NOX2抑制剂黄芩素缓解类风湿性关节炎，并灭活成纤维样滑膜细胞中线粒体氧化应激介导的cGAS STING信号
NOX2 inhibitor baicalein alleviates rheumatoid arthritis and inactivating mitochondrial oxidative stress-mediated cGAS-STING signaling in fibroblast-like synoviocytes.
摘要(中文译文)
类风湿关节炎（RA）是一种慢性自身免疫性疾病，其发病机制复杂，可导致疼痛、残疾甚至死亡。黄芩素是黄芩的一种成分，已被确定为包括RA在内的多种自身免疫性疾病的潜在治疗药物。然而，其精确的分子机制及其直接细胞靶点仍不清楚。本研究旨在揭示黄芩素治疗RA的疗效及分子机制。通过体内实验采用胶原诱导性关节炎（CIA）大鼠模型，评估黄芩素治疗对RA病理的缓解作用、不良反应及潜在机制。体外实验包括CCK8实验、Transwell迁移实验、Western blotting、mtDNA检测、线粒体活性氧（mtROS）检测、Seahorse能量代谢、CETSA和生物素下拉实验，以评估黄芩素对RA-成纤维细胞样滑膜细胞（FLS）的治疗效果及作用机制。研究发现，FLS通过激活线粒体氧化应激（MOS）介导的cGAS-STING信号通路，发展为侵袭性滑膜细胞并产生炎性细胞因子，从而导致RA进展。黄芩素被鉴定为一种新型NADPH氧化酶2（NOX2）抑制剂，可降低mtROS水平，抑制MOS介导的VDAC1寡聚化及mtDNA释放，进而导致cGAS-STING信号通路失活。因此，黄芩素有效缓解了CIA大鼠的关节炎病理，且副作用较少。本研究提出，黄芩素通过调控RA-FLS中的NOX2-cGAS-STING信号通路发挥抗RA药物作用，并阐明了mtROS介导的VDAC1寡聚化激活cGAS的新机制。
Abstract
Rheumatoid arthritis (RA) is a chronic autoimmune disease with a complex pathogenesis, leading to pain, disability, and even death. Baicalein, a constituent of Scutellaria baicalensis, has been identified as a potential therapeutic agent for multiple autoimmune diseases, including RA. Nevertheless, the precise molecular mechanism and its direct cellular targets remain unclear. This study aimed to reveal the therapeutic efficacy and molecular mechanism of baicalein in RA treatment. In vivo experiments were conducted using a collagen-induced arthritis (CIA) rat model to assess the alleviation of RA pathology, adverse effects, and underlying mechanisms of baicalein treatment. In vitro assays included the CCK8 assay, transwell migration assay, Western blotting, mtDNA detection, mitochondrial reactive oxygen species (mtROS) detection, Seahorse energy metabolism, CETSA and biotin pulldown assay to evaluate the therapeutic effects and mechanistic action of baicalein on RA- fibroblast-like synoviocytes (FLS). It was found that FLS developed into invasive synovial cells and produced inflammatory cytokines by activating mitochondrial oxidative stress (MOS)-mediated cGAS-STING signaling. And this led to the progression of RA. Baicalein was identified as a novel NADPH oxidase 2 (NOX2) inhibitor, which decreased mtROS levels and suppressed MOS-mediated VDAC1 oligomerization as well as mtDNA release. This, in turn, led to the inactivation of cGAS-STING signaling. Consequently, baicalein effectively alleviated arthritis pathology of CIA rats with few side effects. The present study posits that baicalein functions as a pharmaceutical agent for RA by modulating the NOX2-cGAS-STING signaling in RA-FLS, and clarify a novel activation mechanism of cGAS through mtROS-mediated VDAC1 oligomerization.
如何引用
AMA
Rui Wang, Weiming Fang, Yansheng Qiao, Xin Zhang, Yuan Gao, Zhaolin Gao, et al. NOX2 inhibitor baicalein alleviates rheumatoid arthritis and inactivating mitochondrial oxidative stress-mediated cGAS-STING signaling in fibroblast-like synoviocytes.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158268.
APA
Rui Wang, Weiming Fang, Yansheng Qiao, Xin Zhang, Yuan Gao, Zhaolin Gao, et al (2026). NOX2 inhibitor baicalein alleviates rheumatoid arthritis and inactivating mitochondrial oxidative stress-mediated cGAS-STING signaling in fibroblast-like synoviocytes.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158268
GB/T 7714
Rui Wang, Weiming Fang, Yansheng Qiao, Xin Zhang, Yuan Gao, Zhaolin Gao, et al. NOX2 inhibitor baicalein alleviates rheumatoid arthritis and inactivating mitochondrial oxidative stress-mediated cGAS-STING signaling in fibroblast-like synoviocytes.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158268.
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