乌头汤通过调控 NF-κB 和 Nrf2 改善实验性类风湿关节炎：基于功效的中药配伍。
Wutou decoction ameliorates experimental rheumatoid arthritis via regulating NF-kB and Nrf2: Integrating efficacy-oriented compatibility of traditional Chinese medicine.
机构信息
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau (SAR).
State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau (SAR); Faculty of Chinese Medicines, Macau University of Science and Technology, Taipa, Macau (SAR).
出版信息
Phytomedicine. 2021 May;85:153522. doi: 10.1016/j.phymed.2021.153522. Epub 2021 Feb 20.
BACKGROUND
Thousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown.
PURPOSE
This study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms.
METHODS
The anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments.
RESULTS
Our data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro.
CONCLUSION
The ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.
背景
乌头汤（WTD）经过几千年的临床应用，其治疗类风湿关节炎（RA）的疗效和安全性得到了可靠验证。然而，其潜在的分子机制尚不清楚，且辅助药物在增强君药治疗 RA 方面的协同作用也尚不明确。
目的
本研究旨在探讨 WTD 中五组药对的疗效导向性配伍及其潜在机制。
方法
采用佐剂诱导关节炎（AIA）大鼠模型和脂多糖诱导 RAW264.7 巨噬细胞进行体内和体外研究，考察 WTD 的抗关节炎作用和五组药对的配伍作用。通过网络药理学分析，确定 WTD 抗关节炎机制中涉及的优势途径，以及五组药对如何协同作用。通过体内和体外实验进一步验证。
结果
研究数据表明，WTD 中的五组药对 RA 具有协同的抗关节炎作用。此外，根据对 AIA 大鼠的治疗效果，乌头（AC）是 WTD 中的主要抗炎成分。体内和体外实验表明，WTD 抑制 NF-κB 磷酸化，同时增加 Nrf2 的表达，这是网络药理学分析确定的主要途径。主要辅助成分麻黄（EP）明显抑制 NF-κB 介导的炎症反应。另一种辅助成分黄芪（AS）单独或与 AC 联合使用时，显著增强 Nrf2 的表达。这些组合在体内和体外对 AIA 大鼠的抗关节炎作用均优于 AC 单独使用。然而，WTD 在体内和体外均始终取得优于任何组合的最佳效果。
结论
君药 EP 和 AS 通过调节 NF-κB 介导的炎症途径和 Nrf2 介导的抗氧化途径，增强了 AC 的抗关节炎作用，这是 WTD 缓解 RA 症状的主要途径。
Zotero 插件