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Ethnobotany, ethnopharmacology, and phytochemistry of traditional medicinal plants used in the management of symptoms of tuberculosis in East Africa: a systematic review

Abstract

Objective

Many studies on the treatment of tuberculosis (TB) using herbal medicines have been undertaken in recent decades in East Africa. The details, however, are highly fragmented. The purpose of this study was to provide a comprehensive overview of the reported medicinal plants used to manage TB symptoms, and to analyze scientific reports on their effectiveness and safety.

Method

A comprehensive literature search was performed in the major electronic databases regarding medicinal plants used in the management of TB in East Africa. A total of 44 reports were retrieved, and data were collected on various aspects of the medicinal plants such as botanical name, family, local names, part(s) used, method of preparation, efficacy, toxicity, and phytochemistry. The data were summarized into percentages and frequencies which were presented as tables and graphs.

Results

A total of 195 species of plants belonging to 68 families and 144 genera were identified. Most encountered species were from Fabaceae (42.6%), Lamiaceae (19.1%), Asteraceae (16.2%), and Euphorbiaceae (14.7%) families. Only 36 medicinal plants (18.5%) have been screened for antimycobacterial activity. Out of these, 31 (86.1%) were reported to be bioactive with minimum inhibitory concentrations ranging from 47 to 12,500 μg/ml. Most tested plant extracts were found to have acceptable acute toxicity profiles with cytotoxic concentrations on normal mammalian cells greater than 200 μg/ml. The most commonly reported phytochemicals were flavonoids, terpenoids, alkaloids, saponins, cardiac glycosides, and phenols. Only Tetradenia riparia, Warburgia ugandensis, and Zanthoxylum leprieurii have further undergone isolation and characterization of the pure bioactive compounds.

Conclusion

East Africa has a rich diversity of medicinal plants that have been reported to be effective in the management of symptoms of TB. More validation studies are required to promote the discovery of antimycobacterial drugs and to provide evidence for standardization of herbal medicine use.

Background

Tuberculosis (TB) is a chronic infectious bacterial disease caused by Mycobacterium tuberculosis (Mtb). It affects mainly the respiratory system but may also affect other organs of the body causing pulmonary and extrapulmonary TB respectively. The World Health Organization (WHO) estimated that a quarter of the world’s population is infected with Mtb and thus at a risk of developing TB [1]. Although TB affects all people, those living with HIV/AIDS are at a higher risk of developing active TB [2]. The burden of TB is still high as it is ranked among the ten diseases of global concern [3]. In 2018, a total of 10 million new cases and 1.49 million deaths due to TB were reported worldwide. In East Africa, 378,000 new cases and 91,000 deaths (24%) occurred. In East Africa, Kenya and Tanzania are still ranked among the 30 countries with a high burden of TB in the world [1].

Treatment of TB remains a challenge due to the emergence of multidrug-resistant Mtb strains and extensively drug-resistant TB cases which poorly respond to the first line antitubercular drugs (rifampicin, isoniazid, pyrazinamide, and ethambutol). These drugs also have side effects and a high potential to interact with antiretroviral drugs resulting in increased toxicity, poor compliance, and treatment failure [4,5,6]. As a result, many TB patients have resorted to using alternative and complementary medicines with herbal remedies being the most widely used in the management of tuberculosis [7]. Due to limited access to health services and chronic poverty in East Africa, many people not only believe that herbal medicines are efficacious and safe but also affordable, available, and culturally acceptable [8,9,10]. Thus, there is widespread use of herbal remedies by many people in the East Africa to manage symptoms of TB [7,8,9,10,11,12,13]. The WHO also reported that approximately 60% of the world’s population depend on non-conventional therapies for primary health care [14].

The search to discover new effective drugs against Mtb has intensified globally in the last decade as the current therapies become less effective and in an attempt to have a world free of TB by 2035 [1]. With natural products being the leading sources of novel drugs, ethnobotanical surveys and scientific validation studies have been conducted on East African flora in the past decades [7,8,9,10]. Several plant species have been documented and some of their extracts, fractions, and isolated pure compounds have been tested for efficacy and safety [15,16,17,18]. However, this information is highly fragmented.

Comprehensive data on medicinal plants used in the management of TB is important for the conservation of these species as some of them are either rare or endangered. It also provides more evidence that increases the confidence in the utilization of these herbal remedies for primary health care as well as their regulation by relevant authorities in case of ineffectiveness and toxicity [19, 20]. The analysis and synthesis of the results may also help in identifying existing gaps and challenges in the current research and stimulates future research opportunities. This can lead to identification of novel molecules that can be developed into new antitubercular drugs with better efficacy and safety profiles [21]. This review was therefore undertaken to compile a comprehensive report on the ethnobotany, ethnopharmacology, and phytochemistry of medicinal plants used in management of symptoms of TB in the East African region so as to generate knowledge on the current status and future opportunities for drug discovery against TB.

Methods

Reporting and protocol registration

This systematic review was reported according to the Preferred Reporting Items for the Systematic Reviews and Meta-Analyses (PRISMA) guidelines [22]. The protocol used in this study was registered with the International Prospective Register of Systematic Reviews (PROSPERO) and can be accessed at their website (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=187098) with the registration number CRD42020187098.

Literature search strategy

Relevant literature pertaining the ethnobotany, phytochemistry, efficacy and safety of medicinal plants utilized in management of symptoms of TB in Uganda, Kenya, Tanzania, Rwanda, Burundi and South Sudan were retrieved from Scopus, Web of Science Core Collection, PubMed, Science Direct and Google Scholar [23,24,25]. Key search words such as tuberculosis, mycobacteria, tuberculosis symptoms, tuberculosis treatment, vegetal, antituberculosis, antitubercular, antimycobacterial, cough, traditional medicine, ethnobotany, alternative medicine, and ethnopharmacology combined with either Uganda, Kenya, Tanzania, Rwanda, Burundi, or South Sudan were used. All publishing years were considered, and reports in the returned results were carefully scrutinized. More searches were carried out at the Google search engine using more general search terms, such as mycobacteria, tuberculosis, antituberculosis, antimycobacterial, cough, vegetal species, vegetal extract, traditional medicine, alternative medicine, plants, plant extract, vegetal, herbal, complementary therapy, natural medicine, ethnopharmacology, ethnobotany, herbal medicine, herb, herbs, decoction, infusion, macerate, and concoction combined with either Uganda, Kenya, Tanzania, Rwanda, Burundi, or South Sudan. The searches were done independently by the authors for each country and the outputs were saved where possible on databases and the authors received notifications of any new searches meeting the search criteria from Science Direct, Scopus, and Google scholar.

Inclusion and exclusion criteria

Only full-text original research articles published in peer-reviewed journals, books, theses, dissertations, patents, and conference papers on plants used in the management of symptoms of TB in Uganda, Kenya, Tanzania, Rwanda, Burundi, and South Sudan written in English and dated until April 2020 were considered.

Study selection

At first, literature screening of the extracted articles involved examining the titles and abstracts for relevant articles for inclusion. This was conducted independently by 6 authors. Then, the full-text articles were evaluated against the inclusion/exclusion criteria. The article selection process resulted in 44 studies included in this systematic review (Figure S1).

Data collection

A data collection tool was designed in Microsoft Excel (Microsoft Corporation, USA) to capture data on different aspects of medicinal plant species used in TB management. These included botanical name, plant family, local name(s), part(s) used, growth habit, mode of preparation and administration, method of extraction, efficacy, toxicity and phytochemical screening of crude extracts, isolated pure compounds, and efficacy and toxicity. Careful review of the articles was done, and data were captured using the tool. The collected data were checked for completeness, processed independently for each country by the authors and later analyzed.

Data analysis

Missing information in some studies (local names and growth habit of the plants), and misspelled botanical names were retrieved from the Google search engine and botanical databases (The Plant List, International Plant Names Index, NCBI taxonomy browser, and Tropicos) respectively.

Descriptive statistical methods were used to analyze the collected data. Results were expressed as ranges, percentages, and frequencies and subsequently presented as tables and charts. The analyses were performed using SPSS statistical software (Version 20, IBM Inc.)

Results and discussion

Ethnobotanical studies

With the current antitubercular drugs becoming less effective in the management of multidrug-resistant Mtb strains, medicinal plants can provide the novel molecules for development of new efficacious and safe drugs [26, 27]. From the electronic survey in multidisciplinary databases, 44 reports on medicinal plants used for management of symptoms of TB in East Africa were retrieved. A total of 195 species of plants belonging to 68 families and 144 genera were identified (Table 1). Some of these documented plant species have also been reported in other regions across the world for management of TB. For example, Psidium guajava, Catha edulis, Carica papaya, Citrus limon, Lantana camara, Aloe vera, Biden pilosa, Piliostigma thonningii, Tamarindus indica, Ficus platyphyla, and Vernonia cinereal in Nigeria, South Africa, Ethiopia, India, and Mexico [60,61,62,63,64]. This implies that plants continue to occupy a critical niche in the environment due to their rich possession of secondary metabolites (phytochemicals) that have potential to be used as medicines for several ailments that affect man. Therefore, the use of herbal medicines in the provision of primary health care remains an integral component of all health systems globally [14].

Table 1 Medicinal plants used in treatment of symptoms of TB in East Africa

Most encountered species were from the family Fabaceae (42.6%), Lamiaceae (19.1%), Asteraceae (16.2%), Euphorbiaceae (14.7%), Moraceae (10.3%), Rubiaceae (10.3%), Rutaceae (8.8%), Burseraceae (7.4%), and Cucurbitaceae (7.4%) (Fig. 1). Fabaceae, Asteraceae, and Lamiaceae were also reported to provide the largest number of plants species used for TB management in South Africa, Ghana, Nigeria, Ethiopia, and India [64,65,66,67,68,69,70,71,72]. From these families, 15 species were the most cited in East Africa (Fig. 2). These families were reported from at least four countries of East Africa. This could probably be attributed to the abundant distribution of the analogue active substances among species from these families [23, 24]. The family Fabaceae has biosynthetic pathways that produce majorly flavonoids, terpenoids, and alkaloids as secondary metabolites [73,74,75]. It is these phytochemicals that are responsible for the antimycobacterial activity against different mycobacterial strains [67, 70, 76, 77]. Other families reported in East Africa to house medicinal plants for management of TB and have also been reported in other countries include Acanthaceae, Apocynaceae, Cariaceae, Combretaceae, Malvaceae, Moraceae, Myrtaceae, Rhamnaceae, Rubiaceae, Solanaceae, and Zingiberaceae [64, 72, 78,79,80,81].

Fig. 1
figure 1

Major botanical families from which TB remedies are obtained in East Africa

Fig. 2
figure 2

The most cited plant species used for treatment of TB and its symptoms in East Africa

Geographically, none of the documented plant species was reported to be used in the management of TB across all the East African countries. However, two plant species (Erythrina abyssinica and Eucalyptus species) are used by at least 4 countries. A total of 30 plant species were reported to be used by at least two countries. Uganda had the highest number of species mentioned followed by Kenya and then Tanzania (Table 1). The differences in species utilization could be attributed to the differences in soil chemistry, rainfall, topography, and climate that results into differences in phytochemical composition of the same species growing in different geographical areas [82]. Additionally, it could also be due to differences in knowledge and experiences as result of different social and cultural backgrounds that exists across the countries. Uganda had many ethnobotanical surveys conducted to document medicinal plants used in the management of tuberculosis as compared to other countries. Most of these medicinal plants were growing as trees (40.0%), herbs (29.7%), shrubs (27.7%), and rarely as climbers, vines, or lianas (Fig. 3).

Fig. 3
figure 3

Growth habit of the plants used for preparation of antitubercular remedies in East Africa

Analysis of ethnomedicinal recipes revealed that mainly leaves (38.6%), stem bark (28.4%), and roots (18.6%) were used for preparing herbal remedies. Root bark, whole plants, fruits, flowers, seeds, and husks were rarely used (Fig. 4). Harvesting of leaves and stem bark allows sustainable utilization of the plants hence promoting their conservation as opposed to use of roots and whole plants. Additionally, leaves are the primary sites for secondary metabolic pathways in plants while stem barks act as major concentration areas (deposition sites) for the synthesized metabolites [9, 57].

Fig. 4
figure 4

Frequency of plant parts used for preparation of antitubercular remedies in East Africa

Most articles reviewed reported that traditional herbal medicine practitioners usually combined different plant species while preparing herbal medicines. However, they did not report how the herbal medicine from individual plant species can be prepared. Decoction was by far the commonest method of herbal medicine preparation cited. Others included cold infusions, drying and pounding into a powder, burning into ash, chewing, and steaming. Use of more than one plant in combination is more effective than single plant perhaps due to the synergistic interactions that occur among the different phytochemicals that result into increased bioactivity (efficacy). But also, the benefit of phytochemicals from one species counteracting the toxicity of another species could be another explanation.

The major route of administration was oral (via the mouth) although sometimes inhalation and topical application were also reported depending on the preparation method used and the toxicity of the plant(s). Cups, bottles, and tablespoons were the most commonly used for determining the posology of herbal remedies [7, 10, 12].

Efficacy and safety studies

Some ethnobotanical studies reported that herbal medicine preparations were effective in the treatment of TB, while some were used in the management of multidrug-resistant tuberculosis [7, 12, 47]. This could be due to the synergistic interaction between the various phytochemicals present in the herbal preparations [27, 83]. However, as much as these herbal medicines might have genuine bioactivity, sometimes they are used concurrently with conventional therapies as supplements and at times adulterated. Therefore, it is important to scientifically validate the claimed efficacy and safety of both the herbal preparations and the individual medicinal plants. Out of the 195 species documented, only 36 plant species (18.5%) have been studied for their antimycobacterial activity. A WHO report [14] indicated that only approximately 10% of the world’s flora have been studied as regards their medicinal potential. This has greatly hindered the discovery of potential lead compounds that could be developed into new antitubercular drugs.

Out of the 36 screened medicinal plants, 31 species (86.1%) were reported to be bioactive with some species exhibiting quite considerable antimycobacterial activity although the current standard drugs had superior bioactivity (Table 2). This is comparable to India where 70% of 365 plants which were studied showed antimycobacterial activity [87]. Among the promising plant species (with minimum inhibitory concentration less than 0.5 mg/ml) were Erythrina abyssinica, Entada abyssinica, Bidens pilosa, Callistemon citrinus, Khaya senegalensis, Lantana camara, Piptadenistrum africana, Rosmarinus officinalis, Tetradenia riparia, and Zanthoxylum leprieurii. Isolated pure compounds from three of the promising plant species had much higher activity against Mtb than the crude extracts and fractions. Indeed, some of the compounds from Zanthoxylum leprieurii had minimum inhibitory concentrations lower than those of standard antitubercular drugs (Table 3). Crude extracts and fractions usually have less pharmacological activity than standard drugs because of the interference from other inactive substances in the matrix that reduce the overall concentration of the active molecules in the tested dose. This explains why isolation of pure compounds is a critical step in natural product drug discovery process. The five documented medicinal plants that were found to be inactive are Acacia ataxacantha, Dalbergia melanoxylon, Indigofera lupatana, Lonchocarpus eriocalyx, and Solanum incanum. This could probably be attributed to the absence of inherent bioactive phytochemicals against Mtb in the plant species. This could be brought about by absence or impaired biosynthetic metabolic pathways due to unfavorable growth conditions in the habitat from where the plants grow. This implies that herbal remedies for TB containing each of these plants singly may not be effective. Therefore, other benefits provided by these species in the concoctions of TB such as detoxification of other toxic phytochemicals, preservation of the herbal medicine, or potentiation of the pharmacological activity of other phytochemicals could be investigated.

Table 2 Efficacy, toxicity, and phytochemical studies on medicinal plants used for treatment of TB in East Africa
Table 3 Isolation and characterization studies on medicinal plants used for management of TB in East Africa

All toxicity studies reviewed evaluated only the acute toxicity profiles of the medicinal plants either in vitro or in vivo but not both. Of the bioactive extracts screened, less than half of them were tested for their acute toxicity. Selectivity index (SI) is used as the best estimate of the relative toxicity of a compound to normal mammalian cells as compared to the pathogen and hence its suitability for being a drug candidate. According to the SI criterion, compounds with higher SI are regarded to have better toxicity profiles than those with lower SI [88]. From the retrieved data, only two plant species (Khaya senegalensis and Rosmarinus officinalis) had acceptable selectivity indices to warrant drug discovery from them. In this study, the SI of only five plant species could be calculated (Table 4) because they were the only plant species with both the inhibitory concentration on Mtb and cytotoxic concentration on normal mammalian cell lines (IC50) reported. Hence, there is need to emphasize dual testing of both toxicity and efficacy of natural products for drug development purposes.

Table 4 Selectivity indices of some antitubercular plant species reported in East Africa

Two other systems of acute toxicity classification: The National Cancer Institute (NCI) and Organization for Economic cooperation and development (OECD) guidelines 423 were used to assess the toxicity profiles of the different extracts [89, 90]. There was no single plant species among those tested for acute toxicity that was reported to be highly toxic (with IC50 less than 20 μg/ml). All the plant species with promising bioactivity that were tested for toxicity had acceptable acute toxicity profiles. These included Rosmarinus officinalis, Lantana camara, Khaya senegalensis, and Erythrina abyssinica (Table 2). Aspilia pluriseta, Cissampelos pareira, Euphorbia ingens, and Gnidia buchananii had moderate toxicity with IC50 between 20 and 200 μg/ml. According to OECD 2001 guidelines, Lantana camara, Erythrina abyssinica, and Cryptolepis sanguinolenta had slight toxicity as their median lethal doses (LD50) were above 500 mg/kg. These results justify the general public belief that traditional medicines are relatively safer as compared to the current conventional therapies. However, toxicity testing should be done on all potential medicinal plants and their phytochemicals before concluding that they are safe for human treatment [91,92,93,94]. This is because toxicity of herbal medicines may be due to presence of inherent poisonous chemicals in the plant species, misidentification of the plant species, adulteration or contamination during harvesting, preparation, and storage [95, 96]. Acute toxicity tests determine a single high dose that kills 50% of the cells or animals in a population. They may not be evident enough to depict the real toxicity situation for herbal remedies taken for a longer time in chronic conditions like TB [18, 97]. Therefore, this may necessitate sub-chronic and chronic toxicity tests to be carried out on a medicinal plant species with a potential lead compound [95].

Phytochemistry of the reported plants

Phytochemical investigation reveals the chemical nature of the pure compounds that are responsible for the pharmacological activity as well as the toxicity of medicinal plants [19, 64, 98,99,100,101]. Chromatographic and spectroscopic techniques are used to identify and elucidate the chemical structures of compounds [102,103,104,105,106,107]. In this study, maceration was the commonly used method of extraction as compared to Soxhlet. Majority of the hexane extracts were reported to be inactive against mycobacterial strains while almost all methanolic extracts were active. Methanol being a polar solvent extracts polar phytochemical while hexane (a non-polar solvent) extracts non-polar compounds. It is reasonable to assert that the antimycobacterial activity of the extracts is largely due to polar phytochemicals. There were variations in bioactivity of different parts of the same plant with no specific patterns. This could be due to differences in their rate of accumulating the bioactive substances.

The phytochemicals that were frequently screened for have been alkaloids, saponins, cardiac glycosides, flavonoids, terpenoids, and phenols. All these secondary metabolites were reported to be present in different bioactive extracts. The most commonly reported phytochemicals were flavonoids, terpenoids, and alkaloids [15, 17, 26, 29, 70, 106, 108]. Flavonoids and alkaloids were reported to be absent in three out of the five inactive plants (Table 2). Out of the 31 bioactive plant species, only three (Tetradenia riparia, Warburgia ugandensis, and Zanthoxylum leprieurii) have been further characterized to identify the pure compounds responsible for their antimycobacterial activity [5, 37, 58, 85] (Table 3). This is attributed to the complexity and the rigorous nature of the process that require extraction, screening, isolation, and characterization [100, 109, 110]. Low extraction yield, compound instability, high costs, low technology especially in developing countries, limited access to advanced chromatographic, and spectroscopic equipment and inadequate funding have made it difficult to undertake herbal medicine research [21, 111, 112]. This is further complicated by the microbiological nature of the Mtb that require bioassays to be conducted in biosafety level 3 laboratories that are not readily available in East Africa [60, 113]. More robust and effective techniques are required to fasten the drug discovery process against TB [3, 77, 92, 114].

A total of seven pure compounds have been isolated and characterized with bioactivity against Mtb (Fig. 5). These are 2-hydroxy-1,3-dimethoxy-10-methyl-9-acridone (1), 1-hydroxy-3- methoxy-10-methyl-9-acridone (2), 3-hydroxy-1, 5, 6-trimethoxy-9-acridone (3), muzigadial (4), muzigadiolide (5), linoleic acid (6), and 15-sandaracopimaradiene-7α, 18-dio1 (7). Compounds 1, 2, and 3 are acridone alkaloids; 4, 5, and 6 are sesquiterpenes, while 7 is a diterpenediol [5, 37, 85]. In Asia and America, several studies have reported pure compounds isolated from medicinal plants to have promising antimycobacterial activity [78, 115,116,117]. For example, Bisbenzylisoquinoline alkaloids from Tiliacora triandra (tiliacorinine, tiliacorine and 2′-nortiliacorinine) were found to have comparable antimycobacterial activity (MIC = 0.7–6.2 μg/ml) to the standard first line drugs against sensitive and resistant Mtb strains [108]. Rukachaisirikul et al. [118] reported that 5- hydroxysophoranone (an isoflavone from Erythrina stricta) had promising antimycobacterial activity (MIC = 12.5 μg/ml) against Mtb H37Ra. Vasicine acetate and 2-acetyl benzylamine isolated from hexane extract of Adhatoda vasica Ness. (Acanthaceae) inhibited one sensitive and multidrug-resistant strain at 50 and 200 μg/ml respectively [119]. Since flavonoids and alkaloids were reported to be absent in three out of the five inactive plants [28] and majority of the isolated bioactive pure compounds belong to the class of alkaloids, terpenoids, and flavonoids [5, 85, 118], it implies that these classes of phytochemicals are the ones most likely to be responsible for the observed antimycobacterial activity.

Fig. 5
figure 5

Structure of antitubercular molecules isolated in claimed medicinal plants in East Africa. The numbers 17 correspond to the molecules mentioned in Table 3

Conclusion

East Africa has a rich diversity of medicinal plants that have been reported to be effective in the management of symptoms of TB. Most of the plants are from the family Fabaceae, Lamiaceae, and Asteraceae. A large proportion of the documented plants have not been scientifically validated for their efficacy and safety. Although the standard drugs had superior activity, majority of the validated plants were found to possess acceptable acute toxicity profile on animal cells and considerable bioactivity with isolated pure compounds showing promising efficacy against Mtb. We recommend more scientific validation studies to be conducted on the remaining plants in order to standardize herbal medicine use and also promote drug discovery and development against TB. More isolation and characterization studies will enrich the chemical diversity of both the natural product and synthetic chemical libraries from which possible lead candidates could be developed. Currently, we are working on isolation and characterization of bioactive compounds from selected medicinal plants from family Fabaceae identified from this study. These include Erythrina abyssinica, Albizia coriaria, and Entada abyssinica.

Availability of data and materials

This is a review article and no raw experimental data were collected. All data generated or analyzed during this study are included in this published article.

Abbreviations

IC50 :

Median cytotoxic concentration

LD50 :

Median lethal dose

Iso:

Isoniazid

MIC:

Minimum inhibitory concentration

Rif:

Rifampicin

H37Rv:

Pan sensitive Mtb strain

TMC331:

Rifampicin-resistant Mtb strain

SI:

Selectivity Index

TB:

Tuberculosis

WHO:

World Health Organization

References

  1. WHO. Global Tuberculosis Report 2019. World Health Organization, Geneva, Switzerland. 2019. 297p. https://apps.who.int/iris/bitstream/handle/10665/329368/9789241565714-eng.pdf?ua=1. Acessed 04 March 2020.

  2. Hiraiwa M, Kim J, Lee H, Inoue S, Becker AL, Weigel KM, et al. Amperometric immunosensor for rapid detection of Mycobacterium tuberculosis. J Micromech Microeng. 2015;25:055013.

    PubMed  Google Scholar 

  3. Yuan T, Sampson NS. Hit generation in TB drug discovery: from genome to granuloma. Chem Rev. 2018;118:1887–916.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Ambrosio LD, Centis R, Sotgiu G, Pontali E, Spanevello A, Migliori GB. New anti-tuberculosis drugs and regimens: 2015 update. ERJ Open Res. 2015;1:00010–2015.

    PubMed  PubMed Central  Google Scholar 

  5. Bunalema L, Fotso GW, Waako P, Tabuti J, Yeboah SO. Potential of Zanthoxylum leprieurii as a source of active compounds against drug resistant Mycobacterium tuberculosis. BMC Complement Altern Med. 2017;17:89.

    PubMed  PubMed Central  Google Scholar 

  6. Godebo A, Abiy H, Toma A. Recent advances in the development of anti-tuberculosis drugs acting on multidrug-resistant strains: a review. Int J Res Pharm Biosci. 2015;2:1–18.

    Google Scholar 

  7. Bunalema L, Obakiro S, Tabuti JRS, Waako P. Knowledge on plants used traditionally in the treatment of tuberculosis in Uganda. J Ethnopharmacol. 2014;151:999–1004.

    PubMed  Google Scholar 

  8. Schultz F, Anywar G, Wack B, Quave CL, Garbe L. Ethnobotanical study of selected medicinal plants traditionally used in the rural greater Mpigi region of Uganda. J Ethnopharmacol. 2020;256:112742.

    CAS  PubMed  Google Scholar 

  9. Tugume P, Kakudidi EK, Buyinza M, Namaalwa J, Kamatenesi M, Mucunguzi P, et al. Ethnobotanical survey of medicinal plant species used by communities around Mabira central Forest reserve, Uganda. J Ethnobiol Ethnomed. 2016;12:5.

    PubMed  PubMed Central  Google Scholar 

  10. Tabuti JRS, Kukunda CB, Waako PJ. Medicinal plants used by traditional medicine practitioners in the treatment of tuberculosis and related ailments in Uganda. J Ethnopharmacol. 2010;127:130–6.

    PubMed  Google Scholar 

  11. Jeruto P, Lukhoba C, Ouma G, Otieno D, Mutai C. An ethnobotanical study of medicinal plants used by the Nandi people in Kenya. J Ethnopharmacol. 2008;116:370–6.

    PubMed  Google Scholar 

  12. Orodho JA, Kirimuhuzya C, Otieno JN, Magadula JJ, Okemo P. Local management of tuberculosis by traditional medicine practitioners in Lake Victoria region. Open Complement Med J. 2011;3:1–9.

    Google Scholar 

  13. Anywar G, Kaduidi E, Byamukama R, Mukonzo J, Schubert A, Oryem-Origa H. Indigenous traditional knowledge of medicinal plants used by herbalists in treating opportunistic infections among people living with HIV/AIDS in Uganda. J Ethnopharmacol. 2020;246:112205.

    CAS  PubMed  Google Scholar 

  14. WHO Global Report on Traditional and Complementary Medicine. 2019. https://www.who.int/traditional-complementary-integrative-medicine/WhoGlobalReportOnTraditionalAndComplementaryMedicine2019.pdf?ua=1. Accessed 04 March 2020.

  15. Bunalema L, Tabuti J, Sekagya Y, Ogwang S, Waako P. Anti-tubercular activity of Callistemon citrinus and Piptadenistrum africanum on resistant strains of Mycobacterium tuberculosis using microplate alamar blue assay. Spat DD. 2015;5:235–40.

    Google Scholar 

  16. Magadula JJ, Otieno JN, Nondo RS, Kirimuhuzya C, Kadukuli E, Orodho JA, et al. Eur J Med Plants. 2012;2:125–31.

    Google Scholar 

  17. Mariita M. Efficacy of medicinal plants used by communities around Lake Victoria region and the Samburu against mycobacteria, selected bacteria and Candida albicans. Nairobi: Kenyatta University; 2011.

    Google Scholar 

  18. Obakiro SB, Bunalema L, Nyatia E, Waako JP. Ulcerogenic potential of Eucalyptus globulus L. leaf extract in Wistar albino rats. J Pharmacol Toxicol. 2018;4:46–51.

    Google Scholar 

  19. Omara T. Plants ised in antivenom therapy in rural Kenya: ethnobotany and future perspectives. J Toxicol. 2020;2020:1–9. https://doi.org/10.1155/2020/1828521.

    Article  Google Scholar 

  20. Alamgeer, Younis W, Asif H, Sharif A, Riaz H, Bukhari IA, et al. Traditional medicinal plants used for respiratory disorders in Pakistan: a review of the ethno-medicinal and pharmacological evidence. Chin Med. 2018;13:48.

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Zuniga ES, Early J, Parish T. The future for early-stage tuberculosis drug discovery. Future Microbiol. 2015;10:217–29.

    CAS  PubMed  Google Scholar 

  22. Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.

    PubMed  PubMed Central  Google Scholar 

  23. Omara T, Kagoya S, Openy A, Omute T, Ssebulime S, Kiplagat KM, et al. Antivenin plants used for treatment of snakebites in Uganda: ethnobotanical reports and pharmacological evidences. Trop Med Health. 2020;48:6.

    PubMed  PubMed Central  Google Scholar 

  24. Omara T, Kiprop AK, Ramkat RC, Cherutoi J, Kagoya S, Nyangena DM, et al. Medicinal plants used in traditional management of cancer in Uganda: a review of ethnobotanical surveys, phytochemistry, and anticancer studies. Evidence-Based Complement Alternat Med. 2020;2020:1–26. https://doi.org/10.1155/2020/3529081.

    Article  Google Scholar 

  25. Omara T. Antimalarial plants used across Kenyan communities. Evidence-Based Complement Alternat Med. 2020;2020:1–31. https://doi.org/10.1155/2020/4538602.

    Article  Google Scholar 

  26. Nimbeshaho F, Mwangi CN, Orina F, Chacha M, Moody JO, Kigondu EM. Antimycobacterial activities, cytotoxicity and phytochemical screening of extracts for three medicinal plants growing in Kenya. J Med Plants Res. 2020; (in press).

  27. Ayaz M, Ullah F, Sadiq A, Ullah F, Ovais M, Ahmed J, et al. Interactions synergistic interactions of phytochemicals with antimicrobial agents : potential strategy to counteract drug resistance. Chem Biol Interact. 2019;308:294–303.

    CAS  PubMed  Google Scholar 

  28. Njeru SN, Obonyo MA. Potency of extracts of selected plant species from Mbeere, Embu County-Kenya against Mycobacterium tuberculosis. J Med Plant Res. 2016;10:149–57.

    CAS  Google Scholar 

  29. Mariita RM, Ogol CKPO, Oguge NO, Okemo PO. Antitubercular and phytochemical investigation of methanol extracts of medicinal plants used by the Samburu community in Kenya. Trop J Pharm Res. 2010;9:379–85.

    Google Scholar 

  30. Musa MS, Abdelrasool FE, Elsheikh EA, Ahmed LAMN, Mahmoud ALE, Yagi SM. Ethnobotanical study of medicinal plants in the Blue Nile state, South-Eastern Sudan. J Med Plant Res. 2011;5:287–4297.

    Google Scholar 

  31. Kimathi KN, Ogutu PA, Mutai C, Jeruto P. Ethnobotanical study of selected medicinal plants used against bacterial infections in Nandi county. Kenya. 2019;7:103–8.

    Google Scholar 

  32. Watt JM, Breyer-Brandwijk G. Medicinal and poisonous plants of southern and eastern Africa. 2nd ed. Edinburgh & London: E. & S. Livingstone Ltd; 1962. 394p.

    Google Scholar 

  33. Shiracko N, Owuor BO, Gakuubi MM, Wanzala W. A survey of ethnobotany of the AbaWanga people in Kakamega county, Western province of Kenya. Indian J Tradit Knowle. 2016;15:93–102.

    Google Scholar 

  34. Fratkin E. Traditional medicine and concepts of healing among samburu pastoralists of Kenya. J Ethnobiol. 1996;16:63–97.

    Google Scholar 

  35. Ghazali GE, Abdalla WE, El H, Khalid S, Khalafalla M. Medicinal plants of Sudan, part V: medicinal plants of Ingassana area. Khartoum, Sudan: National Center for Research, Ministry of Science and Technology; 2003. p. 1–19.

    Google Scholar 

  36. Okello SV, Nyunja RO, Netondo GW, Onyango JC. Ethnobotanical study of medicinal plants used by sabaots of Mt. Elgon Kenya. Afr J Tradit Complement Altern Med. 2010;7:1–10.

    Google Scholar 

  37. Van Puyvelde L, Ntawukiliyayo JD, Portaels F, Hakizamungu E. In vitro inhibition of mycobacteria by Rwandese medicinal plants. Phytother Res. 1994;8:65–9.

    Google Scholar 

  38. Ngezahayo J, Havyarimana F, Hari L, Stévigny C, Duez P. Medicinal plants used by Burundian traditional healers for the treatment of microbial diseases. J Ethnopharmacol. 2015;173:338–51.

    PubMed  Google Scholar 

  39. Gafna DJ, Dolos K, Mahiri IO, Mahiri JG, Obando JA. Diversity of medicinal plants and anthropogenic threats in the Samburu central sub-county of Kenya. Afr J Tradit Complement Altern Med. 2017;14:72–9.

    Google Scholar 

  40. Kiringe JW. A survey of traditional health remedies used by the Maasai of southern Kaijiado district, Kenya. Ethnobot Res Appl. 2006;4:61–73.

    Google Scholar 

  41. Kokwaro JO. Medicinal plants of East Africa. 3rd ed. Nairobi: East Africa Literature Bureau; 1976.

    Google Scholar 

  42. El-Kamalia HH, El-Khalifa KF. Folk medicinal plants of riverside forests of the southern Blue Nile district, Sudan. Fitoterapia. 1999;70:493–7.

    Google Scholar 

  43. Burham BO. Chemical constituents of selected Sudanese medicinal and aromatic plants; 2007.

    Google Scholar 

  44. Bunalema L, Kirimuhuzya C, Tabuti JRS, Waako P, Magadula JJ, Otieno N, et al. The efficacy of the crude root bark extracts of Erythrina abyssinica on rifampicin resistant mycobacterium tuberculosis. Afr Health Sci. 2011;11:587–93.

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Desouter S. Human and veterinary pharmacopoeia, vol. 22. Tervuren; 1991. p. 252.

  46. Amuka O, Okemo PO, Alex K, Mbugua PK. Ethnobotanical survey of selected medicinal plants used by Ogiek communities in Kenya against microbial infections. Ethnobot Res Appl. 2014;12:627–41.

    Google Scholar 

  47. Orodho JA, Okemo P, Tabuti JB, Otieno N, Magadula JJ, Kirimuhuzya C. Indigenous knowledge of communities around Lake Victoria Basin regarding treatment and management of tuberculosis using medicinal plants. Int J Med Sci. 2014;6:16–23.

    Google Scholar 

  48. Kayonga A, Habiyaremye FX. Traditional medicine and Rwandan medicinal plants. Contribution to ethnobotanic study of Rwandan Flora. Gisenyi prefecture. Curfametra: Univ. Nat. University Research Center on pharmacopoeia and traditional medicine; 1987. p. 121.

    Google Scholar 

  49. Sospeter NN, Meshack AO. Potency of extracts of selected plant species from Mbeere, Embu County-Kenya against Mycobacterium tuberculosis. J Med Plants Res. 2016;10:149–57.

    Google Scholar 

  50. Cyrus WG, Daniel GW, Nanyingi MO, Njonge FK, Mbaria JM. Antibacterial and cytotoxic activity of Kenyan medicinal plants. Mem Inst Oswaldo Cruz. 2008;103:650–2.

    PubMed  Google Scholar 

  51. Nanyingi MO, Mbaria JM, Lanyasunya AL, Wagate CG, Koros KB, Kaburia HF, et al. Ethnopharmacological survey of Samburu district, Kenya. J Ethnobiol Ethnomed. 2008;12:1–12.

    Google Scholar 

  52. Abuzeid N, Kalsum S, Larsson M, Glader M, Andersson H, Raffetseder J, et al. Antimycobacterial activity of selected medicinal plants traditionally used in Sudan to treat infectious diseases. J Ethnopharmacol. 2014;157:134–9.

    PubMed  Google Scholar 

  53. Kirimuhuzya C, Waako P, Joloba M, Odyek O. The anti-mycobacterial activity of Lantana camara a plant traditionally used to treat symptoms of tuberculosis in South-Western Uganda. Afr Health Sci. 2009;9:40–5.

    PubMed  PubMed Central  Google Scholar 

  54. EL-Kamali HH. Ethnopharmacology of medicinal plants used in North Kordofan (Western Sudan). Ethnobot Leaf. 2009;13:203–10.

    Google Scholar 

  55. Nankaya J, Nampushi J, Petenya S, Balslev H. Ethnomedicinal plants of the Loita Maasai of Kenya. Environ Dev Sustain. 2019. https://doi.org/10.1007/s10668-019-00311-w.

  56. Nankaya J, Gichuki N, Lukhoba C, Balslev H. Medicinal plants of the Maasai of Kenya: a review. Plants. 2020;9:1–17.

    Google Scholar 

  57. Asiimwe S, Kamatenesi-Mugisha M, Namutebi A, Borg-Karlsson AK, Musiimenta P. Ethnobotanical study of nutri-medicinal plants used for the management of HIV/AIDS opportunistic ailments among the local communities of western Uganda. J Ethnopharmacol. 2013;150:639–48.

    PubMed  Google Scholar 

  58. Mbwambo Z, Erasto P, Innocent E, Masimba P. Antimicrobial and cytotoxic activities of fresh leaf extracts of Warburgia ugandensis. Tanzan J Health Res. 2009;11:75–8.

    Google Scholar 

  59. Okello D, Kang Y. Ethnopharmacological potentials of Warburgia ugandensis on antimicrobial activities. Chin J Integr Med. 2019. https://doi.org/10.1007/s11655-019-3042-6.

  60. Buwa LV, Afolayan AJ. Antimicrobial activity of some medicinal plants used for the treatment of tuberculosis in the eastern Cape Province, South Africa. Afr J Biotechnol. 2009;8:6683–7.

    Google Scholar 

  61. Babalola IT, Adelakun EA. Compendium of medicinal plants for the ethno-therapeutic management of tuberculosis and other respiratory diseases. J Pharmacog Phytochem. 2018;7:1983–94.

    Google Scholar 

  62. Semenya SS, Maroyi A. Medicinal plants used for the treatment of tuberculosis by Bapedi traditional healers in three districts of the Limpopo province, South Africa. Afr J Tradit Complement Altern Med. 2012;10:316–23.

    PubMed  PubMed Central  Google Scholar 

  63. Alvin A, Miller KI, Neilan BA. Exploring the potential of endophytes from medicinal plants as sources of antimycobacterial compounds. Microbiol Res. 2014;169:483–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Semenya SS, Maroyi A. Ethnobotanical survey of plants used by Bapedi traditional healers to treat tuberculosis and its opportunistic infections in the Limpopo Province, South Africa. South Afr J Bot. 2019;122:401–21.

    Google Scholar 

  65. Green E, Samie A, Obi CL, Bessong PO, Ndip RN. Inhibitory properties of selected south African medicinal plants against Mycobacterium tuberculosis. J Ethnopharmacol. 2010;130:151–7.

    PubMed  Google Scholar 

  66. Famewo EB, Clarke AM, Wiid I, Ngwane A, Van Helden P, Afolayan AJ. Anti-mycobacterium tuberculosis activity of polyherbal medicines used for the treatment of tuberculosis in eastern cape, South Africa. Afr Health Sci. 2017;17:780–9.

    PubMed  PubMed Central  Google Scholar 

  67. Ibekwe NN, Ameh SJ. Plant natural products research in tuberculosis drug discovery and development: a situation report with focus on Nigerian biodiversity. Afr J Biotechnol. 2014;13:2307–20.

    Google Scholar 

  68. Mann A, Amupitan JO, Oyewale AO, Okogun JI, Ibrahim K, Oladosu P, et al. Evaluation of in vitro antimycobacterial activity of Nigerian plants used for treatment of respiratory diseases. Afr J Biotechnol. 2008;7:1630–6.

    Google Scholar 

  69. Nguta JM, Appiah-Opong R, Nyarko AK, Yeboah-manu D, Addo PGA, Kissi-Twum A. Antimycobacterial and cytotoxic activity of selected medicinal plant extracts. J Ethnopharmacol. 2016;182:10–5.

    PubMed  PubMed Central  Google Scholar 

  70. Gemechu A, Giday M, Worku A, Ameni G. In vitro anti-mycobacterial activity of selected medicinal plants against Mycobacterium tuberculosis and Mycobacterium bovis strains. BMC Complement Altern Med. 2013;13:291.

    PubMed  PubMed Central  Google Scholar 

  71. Pandit R, Singh PK, Kumar V. Natural remedies against multi-drug resistant Mycobacterium tuberculosis. J Tuberculosis Res. 2015;3:171–83.

    CAS  Google Scholar 

  72. Rai R. Herbal remedies in cure of tuberculosis prevalent among ethnic communities in Central India. Trop Plant Res. 2016;3:344–53.

    Google Scholar 

  73. Mongalo NI, McGaw LJ, Segapelo TV, Finnie JF, Van Staden J. Ethnobotany, phytochemistry, toxicology and pharmacological properties of Terminalia sericea Burch. Ex DC. (Combretaceae) – a review. J Ethnopharmacol. 2016;94:789–802.

    Google Scholar 

  74. Saleh-e-In MM, Van Staden J. Ethnobotany, phytochemistry and pharmacology of Arctotis arctotoides (L.f.) O. Hoffm.: a review. J Ethnopharmacol. 2018;220:294–320.

    CAS  PubMed  Google Scholar 

  75. Sharma A, Flores-Vallejo RC, Cardoso-Taketa A, Villarreal ML. Antibacterial activities of medicinal plants used in Mexican traditional medicine. J Ethnopharmacol. 2017;208:264–329.

    PubMed  Google Scholar 

  76. Ngadino S, Koerniasari E, Sudjarwo SA. Evaluation of antimycobacterial activity of Curcuma xanthorrhiza ethanolic extract against Mycobacterium tuberculosis H37Rv in vitro. Vet World. 2018;11:368–72.

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Tuyiringire N, Tusubira D, Munyampundu JP, Tolo CU, Muvunyi CM, Ogwang PE. Application of metabolomics to drug discovery and understanding the mechanisms of action of medicinal plants with anti-tuberculosis activity. Clin Transl Med. 2018;7:29.

    PubMed  PubMed Central  Google Scholar 

  78. Al-baadani WA, Satyanarayan ND. Anti-tubercular evaluation of Rivea hypocrateriformis (Der.) choisy against Mycobacterium tuberculosis H37Rv strain. J Pharmacognosy Phytochem. 2018;7:2679–82.

    CAS  Google Scholar 

  79. Lawal IO, Grierson DS, Afolayan AJ. Phytotherapeutic information on plants used for the treatment of tuberculosis in eastern Cape Province. South Africa Evidence-based Complement Altern Med. 2014:1–11. https://doi.org/10.1155/2014/735423.

  80. Nguta JM, Appiah-Opong R, Nyarko AK, Yeboah-Manu D, Addo PGA. Medicinal plants used to treat TB in Ghana. Int J Mycobacteriol. 2015;4:116–23.

    PubMed  Google Scholar 

  81. Ogbole OO, Ajaiyeoba EO. Traditional management of tuberculosis in Ogun state of Nigeria: the practice and ethnobotanical survey. Afr J Tradit Complement Altern Med. 2010;7:79–84.

    Google Scholar 

  82. Stewart ZP, Pierzynski GM, Middendorf BJ, Prasad PVV. Approaches to improve soil fertility in sub-Saharan Africa. J Exp Bot. 2020;71:632–41.

    PubMed  Google Scholar 

  83. Ge F, Zheng F, Liu S, Guo N, Ye H, Song Y, et al. In vitro synergistic interactions of oleanolic acid in combination with isoniazid, rifampicin or ethambutol against Mycobacterium tuberculosis. J Med Microbiol. 2010;59:567–72.

    CAS  PubMed  Google Scholar 

  84. Kirimuhuzya C. Efficacy of Cryptolepis sanguinolenta root extract on slow-growing rifampicin resistant Mycobacterium tuberculosis. J Med Plants Res. 2012;6:1140–6.

    Google Scholar 

  85. Wube AA, Bucar F, Gibbons S, Asres K. Sesquiterpenes from Warburgia ugandensis and their antimycobacterial activity. Phytochem. 2005;66:2309–15.

    CAS  Google Scholar 

  86. Kirimuhuzya C, Bunalema L, Tabuti JRS, Kakudidi EK, Orodho J, Magadula J, et al. The in vitro antimycobacterial activity of medicinal plants used by traditional medicine practitioners (TMPs) to treat tuberculosis in the Lake Victoria basin in Uganda. In: A presentation at the 14th NAPRECA symposium held at ICIPE, Kasarani, Nairobi, Kenya; 2011.

    Google Scholar 

  87. Gautam R, Saklani A, Jachak SM. Indian medicinal plants as a source of antimycobacterial agents. J Ethnopharmacol. 2007;110:200–34.

    CAS  PubMed  Google Scholar 

  88. Kaminsky R, Caecilia S, Reto B. An “in vitro selectivity index” for evaluation of cytotoxicity of antitrypanosomal compounds. In vitro Toxicol. 1996;9:315–24.

  89. OECD. OECD guideline for testing of chemicals: acute oral toxicity – acute toxic class method. OECD Guideline for Testing of Chemicals, no. December: 1–14. 2001. doi: https://doi.org/10.1787/9789264070943-en.

  90. Geran RI, Greenberg HM, McDonald M, Abbott BJ. Protocols for screening chemical agents and natural products against animal tumors and other biological systems. Cancer Chemoth Rep. 1972;33:1–17.

    Google Scholar 

  91. Keter L, Too R, Mwikwabe N, Mutai C, Orwa J, Mwamburi L, et al. Risk of fungi associated with aflatoxin and fumonisin in medicinal herbal products in the Kenyan market. Sci World J. 2017;1892972.

  92. Pan S, Zhou S, Gao S, Yu Z, Zhang S, Tang M, et al. “New perspectives on how to discover drugs from herbal medicines: CAM’s outstanding contribution to modern therapeutics. Evidence-based complement. Altern Med. 2013. https://doi.org/10.1155/2013/627375.

  93. Ko RJ. A U.S. perspective on the adverse reactions from traditional Chinese medicines. J Chin Med Assoc. 2004;67:109–16.

    PubMed  Google Scholar 

  94. Chuluun B, Iamchaturapatr J, Rhee J. Phytoremediation of organophosphorus and organochlorine pesticides by Acorus gramineus. Environ Eng Res. 2009;14:226–36.

    Google Scholar 

  95. Ekor M. The growing use of herbal medicines: issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol. 2014;4:177.

    PubMed  PubMed Central  Google Scholar 

  96. Tomlinson B, Chan TY, Chan JC, Critchley JA, But PP. Toxicity of complementary therapies: an eastern perspective. J Clin Pharmacol. 2000;40:451–6.

    CAS  PubMed  Google Scholar 

  97. Aniagu S, Nwinyi F, Akumka DD, Ajoku GD, Dzarma S, Izebe KS. Toxicity studies in rats fed nature cure bitters. Afri J Biotechnol. 2005;4:72–8.

    Google Scholar 

  98. Agyare C, Boakye YD, Bekoe EO, Hensel A, Dapaah SO, Appiah T. Review: African medicinal plants with wound healing properties. J Ethnopharmacol. 2016;177:85–100.

    CAS  PubMed  Google Scholar 

  99. Owor RO, Bedane KG, Zühlke S, Derese S, Ong'amo GO, Ndakala A, et al. Anti-inflammatory flavanones and flavones from Tephrosia linearis. J Nat Prod. 2020. https://doi.org/10.1021/acs.jnatprod.9b0092.

  100. Gavamukulya Y, Maina EN, Meroka A, Madivoli ES, El-Shemy HA, Magom G, et al. Liquid chromatography single quadrupole mass spectrometry (LC/SQ MS) analysis reveals presence of novel antineoplastic metabolites in ethanolic extracts of fruits and leaves of Annona muricata. Pharmacognosy J. 2019;11:660–8.

    CAS  Google Scholar 

  101. Andima M, Coghi P, Yang LJ, Wong VKW, Ngule CM, Heydenreich M, et al. Antiproliferative activity of secondary metabolites from Zanthoxylum zanthoxyloides Lam : in vitro and in silico studies. Pharmacognosy Comm. 2020;10:44–51.

    CAS  Google Scholar 

  102. Bauer A, Brönstrup M. Industrial natural product chemistry for drug discovery and development. Nat Prod Rep. 2014;31:35–60.

    CAS  PubMed  Google Scholar 

  103. Saraswathi VS, Saravanan D, Santhakumar K. Isolation of quercetin from the methanolic extract of Lagerstroemia speciosa by HPLC technique, its cytotoxicity against MCF-7 cells and photocatalytic activity. J Photochem Photobiol B. 2017;171:20–6.

    Google Scholar 

  104. Chraibi MM, Farah A, Lebrazi S, El Amine O, Iraqui Houssaini M, Fikri-Benbrahim K. Antimycobacterial natural products from Moroccan medicinal plants: chemical composition, bacteriostatic and bactericidal profile of Thymus satureioides and Mentha pulegium essential oils. Asian Pac J Trop Biomed. 2016;6:836–40.

    Google Scholar 

  105. Hoerr V, Duggan GE, Zbytnuik L, Poon KKH, Große C, Neugebauer U, et al. Characterization and prediction of the mechanism of action of antibiotics through NMR metabolomics. BMC Microbiol. 2016;16:82.

    PubMed  PubMed Central  Google Scholar 

  106. Esquivel-ferriño PC, Favela-hernández JMJ, Garza-gonzález E, Waksman N, Ríos MY, Camacho-corona MR. Antimycobacterial activity of constituents from Foeniculum vulgare var. Dulce grown in Mexico. Molecules. 2012;17:8471–82.

    PubMed  PubMed Central  Google Scholar 

  107. Zhao J, Evangelopoulos D, Bhakta S, Gray AI, Seidel V. Antitubercular activity of Arctium lappa and Tussilago farfara extracts and constituents. J Ethnopharmacol. 2014;155:796–800.

    CAS  PubMed  Google Scholar 

  108. Sureram S, Senadeera SPD, Hongmanee P, Mahidol C, Ruchirawat S, Kittakoop P. Antimycobacterial activity of bisbenzylisoquinoline alkaloids from Tiliacora triandra against multidrug-resistant isolates of Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2012;22:2902–5.

    CAS  PubMed  Google Scholar 

  109. Gao F, Ye L, Wang Y, Kong F, Zhao S, Xiao J. Benzofuran-isatin hybrids and their in vitro anti-mycobacterial activities against multi-drug resistant Mycobacterium tuberculosis. Eur J Med Chem. 2019;183:111678.

    CAS  PubMed  Google Scholar 

  110. Machelart A, Song O, Hoffmann E, Brodin P. Host-directed therapies offer novel opportunities for the fight against tuberculosis. Drug Discov Today. 2017;22:1250–7.

    PubMed  Google Scholar 

  111. WHO. Global Tuberculosis Report 2017. WHO, Geneva, Switzerland. 2017. 262p. https://reliefweb.int/sites/reliefweb.int/files/resources/9789241565516-eng.pdf. Accessed 4 Mar 2020.

  112. Nguta JM, Appiah-Opong R, Nyarko AK, Yeboah-manu D, Addo PGA. Current perspectives in drug discovery against tuberculosis from natural products. Int J Mycobacteriol. 2017;4:165–83.

    Google Scholar 

  113. Balouiri M, Sadiki M, Ibnsouda SK. Methods for in vitro evaluating antimicrobial activity: a review. J Pharm Anal. 2016;6:71–9.

    PubMed  Google Scholar 

  114. Manjunatha UH, Smith PW. Perspective: challenges and opportunities in TB drug discovery from phenotypic screening. Bioorganic Med Chem. 2015;23:5087–97.

    CAS  Google Scholar 

  115. León-Díaz R, Meckes M, Said-Fernández S, Molina-Salinas GM, Vargas-Villarreal J, Torres J, et al. Antimycobacterial neolignans isolated from Aristolochia taliscana. Mem Inst Oswaldo Cruz. 2010;105:45–51.

    PubMed  Google Scholar 

  116. Bocanegra-Garcia V, Garcia A, Palma-Nicolás JP, Palos I, Rivera G. Antitubercular drugs development: recent advances in selected therapeutic targets and rational drug design. In: A case study based insight into modern strategies. Intech open; 2011. p. 207–42.

    Google Scholar 

  117. Vyas DH, Tala SD, Dhaduk MF, Akbari JD, Joshi HS. Synthesis, antitubercular and antimicrobial activities of some new pyrazoline and isoxazole derivatives. J Indian Chem Soc. 2007;84:1140–4.

    CAS  Google Scholar 

  118. Rukachaisirikul T, Saekee A, Tharibun C, Watkuolham S. Biological activities of the chemical constituents of Erythrina stricta and Erythrina subumbrans. Arch Pharm Res. 2007;30:1398.

    CAS  PubMed  Google Scholar 

  119. Ignacimuthu S, Shanmugam N. Antimycobacterial activity of two natural alkaloids, vasicine acetate and 2-acetyl benzylamine, isolated from Indian shrub Adhatoda vasica ness . Leaves. J Biosci. 2010;35:565–70.

    CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to the World Bank and the Inter-University Council of East Africa (IUCEA) for the scholarship awarded to SBO, MPO, and TO through the Africa Centre of Excellence II in Phytochemicals, Textiles and Renewable Energy (ACE II PTRE) at Moi University, Kenya, which made this communication possible. The authors commend preceding authors for their fruitful quest for knowledge on medicinal plants utilized by rural communities of East Africa, the reports of which the current study was based.

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SBO, AK, IK, EK, MPO, TO, and LB designed the study. SBO, IK, EK, MPO, TO, and LB performed literature search for medicinal plants in Uganda, Burundi, Rwanda, Kenya, Tanzania, and South Sudan, respectively. SBO and TO analyzed the collected data. TO, MPO, and LB verified the plant names in botanical databases and local languages. SBO, MPO, TO, and LB wrote the first draft of the manuscript. AK, IK, and EK reviewed the draft manuscript. All authors revised and approved the final manuscript.

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Correspondence to Samuel Baker Obakiro.

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Additional file 1: Figure S1

. PRISMA flow diagram used for the review.

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Obakiro, S.B., Kiprop, A., Kowino, I. et al. Ethnobotany, ethnopharmacology, and phytochemistry of traditional medicinal plants used in the management of symptoms of tuberculosis in East Africa: a systematic review. Trop Med Health 48, 68 (2020). https://doi.org/10.1186/s41182-020-00256-1

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