大参通过降低HMGB1表达，恢复细胞凋亡和自噬失调，改善类风湿关节炎

IF 6.7 1区医学 Q1 CHEMISTRY, MEDICINAL

Phytomedicine Pub Date : 2025-06-09 DOI:10.1016/j.phymed.2025.156943

Xiayun Pang , Ruotong Song , Zheng Li , Xinbo Shi , Zhen Zhang , Yanru Liu , Hongbo Xu , Zhongxing Song , Rui Zhou , Zhishu Tang

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引用次数: 0

摘要

背景恢复类风湿性关节炎滑膜的自噬和凋亡平衡可能是一种很有前景的治疗方法。我们的前期研究表明，三七总皂苷（RPMTG）通过抑制细胞自噬和诱导细胞凋亡而具有抗ra的作用。本研究提示HMGB1表达增加和Beclin 1-Bcl-2复合物结合减少可能是这种失调背后的关键机制。目的研究RPMTG对大鼠胶原性关节炎（CIA）和TNF-α-诱导的RA成纤维细胞样滑膜细胞（RA- flss）的抗RA作用，重点研究RPMTG通过调节HMGB1表达和Beclin 1-Bcl-2复合物结合恢复自噬和凋亡平衡。方法采用WB、IHC、RT-qPCR检测beclin 1、Bcl-2、HMGB1的表达。Co-IP检测Beclin 1-Bcl-2复合物结合情况。透射电镜观察细胞自噬形态，Hoechst 33342/PI染色观察细胞凋亡。通过CIA大鼠的症状和体征、ELISA检测的炎症细胞因子产生和HE染色的组织病理学变化来评估RPMTG的治疗效果。采用UPLC-Q-TOF-MS/MS法测定含药血清中RPMTG的主要成分。结果与OA患者相比，RA患者滑膜组织的自噬增加，细胞凋亡减少，这可能与HMGB1水平升高和Beclin 1-Bcl-2结合减少有关。RPMTG通过调节Beclin 1、Bcl-2和HMGB1的表达，有效治疗胶原诱导的大鼠关节炎。它还通过降低HMGB1表达和增强复合物结合，降低TNF-α-诱导的RA-FLSs和MH7A细胞的过度增殖。结论强调HMGB1和Beclin 1-Bcl-2复合物在RA自噬和凋亡失调中的调控作用，提示RPMTG治疗RA的潜力。

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Rhizoma Panacis Majoris ameliorates rheumatoid arthritis by restoring apoptosis and autophagy dysregulation through reducing HMGB1 expression

Background

Restoring the autophagy and apoptosis balance in RA synovium may offer a promising RA treatment. Our previous research showed that total saponins from Rhizoma Panacis Majoris (RPMTG) exhibit anti-RA effects by inhibiting autophagy and inducing apoptosis. This study suggests that increased HMGB1 expression and reduced Beclin 1-Bcl-2 complex binding might be key mechanisms behind this dysregulation.

Objective

This study investigated the anti-RA effects of RPMTG on collagen-induced arthritis (CIA) in rats and TNF-α-induced RA fibroblast-like synoviocytes (RA-FLSs), focusing on restoring autophagy and apoptosis balance through regulating HMGB1 expression and the Beclin 1-Bcl-2 complex binding.

Methods

Beclin 1, Bcl-2, and HMGB1 expressions were analyzed using WB, IHC, and RT-qPCR. Beclin 1-Bcl-2 complex binding was examined by Co-IP. Autophagy morphology was observed via TEM, and apoptosis was assessed with Hoechst 33342/PI staining. RPMTG’s therapeutic effect was evaluated through CIA rat symptoms and signs, inflammatory cytokine production via ELISA, and histopathological changes using HE staining. RPMTG’s main component in drug-containing serum was determined by UPLC-Q-TOF-MS/MS.

Results

The study found increased autophagy and decreased apoptosis in RA patients' synovial tissues compared to OA, which might link to higher HMGB1 levels and reduced Beclin 1-Bcl-2 binding. RPMTG effectively treated collagen-induced arthritis in rats by modulating Beclin 1, Bcl-2, and HMGB1 expression. It also reduced TNF-α-induced overproliferation in RA-FLSs and MH7A cells by lowering HMGB1 expression and enhancing the complex binding.

Conclusion

These findings emphasize the regulation of HMGB1 and Beclin 1-Bcl-2 complex in RA autophagy and apoptosis dysregulation, indicating RPMTG’s potential for treating RA.

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来源期刊

Phytomedicine 医学-药学

CiteScore

10.30

自引率

5.10%

发文量

670

审稿时长

91 days

期刊介绍： Phytomedicine is a therapy-oriented journal that publishes innovative studies on the efficacy, safety, quality, and mechanisms of action of specified plant extracts, phytopharmaceuticals, and their isolated constituents. This includes clinical, pharmacological, pharmacokinetic, and toxicological studies of herbal medicinal products, preparations, and purified compounds with defined and consistent quality, ensuring reproducible pharmacological activity. Founded in 1994, Phytomedicine aims to focus and stimulate research in this field and establish internationally accepted scientific standards for pharmacological studies, proof of clinical efficacy, and safety of phytomedicines.