An integrated study of Shenling Baizhu San against hyperuricemia: Efficacy evaluation, core target identification and active component discovery.

ETHNOPHARMACOLOGICAL RELEVANCE: 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. AIM OF THE STUDY: 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. MATERIALS AND 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. CONCLUSION: 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.

[Effect of single-herb traditional Chinese medicine for eliminating dampness on metabolism of uric acid].

Through literature review, it was found that there were many literature reports on the effect of single-herb traditional Chinese medicine for lowering uric acid in comparison with other single-herb traditional Chinese medicines. Then what is the relationship between single-herb traditional Chinese medicines for eliminating dampness and uric acid? How do they play a role in lowering uric acid? In this study, traditional Chinese medicines for eliminating dampness in the 2015 Chinese Pharmacopoeia and the innovative textbook of Clinical Chinese Pharmacy for Chinese medicine colleges and universities in the new century were selected as the research objects, and articles about the effect of single-herb traditional Chinese medicines for eliminating dampness in the treatment of hyperuricemia were searched through CNKI, WanFang and VIP. Afterwards, Excel(2016) was used to establish a database, and Excel screening tool was used to extract the classification statistics of its uric acid lowering effect, pharmacodynamic sites, uric acid lowering pathway and mechanism, so as to clarify the relationship between single-herb traditional Chinese medicines for eliminating dampness and uric acid as well as their mechanism on lowering uric acid. The results showed that there were 16 kinds of traditional Chinese medicines with uric acid lowering effect, accounting for 23.88% of the 67 kinds of traditional Chinese medicines for eliminating dampness. Other medicines with the uric acid lowering effect included traditional Chinese medicine extracts and chemical components. The main ways of reducing uric acid included: inhibiting uric acid synthesis and promoting uric acid excretion; mechanism of action was mainly regulating the two key enzymes generated by uric acid and the ion transporters excreted by uric acid. Therefore, it can be seen that this kind of traditional Chinese medicines have a clear effect in reducing uric acid, providing new ideas for drug screening, prescription compatibility and target determination for the treatment of hyperuricemia as well as a theoretical basis for the clinical treatment and research of hyperuricemia.