Shi Wenqing, Jia Mengqi, Li Xiao, Zhao Xin, Wang Chenxi, Fan Guorong, Lou Yuefen
Department of Pharmacy, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Front Pharmacol. 2025 Apr 23;16:1519054. doi: 10.3389/fphar.2025.1519054. eCollection 2025.
Smilax glabra Roxb (SGR) is a traditional Chinese medicine known for its medicinal and edible properties, with a long history of clinical use in treating hyperuricemia (HUA). However, current research has primarily focused on ethanol extracts, leaving the active ingredients and mechanisms responsible for the uric acid-lowering effects of SGR standard decoction unclear.
Firstly, the chemical components in the standard decoction of SGR were characterized by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS), and the pharmacodynamic experiments in mice with a high uric acid model were used to rapidly screen out the uric acid-lowering active ingredient group. Secondly, metabolic fingerprinting and tissue distribution analysis were performed on plasma and tissue samples from rats orally administered with SGR, respectively, to identify the key components and target organs. Finally, the core targets of these active ingredients were screened and analyzed by molecular docking technology.
We fractionated the ingredients of the SGR standard decoction into large and medium polar compound groups using macroporous resin, identifying 20 components. Then, through the pharmacodynamic experiment in hyperuricemic mice, we verified that the group of medium polar compounds in SGR had significant uric acid-lowering effects. In the metabolic fingerprinting analysis, 8 flavonoids and 24 metabolites were screened in the plasma of SD rats. Tissue distribution analysis revealed that the liver, intestine, kidney, and stomach were the main target organs for the active ingredients, with neoastiblin, astilbin, neoisoastiblin, isoastiblin, engeletin, and metabolites M01, M08, and M15 being the most widely distributed. Molecular docking confirmed that metabolites M08, M11, M15, and M16 exhibited strong binding activities with the target proteins CNT2, XOD, and URAT1.
This study provides valuable references and insights into the pharmacodynamic substance basis and mechanism of action of SGR standard decoction for HUA treatment, through comprehensive analyses of chemical, metabolic, and pharmacodynamic fingerprints.
菝葜是一种具有药用和食用价值的传统中药，在治疗高尿酸血症（HUA）方面有着悠久的临床应用历史。然而，目前的研究主要集中在乙醇提取物上，菝葜标准汤剂降尿酸作用的活性成分和机制尚不清楚。
首先，采用超高效液相色谱-四极杆飞行时间质谱（UPLC-Q-TOF/MS）对菝葜标准汤剂中的化学成分进行表征，并通过高尿酸模型小鼠的药效学实验快速筛选出降尿酸活性成分组。其次，分别对口服菝葜的大鼠血浆和组织样本进行代谢指纹图谱和组织分布分析，以确定关键成分和靶器官。最后，通过分子对接技术筛选和分析这些活性成分的核心靶点。
我们使用大孔树脂将菝葜标准汤剂的成分分为大极性和中极性化合物组，鉴定出20种成分。然后，通过高尿酸血症小鼠的药效学实验，我们验证了菝葜中极性化合物组具有显著的降尿酸作用。在代谢指纹图谱分析中，在SD大鼠血浆中筛选出8种黄酮类化合物和24种代谢产物。组织分布分析表明，肝脏、肠道、肾脏和胃是活性成分的主要靶器官，新异嗪皮素、异嗪皮素、新异异嗪皮素、异异嗪皮素、恩格勒苷以及代谢产物M01、M08和M15分布最为广泛。分子对接证实，代谢产物M08、M11、M15和M16与靶蛋白CNT2、XOD和URAT1表现出很强的结合活性。
本研究通过对化学、代谢和药效学指纹图谱的综合分析，为菝葜标准汤剂治疗HUA的药效物质基础和作用机制提供了有价值的参考和见解。
