基于中药组学策略的二妙散系列方治疗类风湿关节炎的疗效及机制。
Efficacy and mechanism of the Ermiao San series of formulas for rheumatoid arthritis based on Chinmedomics strategy.
机构信息
State Key Laboratory of Integration and Innovation of Classical formula and Modern Chinese Medicines, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
State Key Laboratory of Integration and Innovation of Classical formula and Modern Chinese Medicines, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin 150040, China.
出版信息
Phytomedicine. 2024 Sep;132:155903. doi: 10.1016/j.phymed.2024.155903. Epub 2024 Jul 22.
BACKGROUND
The Ermiao San Series of Formulas (ESSF) refers to Ermiao San (TS), Sanmiao Wan (TW), and Simiao Wan (FW), which are widely used traditional Chinese medicine (TCM) formulas for treating rheumatoid arthritis (RA). However, the therapeutic advantages and underlying mechanisms of ESSF treatment are unclear, especially regarding the improper selection of these three formulas when treating RA.
PURPOSE
To explore the efficacy and mechanisms of ESSF treatment for RA.
METHODS
Complete Freund's adjuvant was used to induce RA in rats. Chinmedomics strategy, which included metabolomics, serum pharmacochemistry of TCM, molecular docking, western blotting and qPCR, was applied to reveal the therapeutic advantages, pathways, and targets of ESSF.
RESULTS
In the early stages of treatment, TS quickly reduced joint swelling and the arthritis score index and regulated pathways such as arachidonic acid metabolism and purine metabolism. TW increases the regulation of tryptophan metabolism and pyrimidine metabolism pathways, promoting the recovery of the thymus and spleen. FW increases the regulation of linoleic acid metabolism and has the greatest effect on immune organ and bone recovery. In addition, 54, 67, and 86 bioactive compounds were detected in the serum from TS, TW, and FW, respectively. Berberine, phellodendrine, atractylolide III, limonin, 25R-inokosterone, coixol, and stigmasterol were found to act on the key enzymes COX-2, mPGES-1, ALOX5, and XDH in arachidonic acid metabolism and purine metabolism pathways. Western blot and qPCR results showed that ESSF can reduce the activity of these targets, thereby inhibiting the expression of the inflammatory factors IL-1β, IL-6, IL-17, and TNF-α; the tissue injury factors MMP-3 and CRP; and the rheumatoid factors CCP Ab and RF, thereby achieving anti-RA efficacy.
CONCLUSION
ESSF has a good therapeutic effect on RA. TS focus on rapid swelling reduction in the early stages of RA, TW focus on the recovery of immune organ function, and FW can be used for bone recovery in the later stage of RA treatment. The key mechanism of treating RA is that ESSF reduces the activity of COX-2, mPGES-1, ALOX5, and XDH. These findings provide valuable guidance for targeted therapy for RA and for the clinical application of ESSF.
背景
二妙散系列方（ESSF）包括二妙散（TS）、三妙丸（TW）和四妙丸（FW），是治疗类风湿关节炎（RA）的常用中药方剂。然而，ESSF 治疗的优势和潜在机制尚不清楚，尤其是在治疗 RA 时这三种方剂的选择不当。
目的
探讨 ESSF 治疗 RA 的疗效和机制。
方法
采用完全弗氏佐剂诱导 RA 大鼠模型。采用中药代谢组学策略，包括代谢组学、中药血清药物化学、分子对接、Western blot 和 qPCR，揭示 ESSF 的治疗优势、途径和靶点。
结果
在治疗早期，TS 迅速降低关节肿胀和关节炎评分指数，并调节花生四烯酸代谢和嘌呤代谢途径。TW 增加色氨酸代谢和嘧啶代谢途径的调节，促进胸腺和脾脏的恢复。FW 增加亚油酸代谢的调节，对免疫器官和骨骼恢复的作用最大。此外，在 TS、TW 和 FW 的血清中分别检测到 54、67 和 86 种生物活性化合物。在花生四烯酸代谢和嘌呤代谢途径中，检测到小檗碱、黄柏碱、苍术内酯 III、柠檬苦素、25R-豆甾-4-烯-3-酮、薏苡仁油、豆甾醇等 54 种生物活性化合物，作用于关键酶 COX-2、mPGES-1、ALOX5 和 XDH。Western blot 和 qPCR 结果表明，ESSF 可降低这些靶点的活性，从而抑制炎症因子 IL-1β、IL-6、IL-17 和 TNF-α；组织损伤因子 MMP-3 和 CRP；以及类风湿因子 CCP Ab 和 RF 的表达，从而达到抗 RA 疗效。
结论
ESSF 对 RA 有较好的治疗效果。TS 侧重于 RA 早期的快速消肿，TW 侧重于免疫器官功能的恢复，FW 可用于 RA 后期的骨骼恢复。治疗 RA 的关键机制是 ESSF 降低 COX-2、mPGES-1、ALOX5 和 XDH 的活性。这些发现为 RA 的靶向治疗和 ESSF 的临床应用提供了有价值的指导。
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