Department of General Endocrinology, The First People's Hospital of Yongkang, affiliated to Hangzhou Medical College, Jinhua 321300, PR China.
Department of Pharmacy, The People's Hospital of Jinyun, Jinyun 321400, PR China.
Phytomedicine. 2023 Sep;118:154905. doi: 10.1016/j.phymed.2023.154905. Epub 2023 May 31.
The traditional She medicine is a notable type of traditional Chinese medicine, which has been applied for a long history despite the lack of sufficient mechanistic understanding. Our study revealed the possible molecular mechanism of sesquiterpene 5α-Hydroxycostic acid, active ingredient of traditional She medicine Artemisia lavandulaefolia DC., in the treatment of rheumatoid arthritis (RA).
RA-fibroblast like synoviocytes (RA-FLSs) were treated with 5α-Hydroxycostic acid, Anthemidin, and methotrexate (MTX). CCK-8 and ELISA were used to measure the resultant viability of RA-FLSs and to quantify pro-inflammatory cytokines. Target genes of 5α-Hydroxycostic acid and Anthemidin, RA-related differentially expressed genes, and RA-related genes were retrieved by bioinformatics analyses, results of which were further intersected to identify candidate genes. The protein-protein interaction network was constructed to develop the pharmacophore model. The molecular docking was simulated to determine the core target androgen receptor (AR) for subsequent molecular mechanism investigation in vitro.
The 5ɑ-Hydroxycostic acid, Anthemidin, or MTX of different concentrations inhibited the viability of RA-FLSs, and downregulated the levels of proinflammatory cytokines. The pharmacophore model and molecular docking of 10 candidate targets with 5α-Hydroxycostic acid were successfully established. In vitro experiments provided evidence confirming that 5α-Hydroxycostic acid elevated AR expression to inhibit inflammatory responses of RA-FLSs and degradation of extracellular matrix.
Therefore, this study reveals the active ingredient sesquiterpene 5α-Hydroxycostic acid of traditional She medicine Artemisia lavandulaefolia DC., and illustrates potential molecular mechanism in RA treatment by upregulating AR expression. This study is the first to report the effect of the active ingredient sesquiterpenes in traditional She medicine A.lavandulaefolia DC on RA and elucidate the underlying molecular mechanism associated with up-regulated AR expression. This study provides new insights into the mechanistic understanding of traditional She medicine in the treatment of RA.
传统畲药是一种显著的中药类型，尽管缺乏充分的机制理解，但已经应用了很长时间。我们的研究揭示了传统畲药艾纳香中的活性成分 5α-羟基乌头酸，在治疗类风湿关节炎（RA）中的可能分子机制。
用 5α-羟基乌头酸、 anthemidin 和甲氨蝶呤（MTX）处理 RA-成纤维样滑膜细胞（RA-FLS）。CCK-8 和 ELISA 用于测量 RA-FLS 的活力和定量促炎细胞因子。通过生物信息学分析检索 5α-羟基乌头酸和 anthemidin 的靶基因、RA 相关差异表达基因和 RA 相关基因，进一步交叉识别候选基因。构建蛋白-蛋白相互作用网络，建立药效团模型。模拟分子对接，确定核心靶标雄激素受体（AR），并进行后续的体外分子机制研究。
不同浓度的 5ɑ-羟基乌头酸、anthemidin 或 MTX 抑制 RA-FLS 的活力，并下调促炎细胞因子的水平。成功建立了与 5α-羟基乌头酸的 10 个候选靶点的药效团模型和分子对接。体外实验证实，5α-羟基乌头酸通过上调 AR 表达抑制 RA-FLS 的炎症反应和细胞外基质的降解。
因此，本研究揭示了传统畲药艾纳香的活性成分 5α-羟基乌头酸，并通过上调 AR 表达阐明了其在 RA 治疗中的潜在分子机制。本研究首次报道了传统畲药活性成分 sesquiterpenes 在 RA 中的作用，并阐明了与 AR 表达上调相关的潜在分子机制。本研究为传统畲药治疗 RA 的机制理解提供了新的视角。
