Chen Xueting, Zhong Xiaomei, Guo Jiemei, Jin Tong, Guan Huaying, Lin Jing, Zeng Minjie, Zhang Yiqian, Lin Yanxiang, Chang Dennis, Zheng Yanfang, Zhou Xian, Huang Mingqing, Su Youxin
The Affiliated People's Hospital, College of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350108, China.
Key Laboratory of Orthopedics & Traumatology of Traditional Chinese Medicine and Rehabilition, Ministry of Education, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian, 350122, China.
J Ethnopharmacol. 2025 May 12;347:119731. doi: 10.1016/j.jep.2025.119731. Epub 2025 Apr 3.
Huazhuo Sanjie Chubi Decoction (HSCD), a Chinese herbal formula, is traditionally used for the treatment of spleen deficiency with dampness accumulation and is commonly used to treat gouty arthritis (GA). However, the potential active compounds and mechanisms of HSCD remain unclear.
To elucidate the key bioactive compounds and pharmacological mechanisms of HSCD in treating GA.
The chemical compounds in HSCD were qualitatively and quantitatively analyzed using ultraperformance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Network pharmacology and molecular docking were employed to identify key active compounds and associated molecular pathways. Monosodium urate (MSU)-induced RAW264.7 macrophages and GA rat model were used to explore the potential therapeutic effects and mechanisms of HSCD in treating GA.
UPLC-MS/MS identified 184 compounds in HSCD, with 28 key compounds quantified. Network pharmacology revealed that verbenalin, limonin, and quercitrin are strongly associated with the molecular mechanisms of HSCD in treating GA via the PI3K-AKT signaling pathway. These compounds exhibited strong binding affinity to PI3K and AKT proteins. In RAW264.7 cells, HSCD and the three identified compounds dose-dependently reduced inflammation by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS). They also downregulated both the PI3K-AKT and apoptosis signaling pathways. In rats, HSCD exerted therapeutic effects against acute GA by alleviating swelling and pathological damage to the ankle joints. Moreover, the molecular mechanisms in vivo were confirmed to be associated with the PI3K-AKT and apoptosis signaling pathways.
This study employed a multivariant approach to demonstrate the main bioactive compounds and molecular mechanisms of HSCD in treating GA, thereby supporting its traditional use.
化浊散结除痹汤（HSCD）是一种中药方剂，传统上用于治疗脾虚湿蕴，常用于治疗痛风性关节炎（GA）。然而，HSCD的潜在活性成分和作用机制仍不清楚。
阐明HSCD治疗GA的关键生物活性成分和药理机制。
采用超高效液相色谱串联质谱法（UPLC-MS/MS）对HSCD中的化学成分进行定性和定量分析。运用网络药理学和分子对接技术来鉴定关键活性成分和相关分子途径。使用尿酸钠（MSU）诱导的RAW264.7巨噬细胞和GA大鼠模型来探究HSCD治疗GA的潜在治疗效果和机制。
UPLC-MS/MS鉴定出HSCD中的184种化合物，其中28种关键化合物被定量。网络药理学显示，马鞭草苷、柠檬苦素和槲皮苷通过PI3K-AKT信号通路与HSCD治疗GA的分子机制密切相关。这些化合物对PI3K和AKT蛋白表现出强烈的结合亲和力。在RAW264.7细胞中，HSCD和三种鉴定出的化合物通过抑制核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、环氧化酶-2（COX-2）和诱导型一氧化氮合酶（iNOS），剂量依赖性地减轻炎症。它们还下调了PI3K-AKT和凋亡信号通路。在大鼠中，HSCD通过减轻踝关节肿胀和病理损伤对急性GA发挥治疗作用。此外，体内分子机制被证实与PI3K-AKT和凋亡信号通路有关。
本研究采用多变量方法证明了HSCD治疗GA的主要生物活性成分和分子机制，从而支持了其传统用途。
