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Review

Are Plants Used as a Combating Strategy against Tuberculosis in the Mpumalanga Province, South Africa?

by
Idowu Jonas Sagbo
* and
Ahmed A. Hussein
*
Department of Chemistry, Cape Peninsula University of Technology, Symphony Road, Bellville Campus, Bellville 7535, South Africa
*
Authors to whom correspondence should be addressed.
Appl. Sci. 2023, 13(8), 5008; https://doi.org/10.3390/app13085008
Submission received: 20 March 2023 / Revised: 3 April 2023 / Accepted: 14 April 2023 / Published: 16 April 2023
(This article belongs to the Special Issue Chemical and Functional Properties of Food and Natural Products)
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Abstract

:
The burden of tuberculosis (TB) disease is a global health challenge accounting for thousands of deaths. TB is unevenly distributed in South Africa, with some provinces having more than 70% of the TB burden. In Mpumalanga Province, TB is ranked as the sixth leading cause of death. Antituberculosis agents are usually costly, with numerous unwanted side effects. This has prompted the major use of herbs which have an imperative biological role against tuberculosis and are easily accessible. A comprehensive review of plants used as a combating strategy against tuberculosis in Mpumalanga Province was conducted. An in-depth literature search was performed using scientific databases, theses, dissertations and ethnobotanical books. Twenty-four (24) plant species were reported by the people of Mpumalanga for the treatment of tuberculosis. Fifteen (15) plant species have been investigated for antituberculosis activities, and seven antimycobacterial compounds were successfully isolated. This review validates the use of plants against tuberculosis in Mpumalanga Province and, thus, identified species that may be explored for further scientific studies.

1. Introduction

Tuberculosis (TB) is a multisystemic infectious bacterial disease caused by Mycobacterium tuberculosis, a rod-shaped bacterium [1]. It is a deadly transmissible disease that affects almost any body part, but it is primarily an infection of the lungs. TB occurs when an individual breathes in TB bacteria (M. tuberculosis). The bacteria can settle in the lungs and then begin to grow, thereby moving through the blood and to other parts of the body. The disease attacks persons of all ages, including babies, preschool children, and the elderly as they have a declining immune system compared to healthy adults. A person only needs to breathe in a few germs to become infected. TB disease can be easily spread in overcrowded settings and in conditions of malnutrition and poverty [2].
TB transmission occurs when a person inhales droplet nuclei (about 1–5 microns in diameter) containing M. tuberculosis (also called tubercle bacilli), and the droplet nuclei traverse the mouth or nasal passages, upper respiratory tract, and bronchi to reach the alveoli of the lungs [3]. A number of tubercle bacilli enter the bloodstream and start spreading throughout the body. The tubercle bacilli can reach any part of the body (such as the brain, larynx, lymph node, spine and bones) [3]. If the immune system becomes too weak to keep the tubercle bacilli under control or fails to stop the bacilli from growing, the bacilli begin to multiply rapidly.
TB symptoms are very variable, and they depend on the part of the body which has been infected. For example, if TB spreads to the lymph nodes, it may cause swollen glands at the sides of the neck or below the arms. In some other cases, some people are infected with the TB bacteria, but do not experience any significant symptoms, and this condition is known as latent TB [4]. This condition can stay dormant for years before developing into active TB disease. Generally, active TB disease symptoms (Figure 1) include chest pain, coughing of blood, fever, loss of appetite, night sweats and weight loss, and chills [1,4]. If not treated, complications such as liver or kidney problems, heart disorders, and fluid collection between the lungs frequently occur resulting in shortness of breath [5].

1.1. Tuberculosis: A Global Pandemic

TB is a global disease, found in every country. It is one of the top 10 leading causes of death and one of the most burden-inflicting diseases in the world [1]. In 1993, the World Health Organization (WHO) proclaimed TB as a global pandemic and urged coordinated efforts by all countries to prevent millions of deaths caused by this disease in the coming years [6]. In 2021, a report revealed by the WHO also showed that approximately 10.6 million people (accounting for 6 million men, 3.4 million women, and 1.2 million children) fell sick with TB, and even though it is a preventable and curable disease, about 1.5 million people died from this disease (including 187,000 people with HIV) worldwide, thereby making it the world’s second-most infectious killer after COVID-19 [7]. Recently, new TB cases have been reported to occur in thirty (30) high TB burden countries. Out of these 30 burden countries, eight countries accounted for two-thirds (2/3) of the new TB cases with India leading the list, followed by China, Indonesia, Philippines, Pakistan, Nigeria, Bangladesh and South Africa [7]. Although progress is being made in reducing the incidence of TB cases, it has been very slow, and it is projected that the world will not eliminate TB as a global public health threat by 2035 as envisaged. South Africa has been reported as one of the 30 high-TB-burden countries which account for a total of 87% of the estimated incident cases globally; South Africa accounts for 3% of TB cases worldwide [8]. This high rate of TB cases in South Africa has been fueled since the early 1990s by the HIV/AIDS epidemic that has negatively affected the country’s TB control [8].
Tuberculosis is unevenly dispersed in South Africa, with some provinces having more than 70% of the TB burden. Mpumalanga has reported increasing numbers of positive cases of TB since 2018 [9]. This plague has deprived many families of their loved ones, communities of their leaders, and the province of its future. Recently, the province was ranked sixth with a high incidence rate of TB (402 per 100,000) in South Africa [8]. In addition, Mpumalanga was also recently identified as one of the provinces with the highest rate of TB that is resistant to rifampin (a drug used for the treatment of TB) [10]. This incidence of TB in the province is large because of unemployment, poverty, migration, a high rate of population growth, and HIV/AIDS [11]. Thus, there is a need for effective strategies to control and manage this disease.

1.2. Anti-Tuberculosis Agents and Their Potential Side Effects

There have been numerous anti-tuberculosis drugs or agents (Table 1) used to treat TB. The most common drugs are ethambutol, Isoniazid, linezolid, pyrazinamide, rifampin, and streptomycin (Figure 2). A comprehensive description of these antituberculosis agents together with their potential side effects is given below.
Ethambutol, an essential first-line antituberculosis drug, possesses bacteriostatic action against Mycobacterium tuberculosis [12]. It is also used as part of a combination regimen to treat non-tuberculous mycobacterial infections [13]. This medication works by blocking the bacteria that cause TB from growing or increasing in number [13]. Although the exact mechanism of action of ethambutol is not fully known, evidence suggests that ethambutol performs its bacteriostatic activity against TB bacilli by exhibiting inhibition against arabinosyl [13]. Disruption of arabinogalactan formation inhibits the synthesis of the mycolic-arabinogalactan–peptidoglycan complex, thereby leading to increased permeability of the cell wall. However, several reports have indicated that ethambutol causes serious side effects that can reduce its usage for the treatment of TB. Some of the most common side effects of the drug include vomiting, swelling of the face, blurred vision, rash, breathlessness and nausea [14].
Isoniazid is one of the more potent antimicrobial agents mostly used to treat tuberculosis. It is used to treat both active and latent TB. This drug was recommended in 1963 for use as monotherapy in the deterrence of activation of tuberculosis in patients suffering from latent tuberculosis [15]. It is listed as one of the vital medicines for the treatment of TB in the WHO’s list of essential medicines. Isoniazid works by inhibiting the lipid and DNA synthesis of M. tuberculosis, thereby resulting in the inhibition of cell wall formation and development [16]. However, this drug is frequently used together with other antituberculosis agents such as rifampicin, pyrazinamide, and either streptomycin or ethambutol. The common side effects of isoniazid include liver inflammation, numbness in the hand and feet, liver failure and increased blood levels of liver enzymes [17].
Linezolid is the first in a new class of oxazolidinone antibiotic drugs used to treat various types of infections, including drug-resistant TB [18]. It is among the list of essential drugs recommended by WHO against the activity of M. tuberculosis [19]. Linezolid works by disrupting bacterial growth, thereby inhibiting bacterial protein production [20]. This mechanism of action is unique in that it prevents the start of bacterial protein synthesis. Despite the effectiveness of this drug in the treatment of TB, safety is one of the key concerns. Some of the potential side effects of linezolid are headache, nausea, difficulty breathing, swelling in your face or throat, discoloration of the tongue and diarrhea [21]
Pyrazinamide is another anti-tuberculosis agent that is structurally related to nicotinamide and very effective against M. tuberculosis and other mycobacterium strains [22]. Recently, pyrazinamide was reinstated as first-line therapy to solve challenges related to resistant strains as the incidence of tuberculosis is surging [23]. Though the mechanism of action of pyrazinamide is not fully known, its structure is similar to that of nicotinamide, and so it is assumed that pyrazinamide intervenes with the nucleic acid metabolism of bacterial cells. However, one of the major therapeutic limitations of the use of pyrazinamide is hepatoxicity [23]. Other limitations include gastrointestinal upset, and skin rashes can be associated with pyrazinamide administration [24]. In addition, the use of pyrazinamide treatment has also been linked to liver injury, notably resulting in a hepatitis-like liver injury in a patient suffering from tuberculosis [25,26].
Rifampin, also commonly known as rifampicin, is an antibiotic used for the treatment of various types of mycobacterial infections and in combination with other antituberculosis agents (ethambutol, isoniazid, and pyrazinamide) to treat active or latent TB [27]. It has a wide-ranging antibacterial spectrum, including activity against numerous forms of Mycobacterium. It works by inhibiting the bacterial DNA-dependent RNA polymerase, thus leading to a suppression of RNA by bacteria [28]. Rifampin is part of the recommended drugs used for the treatment of active TB during pregnancy (first-line medication to treat TB during pregnancy), although the safety of this drug during pregnancy is not yet known [29]. However, studies have indicated that the most severe side effect of rifampin is hepatotoxicity, and it is advisable that the patient receiving it should frequently undertake baseline and regular liver function tests for early detection of liver damage [30]. Other commonly reported side effects include diarrhea, nausea, loss of appetite and vomiting [31].
Streptomycin is one of the antibiotic medications used for the treatment of bacterial infections, including TB [32]. For the treatment of active TB, streptomycin is frequently used in combination with other antituberculosis drugs such as pyrazinamide, rifampicin and isoniazid [33,34]. However, streptomycin is not usually used as first-line treatment, except in medically under-served populations where the cost of more expensive treatments is prohibitive. Streptomycin works by two mechanisms depending on the isomer (conformation): (1) the streptomycin isomer A functions as a protein synthesis inhibitor. This occurs by binding the isomer A to the small 16S rRNA of the 30S subunit of the bacterial ribosome irreversibly, thereby interfering with the binding of formyl-methionyl-tRNA to the 30S subunit. (2) Streptomycin isomer B is an inhibitor of peptidoglycan synthesis inhibitor [35]. The isomer B binds to the glycosidic linkages and breaks them through an SN2 mechanism, thereby leading to the integrity of the bacterial cell walls being compromised, eventually resulting in the death of microbial cells [35]. Even though this drug is administered intravenously, several side effects have been reported, including rash, vertigo, numbness of the face and fever [36]. In addition, a report has also indicated that the use of streptomycin during pregnancy may cause permanent hearing loss in the developing baby [37].
Table
Table 1. Antituberculosis agents with their limitations in the treatment of tuberculosis.
Table 1. Antituberculosis agents with their limitations in the treatment of tuberculosis.
Anti-Tuberculosis AgentsMechanism of ActionReported Side EffectsReferences
EthambutolNot known.Vomiting, blurred vision, rash, nausea, swelling of the face, breathlessness.[14]
IsoniazidIt inhibits the synthesis of mycolic acids (components of the mycobacterial cell wall), thereby interfering with cell wall synthesis.Liver inflammation, numbness in hand and feet, liver failure, and increased blood levels of liver enzymes.[16,17]
LinezolidPrevents the initiation of bacterial protein synthesis.Headache, nausea, difficulty breathing, swelling in face or throat.[20,21]
PyrazinamideIntervenes with the nuclei acid metabolism of bacterial cells due to its structure similar to that of nicotinamide.Liver injury, gastrointestinal upset, skin rashes, arthralgias, anorexia, nausea and vomiting.[23,25]
RifampinInhibit bacterial DNA-dependent RNA polymerase.Hepatotoxicity.[28,31]
StreptomycinBlocks the ability of the 30S ribosomal subunits to make proteins.Rash, vertigo, numbness of the face, fever, and rash.[35,36]

1.3. Medicinal Plants with Antituberculosis Properties

Due to the several reported side effects associated with the use of antituberculosis agents, many TB patients have now resorted to using several medicinal plants to treat TB [38,39,40]. These medicinal plants have been reported to contain numerous bioactive compounds with antimycobacterial activity [41]. Recently, there has been a search for medicinal plants with ethno-pharmacological abilities for the treatment of TB and several ethnobotanical studies have also documented these medicinal plants. For example, Gupta et al. [42] tested four plant (Allium sativum, Aloe vera, Acalypha indica and Allium cepa) extracts against the H37Rv strain of M. tuberculosis with a zone of inhibition between 2.5 and 17.3 mm at the tested concentrations (0.02–0.04 mg/mL). Mohamed et al. [43] also reported that the n-hexane partition of Costus speciosus, Cymbopogon citratus and Tabernaemontana coronaria exhibited anti-TB activity against M. tuberculosis H37Rv with minimum inhibitory concentrations (MICs) of 100–200 μg/mL and a minimum bactericidal concentration (MBC) of 200 μg/mL. In the study, the authors proposed that the antituberculosis activity of these extracts was due to their destructive effects on the integrity of the mycobacterial cellular structure. Another study conducted by Kahaliw et al. [44] reported that the chloroform extracts of Pterolobium stellatum exhibited anti-TB activity against M. tuberculosis strain H37RV with MIC values of 0.039 mg/mL. A review conducted by Xu et al. [45] also reported and compiled several medicinal plants as a source of anti-TB drugs. Kaur and Kaur [46] reported the antituberculosis activity of methanolic extract of Aegle marmelos, Glycyrrhiza glabra, Lawsonia inermis, Piper nigrum and Syzygium aromaticum microplate alamar blue assay. In the study, the extracts exhibited antituberculosis activity against M. tuberculosis strain H37RV at a range of 0.8 to 100 μg/mL. Interestingly, despite the widespread usage of medicinal plants for the management of TB, there are still many plants that are yet to be scientifically documented. It is in this context that this review focused on medicinal plants used as a combating strategy against TB in the Mpumalanga Province of South Africa with a view to prevent the loss of these important plants for future generations in the Mpumalanga Province.

2. Material and Methods

A detailed literature review was carried out (between August 2021 to January 2023). Information on plants traditionally used to manage TB in the Mpumalanga Province was obtained from numerous databases, namely PubMed, Medline, Scopus, Science Direct, Web of Science and Google Scholar. Additional information was also obtained from ethnobotanical books, dissertations and theses using various university libraries. Some of the keywords and terms used when searching for relevant articles or research papers were “Medicinal plants”, “tuberculosis”, “Mpumalanga”, and “ethnopharmacology”.

3. Results and Discussion

3.1. Medicinal Plants with Antituberculosis Potential Used in the Mpumalanga Province

Twenty-four plant species belonging to different botanical families have been reported by the people of Mpumalanga for the treatment of antituberculosis (Table 2). Some of these plant species have been scientifically validated (Table 3), and only nine are yet to be scientifically investigated for their antituberculosis activity. A broad description of some of these plants with isolated antituberculosis compounds (Figure 3) is given below.

3.2. Agapanthus inapertus

Agapanthus inapertus (Figure 4) is a plant belonging to the family Agapanthaceae. The plant grows in grassland and in between rocks in mountainous terrain, forming large clumps. The leaves of the plant are mainly erect while the flower stalk is about 0.8 m high [47]. A. inapertus is dispersed in the Mpumalanga Province of South Africa [47]. The plant is also found in the Limpopo province and Mozambique [47]. Traditionally, the tuber part of the plant is cooked, and the extract is then taken by the people of Mpumalanga Province for the treatment of tuberculosis [48]. The literature survey showed no reported antituberculosis activity of A. inapertus and its phytoconstituents.

3.3. Combretum hereroense

Combretum hereroense is a semi-deciduous shrub that grows to about 5–12 m in height [49]. The plant belongs to the family Combretaceae. The leaves of the plant are very simply shaped and obovate. The plant is found in the Mpumalanga, Gauteng, Limpopo and KwaZulu-Natal provinces [49]. In traditional medicine, the seed of the plant is burnt in a hut and the smoke is inhaled for the treatment of TB [50]. Magwenzi et al. [51] reported that C. hererosene exhibited no antimycobacterial effects against Mycobacterium aurum and Mycobacterium smegmatis at the tested concentrations but showed an efflux pumping inhibitory activity in Mycobacterium smegmatis. Another study reported by Masoko and Nxumalo [52] indicated that the acetone extracts of C. hereroense inhibited the growth of M. smegmatis with MIC value of 0.47 mg/mL. Despite the widely reported antituberculosis activity of C. hereroense, there has been no scientific information on its isolated antimycobacterial compounds.

3.4. Helichrysum odoratissimum

Helichrysum odoratissimum is an aromatic that belongs to the family of Asteraceae. H. odoratissimum is a perennial plant with tiny grey leaves [53]. The plant’s leaves can vary between being linear, oblong, lingulate, and lanceolate. It is found in Mpumalanga, Limpopo, and KwaZulu-Natal provinces [53]. It is also found in the mountains and coastal areas of the Eastern Cape province, South Africa [53]. The leaves or whole plant parts are used for the treatment of TB in the Mpumalanga Province [54]. The antituberculosis activity of H. odoratissimum has been reported in the literature. Several reports have indicated that the extract of H. odoratissium has antituberculosis activities. For example, a study revealed that the whole-plant extract demonstrated inhibition against M. tuberculosis at MICs ranging from 300 to 500 μg/mL [54]. Another study conducted by Seaman et al. [55] also indicated that the acetone extracts of H. odoratissimum inhibited M. smegmatis and M. aurum with MIC values range from 0.3 mg/mL to 2.0 mg/mL. No reported active antimycobacterial tuberculosis compound has been isolated from this plant.

3.5. Lippia javanica

Lippia javanica is a medicinal plant with dense creamy white flower heads and aromatic leaves. It is a woody shrub 1 to 2 m in height belonging to the family of Verbenaceae [56]. It is one of the most aromatic indigenous shrubs in South Africa [56]. The plant is prevalent throughout large parts of South Africa. The leaf of the plant is placed in water and the steam is inhaled to treat TB [57]. A study conducted by Masoko and Nxumalo revealed the antituberculosis activity of L. javanica against mycobacterial strains. In the study, the authors reported that L. javanica acetone extract displayed inhibition against M. smegmatis with an MIC value of 0.47 mg/mL [52]. Another study reported by Mujovo also showed that the acetone extract of L. javanica exhibited inhibition against M. tuberculosis (H37Rv) at a concentration of 0.5 mg/mL [58]. In the same study, 6-Methoxyluteolin 4′-methyl ether (1), a compound isolated from L. javanica, demonstrated significant inhibition against M. tuberculosis with an MIC value of 200 μg/mL [58].

3.6. Protorhus longifolia

Protorhus longifolia (Anacardiaceae family) is an excellent evergreen garden tree that is easily grown from seed. It is up to 15 m in height and single-stemmed with a dark rounded crown [59]. The leaves of the plants are simple, and are dark green with a paler underside. The plant is broadly distributed in the Eastern Cape, KwaZulu-Natal, Limpopo and Mpumalanga Provinces [59]. A decoction of the bark is taken orally to treat TB [60]. Some researchers have reported the antimycobacterial TB of P. longifolia [61]. A study conducted by Kabongo-Kayoka, reported that P. longifolia extract exhibited inhibition against M. aurum and M. fortuitum with an MIC value of 0.11 mg/mL [61]. The author also revealed that the plant extract also caused inhibition against M. smegmatis with an MIC value of 0.07 mg/mL [61]. Interestingly, another study reported by Mdikizela and McGaw also reported that P. longifolia leaf acetone extract reported good activity against M. smegmatis and M. bovis with MIC values of 0.008 mg/mL [62]. There have been no reports of antimycobacterial compounds isolated from this plant.

3.7. Phymaspermum acerosum

Phymaspermum acerosum is an erect straggly shrub that belongs to the Asteraceae family. The plant reaches a height and width of 1.5–2 m. The plant leaves are up to 10 to 45 mm long with a bright yellow flower [63]. P. acerosum is found in the Mpumalanga, Eastern Cape, Gauteng, Northern Province and Free State provinces of South Africa, as well as Lesotho [63]. In Mpumalanga Province, the infusion of the root is taken orally for TB management [60]. A report has indicated that P. acerosum roots and leaf (ethanol and water) extracts exhibited inhibition against the mycobacterium strain with an MIC value of 0.02 mg/mL [62]. There have been no reports of antimycobacterial compounds isolated from P. acerosum.

3.8. Ranunculus multifidus

Ranunculus multifidus is an evergreen herb that grows well in damp grassland. The plant is a flowering plant in the family Ranunculaceae. R. multifidus has bright green leaves that grow from a basal rosette and are covered with hairs, and is therefore described as an excellent candidate for an undercover spot [64]. The plant is naturally found across the Eastern Cape, KwaZulu-Natal, Limpopo, Mpumalanga, Northern Cape, Northwest and Western Cape provinces [65]. The infusion of the root is used for TB management [60]. Nevertheless, there is no scientific evidence of its antituberculosis properties yet, and there have been no reported antituberculosis compounds isolated from this plant.

3.9. Tetradenia riparia

Tetradenia riparia (Lamiaceace family) is a tall, aromatic plant that has a height of up to 3 m. The plant has glandular hairs that cover the surfaces of the leaves, thereby making them slightly sticky to the touch [66]. T. riparia leaves are light green, and they are softly heart-shaped with the margin intermittently and openly toothed. The natural distribution of the plant ranges from Mpumalanga, KwaZulu-Natal, and Northern Province in South Africa [66]. The plant is used traditionally as an infusion to treat respiratory diseases, including TB [67]. The anti-mycobacterium tuberculosis activity of essential oil from T. riparia was reported by Baldin et al. [68]. In that study, the authors discovered that the essential oil of T. riparia displayed inhibition against M. tuberculosis H37Rv with an MIC value of 62.5 µg/mL. Another study conducted by van Puyvelde et al. [69] also reported significant inhibition towards M. simiae and M. tuberculosis at the concentration of 1000 μg/mL and 500 μg/mL respectively. The compound, 6,7-dehydroroyleanone (6) isolated from T. riparia was reported to show activity against M. tuberculosis H37Rv with an MIC value of 62.5 µg/mL [68]. Another compound, 8(14), 15-sandaracopimaradiene-7α, 18-diol (7), also isolated from the T. riparia, was shown to exhibit antimycobacterial activity against M. tuberculosis at concentrations ranging from 25 μg/mL to 100 μg/mL [69].

3.10. Withania somnifera

Withania somnifera is a tiny flowering shrub belonging to the family Solanaceae. The whole plant is covered with short and branched hair and reaches 2 m high and 1 m across [70]. The plant leaves are simple, alternate, ovate and oblong with 30–80 mm long margins. W. somnifera is widespread in several provinces of South Africa, including Mpumalanga [70]. In Mpumalanga, the infusion of the plant is used against TB [71]. The literature search revealed some notable works on the antimycobacterial tuberculosis activity of W. somnifera. Adaikkappan et al. [72] discovered that W. somnifera aqueous extract showed a significant effect against M. tuberculosis at concentrations ranging from 0.01 to 1.0 mg/mL. There have been no reports on the antimycobacterial activity of active isolated compounds from W. somnifera.

3.11. Ziziphus mucronata

Ziziphus mucronate is a small to medium-sized plant 3–10 m in height. The plant belongs to the family of Rhamnaceae. The leaves of the plant are simple, alternate and broadly ovate in size [73]. Z. mucronata is mostly dispersed throughout the summer rainfall areas of sub-Saharan Africa, spreading from South Africa [73]. The plant is predominant in Mpumalanga, Eastern Cape, Free State, Gauteng and KwaZulu-Natal provinces [73]. Traditionally, the infusion prepared from the leaves is used to treat TB [71]. The acetone extract of Z. mucronata exhibited inhibition against M. tuberculosis with an MIC value of 0.156 mg/mL [74,75]. The authors also indicated that the extract displayed inhibition against M. fortuitum and M. aurum with an MIC value of 2.5 mg/mL [75]. Another study conducted by Iloga [76] revealed that dichloromethane extract of Z. mucronata demonstrated inhibition against M. terrae at MIC values of <0.156 mg/mL. A report by Sigidi et al. [77] revealed that Z. mucronata aqueous extract displayed an MIC value of >500 µg/mL against the pathogenic M. tuberculosis H37V strain. The literature search conducted showed no reported antimycobacterial compounds isolated from this plant.
Table
Table 2. Medicinal plants used traditionally to treat tuberculosis in the Mpumalanga Province of South Africa.
Table 2. Medicinal plants used traditionally to treat tuberculosis in the Mpumalanga Province of South Africa.
S/NScientific NameLocal NameFamilyPlant Part UsedMode of Preparation/AdministrationReference
1Agapanthus inapertus P.Beauv. subsp. IntermediusisicakathiAgapanthaceaeTuberThe tuber part of the plant is cooked for 10 min, and the extract (one cup) is taken orally 3 times a day.[48]
2Combretum hereroense SchinzumhlalavaneCombretaceaeSeedsThe seed of the plant is burnt in a hut and the smoke is inhaled 2 times a day.[50]
3Dicoma anomala Sond.inyonganaAsteraceaeLeavesThe leaves of the plant are chewed.[78]
4Eucomis autumnalis (Mill.) ChittesimathunziHyacinthaceaeBulbThe infusion prepared from the bulbs is drunk for tuberculosis management.[78]
5Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall.lezithunzelaHypoxidaceaeTuberThe tuber of the plant is cooked for 5–20 min, and the extract (one cup) taken 3 times a day.[48]
6Helichrysum odoratissimum (L.) Sweet.imphephoAsteraceaeLeavesUnspecified.[79]
7Heteromorpha arborescens (Spreng.) Cham. & Schltdl.umbangezaApiaceaeRootAn infusion obtained from the root is taken orally.[62]
8Lippia javanica (Burm. f.)umsutaneVerbenaceaeLeavesThe leaves of the plant are placed in water and the steam is inhaled 3 times a day.[48,57]
9Leonotis leonurus (L.) R.Br. LamiaceaeLeaves andstemsUnspecified.[78]
10Merwilla plumbea (Lindl.) SpetainguduzaHyacinthaceaeBulbThe bulb of the plant is cooked for approximately 8 min and the extract (on cup) is taken 3 times a day.[48]
11Mentha longifoliaufuthanaLamiaceaeLeavesInfusion made from the leaves is taken orally 3 times a day for 2 months.[71]
12Pelargonium sidoides DCiyezaGeraniaceaeTuberUnspecified.[78]
13Pellaea calomelanos (Sw.) LinkinkomankomoPteridaceae The infusion of the roots is prepared, and one cup of the extract is taken orally.[48]
14Protorhus longifolia (Bernh.) EnglisifuceAnacardiaceaeBarkAn infusion of the bark is taken orally.[60]
15Phymaspermum acerosum (DC.) Källersjöumhlonishwa AsteraceaeRootInfusion of the root is taken orally.[60]
16Ranunculus multifidus Forssk.UnspecifiedRanunculaceaeaRootInfusion of the root is taken orally.[60]
17Schotia latifolia Jacq. umXamoFabaceaeBarkThe decoction of the bark is taken orally.[60]
18Strychnos henningsii GilgUmanonoLoganiaceaeBarkThe bark of the plant is chewed.[60]
19Silene undulata AitonubulawuCaryophyllaceaeLeavesThe infusion made from the leaves is taken orally.[71]
20Talinum caffrum (Thunb.) Eckl. & Zeyh.impunyuTalinaceaeRootThe decoction made from the root is taken orally[60]
21Tetradenia riparia (Hochst.) CoddIbozaneLamiaceaeLeavesThe plant infusion is used to treat respiratory diseases, including tuberculosis [79]
22Withania somnifera (L.) DunalubuvumaSolanaceaeLeaves Infusion from the
herbs is taken orally		[71]
23Xysmalobium undulatum (L.) Aiton f. var. undulatumnwachabaApocynaceaeWhole plantUnspecified[78]
24Ziziphus mucronata (Willd subsp) RhamnaceaeLeavesThe infusion prepared from the leaves is taken orally[71]
Table
Table 3. Reported antituberculosis activity of medicinal plants used in the Mpumalanga Province.
Table 3. Reported antituberculosis activity of medicinal plants used in the Mpumalanga Province.
S/NScientific NamePlant Part UsedExtractAntimycobacterial Isolated CompoundsAntituberculosis Mechanism of Action References
1C. hereroense***Exhibited no activity against Mycobacterium aurum and Mycobacterium smegmatis. Exhibited efflux pumping inhibitory activity in Mycobacterium smegmatis[51]
2D. anomala.LeavesAcetone, Ethanol*Inhibited Mycobacterial tuberculosis at MIC values of 0.195 mg/mL.[78]
3E. autumnalisBulbAqueous*Displayed inhibition against Mycobacterial tuberculosis at MIC values of 3.125 mg/mL.[78]
4H. odoratissimumLeavesAcetone*Inhibited Mycobacterial tuberculosis at MIC values of 0.5 mg/mL.[80]
5H. arborescensLeavesAqueous, acetone, and ethanol leaf extracts*Displayed inhibition against M. aurum, M. bovis, M. bovis BCG,
M. gordonae, M. fortuitum, M.
smegmatis, M. tuberculosis and M. tuberculosis H37RV with MIC values ranging between 0.08 mg/mL to 5.0 mg/mL.		[62,81]
6L. javanicaLeavesAcetone6-Methoxyluteolin 4′-methyl ether (1)The acetone extract displayed inhibition against M. smegmatis with an MIC value of 0.47 mg/mL. The isolated compound “6-Methoxyluteolin 4′-methyl ether”
exhibited an MIC value of 200 µg/mL against M. tuberculosis.		[52,58]
7L. leonurusLeavesAqueous*No activity against M. smegmatis[79]
8P. sidoidesRootButanolEpigallocatechin (2), scopoletin (3), catechin (4) and umckalin (5)The butanol extract displayed inhibition against M. tuberculosis H37Rv. The isolated compounds (epigallocatechinand scopoletin) showed good inhibitory activity against
M. smegmatis, thereby exhibiting a MIC value of 7.8 mg/mL. Another isolated compound (catechin and umckalin) inhibited M. smegmatis with a MIC value of 31.25 and 62.5 mg/mL respectively.		[82,83]
9P. longifoliaLeavesAcetone*Inhibited M. aurum and M. fortuitum with an MIC value of 0.11 mg/mL while for the M. smegmatis with an MIC value of 0.07 mg/mL.[61]
10P. acerosumRootWater and Ethanol*Inhibited Mycobacterium strain with an MIC value of 0.02 mg/mL[62]
11T. caffrumRhizomeAcetone*Displayed no antituberculosis activity against Mycobacterium strains[62]
12T. riparialeavesEssential oil6,7-dehydroroyleanone (6), 8(14), 15-sandaracopimaradiene-7α, 18-diol (7)The essential oil displayed inhibition against M. tuberculosis H37Rv MIC value of 62.5 µg/mL. The isolated compound (6,7-dehydroroyleanone) inhibited M. tuberculosis H37Rv with an MIC value of 62.5 µg/mL while, 8(14), 15-sandaracopimaradiene-7α, 18-diol inhibited M. tuberculosis between the concentration range of 25 μg/mL to 100 μg/mL[68]
13W. somniferaleavesAqueous*Exhibited inhibition against M. tuberculosis H37Rv between 0.01–1.0 mg/mL[72]
14X. undulatumLeavesMethanol*Displayed no inhibition against M. tuberculosis[78]
15Z. mucronataBarkEthanol*No inhibition against M. smegmatis and M. tuberculosis[84]
*: No reported antimycobacterial isolated compound.
Applsci 13 05008 g004a 550Applsci 13 05008 g004b 550Applsci 13 05008 g004c 550Applsci 13 05008 g004d 550
Figure 4. Medicinal plants used traditionally to treat tuberculosis in Mpumalanga Province. Pictures obtained from SANBI [85].
Figure 4. Medicinal plants used traditionally to treat tuberculosis in Mpumalanga Province. Pictures obtained from SANBI [85].
Applsci 13 05008 g004aApplsci 13 05008 g004bApplsci 13 05008 g004cApplsci 13 05008 g004d

4. Conclusions and Recommendations

In the Mpumalanga Province, the number of people using herbs for the treatment of TB is steadily increasing. This is ascribed to their cultural beliefs, low cost, availability, and efficacy of these medicinal plants in combating tuberculosis. However, despite their usage, many of these plants have not been scientifically explored. Thus, there is a need for researchers or pharmaceutical industries to explore these species. It is also important that efforts should be made to isolate more antimycobacterial compounds that can be developed into new anti-tuberculosis drugs with better efficacy and safety profiles.

Author Contributions

Conceptualization: I.J.S. and A.A.H.; Methodology: I.J.S. and A.A.H.; Resources: A.A.H. Investigation: I.J.S.; Writing of the original draft: I.J.S.; Editing: I.J.S. and A.A.H.; Supervision: A.A.H. All authors have read and agreed to the published version of the manuscript.

Funding

This review work received no research/external funding.

Institutional Review Board Statement

No ethical approval was required for this review article.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors thank the Cape Peninsula University of Technology, for publication support.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. Typical symptoms of TB.
Figure 1. Typical symptoms of TB.
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Figure 2. The chemical structure of antituberculosis drugs.
Figure 2. The chemical structure of antituberculosis drugs.
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Figure 3. Antimycobacterial tuberculosis compounds isolated from plants used against tuberculosis in Mpumalanga Province. The numbers 1 to 7 correspond to the compound reported in Table 2.
Figure 3. Antimycobacterial tuberculosis compounds isolated from plants used against tuberculosis in Mpumalanga Province. The numbers 1 to 7 correspond to the compound reported in Table 2.
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Sagbo, I.J.; Hussein, A.A. Are Plants Used as a Combating Strategy against Tuberculosis in the Mpumalanga Province, South Africa? Appl. Sci. 2023, 13, 5008. https://doi.org/10.3390/app13085008

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Sagbo IJ, Hussein AA. Are Plants Used as a Combating Strategy against Tuberculosis in the Mpumalanga Province, South Africa? Applied Sciences. 2023; 13(8):5008. https://doi.org/10.3390/app13085008

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Sagbo, Idowu Jonas, and Ahmed A. Hussein. 2023. "Are Plants Used as a Combating Strategy against Tuberculosis in the Mpumalanga Province, South Africa?" Applied Sciences 13, no. 8: 5008. https://doi.org/10.3390/app13085008

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