ICMR-National Institute of Traditional Medicine, Belagavi, Karnataka, 590010, India.
KLE College of Pharmacy, Belagavi, KLE Academy of Higher Education and Research, Belagavi, Karnataka, 590010, India.
Pharmacol Rep. 2023 Dec;75(6):1454-1473. doi: 10.1007/s43440-023-00543-8. Epub 2023 Nov 6.
Snake bite is a neglected disease that affects millions of people worldwide. WHO reported approximately 5 million people are bitten by various species of snakes each year, resulting in nearly 1 million deaths and an additional three times cases of permanent disability. Snakes utilize the venom mainly for immobilization and digestion of their prey. Snake venom is a composition of proteins and enzymes which is responsible for its diverse pharmacological action. Snake venom phospholipase A (SvPLA) is an enzyme that is present in every snake species in different quantities and is known to produce remarkable functional diversity and pharmacological action like inflammation, necrosis, myonecrosis, hemorrhage, etc. Arachidonic acid, a precursor to eicosanoids, such as prostaglandins and leukotrienes, is released when SvPLA catalyzes the hydrolysis of the sn-2 positions of membrane glycerophospholipids, which is responsible for its actions. Polyvalent antivenom produced from horses or lambs is the standard treatment for snake envenomation, although it has many drawbacks. Traditional medical practitioners treat snake bites using plants and other remedies as a sustainable alternative. More than 500 plant species from more than 100 families reported having venom-neutralizing abilities. Plant-derived secondary metabolites have the ability to reduce the venom's adverse consequences. Numerous studies have documented the ability of plant chemicals to inhibit the enzymes found in snake venom. Research in recent years has shown that various small molecules, such as varespladib and methyl varespladib, effectively inhibit the PLA toxin. In the present article, we have overviewed the knowledge of snake venom phospholipase A, its classification, and the mechanism involved in the pathophysiology of cytotoxicity, myonecrosis, anticoagulation, and inflammation clinical application and inhibitors of SvPLA, along with the list of studies carried out to evaluate the potency of small molecules like varespladib and secondary metabolites from the traditional medicine for their anti-PLA effect.
蛇咬伤是一种被忽视的疾病，影响着全球数百万人。世界卫生组织报告称，每年约有 500 万人被各种蛇咬伤，导致近 100 万人死亡，另有三倍的病例出现永久性残疾。蛇利用毒液主要是为了使猎物瘫痪和消化。蛇毒是一种由蛋白质和酶组成的物质，这使其具有多种药理学作用。蛇毒磷脂酶 A（SvPLA）是一种存在于各种蛇类中的酶，其数量不同，已知具有显著的功能多样性和药理学作用，如炎症、坏死、肌坏死、出血等。花生四烯酸是前列腺素和白三烯等类二十烷酸的前体，当 SvPLA 催化膜甘油磷脂 sn-2 位置的水解时释放出来，这是其作用的原因。多价抗蛇毒血清是治疗蛇咬伤的标准方法，这种抗蛇毒血清是从马或羊中产生的，但它有许多缺点。传统的医疗从业者使用植物和其他药物来治疗蛇咬伤，作为一种可持续的替代方法。据报道，有 100 多个科的 500 多种植物具有中和毒液的能力。植物衍生的次生代谢产物具有减轻毒液不良后果的能力。许多研究已经证明植物化学物质能够抑制蛇毒中的酶。近年来的研究表明，各种小分子，如 varespladib 和甲基 varespladib，能够有效地抑制 PLA 毒素。在本文中，我们综述了蛇毒磷脂酶 A 的知识，包括其分类、在细胞毒性、肌坏死、抗凝和炎症的病理生理学中的作用机制、SvPLA 的临床应用以及抑制剂，以及为评估小分子如 varespladib 和来自传统医学的次生代谢物的抗 PLA 作用而进行的研究列表。
