Department of Biomedical Engineer, General Hospital of Western Theater Command, Chengdu, Sichuan, People's Republic of China.
Department of Traditional Chinese Medicine, General Hospital of Western Theater Command, Chengdu, Sichuan, People's Republic of China.
Drug Des Devel Ther. 2023 Aug 2;17:2287-2301. doi: 10.2147/DDDT.S419130. eCollection 2023.
Dispelling dampness, relieving turbidity and dredging collaterals decoction (DED), is a traditional Chinese medicine used in the treatment of hyperuricemia. We aimed to explore the effect and mechanism of DED in the treatment of hyperuricemia.
The effects of DED (9.48, 4.74, and 2.37 g/kg/d) on potassium oxonate (750 mg/kg/d)-induced hyperuricemia in rats were evaluated by serum uric acid (UA), creatinine (CRE), blood urea nitrogen (BUN), and renal pathological changes. Network pharmacology was used to identify the effective components and targets of DED, and the key targets and signaling pathways for its effects on hyperuricemia were screened. Molecular docking was used to predict the action of DED. H&E, immunohistochemistry, WB, and PCR were used to validate the network pharmacology results.
DED can effectively alleviate hyperuricemia, inhibit UA, CRE, BUN, and xanthine oxidase (XOD) activity, and reduce renal inflammatory cell infiltration and glomerular atrophy. The experiment identified 27 potential targets of DED for hyperuricemia, involving 9 components: wogonin, stigmasterol 3-O-beta-D-glucopyranoside, 3β-acetoxyatractylone, beta-sitosterol, stigmasterol, diosgenin, naringenin, astilbin, and quercetin. DED can relieve hyperuricemia mainly by inhibiting RAGE, HMGB1, IL17R, and phospho-TAK1, and by regulating the AGE-RAGE and IL-17 signaling pathways.
DED can alleviate hyperuricemia by inhibiting XOD activity and suppressing renal cell apoptosis and inflammation via the AGE-RAGE signaling pathway and IL-17 signaling pathway. This study provides a theoretical basis for the clinical application of DED.
祛湿泄浊通络方（DED）是一种用于治疗高尿酸血症的中药。本研究旨在探讨 DED 治疗高尿酸血症的作用及机制。
采用氧嗪酸钾（750 mg/kg/d）诱导的高尿酸血症大鼠模型，观察 DED（9.48、4.74 和 2.37 g/kg/d）对大鼠血清尿酸（UA）、肌酐（CRE）、血尿素氮（BUN）及肾脏病理改变的影响。采用网络药理学方法预测 DED 的有效成分和作用靶点，并筛选其治疗高尿酸血症的关键靶点及信号通路。采用分子对接预测 DED 的作用。采用 H&E、免疫组化、WB 和 PCR 验证网络药理学结果。
DED 能有效缓解高尿酸血症，降低血清 UA、CRE、BUN 及黄嘌呤氧化酶（XOD）活性，减轻肾脏炎性细胞浸润和肾小球萎缩。实验共鉴定出 27 个 DED 治疗高尿酸血症的潜在靶点，涉及 9 个成分：汉黄芩素、豆甾-3-O-β-D-吡喃葡萄糖苷、3β-乙酰氧基吴茱萸酮、β-谷甾醇、豆甾醇、薯蓣皂苷元、柚皮苷、马兜铃酸 A、槲皮素。DED 可能通过抑制 RAGE、HMGB1、IL17R、磷酸化 TAK1，调控 AGE-RAGE 和 IL-17 信号通路，从而发挥缓解高尿酸血症的作用。
DED 可能通过抑制 XOD 活性，抑制肾细胞凋亡和炎症反应，发挥治疗高尿酸血症的作用，其作用机制与 AGE-RAGE 信号通路和 IL-17 信号通路有关。本研究为 DED 的临床应用提供了理论依据。
