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含甾体皂甙的龙葵果提取物可预防慢性缩窄性损伤诱导的大鼠神经病理性疼痛:TRPV1 受体和细胞因子抑制的体内外证据。

Solasodine Containing Solanum torvum L. Fruit Extract Prevents Chronic Constriction Injury-Induced Neuropathic Pain in Rats: In Silico and In Vivo Evidence of TRPV1 Receptor and Cytokine Inhibition.

机构信息

Department of Pharmaceutical Sciences, Mohanlal Sukhadia University, Udaipur, Rajasthan, India.

Department of Pharmacy, Banasthali Vidyapith, Banasthali, Rajasthan, India.

出版信息

Mol Neurobiol. 2023 Sep;60(9):5378-5394. doi: 10.1007/s12035-023-03412-w. Epub 2023 Jun 14.

Abstract

This study aimed to assess the efficacy of ethanolic extract of Solanum torvum L. fruit (EESTF) containing solasodine in treating chronic constriction injury (CCI)-induced neuropathic pain in rats. Three-dimensional (3D) simulation studies of solasodine binding were conducted on the TRPV1 receptor, IL-6, and TNF-α structures. For in vivo justification, an assessment of behavioral, biochemical, and histological changes was designed after a CCI-induced neuropathic pain model in rats. On days 7, 14, and 21, CCI significantly increased mechanical, thermal, and cold allodynia while producing a functional deficit. IL-6, TNF-α, TBARS, and MPO levels also increased. SOD levels of catalase and reduced glutathione levels also decreased. Administration of pregabalin (30 mg/kg, oral), solasodine (25 mg/kg, oral), and EESTF (100 and 300 mg/kg, oral) significantly reduced CCI-induced behavioral and biochemical changes (P < 0.05). The protective nature of EESTF was also confirmed by histological analysis. Capsaicin, a TRPV1 receptor agonist, abolished the antinociceptive effects of EESTF when used previously. From the observations of the docking studies, solasodine acted as an antagonist at TRPV1, whereas the docking scores of solasodine against TNF-α and IL-6 were reported to be -11.2 and -6.04 kcal/mol, respectively. The attenuating effect of EESTF might be related to its antagonistic effects on TRPV1, suppression of cytokines, and anti-inflammatory and antioxidant properties.

摘要

本研究旨在评估含有茄碱的龙葵果乙醇提取物(EESTF)治疗大鼠慢性缩窄性损伤(CCI)诱导的神经病理性疼痛的疗效。对 TRPV1 受体、IL-6 和 TNF-α 结构进行了茄碱结合的三维(3D)模拟研究。为了进行体内验证,在大鼠CCI 诱导的神经病理性疼痛模型中设计了行为、生化和组织学变化的评估。在第 7、14 和 21 天,CCI 显著增加机械、热和冷感觉过敏,并产生功能缺陷。IL-6、TNF-α、TBARS 和 MPO 水平也升高。过氧化氢酶的 SOD 水平和还原型谷胱甘肽水平也降低。给予普瑞巴林(30mg/kg,口服)、茄碱(25mg/kg,口服)和 EESTF(100 和 300mg/kg,口服)可显著降低 CCI 诱导的行为和生化变化(P<0.05)。组织学分析也证实了 EESTF 的保护作用。辣椒素,一种 TRPV1 受体激动剂,在先前使用时可消除 EESTF 的抗伤害感受作用。从对接研究的观察结果来看,茄碱作为 TRPV1 的拮抗剂,而茄碱对 TNF-α 和 IL-6 的对接评分分别为-11.2 和-6.04kcal/mol。EESTF 的减弱作用可能与其对 TRPV1 的拮抗作用、细胞因子的抑制作用以及抗炎和抗氧化特性有关。

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