Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
Department of Clinical Chinese Pharmacy, School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing, 100029, China.
J Ethnopharmacol. 2022 Sep 15;295:115450. doi: 10.1016/j.jep.2022.115450. Epub 2022 Jun 7.
Shenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories.
This study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets.
In the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid, and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents.
Data from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone, an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin, two active components of SLBZ against hyperuricemia.
In summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.
参苓白术散（SLBZ）是一种著名的中药方剂，具有健脾补气、祛湿利尿、止泻的功效。结合中医理论认为湿是高尿酸血症发生和发展的重要病机因素，SLBZ 从中医理论角度对高尿酸血症具有很好的应用潜力。
本研究旨在探讨 SLBZ 对高尿酸血症的疗效及其可能的机制，重点关注活性成分和核心靶点。
本研究采用荟萃分析和高尿酸鹌鹑模型来评估 SLBZ 的降尿酸作用。检测鹌鹑的体重、血清尿酸和尿尿酸水平。然后，我们通过网络药理学分析和分子对接计算来分析 SLBZ 治疗高尿酸血症的潜在活性成分和核心靶点，并使用干扰核心靶点的试剂建立高尿酸血症大鼠模型，以确定所选靶点在高尿酸血症进展中的中心作用。此外，我们还分离和鉴定了鹌鹑的原代肾小管上皮细胞，以验证 SLBZ 治疗高尿酸血症的活性成分和核心靶点。用活性成分处理干扰试剂后，采用 Western blot 观察核心靶点的表达情况。
荟萃分析和动物实验数据表明，SLBZ 能有效治疗高尿酸血症。用 SLBZ 处理的高尿酸鹌鹑血清尿酸水平显著降低，同时尿酸排泄增加。根据网络药理学和分子对接结果，鉴定出 34 种 SLBZ 治疗高尿酸血症的潜在活性成分和核心靶点过氧化物酶体增殖物激活受体γ（PPARγ）。用 PPARγ激动剂罗格列酮治疗高尿酸血症大鼠，可降低血清尿酸水平，证实 PPARγ 在高尿酸血症的病理过程中起关键作用。此外，我们首次成功分离和鉴定了鹌鹑的原代肾小管上皮细胞，并观察到高尿酸处理后细胞中 PPARγ 的丝氨酸 273 磷酸化增强。然而，SLBZ 治疗高尿酸血症的两种活性成分木犀草素和柚皮素可下调 PPARγ Ser273 的表达。
综上所述，SLBZ 是一种很有前途的抗高尿酸血症药物，木犀草素和柚皮素通过下调 PPARγ Ser273 的磷酸化，成为 SLBZ 抗高尿酸血症的活性成分。
