[Mechanism study on anti-hyperuricemic effects of Zhejiang Plantaginis Semen glycosides based on metabolomics and metagenomics].
摘要
A rat model of hyperuricemia was established using potassium oxonate, hypoxanthine, and adenine. The anti-hyperuricemic mechanisms of Zhejiang Plantaginis Semen glycosides(ZPG) were subsequently explored utilizing metabolomics and metagenomics approaches. Forty SD rats were randomly divided into five groups: control, model, benzbromarone(20 mg·kg~(-1)), low-dose ZPG(100 mg·kg~(-1)), and high-dose ZPG(400 mg·kg~(-1)), with 8 rats in each group. Hyperuricemia was induced by continuous intragastric administration of potassium oxonate(200 mg·kg~(-1)), hypoxanthine(500 mg·kg~(-1)), and adenine(50 mg·kg~(-1)) for 21 days, while drug treatment was administered simultaneously. Serum and liver tissues were collected to measure the levels of uric acid(UA), creatinine(Cr), blood urea nitrogen(BUN), and xanthine oxidase(XOD). Renal tissues were subjected to histopathological examination. Additionally, untargeted metabolomics analysis was performed on serum samples, and fecal metagenomics sequencing was conducted to analyze the composition of the gut microbiota. The results showed that ZPG effectively reduced the levels of serum UA, Cr, and BUN in hyperuricemic rats, inhibited XOD activity in both serum and liver, alleviated renal pathological damage, and mitigated inflammatory responses. Metabolomics analysis identified 16 differential metabolites, mainly involved in lipid metabolism, purine metabolism, and amino acid metabolism pathways. The results of fecal metagenomics analysis revealed that ZPG restored the Firmicutes-to-Bacteroidetes ratio and increased the relative abundance of probiotics such as Lactobacillus＿johnsonii, Limosilactobacillus＿reuteri, and Ligilactobacillus＿murinus. In summary, ZPG effectively reduces serum UA levels, improves renal injury, and attenuates inflammatory symptoms in hyperuricemic rats. These effects may be attributed to its inhibition of XOD activity, correction of inflammatory lipid metabolism abnormalities, regulation of disordered purine met