Antimalarial Use of Malagasy Plants Is Poorly Correlated with Performance in Antimalarial Bioassays

Abstract

Bioassay screening of plant extracts can identify unique lead compounds for drug development, but the “hit rate” from random screening is very low. Targeted screening of medicinal plants has been repeatedly reported to increase the percentage of samples displaying bioactivity. Contrarily, Maranz (2012) suggested that African antimalarial plants were unsuitable sources of antimalarial drugs because high prevalence of malaria would result in rapid evolution of resistance to active compounds that directly targeted the parasite. As malaria is highly prevalent in much of Madagascar, it was of interest to determine whether Malagasy antimalarial plants would outperform randomly selected plants in conventional antimalarial assays being conducted as part of a discovery program. Of 1294 plant samples screened for antimalarial activity, 39.6% had an IC50 <50 μg/ml and 21.1% had an IC50 <20 μg/ml (the minimum to qualify as a first-pass “hit”). Ethnobotanical uses were coded at both the generic and the species level, as neither samples nor use reports in literature were always identifiable to species level. The 526 samples belonging to genera having reported uses for malaria were slightly more likely than average to display activity (44.3% with IC50 <50 μg/ml, p < .01; 23.2% with IC50 <20 μg/ml). Of these, 67 samples from individual species with documented use were still more likely to be modestly active (49.3% with IC50 <50 μg/ml), yet less likely to be highly active (17.9% with IC50 <20 μg/ml). Thus, in this specific context, ethnobotanically directed screening would not have substantially improved screening efficiency, and would have missed most of the potential hits.

Antiplasmodial, antimalarial activities and toxicity of African medicinal plants: a systematic review of literature

“…However, a few studies show that plant activity could also increase from in vitro to in vivo. For example, Ngbolua et al [211] showed that the activity of Vernonia ambigua increased from in vitro to in vivo analysis. Other examples include studies by Muthaura et al [20] using Boscia angustifolia, Kweyamba et al [162] using Commiphora Africana, and Ajaiyeoba et al [204] using Annona senegalensis.…”

“…There was also variation between the different assay types. For example, the activities of Vernonia ambigua [211] and Annona senegalensis [204] have been reported to increase from inactive in vitro to very good in vivo. However, a few plant species including Alchornea cordifolia, and Zanthoxylum chalybeum, were observed to be consistently very good between studies.…”

Language extinction triggers the loss of unique medicinal knowledge

“…Therefore, assessing to what degree linguistically unique medicinal services are truly effective in the Western sense is beyond the scope of this paper. In many instances, these plants have been proven medicinally effective (12,(22)(23)(24)(25)(26)(27), albeit there are also exceptions (28,29). Regardless of that, here, we treat this knowledge as what it is: part of the cultural heritage of indigenous people.…”

Homo medicus: The transition to meat eating increased pathogen pressure and the use of pharmacological plants in Homo

“…Databases of plants used in traditional medicine are widely screened for medically useful compounds (Anand et al, 2019; Pushpangadan et al, 2018; Wink, 2015; Yeung et al, 2020). Although the “jungle medicine” narrative has its share of hype, Western romanticism, and exploitation (Voeks, 2018), and some systematic assays of ethnomedicines have been disappointing (e.g., Applequist et al, 2017), there have been about 60,000 publications on ethnopharmacology, with research increasing dramatically on inflammation, infection, pain, toxicity, cancer and diabetes (Yeung et al, 2020).…”