article · Frontiers in Pharmacology
<b>Background:</b> The present study investigated the efficacy of <i>Conyza bonariensis, Commiphora africana, Senna obtusifolia, Warburgia ugandensis, Vernonia glabra,</i> and <i>Zanthoxylum usambarense</i> against <i>Bitis arietans</i> venom (BAV), <i>Naja ashei</i> venom (NAV), and <i>Naja subfulva</i> venom (NSV). <b>Methods:</b> 40 extracts and fractions were prepared using n-hexane, dichloromethane, ethyl acetate, and methanol. <i>In vitro</i> efficacy against snake venom phospholipase A<sub>2</sub> (svPLA<sub>2</sub>) was determined in 96-well microtiter and agarose-egg yolk coagulation assays. <i>in vivo</i> efficacy against venom-induced cytotoxicity was determined using <i>Artemia salina</i>. Two commercial antivenoms were used for comparison. <b>Results:</b> The 96-well microtiter assay revealed poor svPLA<sub>2</sub> inhibition of BAV by antivenom (range: 20.76% ± 13.29% to 51.29% ± 3.26%) but strong inhibition (>90%) by dichloromethane and hexane fractions of <i>C. africana</i>, hexane and ethyl acetate extracts and fraction of <i>W. ugandensis</i>, dichloromethane fraction of <i>V. glabra</i>, and the methanol extract of <i>S. obtusifolia</i>. The methanol extract and fraction of <i>C. africana</i>, and the hexane extract of <i>Z. usambarense</i> strongly inhibited (>90%) svPLA<sub>2</sub> activity in NAV. The hexane and ethyl acetate fractions of <i>V. glabra</i> and the dichloromethane, ethyl acetate, and methanol extracts of <i>C. africana</i> strongly inhibited (>90%) svPLA<sub>2</sub> in NSV. The agarose egg yolk coagulation assay showed significant inhibition of BAV by the dichloromethane fraction of <i>C. africana</i> (EC<sub>50</sub> = 3.51 ± 2.58 μg/mL), significant inhibition of NAV by the methanol fraction of <i>C. africana</i> (EC<sub>50</sub> = 7.35 ± 1.800 μg/mL), and significant inhibition of NSV by the hexane extract of <i>V. glabra</i> (EC<sub>50</sub> = 7.94 ± 1.50 μg/mL). All antivenoms were non-cytotoxic in <i>A. salina</i> but the methanol extract of <i>C. africana</i> and the hexane extracts of <i>V. glabra</i> and <i>Z. usambarense</i> were cytotoxic. The dichloromethane fraction of <i>C. africana</i> significantly neutralized BAV-induced cytotoxicity<i>,</i> the methanol fraction and extract of <i>C. africana</i> neutralized NAV-induced cytotoxicity, while the ethyl acetate extract of <i>V. glabra</i> significantly neutralized NSV-induced cytotoxicity. Glycosides, flavonoids, phenolics, and tannins were identified in the non-cytotoxic extracts/fractions. <b>Conclusion:</b> These findings validate the local use of <i>C. africana</i> and <i>V. glabra</i> in snakebite but not <i>C. bonariensis, S. obtusifolia, W. ugandensis</i>, and <i>Z. usambarense.</i> Further work is needed to isolate pure compounds from the effective plants and identify their mechanisms of action.
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DOI: 10.3389/fphar.2024.1369768
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