Ethnopharmacology of medicinal plants traditionally used in the Greater Mpigi region, Uganda
Relevance: This PhD thesis provides an ethnopharmacological assessment of 16 medicinal plant species used by traditional healers for the treatment of various infectious and inflammatory diseases in the Greater Mpigi region of Uganda. It includes the first detailed report on selected medicinal plant use in the local traditional medicine system. The ethnobotanical data obtained supports the conservation of local traditional knowledge and will enable future drug discovery research. As conventional drug therapies are becoming increasingly limited and inefficacious, some of the greatest threats to global health today are addressed in this work, including antibiotic resistance, malaria, cancer, inflammation, and related symptoms such as pain and fever. Aims of the PhD thesis: The overarching objectives were 1) the documentation of the medicinal use of (often understudied) plant species; 2) the development of a bibliographic assessment tool for selection of medicinal plants for lab studies; 3) the creation of a plant extract library; 4) the pharmacological in vitro assessment of these species regarding their respective traditional uses; 5) the contribution to early drug discovery stages and thereby the provision of a scientific basis for future drug lead identification endeavors; and 6) the integration of aspects of community work while fostering a bidirectional communication with indigenous communities. Methods: The results of diverse ethnopharmacological field research methods and pharmacological lab assays are reported in this dissertation, including a) an ethnobotanical survey using structured interviews with 39 traditional healers from 29 villages; b) the novel Degrees of Publication (DoP) method; c) antibacterial screenings against a panel of clinical isolates of multidrug-resistant human pathogens; d) antivirulence experiments, e.g., monitoring of quorum sensing inhibition and direct protein output (δ-toxin) in Staphylococcus aureus; e) antiinflammatory investigations (e.g., cyclooxygenase-2 inhibition); f) antimalarial studies against chloroquine-resistant Plasmodium falciparum K1; g) cytotoxicity counterscreens (e.g., against human MRC-5SV2 lung fibroblasts and HaCaT keratinocytes); h) a genotoxicity assessment model with simulation of human liver metabolism; and i) a method for transferring research results back to traditional healers in rural indigenous communities. Results: The results of the survey indicated a high level of local traditional use, as the 16 plant species are frequently used to treat a total of 75 different medical disorders. Many of these use reports were documented for the first time. The development and application of the DoP method allowed for assessment of what was already known about a species, while also estimating the quality of the evidence. In total, 634 peer-reviewed publications covering the period of 1960-2019 were reviewed. Six of the 16 species were then classified as being highly understudied, and three species as being understudied, which provided further justification for the subsequent lab investigations. The results of the pharmacological experiments generally showed a high correlation between the pharmacological activity and the respective traditional use. In the following, some examples of the strongest bioactive extracts are provided for a) growth inhibition activity: extracts of Zanthoxylum chalybeum and Harungana madagascariensis stem bark against S. aureus (MIC: 16 and 32 μg/mL) and Enterococcus faecium (MIC: 32 μg/mL); b) quorum sensing inhibition activity against four S. aureus accessory gene regulator (agr) alleles: extracts of Solanum aculeastrum root bark and Sesamum calycinum subsp. angustifolium leaves (IC50: 1–64 μg/mL); c) selective COX-2 inhibition activity: an extract of Leucas calostachys leaves (IC50: 0.66 μg/mL); and d) antiplasmodial activity against P. falciparum K1: extracts of W. ugandensis stem bark and L. calostachys leaves (IC50: 0.5 and 5.7 μg/mL). The transfer of lab results back to the traditional healers culminated in a video article showing a two-day workshop. Conclusions: The conservation of traditional knowledge continues to be vital for future generations, especially when facing the need for novel and more effective drugs, which have often been discovered from natural products in the past. The newly introduced DoP method is a useful tool for selecting traditionally used species for future lab studies, like costly pharmacological experiments and time-consuming isolation procedures. The results of the pharmacological studies provided scientific support for the potential therapeutic effects of the medicinal plants used in the Greater Mpigi region.
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