Department of Studies in Biochemistry, University of Mysore, Manasagangotri, Mysore, Karnataka, India.
Bioinformatics infrastructure facility, Gauhati University, Guwahati, Assam, India.
Toxicon. 2020 Aug;183:1-10. doi: 10.1016/j.toxicon.2020.05.009. Epub 2020 May 21.
Echis carinatus (EC) envenomation causes severe immune response by the accumulation of tissue debris in the form of DAMPs resulting in chronic inflammation and progressive tissue necrosis at the bitten site. Clearing of tissue debris is a prerequisite to enhance the healing of venom-induced necrotic wounds. Tricosanthus tricuspidata is a medicinal plant used extensively for the treatment of snake bite-induced toxicities. The active component responsible for the observed pharmacological action is a serine protease, tricuspidin. The topical application of tricuspidin was able to neutralize ECV-induced mouse footpad tissue necrosis and open wound in rabbits. Tricuspidin exerted its healing action via proteolytic activity as a consequence of upregulation of MMP-8 and down regulation of MMP-9. Further, tricuspidin reduced ECV-induced inflammation by decreasing the expression of TNF-α, IL-6 and MPO, and by increasing the level of VEGF-A and TGF-β1. The modulation of ECV induced immune/inflammatory mediators by tricuspidin was found to be more effective than trypsin. Moreover, tricuspidin and trypsin activated MAPKs via protease activated receptors-2 (PAR-2). These data indicate that the proteolytic activity of tricuspidin directly involved in the healing of ECV-induced chronic wound.
矛头蝮蛇（EC）毒液会引起严重的免疫反应，导致 DAMPs （损伤相关分子模式）在咬伤部位积累，引发慢性炎症和进行性组织坏死。清除组织碎片是增强毒液引起的坏死性伤口愈合的前提条件。三叉苦是一种广泛用于治疗蛇咬伤中毒的药用植物。负责观察到的药理作用的活性成分是一种丝氨酸蛋白酶，三尖杉。三尖杉在局部应用时能够中和 ECV 诱导的小鼠爪垫组织坏死和兔子的开放性伤口。三尖杉通过上调 MMP-8 和下调 MMP-9 的蛋白酶活性发挥其愈合作用。此外，三尖杉通过降低 TNF-α、IL-6 和 MPO 的表达，增加 VEGF-A 和 TGF-β1 的水平，减轻 ECV 诱导的炎症。与胰蛋白酶相比，三尖杉对 ECV 诱导的免疫/炎症介质的调节作用更有效。此外，三尖杉和胰蛋白酶通过蛋白酶激活受体-2（PAR-2）激活 MAPKs。这些数据表明，三尖杉的蛋白水解活性直接参与了 ECV 诱导的慢性伤口的愈合。
