Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：参苓白术散（SLBZ）是一种著名的中医（TCM）配方，具有健脾益气作用，祛湿,并诱导利尿以缓解腹泻。结合中医解释，湿是高尿酸血症发生发展的重要病机因素，从中医理论的角度来看，SLBZ具有良好的抗高尿酸血症潜力。
目的：本研究旨在探讨SLBZ抗高尿酸血症的疗效及其可能的作用机制，重点探讨SLBZ的活性成分和核心靶点。
方法：在本研究中，我们采用meta分析和高尿酸血症鹌鹑模型评价SLBZ的降尿酸作用.体重,血清尿酸，并对鹌鹑的排泄物尿酸水平进行了评估。随后，我们通过网络药理学分析了SLBZ抗高尿酸血症的潜在活性成分和核心靶点,并使用分子对接计算了它们之间的相互作用.此外，建立了用核心靶点干扰剂治疗的高尿酸血症大鼠,以确定选定靶点在高尿酸血症进展中的核心作用.此外,我们分离并表征了鹌鹑的原代肾小管上皮细胞，以验证SLBZ抗高尿酸血症的活性成分和核心靶标。Western印迹用于观察在干扰剂的刺激下用活性成分处理的核心靶标的表达。
结果：来自荟萃分析和动物实验的数据表明，SLBZ可以有效地对抗高尿酸血症。用SLBZ治疗的高尿酸血症鹌鹑显示出血清尿酸水平显着降低，同时尿酸排泄增加。根据网络药理学和分子对接结果,确定了34种潜在的活性成分和SLBZ抗高尿酸血症的核心目标过氧化物酶体增殖物激活受体γ（PPARγ）。罗格列酮治疗高尿酸血症大鼠血清尿酸水平降低,PPARγ的激动剂，证实了PPARγ在高尿酸血症病理过程中的重要作用。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,并观察到高水平尿酸处理的细胞中PPARγ在Ser273处的磷酸化增强.然而,p-PPARγSer273的表达增强可被木犀草素和柚皮素下调，SLBZ抗高尿酸血症的两种活性成分。
结论：总之，SLBZ是一种很有前途的抗高尿酸血症药，木犀草素和柚皮素是SLBZ通过下调PPARγ在Ser273处的磷酸化来对抗高尿酸血症的活性成分。
目的：本研究旨在探讨SLBZ抗高尿酸血症的疗效及其可能的作用机制，重点探讨SLBZ的活性成分和核心靶点。
方法：在本研究中，我们采用meta分析和高尿酸血症鹌鹑模型评价SLBZ的降尿酸作用.体重,血清尿酸，并对鹌鹑的排泄物尿酸水平进行了评估。随后，我们通过网络药理学分析了SLBZ抗高尿酸血症的潜在活性成分和核心靶点,并使用分子对接计算了它们之间的相互作用.此外，建立了用核心靶点干扰剂治疗的高尿酸血症大鼠,以确定选定靶点在高尿酸血症进展中的核心作用.此外,我们分离并表征了鹌鹑的原代肾小管上皮细胞，以验证SLBZ抗高尿酸血症的活性成分和核心靶标。Western印迹用于观察在干扰剂的刺激下用活性成分处理的核心靶标的表达。
结果：来自荟萃分析和动物实验的数据表明，SLBZ可以有效地对抗高尿酸血症。用SLBZ治疗的高尿酸血症鹌鹑显示出血清尿酸水平显着降低，同时尿酸排泄增加。根据网络药理学和分子对接结果,确定了34种潜在的活性成分和SLBZ抗高尿酸血症的核心目标过氧化物酶体增殖物激活受体γ（PPARγ）。罗格列酮治疗高尿酸血症大鼠血清尿酸水平降低,PPARγ的激动剂，证实了PPARγ在高尿酸血症病理过程中的重要作用。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,并观察到高水平尿酸处理的细胞中PPARγ在Ser273处的磷酸化增强.然而,p-PPARγSer273的表达增强可被木犀草素和柚皮素下调，SLBZ抗高尿酸血症的两种活性成分。
结论：总之，SLBZ是一种很有前途的抗高尿酸血症药，木犀草素和柚皮素是SLBZ通过下调PPARγ在Ser273处的磷酸化来对抗高尿酸血症的活性成分。
