Chapter 4
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Hypoxis hemerocallidea (African potato):
A Botanical Whose Time Has Come?
David R. Katerere*
Department of Pharmaceutical Science, Faculty of Science, Tshwane
University of Technology, Arcadia campus, Pretoria, 0001, South Africa
*E-mail: david.katerere@mrc.ac.za.
Hypoxis hemerocallidea is one of Southern Africa’s most
important and popular medicinal plants. It is used for a wide
a range of traditional medical treatments including urinary
tract infections, heart disease, infertility and anxiety. It’s
most popular contemporary use is for prostate disorders for
which there is increasingly good evidence about it’s eficacy.
Phytosterols are thought to be the main bioactive compounds
for this indication and also for anti-lipidemic, anti-diabetic and
anti-inlammatory properties exhibited by hypoxis extracts.
Despite the popularity of hypoxis as a herbal and botanical
medicine, the research into it’s pharmacological application has
not been of suficient depth and width to prove it’s utility in
modern medicine. Recent data using a colitis model presents
an exciting new avenue which might inally yield products.
However there continues to be a need for sustained in vitro and
more importantly in vivo studies if this useful plant is be fully
explored.
Introduction
Traditional medicine has experienced a resurgence in Africa in recent times.
This is largely to do with a new sense of cultural pride following independence
from colonial authorities who sought to suppress such practices during their
tenure (1). In post-colonial Africa, there has also been limited access to allopathic
medical services. Further, the emergence of new diseases such as HIV, and
© 2013 American Chemical Society
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previously unknown chronic diseases e.g. diabetes and cancer, most of which
have no known medical cures has accelerated the growth of Complementary and
Alternative Medicine (CAM) (2, 3)
WHO estimates that 80% of the world’s population still largely relies on
traditional medicine to meet it’s healthcare needs (4). South Africa has 7000
plants which are used in traditional medicine (5–7). One of the most famous, and
certainly the most controversial is Hypoxis hemerocallidea. Commonly known as
African potato, this herb was until recently widely promoted by a now deceased
South African minister of health as an alternative to treatment of HIV / AIDS (8,
9) this despite little or no supporting scientiic evidence (10).
Botanical Information
Hypoxis hemerocallidea Fisch. & C.A. Mey, previously known as H. rooperi
belongs to the family Hypoxidaceae which consists of 8 genera (11). Based on
similarities with species of the Amaryllidaceae and Liliaceae family, the genera
were previously classiied in these taxa (12).
The hypoxis genus contains 130 species including H. hemerocallidea, H.
acuminate, H. iridifolia and H. rigidula of which the irst is most widely used
and is therefore the primary focus of this chapter. The moniker African potato is
to some extent a misnomer as the rootstock is a corm rather than a tuber and the
name causes confusion with tuberous Plectranthus esculentus (13). There is some
evidence that the common hypoxis species are used interchangeably in traditional
medical practice, sometimes inadvertently because of their close similarities (14).
Hypoxis grows as a stemless, perennial geophyte with large black ibrous
corms which are bright yellow inside when freshly cut (15). The leaves are
organized typically into three ranks and maybe slightly hairy. The lowers
which appear between October and January (16) are star-shaped and bright
yellow and the number per inlorescence may vary from two to twelve (15,
17). While it is indigenous to southern Africa, hypoxis has a world-wide
cosmopolitan distribution. It grows widely in the savanna grasslands of South
Africa, Swaziland, Lesotho , Mozambique, Zimbabwe and into some parts of
East Africa (11, 16). It has also been reported to grow in meanders, grasslands
and mountains of South America, Australia and coastal areas of Asia (18).
Traditional and Contemporary Use
The rootstock of Hypoxis is the plant part of choice for medicinal and dietary
use. It is the iconic African potato promoted by proponents of African traditional
medicine in South Africa as a cure-all and derided by opponents as quackery (19)
in the country’s highly charged political environment at the turn of the century.
In Zulu traditional medicine it is widely known as “zifozonke” literally meaning
“panacea” (20). It is known as African potato, starlower / South African star
grass, Ilabatheka, Inkofe (in Zulu), sterretjie (in Afrikaans), moli kharatsa, monna
wa maledu, thitidi (in Sotho), hodzori (in Shona) (21).
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The aqueous infusion is used as tonic in children and to treat dizziness and
mental disorders in adults (16). Hypoxis is widely used traditionally particularly
in Zulu society for heart disease, bad dreams, anxiety, insanity, barrenness,
intestinal parasites, urinary tract infections among other indications (11, 22).
Related species mainly H. colchicifolia (syn. H. oligotricha), H obtuse, H.
nyasica and H. angustifolia are also used for similar indications (11). In addition
H. obtuse, which more commonly grows north of South Africa’s border is used
traditionally for infertility in women, abdominal pains, heart pains, bile emesis,
gonorrhea and for aphrodisiac effects (21).
Hypoxis also has ethnoveterinary uses.
In South Africa Hypoxis
hemerocallidea and H.rigidula have been reportedly used for fertility
enhancement, general ailments, heartwater, and to prevent abortion in cattle by
the Tswana people (23) . Kambizi (24) has reported that fresh cut corms are
applied to the face by Xhosa women as facial treatments or used to treat burns.
In contemporary society, the use of hypoxis encompasses many of the
traditional uses and more recent indications. Today it is marketed both in its crude
unprocessed form (at traditional medicine (so-called muthi) markets) (7) and
also in pharmaceutical formulations and packaging as a phytomedicine in retail
pharmacies. In both formats the marketing materials carry many unsubstantiated
claims viz. HIV / AIDS, arthritis, myalgic encephalomyelitis (ME), hypertension,
asthma, diabetes mellitus, cancer, arthritis, psoriasis, tuberculosis and epilepsy
(22, 25–28). It is also increasingly being formulated into dermatological products
with purported antiviral and antifungal actions (11). In Germany, hypoxis extracts
have been widely marketed since the late 1970’s for the treatment of prostate
adenoma and benign prostate hypertrophy (BPH) (11, 29, 30). This indication is
based on the inhibition of 5α-reductase metabolism of testosterone by phytosterols
from hypoxis (11).
Dold and Cocks (7) estimated that trade in hypoxis exceeds 11 metric tons
per year in South Africa alone. Because of the high demand, hypoxis populations
are declining and under pressure (31). The use of corms is particularly destructive
and (32) investigated the possible use of the aerial parts as substitutes. They found
clear differences between the two plant parts both in chemical constitution and
biological activity making the substitution of corms for leaves less attractive.
Phytochemistry
Several compounds have been isolated from hypoxis species and some of them
have been linked to their putative biological activity. Hypoxoside, a norlignan
diglucoside is an aglycone consisting of a diphenyl-1-en-4-yne-pentane unit (33)
and has been isolated from all the common Hypoxis species (34). have suggested
that this compound maybe unique to the genus. Hypoxoside is hydrolysed by
β-glucosidase to rooperol which appears to be the active bioavailable compound
(26).
However it is for its high concentration of phytosterols that hypoxis is best
known for, especially sterols, sterolins and stanols. The patent by (29) claimed
that aqueous extracts of H. hemerollicadea had phytosterol yield of 9 mg /
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100g, however this could not be reproduced in recent studies by (13). These
workers found less than 0.01% w/w inal extract recovery they have dismissed the
therapeutic importance of sterolins in hypoxis based on that data. The likelihood
is that they were not using the same material and hence the differences are
inconclusive.
The plant hormone (cytokinin) zeatin and it’s derivatives were isolated from
the corms by Van Staden (35).
Biological Activity
It is fair to say that because of its high proile status in South African materia
medica, hypoxis has been well studied for its biological effects (Table 1). Methanol
extracts of H. hemerocallidea corms showed no activity against Staphylococcus
aureus, Escherichia coli, and Enterococcus faecalis (14). Using freshly harvested
corms grown in the laboratory (32) previously showed that acetone and ethanol
extracts of the leaves had relatively good activity against both E. coli (MIC < 0.31
mg /ml) and to some extent Pseudomonas aeruginosa (MIC < 0.61 mg / ml). The
aerial parts of hypoxis have not been previously investigated so this study was
important in showing their possible utility.
Steenkamp et al. (36) showed inhibition of E. coli by both water and ethanolic
extracts of H. hemerocallidea with MIC of 62.5 ug / ml, though they estimated
that it would not translate to a therapeutic dose in humans (based on the dosage).
They further suggested that the antimicrobial activity maybe another reason why
hypoxis is used in prostatitis and prostate indications.
Hypoxoside and rooperol showed good activity against E. coli and S. aureus,
with the latter being more active than the positive control (neomycin) (37). They
also possess good antimuagenic and cytotoxic properties (38)
Sathegke (14) showed that methanol extracts of hypoxis is non-toxic in a
cytcoxicity assay done using Vero cells (African green monkey kidney cell line)
and no activity was seen in HeLa cancer cell line. H. iridifolia and H. rigidula
showed slightly better activity in the HeLa cytotoxicity assays. Albrecht et al
(26) have previously reported that rooperol, the hydrolytic product of hypoxoside
showed activity against HeLa cells under 10 µg/ml, while the glycoside was
inactive in the same cell line.
Cytotoxic activity against HeLa, HT-29 and MCF-7 cancer cells appeared
to increase when β-glucosidase was added to H. hemerocallidea which seemed
to imply that there were certain compounds (other than hypoxoside) which were
being hydrolyzed to active metabolites (39)
Van der Merwe et al (40) demonstrated that rooperol inhibits leucotriene
synthesis in leukocytes and prostaglandin synthesis in platelet microsomes, thus
showing in vitro antioxidant and anti-inlammatory activity. Good free radical
scavenging ability was of aqueous and ethanolic extracts of H. hemerocallidea
was shown by Steenkamp et al (36). Antioxidant and free radical scavenging
activities of rooperol has been conirmed in various assays (11, 18, 33) as would
be expected of most phenolic compounds.
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Ojewole (25) found that an aqueous decoction of the corms of hypoxis
had signiicant antinociceptive and anti-inlammatory activity which was dose
dependent (50 – 800 mg / kg p.o.). In the same study, hypoxis extract showed
hypoglycemia in both normal and streptozotocin (STZ)-induced diabetes mellitus
rats. Gaidamashvili and Van Staden (41) showed that lectins isolated from H.
hemerocallidea may partly explain the anti-inlammatory activity as it elicited
a 29% inhibition of cyclooxygenase enzymes which catalyze the conversion
of arachidonic acid to prostaglandin. In a study by Laporta et al (37), using
concentrations below 0.5 mg / ml, there was no inhibition of COX-1 and COX-2
by either the crude extract or the compound hypoxoside. Rooperol, however
showed strong inhibition against both COX enzymes with a COX-2 / COX-1 IC50
ratio of 2. It is thought that the compound exerts it’s anti-inlammatory actions by
also inhibiting the production of NF-κB, AP-1 and similar transcriptional factors
important in inlammatory processes (42)
Ojewole (43) has attempted to validate the ethnobotanical use of hypoxis in
managing hysterical its and epilepsy. Using a rat model, he found that aqueous
corm extracts (100 – 800 mg / kg i.p.) delayed the onset of, and signiicantly
inhibited, seizures. In other similar studies in rodent models, Ojewole and
his colleagues tried to validate the use of hypoxis in gastroinstestinal and
uterine – related conditions, speciically, how do aqueous extracts of hypoxis
modulate smooth muscle? (44–46). They found that hypoxis extracts reduced
gastrointestinal motility, the frequency of defaecation and hence the severity of
diarrhea in experimental rats (43). The uterolytic effects were also conirmed
(46). In these experiments the muscle relaxant effects were found to be refractory
to β-adrenoceptor, cholinergic and histaminergic blockers leading the workers to
conclude that the mode of action might be through a non-speciic spasmolytic
mechanism.
The dichloromethane (DCM) extract of H. colchicifolia leaves was the only
one with signiicant activity of 16 plant extracts assayed for anthelmintic activity
using an in vitro colorimetric assay measuring free-living nematode larvae viability
(47). H. hemerocallidea was inactive in this study.
A systematic review by (48) of various phytotherapies used to ameliorate
the symptoms of Benign Prostatic Hyperplasia (BPH) Serenoa repens (saw
palmetto), Pygeum africanum (African plum) and H. hemerocallidea, showed
that the latter two improved urinary low rates and symptoms compared to
placebo. Several clinical studies have demonstrated that the use of hypoxis
extracts in BPH patients resulted in signiicant sustained symptomatic relief (49).
The effects of hypoxis on the prostate have always been linked to the purported
occurrence of high concentrations of phytosterols. These compounds are known
to inhibit 5α-reductase, the enzyme catalyzing the conversion of testosterone to
dihydroxytestorone (DHT).
BPH is prevalent in 50% of men over 50 years of age and in 90% of men
over 80 years old and it is known to depend on androgens, especially DHT (50).
Inhibitors of 5α-reductase can also be used for male pattern baldness, hirsutism
and prostate cancer. Hypoxis has been widely marketed and used for prostate
disorders but there is need for more studies especially in light of recent indings
that concentration of phytosterols in the species may actually be much lower than
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previously recorded (13). When this is considered in the light of the eficacy
demonstrated in the systematic review of Dedhia and McVary (48), it may imply
that other compounds which are yet to be identiied or tested are responsible for
the purported activity.
Phytosterols from hypoxis (mainly stigmasterol, β-sitosterol, brassicasterol
and ergosterol) are also marketed for their anti-lipidemic, cholesterol - lowering
actions. They accomplish this inhibiting Delta24 ( δ 24) reductase enzymes in the
cholesterol synthetic pathway (51). The lipid lowering effects of phytosterols are
however equivocal because the bioavailability of these compounds is variable and
dependant on formulation and other co-ingested foods (39)
The putative anti-inlammatory, antidiabetic and immune modulating
properties of hypoxis have been attributed to β-sitosterol (52). The amount
of sitosterol in hypoxis on average is variable. A study by (53) on immune
modulation showed that hypoxis extract was inferior to control in the survival
rates of FIV+ (Feline immunodeiciency virus infected) laboratory cat model.
However, a sitosterol enriched product showed signiicantly improved survival
rates.
Toxicology and Adverse Effects
The African Herbal Pharmacopeia (54) suggests that oral ingestion of
hypoxoside showed no toxicity, and no lethality was seen in the brine shrimp
assays nor cytotoxicity in Vero monkey cells.
However, it would appear that the use of crude herbal extracts of hypoxis
has caused some concern. A study on renal function of wistar rats after both
acute and chronic exposure to aqueous H. hemerocallidea extracts found that
there was impaired function with signiicant decrease in glomerular iltration rate
(GFR) and increased plasma creatinine concentration (55). A human study on the
safety and eficacy of hypoxis extracts in HIV positive patients in South Africa
was prematurely terminated by regulatory authorities reportedly because of bone
marrow suppression and immune suppression which has been also been reported
in a feline study (56). Steroids are known to be both immunesuppressive and
may cause osteoporosis (57) and this maybe evidence of the high concentration
of steroidal compounds in hypoxis.
In mice the LD50 of aqueous extracts of the corm of hypoxis was about 2g /
kg meaning that the species shows low acute toxicity (58). Low doses of alcoholic
and aqueous extracts of hypoxis, while causing a signiicant increase of weight in
suckling rats, did not show any morphometric changes in the small intestine of the
test animals (59). These workers concluded that hypoxis had no adverse effects
on suckling rats.
Dichloromethane and 90% methanol aqueous extracts of hypoxis showed
no mutagenic or antimutagenic activity in the Ames Salmonella / microsome
mutagenicity assay (60).
Daily doses of up to 3.2 g of hypoxis extract showed no clinical toxicity
or adverse changes in biochemical or haematological measurements in a phase I
clinical trial in human lung cancer patients (61). While hypoxis has generally been
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proved to cause little toxicity, it is the potential for drug-herb interactions which
still requires more extensive research. This is an increasingly important direction
of research as the concomitant ingestion of herbs with pharmaceuticals is common
especially in the treatment of HIV / AIDS (62). Therefore the potential for drugherb adverse reactions is high. Nair et al. (10) have shown that hypoxis inhibits
human drug metabolizing enzymes, CYP3A5, 3A4 and CYP19 by 11%, 33% and
41% respectively while rooperol showed almost total inhibition of CYP3A4 and
3A5. At concentrations of 5 mg / ml, hypoxis extracts showed high induction of
the polyglycoprotein (Pg-p) transporter. No effect was shown on Pg-p by sterols
or rooperol (10).
Future Directions of Research
Liu et al (42) have recently for the irst time used a colitis model to
demonstrate that methanolic extracts of hypoxis ameliorates severe typhlocolitis
in mice. The extract reduced weight loss, severity of bacteria – induced colitis,
neutrophil iniltration and intestinal epithelial proliferation making hypoxis and
it’s constituents an interesting lead in the search for prophylactic therapies for
inlammatory bowel diseases. However the extract did not show similar eficacy
in a non-bacteria-induced, dextran sodium sulfate (DSS) – induced colitis model.
This is certainly an interesting and innovative direction in which research can
move.
There remain many unanswered questions e.g. environmental variation and
how it impacts on the chemistry and biological activity of hypoxis, the apparently
contentious issue of the amounts of sterols and sterolins and their putative activity.
Despite all the work that has been done so far, there remains a need to understand
the phytochemistry of hypoxis in it’s entirety and then to test the compounds in
various in vitro and in vitro assays. Finding the bioactive compound (s) may lead
to the progression of such a compound in the pharmaceutical drug pipeline and /or
to the standardization of hypoxis extracts.
Conclusion
Hypoxis hemerocallidea is an important medicinal and dietary plant in
Southern Africa. However it’s contemporary use (particularly in HIV / AIDS
and so-called immune-boosting products) has been controversial and political.
This may have compromised the scientiic research into it’s use in these areas.
There are some important data which have been gathered from in vitro and rodent
studies which may form a good basis for the design of further pre-clinical studies.
However there is a general lack of extensive phytochemical studies which may
be the irst step towards developing evidence – based botanical / phytomedicine
products.
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Acknowledgments
I wish to thank Dr. Learnmore Kambizi (CPUT) for proofreading the inal
draft and useful comments.
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