Department of Zoology, Osun State University, Osogbo, Nigeria; Animal Physiology Unit, Department of Zoology, University of Ibadan, Ibadan, Nigeria.
Biochemistry Unit, Department of Chemical Sciences, Kings University, Ode-Omu, Nigeria.
Toxicon. 2023 Sep;233:107242. doi: 10.1016/j.toxicon.2023.107242. Epub 2023 Aug 8.
Bitis arietans venom (BAV) can induce severe pathophysiological disorders after envenoming. However, studies have shown that the Moringa oleifera fraction is effective against BAV toxicities and contains bioactive compounds with significant antivenom potency. This research aimed to identify the main active antivenom compound in the M. oleifera fraction responsible for neutralizing the toxicities induced by BAV. The compounds identified from M. oleifera fraction were docked in silico against the catalytic site of the Snake Venom Metalloproteinase (SVMP) to determine the lead inhibitor compound. The antivenom potency of the lead inhibitor compound was tested against BAV toxicities and metalloproteinase isolated from BAV using in vitro and in vivo methods, while EchiTab-Plus polyvalent antivenom served as a standard drug. The in silico prediction revealed kaempferol as the lead inhibitor compound with a docking score of -7.0 kcal/mol. Kaempferol effectively inhibited metalloproteinase activity at 0.2 mg/ml, compared to antivenom (0.4 mg/ml) and demonstrated significant antihaemorrhagic, antihaemolytic and coagulant effects against BAV activities. Furthermore, kaempferol showed a significant dose-dependent effect on altered haematological indices observed in rats challenged with LD of BAV. Envenomed rats also showed an increase in oxidative stress biomarkers and antioxidant enzyme activity in the heart and kidney. However, treatment with kaempferol significantly (P < 0.05) decreased malondialdehyde levels and SOD activity with concomitant enhancement of glutathione levels. Severe histopathological defects noticed in the organ tissues of envenomed rats were ameliorated after kaempferol treatment. Kaempferol is identified as the main active antivenom compound in M. oleifera, and this research highlights the potential of the compound as an effective alternative to snakebite treatment.
矛头蝮蛇毒液（BAV）中毒后会引起严重的病理生理紊乱。然而，研究表明，辣木部分对 BAV 毒性有效，并且含有具有显著抗蛇毒作用的生物活性化合物。本研究旨在鉴定辣木部分中负责中和 BAV 毒性的主要活性抗蛇毒化合物。从辣木部分鉴定的化合物在计算机上对接蛇毒金属蛋白酶（SVMP）的催化位点，以确定主要抑制剂化合物。使用体外和体内方法，针对 BAV 毒性和从 BAV 分离的金属蛋白酶测试主要抑制剂化合物的抗蛇毒效力，而 EchiTab-Plus 多价抗蛇毒血清作为标准药物。计算机预测表明，山奈酚是具有-7.0 kcal/mol 对接评分的主要抑制剂化合物。山奈酚在 0.2 mg/ml 时有效抑制金属蛋白酶活性，与抗蛇毒血清（0.4 mg/ml）相比，显示出显著的抗出血、抗溶血和抗凝血作用。此外，山奈酚对 BAV 活性引起的改变的血液学参数表现出显著的剂量依赖性效应。用 BAVLD 攻击的大鼠中，山奈酚还显示出对心脏和肾脏中氧化应激生物标志物和抗氧化酶活性的显著增加。然而，用山奈酚治疗可显著（P < 0.05）降低丙二醛水平和 SOD 活性，同时增加谷胱甘肽水平。山奈酚治疗后，中毒大鼠的器官组织中严重的组织病理学缺陷得到改善。山奈酚被鉴定为辣木中的主要活性抗蛇毒化合物，本研究强调了该化合物作为蛇咬伤治疗的有效替代物的潜力。
