Inflammation is an intrinsic protective mechanism against various forms of cellular injuries in humans; however, its undesired activation results in tissue damage and cell death. The onset of chronic inflammation and oxidative stress are the key characteristics of autoimmune inflammatory diseases such as rheumatoid arthritis (RA), for which an effective treatment is yet to be developed. Therefore, in this study, we investigated the protective effects and molecular mechanisms of a novel herbal preparation, Jing‐Si herbal tea (JS), against H2O2‐induced inflammation and cellular damage in HIG‐82 synoviocytes. We found that JS did not show any significant alterations in cell viability at <188 μg/mL; however, a cytotoxic effect was observed at 188–1883 μg/mL concentrations tested. We found that expressions of inflammation associated extracellular matrix (ECM)‐degrading proteases MMP‐13, ADAMTS‐2, ‐8, and ‐17 were abnormally enhanced under H2O2‐induced pathological oxidative stress (ROS) in HIG‐82 cells. Interestingly, JS treatment not only reduced the ROS levels but also significantly repressed the protein expressions of collagen degrading proteases in a dose‐dependent manner. Treatment with JS showed enhanced cell viability against H2O2‐induced toxic ROS levels. The expressions of cell protective aggrecan, Collagen II, and Bcl‐2 were increased, whereas MMP‐13, ADAMTS‐2, Cytochrome C, and cleaved Caspase 3 were decreased by JS under inflammatory agents H2O2, MIA, LPS, and TNF‐α treatment, respectively, in HIG‐82 cells. Interestingly, the cytoprotective effect of JS treatment was attributed to a decreased mitochondrial localization of Bax and a reduction of Cytochrome C release into the cytoplasm of H2O2‐treated HIG‐82 cells. Collectively, our results suggest a novel protective mechanism of JS for RA treatment, which could be potentially applied as a complementary treatment or as an alternative therapeutic approach to mitigate inflammatory diseases.

中文翻译：

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Jing-Si 凉茶通过抑制 HIG-82 滑膜细胞中 Bax 和线粒体细胞色素 C 的释放来抑制 H2O2 引发的炎症和细胞凋亡


炎症是人类对各种形式的细胞损伤的内在保护机制;然而，其意外激活会导致组织损伤和细胞死亡。慢性炎症和氧化应激的发作是类风湿性关节炎 （RA） 等自身免疫性炎症性疾病的关键特征，尚未开发出有效的治疗方法。因此，在这项研究中，我们研究了一种新型草药制剂 Jing‐Si 凉茶 （JS） 对 H2O2 诱导的 HIG-82 滑膜细胞炎症和细胞损伤的保护作用和分子机制。我们发现 JS 在 <188 μg/mL 时细胞活力没有显示任何显着变化;然而，在测试的 188–1883 μg/mL 浓度下观察到细胞毒作用。我们发现在 H2O2 诱导的病理性氧化应激 （ROS） 下，炎症相关的细胞外基质 （ECM） 降解蛋白酶 MMP-13 、 ADAMTS-2 、 -8 和 -17 的表达在 HIG-82 细胞中异常增强。有趣的是，JS 处理不仅降低了 ROS 水平，而且以剂量依赖性方式显着抑制了胶原蛋白降解蛋白酶的蛋白质表达。JS 处理显示细胞活力增强，对抗 H 2 O 2 诱导的毒性 ROS 水平。在炎症剂 H2O2 、 MIA 、 LPS 和 TNF-α 处理下，细胞保护性聚集蛋白聚糖、胶原蛋白 II 和 Bcl-2 的表达增加，而 JS 分别降低 MMP-13 、 ADAMTS-2 、 细胞色素 C 和裂解的 Caspase 3 在 HIG-82 细胞中。有趣的是，JS 治疗的细胞保护作用归因于 Bax 线粒体定位的减少和细胞色素 C 释放到 H 2 O 2 处理的 HIG-82 细胞细胞质中的减少。 总的来说，我们的结果表明 JS 对 RA 治疗的一种新的保护机制，它可能被用作补充治疗或作为缓解炎症性疾病的替代治疗方法。