotoxic, Antifungal Activities
and Acute Toxicity Studies of the Crude Extract and Compounds from Diospyros canaliculata. Nat. Prod. Res. 2011, 25, 741–749.
[CrossRef] [PubMed]
127. Surapuram, V.; Setzer, W.N.; McFeeters, R.L.; McFeeters, H. Antifungal Activity of Plant Extracts against Aspergillus niger and
Rhizopus stolonifer. Nat. Prod. Commun. 2014, 9, 1934578X1400901. [CrossRef]
128. Ilaria, C.; Queiroz, E.; Brusotti, G.; Favre-Godal, Q.; Caccialanza, G.; Moundipa, P.; Wolfender, J. Antifungal Compounds Isolated
from Diospyros bipindensis. Planta Med. 2012, 78, PI427. [CrossRef]
129. Cesari, I.; Queiroz, E.F.; Favre-Godal, Q.; Marcourt, L.; Caccialanza, G.; Moundipa, P.F.; Brusotti, G.; Wolfender, J.-L. Extensive
Phytochemical Investigation of the Polar Constituents of Diospyros bipindensis Gürke Traditionally Used by Baka Pygmies.
Phytochemistry 2013, 96, 279–287. [CrossRef]
130. Cesari, I.; Hoerlé, M.; Simoes-Pires, C.; Grisoli, P.; Queiroz, E.F.; Dacarro, C.; Marcourt, L.; Moundipa, P.F.; Carrupt, P.A.;
Cuendet, M.; et al. Anti-Inflammatory, Antimicrobial and Antioxidant Activities of Diospyros bipindensis (Gürke) Extracts and Its
Main Constituents. J. Ethnopharmacol. 2013, 146, 264–270. [CrossRef]
131. Wang, X.; Habib, E.; León, F.; Radwan, M.M.; Tabanca, N.; Gao, J.; Wedge, D.E.; Cutler, S.J. Antifungal Metabolites from the Roots
of Diospyros virginiana by Overpressure Layer Chromatography. Chem. Biodivers 2011, 8, 2331–2340. [CrossRef]
132. Prajoubklang, A.; Sirithunyalug, B.; Charoenchai, P.; Suvannakad, R.; Sriubolmas, N.; Piyamongkol, S.; Kongsaeree, P.;
Kittakoop, P. Bioactive Deoxypreussomerins and Dimeric Naphthoquinones from Diospyros ehretioides Fruits: Deoxypreussomerins
May Not Be Plant Metabolites But May Be from Fungal epiphytes or endophytes. Chem. Biodivers 2005, 2, 1358–1367. [CrossRef]
133. Olasehinde, G.I.; Ojurongbe, O.; Adeyeba, A.O.; Fagade, O.E.; Valecha, N.; Ayanda, I.O.; Ajayi, A.A.; Egwari, L.O. In vitro Studies
on the Sensitivity Pattern of Plasmodium falciparum to Anti-Malarial Drugs and Local Herbal Extracts. Malar. J. 2014, 13, 63.
[CrossRef]
134. Hazra, B.; Ghosh, R.; Banerjee, A.; Kirby, G.C.; Warhurst, D.C.; Phillipson, J.D. In vitro Antiplasmodial Effects of diospyrin, a
Plant-Derived naphthoquinoid, and a Novel Series of Derivatives. Phytother. Res. 1995, 9, 72–74. [CrossRef]
135. Uliassi, E.; Fiorani, G.; Krauth-Siegel, R.L.; Bergamini, C.; Fato, R.; Bianchini, G.; Carlos Menéndez, J.; Molina, M.T.;
López-Montero, E.; Falchi, F.; et al. Crassiflorone Derivatives That Inhibit Trypanosoma brucei glyceraldehyde-3-phosphate
dehydrogenase (Tb GAPDH) and Trypanosoma cruzi trypanothione reductase (Tc TR) and Display Trypanocidal Activity. Eur. J.
Med. Chem. 2017, 141, 138–148. [CrossRef] [PubMed]
136. Kantamreddi, V.S.S.; Wright, C.W. Investigation of Indian Diospyros Species for Antiplasmodial Properties. Evid.-Based Complement.
Altern. Med. 2008, 5, 187–190. [CrossRef] [PubMed]
137. Rajarajeshwari, N.; Ganapaty, S.; Harish Kumar, D.H. In vitro Anthelmintic Activity of Five Rare Species of Diospyros. Int. J.
Pharm. Sci. 2010, 2, 445–447.
138. Amar Dev, M.J.; Rajarajeshwari, N.; Ganapaty, S.; Parixit, B.; Brun, R. Antiprotozoal and Anthelmintic Naphthoquinones from
Three Unexplored Species of Diospyros. J. Nat. Remedies 2012, 12, 129–134.
139. Yue, X.; Yang, H.; Wang, T.; Dong, S.; Sun, Z.; Wang, Y.; Luo, X.; Chen, B.; Yao, G.; Gao, Y.; et al. Molecules and Medical Function
of Diospyros lotus L. Therm. Sci. 2020, 24, 1705–1712. [CrossRef]
140. Ayoub, A.; Singh, J.; Hameed, F.; Mushtaq, M. Evaluation of Secondary Metabolites (Antibacterial and Antioxidant Activity) of
Amlok (Diospyros lotus L) Fruit Extracts of Jammu Region. J. Pharm. Res. Int. 2021, 32, 8–19. [CrossRef]
141. Yang, H.-Q.; Chen, G.-H.; Dong, S.; Sun, Z.; Wang, Y.; Luo, X.; Chen, B.; Yao, G.; Gao, Y.; Lv, C.; et al. Chemical Constituents and
Medical Function of Leaves of Diospyros lotus L. Therm. Sci. 2020, 24, 1633–1639. [CrossRef]
Plants 2023, 12, 2833
33 of 34
142. Rouf, R.; Uddin, S.J.; Shilpi, J.A.; Toufiq-Ur-Rahman, M.; Ferdous, M.M.; Sarker, S.D. Anti-Diarrhoeal Properties of Diospyros
peregrina in the Castor Oil-Induced Diarrhoea Model in Mice. Ars. Pharm. 2006, 47, 81–89.
143. Dewanjee, S.; Kundu, M.; Maiti, A.; Majumdar, R.; Majumdar, A.; Mandel, S.C. In Vitro Evaluation of Antimicrobial Activity of
Crude Extract from Plants Diospyros peregrina, Coccinia grandis and Swietenia macrophylla. Trop. J. Pharm. Res. 2007, 6, 773–778.
[CrossRef]
144. Sinha, B.N.; Bansal, S.K.; Pattnaik, A.K. Phytochemical and Antimicrobial Activity of Extracts, Fractions and Betulin, 7-Methyl
Juglone Obtained from Diospyros paniculata. J. Nat. Remedies 2009, 9, 99–102.
145. Rao, N.H.; Lakshmidevi, N.; Pammi SV, N.; Kollu, P.; Ganapaty, S.; Lakshmi, P. Green Synthesis of Silver Nanoparticles Using
Methanolic Root Extracts of Diospyros paniculata and Their Antimicrobial Activities. Mater. Sci. Eng. C 2016, 62, 553–557.
[CrossRef]
146. Hu, J.-F.; Garo, E.; Goering, M.G.; Pasmore, M.; Yoo, H.-D.; Esser, T.; Sestrich, J.; Cremin, P.A.; Hough, G.W.; Perrone, P.; et al.
Bacterial Biofilm Inhibitors from Diospyros dendo. J. Nat. Prod. 2006, 69, 118–120. [CrossRef]
147. Yogeeswari, P.; Sriram, D. Betulinic acid and Its Derivatives: A Review on Their Biological Properties. Curr. Med. Chem. 2005,
12, 657–666. [CrossRef] [PubMed]
148. Baglin, I.; Mitaine-Offer, A.C.; Nour, M.; Tan, K.; Cave, C.; Lacaille-Dubois, M.A. A Review of Natural and Modified betulinic,
ursolic and echinocystic acid derivatives as Potential Antitumor and Anti-HIV Agents. Mini-Rev. Med. Chem. 2003, 3, 525–539.
[CrossRef]
149. Fouokeng, Y.; Feumo Feusso, H.M.; Mbosso Teinkela, J.E.; Siwe Noundou, X.; Wintjens, R.; Isaacs, M.; Hoppe, H.C.;
Krause, R.W.M.; Azebaze, A.G.B.; Vardamides, J.C. In vitro Antimalarial, Antitrypanosomal and HIV-1 Integrase Inhibitory
Activities of Two Cameroonian Medicinal Plants: Antrocaryon klaineanum (Anacardiaceae) and Diospyros conocarpa (Ebenaceae).
South Afr. J. Bot. 2019, 122, 510–517. [CrossRef]
150. Juárez-Méndez, M.T.; Borges-Argáez, R.; Ayora-Talavera, G.; Escalante-Rebolledo, S.E.; Escalante-Erosa, F.; Cáceres-Farfán, M.
Diospyros anisandra Phytochemical Analysis and Anti-Hemagglutinin-Neuraminidase Activity on Influenza AH1N1pdm09 Virus.
Nat. Prod. Res. 2022, 36, 2666–2672. [CrossRef]
151. Cetina-Montejo, L.; Ayora-Talavera, G.; Borges-Argáez, R. Zeylanone Epoxide Isolated from Diospyros anisandra Stem Bark Inhibits
Influenza Virus in vitro. Arch. Virol. 2019, 164, 1543–1552. [CrossRef]
152. Liu, M.; Yang, K.; Wang, J.; Zhang, J.; Qi, Y.; Wei, X.; Fan, M. Young Astringent Persimmon Tannin Inhibits Methicillin-Resistant
Staphylococcus aureus Isolated from Pork. LWT 2019, 100, 48–55. [CrossRef]
153. Maugeri, A.; Lombardo, G.E.; Cirmi, S.; Süntar, I.; Barreca, D.; Laganà, G.; Navarra, M. Pharmacology and Toxicology of tannins.
Arch. Toxicol. 2022, 96, 1257–1277. [CrossRef] [PubMed]
154. Arakawa, H.; Takasaki, M.; Tajima, N.; Fukamachi, H.; Igarashi, T. Antibacterial Activities of Persimmon Extracts Relate with
Their Hydrogen Peroxide Concentration. Biol. Pharm. Bull. 2014, 37, 1119–1123. [CrossRef] [PubMed]
155. Thatoi, H.N.; Panda, S.K.; Rath, S.K.; Dutta, S.K. Antimicrobial Activity and Ethnomedicinal Uses of Some Medicinal Plants from
Similipal Biosphere Reserve, Orissa. Asian J. Plant Sci. 2008, 7, 260–267. [CrossRef]
156. Dutta, S.; Panda, S.; Dubey, D. Anticandidal Activity of Diospyros melanoxylon Roxb. Bark from Similipal Biosphere Reserve,
Orissa, India. Int. J. Green Pharm. 2010, 4, 102. [CrossRef]
157. Supriya, K.A.; Growther, L. In-vitro Antioxidant and Antibacterial Activity of Different Extracts of Diospyros melanoxylon Roxb.
Int. J. Pharm. Sci. Res. 2019, 10, 1820–1827.
158. Kanta Rath, S.; Kumar Patra, J.; Gouda, S.; Kumar Sahoo, S.; Thatoi, H.; Kumar Dutta, S. Evaluation of Antioxidant Potential,
Phytochemical Analysis and Chromatographic Separation of Bark Extracts of Diospyros melanoxylon Roxb. J. Biol. Act. Prod. Nat.
2014, 4, 377–390. [CrossRef]
159. Kamaraj, C.; Rahuman, A.A.; Siva, C.; Iyappan, M.; Kirthi, A.V. Evaluation of Antibacterial Activity of Selected Medicinal Plant
Extracts from South India against Human Pathogens. Asian Pac. J. Trop. Dis. 2012, 2, S296–S301. [CrossRef]
160. Wangensteen, H.; Klarpås, L.; Alamgir, M.; Samuelsen, A.; Malterud, K. Can Scientific Evidence Support Using Bangladeshi
Traditional Medicinal Plants in the Treatment of Diarrhoea? A Review on Seven Plants. Nutrients 2013, 5, 1757–1800. [CrossRef]
161. Vijayan, G.S.; Chandra, J. Effect of Methanolic and Ethyl Acetate Leaf Extract of Diospyros discolor against gram positive and gram
negative bacteria. J. Pharm. Sci. 2015, 8, 389–392.
162. Dhawefi, N.; Jedidi, S.; Rtibi, K.; Jridi, M.; Sammeri, H.; Abidi, C.; Zouari, N.; Sebai, H. Antidiarrheal, Antimicrobial, and
Antioxidant Properties of the Aqueous Extract of Tunisian Persimmon (Diospyros kaki Thunb.) Fruits. J. Med. Food 2021,
24, 1100–1112. [CrossRef]
163. Tomiyama, K.; Mukai, Y.; Saito, M.; Watanabe, K.; Kumada, H.; Nihei, T.; Hamada, N.; Teranaka, T. Antibacterial Action of a
Condensed tannin Extracted from Astringent Persimmon as a Component of Food Addictive Pancil PS-M on Oral Polymicrobial
Biofilms. Biomed. Res. Int. 2016, 2016, 1–7. [CrossRef]
164. Tahir, L.; Aslam, A.; Ahmed, S. Antibacterial Activities of Diospyros blancoi, Phoenix Dactylifera and Morus nigra against Dental
Caries Causing Pathogens: An in vitro Study. Pak. J. Pharm. Sci. 2017, 30, 163–169. [PubMed]
165. Senthilkumar, S.; Ashok, M.; Kashinath, L.; Sanjeeviraja, C.; Rajendran, A. Phytosynthesis and Characterization of TiO2
Nanoparticles Using Diospyros ebenum Leaf Extract and Their Antibacterial and Photocatalytic Degradation of Crystal Violet.
Smart Sci. 2018, 6, 1–9. [CrossRef]
Plants 2023, 12, 2833
34 of 34
166. Bharadwaj, K.K.; Rabha, B.; Pati, S.; Choudhury, B.K.; Sarkar, T.; Gogoi, S.K.; Kakati, N.; Baishya, D.; Kari, Z.A.;
Edinur, H.A. Green Synthesis of Silver Nanoparticles Using Diospyros malabarica Fruit Extract and Assessments of Their
Antimicrobial, Anticancer and Catalytic Reduction of 4-Nitrophenol (4-NP). Nanomaterials 2021, 11, 1999. [CrossRef]
167. Polash, S.A.; Hamza, A.; Hossain, M.M.; Tushar, M.H.; Takikawa, M.; Shubhra, R.D.; Saiara, N.; Saha, T.; Takeoka, S.; Sarker, S.R.
Diospyros malabarica Fruit Extract Derived Silver Nanoparticles: A Biocompatible Antibacterial Agent. Front. Nanotechnol. 2022,
4, 888444. [CrossRef]
168. Ueda, K.; Kawabata, R.; Irie, T.; Nakai, Y.; Tohya, Y.; Sakaguchi, T. Inactivation of Pathogenic Viruses by Plant-Derived tannins:
Strong Effects of Extracts from Persimmon (Diospyros kaki) on a Broad Range of Viruses. PLoS ONE 2013, 8, e55343. [CrossRef]
169. Kamimoto, M.; Nakai, Y.; Tsuji, T.; Shimamoto, T.; Shimamoto, T. Antiviral Effects of Persimmon Extract on Human Norovirus
and Its Surrogate, Bacteriophage MS2. J. Food Sci. 2014, 79, M941–M946. [CrossRef]
170. Dewanjee, S.; Maiti, A.; Kundu, M.; Mandal, S.C. Evaluation of Anthelmintic Activity of Crude Extracts of Diospyros peregrina,
Coccinia grandis, Schima wallichii. Dhaka Univ. J. Pharm. Sci. 1970, 6, 121–123. [CrossRef]
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual
author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to
people or property resulting from any ideas, methods, instructions or products referred to in the content.