College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan 430065, China.
Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
Chin J Nat Med. 2023 Oct;21(10):730-744. doi: 10.1016/S1875-5364(23)60466-2.
Traditionally, Tripterygium hypoglaucum (Levl.) Hutch (THH) are widely used in Chinese folk to treat rheumatoid arthritis (RA). This study aimed to investigate whether the anti-RA effect of THH is related with the gut microbiota. The main components of prepared THH extract were identified by HPLC-MS. C57BL/6 mice with adjuvant-induced arthritis (AIA) were treated with THH extract by gavage for one month. THH extract significantly alleviated swollen ankle, joint cavity exudation, and articular cartilage destruction in AIA mice. The mRNA and protein levels of inflammatory mediators in muscles and plasma indicated that THH extract attenuated inflammatory responses in the joint by blocking TLR4/MyD88/MAPK signaling pathways. THH extract remarkably restored the dysbiosis of the gut microbiota in AIA mice, featuring the increases of Bifidobacterium, Akkermansia, and Lactobacillus and the decreases of Butyricimonas, Parabacteroides, and Anaeroplasma. Furthermore, the altered bacteria were closely correlated with physiological indices and drove metabolic changes of the intestinal microbiota. In addition, antibiotic-induced pseudo germ-free mice were employed to verify the role of the intestinal flora. Strikingly, THH treatment failed to ameliorate the arthritis symptoms and signaling pathways in pseudo germ-free mice, which validates the indispensable role of the intestinal flora. For the first time, we demonstrated that THH extract protects joint inflammation by manipulating the intestinal flora and regulating the TLR4/MyD88/MAPK signaling pathway. Therefore, THH extract may serve as a microbial modulator to recover RA in clincial practice.ver RA in clincial practice.
雷公藤（Tripterygium hypoglaucum（Levl.）Hutch）传统上被广泛用于中国民间治疗类风湿关节炎（RA）。本研究旨在探讨雷公藤的抗 RA 作用是否与肠道微生物群有关。通过 HPLC-MS 鉴定了制备的雷公藤提取物的主要成分。用雷公藤提取物灌胃治疗佐剂诱导关节炎（AIA）的 C57BL/6 小鼠一个月。雷公藤提取物显著缓解 AIA 小鼠肿胀的踝关节、关节腔渗出物和关节软骨破坏。肌肉和血浆中炎症介质的 mRNA 和蛋白水平表明，雷公藤提取物通过阻断 TLR4/MyD88/MAPK 信号通路，减轻关节的炎症反应。雷公藤提取物显著恢复了 AIA 小鼠肠道微生物群的失调，双歧杆菌、阿克曼氏菌和乳杆菌增加，丁酸单胞菌、副拟杆菌和厌氧原体减少。此外，改变的细菌与生理指标密切相关，并驱动肠道微生物群的代谢变化。此外，还采用抗生素诱导的假无菌小鼠来验证肠道菌群的作用。令人惊讶的是，雷公藤治疗未能改善假无菌小鼠的关节炎症状和信号通路，这验证了肠道菌群的不可或缺作用。这是首次证明雷公藤提取物通过操纵肠道菌群和调节 TLR4/MyD88/MAPK 信号通路来保护关节炎症。因此，雷公藤提取物可能作为一种微生物调节剂，用于恢复临床实践中的 RA。
