Molecular Toxinology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam, India.
Molecular Virology Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University, Tezpur 784028, Assam, India.
Int J Biol Macromol. 2020 Dec 15;165(Pt A):1066-1078. doi: 10.1016/j.ijbiomac.2020.09.223. Epub 2020 Oct 6.
Medicinal plants have always been used for snakebite treatment by traditional healers but they lack scientific evidence of action. However secondary metabolites of such plants have been explored and found to inhibit the toxic effect of venom proteins. Literature survey from 2003 to 2019 resulted in identification of 251 secondary metabolites with such properties. In silico docking studies of these metabolites with modelled structure of Daboxin P, a PLA from Indian Daboia russelii revealed that butein, mimosine and bakuchiol bind to Daboxin P with high affinity. Butein interacted with the catalytic triad but mimosine and bakuchiol interacted with the Ca binding residues of Daboxin P. In vitro validation showed that the molecules inhibited the sPLA activity of Daboxin P. Interestingly, mimosine and bakuchiol could also neutralize the anti-coagulatory activity of Daboxin P. Further, it was observed that butein and mimosine could neutralize the PLA activity of Indian big four venoms dose dependently. On the other hand, mimosine and bakuchiol could also neutralize the pro/anti-coagulatory effect of big four crude venom. Thus, in this study, three molecules have been identified which can neutralize the PLA activity and pro/anti-coagulatory effect of Daboxin P as well as crude venom of big four.
药用植物一直被传统治疗师用于治疗蛇咬伤，但缺乏作用的科学证据。然而，这些植物的次生代谢物已经被探索出来，并发现可以抑制毒液蛋白的毒性作用。对 2003 年至 2019 年文献的调查结果表明，有 251 种具有这种特性的次生代谢物。这些代谢物与印度眼镜蛇蛇毒（Daboxin P）的模型结构进行计算机对接研究表明，布替丁、含羞草碱和补骨脂素与 Daboxin P 具有高亲和力。布替丁与催化三联体相互作用，但含羞草碱和补骨脂素与 Daboxin P 的 Ca 结合残基相互作用。体外验证表明，这些分子抑制了 Daboxin P 的 sPLA 活性。有趣的是，含羞草碱和补骨脂素还可以中和 Daboxin P 的抗凝血活性。此外，还观察到布替丁和含羞草碱可以剂量依赖性地中和印度四大毒液的 PLA 活性。另一方面，含羞草碱和补骨脂素还可以中和四大粗毒液的促凝/抗凝作用。因此，在这项研究中，已经确定了三种可以中和 Daboxin P 的 PLA 活性以及粗毒液的促凝/抗凝作用的分子。
