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Polygonum cuspidatum alleviates hyperuricemia-induced renal injury via rectifying amino acid metabolism disorders
Yuqing Ma1, Lei Peng2, Honghao Song2
1Nautical medicine experimental teaching demonstration center of educational institutions, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China; Department of Radiation Medicine, Faculty of Naval Medicine, Naval Medical University, Shanghai 200433, China.
Background:
Hyperuricemia has been identified as a causal factor in renal injury and metabolic disorders. P. cuspidatum, a traditional Chinese medicine, has demonstrated potential in reducing serum uric acids and providing renoprotective effects, although its mechanisms remain to be fully elucidated.
Objective:
This study aimed to elucidate the systemic mechanism through which P. cuspidatum ameliorated hyperuricemia-induced renal injury, focusing on amino acid metabolism and associated inflammatory pathways.
Methods:
Untargeted and targeted amino acid metabolomic analyses were conducted on serum samples from hyperuricemia patients and healthy controls. Alterations in amino acid profiles in hyperuricemia patients were validated using a hyperuricemia rat model. To investigate the therapeutic mechanisms of P. cuspidatum in ameliorating hyperuricemia-induced renal injury, targeted amino acid metabolomics, transcriptomics, and microbiomics were performed on hyperuricemia rats.
Results:
Serum metabolomic analysis in patients demonstrated a significant correlation between hyperuricemia and increased concentrations of leucine, phenylalanine, and tyrosine. In hyperuricemia rats, treatment with P. cuspidatum was found to reverse these amino acid dysbiosis, mitigate renal damage, and alter the composition of the gut microbiota. This alteration was associated with a decrease in gut-derived uremic toxins. Additionally, transcriptomics of rat kidneys suggested that the renoprotective effects of P. cuspidatum may be attributed to the modulation of leucine metabolism and glycolysis-related pathways, ultimately leading to the suppression of NLRP3 inflammasome activation.
Conclusions:
Our findings suggest that the therapeutic effect of P. cuspidatum against hyperuricemia-induced renal injury is preliminarily associated with rectifying amino acid metabolism disorders through regulating gut microbiota dysbiosis. These results position P. cuspidatum as a promising multi-target therapeutic candidate for hyperuricemia management, warranting further investigation to delineate the precise causal relationships and long-term effects.
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