Chen De-Ta, Wan Zi-Jian, Sheng Xiao-Ping, Rao Wu, Zhan Xin-Hua, Gu Jing-Liang, Wei Xian-Zhen, Fan Tian-You
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China.
Cell Signal. 2025 Oct;134:111905. doi: 10.1016/j.cellsig.2025.111905. Epub 2025 May 27.
This study investigated the therapeutic efficacy of Higenamine (HG), an extract from Monkshood, in the context of rheumatoid arthritis (RA). As an autoimmune disorder, RA is characterized by significant bone destruction primarily driven by inflammatory processes. Analysis demonstrated marked infiltration of macrophages within RA immune cells. HG inhibited iNOS, TNF-α, and IL-1β expression in M1 macrophages while enhancing IL-10, Arg-1, and MCP-1 levels in M2 macrophages. Flow cytometry confirmed HG's capacity to promote the M1 to M2 macrophage transition. Transcriptomic analysis established connections between HG, RA, osteoclast differentiation, and the THBS-1/TGF-β signaling pathway, indicating its potential to mitigate bone destruction. In vitro studies showed that HG diminished osteoclast differentiation and downregulated V-ATPase, Ctsk, TRAP, THBS-1, and TGF-β expression. In vivo, HG alleviated arthritis symptoms in collagen-induced arthritis (CIA) mice, reduced M1 macrophage accumulation, modulated THBS-1/TGF-β signaling, and lessened joint damage. Micro-CT imaging and staining corroborated the reduction in osteoclast numbers and improvement in bone homeostasis. In summary, HG presents a promising therapeutic avenue for RA and associated bone destruction through modulation of the THBS-1/TGF-β signaling pathway.
本研究调查了附子提取物去甲乌药碱（HG）在类风湿性关节炎（RA）背景下的治疗效果。作为一种自身免疫性疾病，RA的特征是主要由炎症过程驱动的显著骨破坏。分析表明，RA免疫细胞内巨噬细胞有明显浸润。HG抑制M1巨噬细胞中诱导型一氧化氮合酶（iNOS）、肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达，同时提高M2巨噬细胞中白细胞介素-10（IL-10）、精氨酸酶-1（Arg-1）和单核细胞趋化蛋白-1（MCP-1）的水平。流式细胞术证实了HG促进M1向M2巨噬细胞转变的能力。转录组分析建立了HG、RA、破骨细胞分化和血小板反应蛋白-1（THBS-1）/转化生长因子-β（TGF-β）信号通路之间的联系，表明其减轻骨破坏的潜力。体外研究表明，HG减少破骨细胞分化，并下调V-ATP酶、组织蛋白酶K（Ctsk）、抗酒石酸酸性磷酸酶（TRAP）、THBS-1和TGF-β的表达。在体内，HG减轻了胶原诱导性关节炎（CIA）小鼠的关节炎症状，减少了M1巨噬细胞的积累，调节了THBS-1/TGF-β信号通路，并减轻了关节损伤。显微CT成像和染色证实破骨细胞数量减少，骨稳态得到改善。总之，HG通过调节THBS-1/TGF-β信号通路，为RA及相关骨破坏提供了一条有前景的治疗途径。
