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雷公藤甲素联合藏红花素对小鼠关节炎的影响：从减轻副作用到治疗作用

The Effect of Triptolide Combined With Crocin on Arthritis in Mice: From Side Effect Attenuation to Therapy.

作者信息

Yan Min, Yan Yinyin, Zhang Zhenqiang, Wang Guoqiang, Shi Wenbo, Jiang Mengyuan, Zhao Junwei, Wu Xiangxiang, Zeng Huahui

机构信息

Academy of Chinese Medicine Sciences, Henan University of Chinese Medicine, Zhengzhou, China.

School of Medicine, Henan University of Chinese Medicine, Zhengzhou, China.

出版信息

Front Pharmacol. 2022 Jun 23;13:908227. doi: 10.3389/fphar.2022.908227. eCollection 2022.

DOI:10.3389/fphar.2022.908227
PMID:35814255
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9260116/
Abstract

Clinical use of triptolide (TP) is restricted due to severe toxicity. This study assessed the protective effect of crocin (CR) as a natural antioxidant against TP-induced toxicity in bovine collagen type II-induced arthritis (CIA) in mice. The mice in the CIA model group showed macroscopic signs of severe arthritis. The anti-arthritis effects in the control, TP + CR, and TP groups were evaluated through assessment of foot volume, arthritis score, and proinflammatory cytokines, and collagen antibody assay. Crocin reduced TP-induced toxicity, as evidenced by evaluation of survival rate, body weight, visceral index, hepatic and renal functions, histopathologic analyses, and antioxidant enzyme activities. Transcriptome sequencing resulted in identification of 76 differentially expressed genes (DEGs) associated with hepatotoxicity between the TP and TP + CR groups. Of these, Three DEGs (Cyp1a2,Gsta4, and Gstp1) were validated using quantitative real-time PCR analysis. In conclusion, CR protected CIA mice from TP-induced toxicity through modulation of the cytochrome P450 and glutathione metabolism pathways.

摘要

雷公藤甲素（TP）因毒性严重，其临床应用受到限制。本研究评估了天然抗氧化剂西红花苷（CR）对小鼠牛II型胶原诱导性关节炎（CIA）中TP诱导的毒性的保护作用。CIA模型组小鼠出现严重关节炎的宏观体征。通过评估足容积、关节炎评分、促炎细胞因子和胶原抗体检测，对对照组、TP + CR组和TP组的抗关节炎作用进行了评估。通过评估存活率、体重、脏器指数、肝肾功能、组织病理学分析和抗氧化酶活性，证实西红花苷降低了TP诱导的毒性。转录组测序结果显示，TP组和TP + CR组之间有76个与肝毒性相关的差异表达基因（DEG）。其中，使用定量实时PCR分析验证了3个DEG（Cyp1a2、Gsta4和Gstp1）。总之，CR通过调节细胞色素P450和谷胱甘肽代谢途径，保护CIA小鼠免受TP诱导的毒性。

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