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OA-DHZ的抗炎和镇痛潜力;一种新型的脱氢姜酮半合成衍生物。

Anti-inflammatory and analgesic potential of OA-DHZ; a novel semisynthetic derivative of dehydrozingerone.

作者信息

Chibber Pankaj, Kumar Chetan, Singh Amarinder, Assim Haq Syed, Ahmed Irfan, Kumar Anil, Singh Surjeet, Vishwakarma Ram, Singh Gurdarshan

机构信息

Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; PK-PD Toxicology and Formulation Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir 180001, India.

Academy of Scientific & Innovative Research (AcSIR), Ghaziabad 201002, India; Natural Product Chemistry Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, Jammu and Kashmir 180001, India.

出版信息

Int Immunopharmacol. 2020 Jun;83:106469. doi: 10.1016/j.intimp.2020.106469. Epub 2020 Apr 3.

Abstract

Despite various advances in the arena of the current system of medicine, there are numerous side effects associated with the therapeutics which essentially demand research on the development of safer therapeutics. One way is to explore the bioactive plant secondary metabolites and their semisynthetic derivatives. In context to this, we analyzed OA-DHZ, a dehydrozingerone derivative as the later has been reported to show anti-inflammatory and analgesic properties. OA-DHZ was found to be having promising anti-inflammatory and analgesic potential. OA-DHZ was found to inhibit the carrageenan-induced edema and leukocyte migration, acetic acid-induced increase in vascular permeability and lipopolysaccharide-induced pro-inflammatory cytokines like TNF-α, IL-6, and IL-1β. Meanwhile, it was also found to potentially inhibit thermally as well as chemically induced pain signifying its analgesic/nociceptive potential. Further, safety pharmacology studies using in vivo animal models for the central nervous system, gastrointestinal tract, the cardio-respiratory system suggest that optimum functioning of vital organ systems does not get altered after single oral administration. Also, the acute toxicity study revealed its nontoxic nature up to 2000 mg/kg. This study paves the way for future exploration and development of OA-DHZ based on its potent activity and nontoxic nature.

摘要

尽管当前医学体系领域取得了各种进展,但治疗方法仍存在许多副作用,这从根本上要求开展更安全治疗方法的研究。一种方法是探索生物活性植物次生代谢产物及其半合成衍生物。在此背景下,我们分析了OA-DHZ,一种脱氢姜辣素衍生物,因为据报道后者具有抗炎和镇痛特性。发现OA-DHZ具有良好的抗炎和镇痛潜力。发现OA-DHZ可抑制角叉菜胶诱导的水肿和白细胞迁移、醋酸诱导的血管通透性增加以及脂多糖诱导的促炎细胞因子如TNF-α、IL-6和IL-1β。同时,还发现它可能抑制热诱导和化学诱导的疼痛,表明其具有镇痛/伤害感受潜力。此外,使用体内动物模型对中枢神经系统、胃肠道、心肺系统进行的安全药理学研究表明,单次口服给药后重要器官系统的最佳功能不会改变。而且,急性毒性研究表明其在高达2000mg/kg的剂量下无毒。这项研究基于OA-DHZ的强大活性和无毒性质,为其未来的探索和开发铺平了道路。

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