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天然抑制剂在抗蛇毒磷脂酶A(2)治疗中的应用

Therapeutic application of natural inhibitors against snake venom phospholipase A(2).

作者信息

Perumal Samy Ramar, Gopalakrishnakone Ponnampalam, Chow Vincent Tk

出版信息

Bioinformation. 2012;8(1):48-57. doi: 10.6026/97320630008048. Epub 2012 Jan 6.

Abstract

Natural inhibitors occupy an important place in the potential to neutralize the toxic effects caused by snake venom proteins and enzymes. It has been well recognized for several years that animal sera, some of the plant and marine extracts are the most potent in neutralizing snake venom phospholipase A(2) (svPLA(2)). The implication of this review to update the latest research work which has been accomplished with svPLA(2) inhibitors from various natural sources like animal, marine organisms presents a compilation of research in this field over the past decade and revisiting the previous research report including those found in plants. In addition to that the bioactive compounds/inhibitor molecules from diverse sources like aristolochic alkaloid, flavonoids and neoflavonoids from plants, hydrocarbones -2, 4 dimethyl hexane, 2 methylnonane, and 2, 6 dimethyl heptane obtained from traditional medicinal plants Tragia involucrata (Euphorbiaceae) member of natural products involved for the inhibitory potential of phospholipase A(2) (PLA(2)) enzymes in vitro and also decrease both oedema induced by snake venom as well as human synovial fluid PLA(2). Besides marine natural products that inhibit PLA(2) are manoalide and its derivatives such as scalaradial and related compounds, pseudopterosins and vidalols, tetracylne from synthetic chemicals etc. There is an overview of the role of PLA(2) in inflammation that provides a rationale for seeking inhibitors of PLA(2) as anti-inflammatory agents. However, more studies should be considered to evaluate antivenom efficiency of sera and other agents against a variety of snake venoms found in various parts of the world. The implications of these new groups of svPLA(2) toxin inhibitors in the context of our current understanding of snake biology as well as in the development of new novel antivenoms therapeutics agents in the efficient treatment of snake envenomations are discussed.

摘要

天然抑制剂在中和蛇毒蛋白和酶所产生的毒性作用方面具有重要地位。多年来人们已经充分认识到,动物血清、一些植物提取物和海洋提取物在中和蛇毒磷脂酶A2(svPLA2)方面最为有效。本综述的意义在于更新利用来自动物、海洋生物等各种天然来源的svPLA2抑制剂所完成的最新研究工作,呈现过去十年该领域的研究汇编,并重新审视之前的研究报告,包括在植物中发现的那些。此外,来自不同来源的生物活性化合物/抑制剂分子,如植物中的马兜铃生物碱、黄酮类和新黄酮类,从传统药用植物刺苞叶大戟(大戟科)中获得的碳氢化合物——2,4 - 二甲基己烷、2 - 甲基壬烷和2,6 - 二甲基庚烷,这些天然产物在体外对磷脂酶A2(PLA2)酶具有抑制潜力,并且还能减轻蛇毒诱导的水肿以及人滑液PLA2的活性。除了海洋天然产物如 manoalide 及其衍生物(如 scalaradial 和相关化合物、pseudopterosins 和 vidalols)、合成化学品中的四环素等可抑制 PLA2 外,还概述了 PLA2 在炎症中的作用,为寻找 PLA2 抑制剂作为抗炎剂提供了理论依据。然而,应开展更多研究来评估血清和其他制剂对世界不同地区发现的各种蛇毒的抗蛇毒效率。本文还讨论了这些新的svPLA2毒素抑制剂在我们当前对蛇生物学的理解背景下以及在开发新型抗蛇毒治疗剂以有效治疗蛇咬伤方面的意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7dd5/3282276/28dc73b84271/97320630008048F1.jpg

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