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药理学再评估传统药用植物来源的抑制剂作为抗蛇毒咬伤的解毒剂:批判性综述。

Pharmacological re-assessment of traditional medicinal plants-derived inhibitors as antidotes against snakebite envenoming: A critical review.

机构信息

Department of Molecular Biology and Biotechnology, School of Sciences, Tezpur University, Tezpur, 784028, Assam, India.

LAQV@REQUIMTE, Departamento de Química e Bioquímica, Faculdade De Ciências, Universidade do Porto, Rua Do Campo Alegre S/N, 4169-007, Porto, Portugal.

出版信息

J Ethnopharmacol. 2022 Jun 28;292:115208. doi: 10.1016/j.jep.2022.115208. Epub 2022 Mar 18.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Traditional healers have used medicinal plants to treat snakebite envenomation worldwide; however, mostly without scientific validation. There have been many studies on the therapeutic potential of the natural products against snake envenomation.

AIM OF THE STUDY

This review has highlighted snake venom inhibitory activity of bioactive compounds and peptides from plants that have found a traditional use in treating snakebite envenomation. We have systematically reviewed the scenario of different phases of natural snake venom inhibitors characterization covering a period from 1994 until the present and critically analysed the lacuna of the studies if any, and further scope for their translation from bench to bedside.

MATERIALS AND METHODS

The medicinal plant-derived compounds used against snakebite therapy were reviewed from the available literature in public databases (Scopus, MEDLINE) from 1994 till 2020. The search words used were 'natural inhibitors against snakebite,' 'natural products as therapeutics against snakebite,' 'natural products as antidote against snake envenomation,' ' snake venom toxin natural inhibitors,' 'snake venom herbal inhibitors'. However, the scope of this review does not include computational (in silico) predictions without any wet laboratory validation and snake venom inhibitory activity of the crude plant extracts. In addition, we have also predicted the ADMET properties of the identified snake venom inhibitors to highlight their valuable pharmacokinetics for future clinical studies.

RESULTS

The therapeutic application of plant-derived natural inhibitors to treat snakebite envenomation as an auxiliary to antivenom therapy has been gaining significant momentum. Pharmacological reassessment of the natural compounds derived from traditional medicinal plants has demonstrated inhibition of the principal toxic enzymes of snake venoms at various extents to curb the lethal and/or deleterious effects of venomous snakebite. Nevertheless, such molecules are yet to be commercialized for clinical application in the treatment of snakebite. There are many obstacles in the marketability of the plant-derived natural products as snake envenomation antidote and strategies must be explored for the translation of these compounds from drug candidates to their clinical application.

CONCLUSION

In order to minimize the adverse implications of snake envenomation, strategies must be developed for the smooth transition of these plant-derived small molecule inhibitors from bench to bedside. In this article we have presented an inclusive review and have critically analysed natural products for their therapeutic potential against snake envenomation, and have proposed a road map for use of natural products as antidote against snakebite.

摘要

民族药理学相关性

世界各地的传统治疗师都曾使用药用植物来治疗蛇咬伤中毒;然而,大多数情况下都没有经过科学验证。已经有许多关于天然产物治疗蛇咬伤中毒的治疗潜力的研究。

研究目的

本综述强调了植物中生物活性化合物和肽对蛇毒的抑制活性,这些植物在治疗蛇咬伤中毒方面具有传统用途。我们系统地回顾了不同阶段的天然蛇毒抑制剂特征的情况,涵盖了 1994 年至今的时期,并批判性地分析了研究中的空白,如果有的话,并进一步探讨了将它们从实验室转化为临床的可能性。

材料和方法

从 1994 年至 2020 年,从公共数据库(Scopus、MEDLINE)中检索有关用于治疗蛇咬伤的药用植物衍生化合物的文献,使用的检索词是“天然抗蛇咬伤抑制剂”、“天然产物作为抗蛇咬伤治疗药物”、“天然产物作为蛇毒解毒剂”、“蛇毒毒素天然抑制剂”、“蛇毒草药抑制剂”。然而,本综述的范围不包括未经任何湿实验室验证的计算(计算)预测和粗提植物提取物对蛇毒的抑制活性。此外,我们还预测了鉴定出的蛇毒抑制剂的 ADMET 特性,以突出其对未来临床研究的有价值的药代动力学。

结果

植物来源的天然抑制剂治疗蛇咬伤中毒作为抗蛇毒血清治疗的辅助治疗方法的应用正在取得显著进展。对传统药用植物衍生的天然化合物的药理学重新评估表明,这些天然化合物在不同程度上抑制了蛇毒的主要毒性酶,以遏制毒蛇咬伤的致命和/或有害影响。然而,这些分子尚未商业化用于蛇咬伤的临床治疗。植物来源的天然产物作为蛇咬伤解毒剂的可市场化存在许多障碍,必须探索将这些化合物从候选药物转化为临床应用的策略。

结论

为了最大限度地减少蛇咬伤中毒的不利影响,必须制定策略,使这些植物来源的小分子抑制剂从实验室顺利过渡到临床。在本文中,我们进行了全面的综述,并对天然产物治疗蛇咬伤中毒的治疗潜力进行了批判性分析,并提出了将天然产物用作抗蛇咬伤解毒剂的路线图。

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