Enhanced anti-hyperuricemic effect of Simiao pill by composite lactic acid bacteria fermentation: ferulic acid and berberine enrichment and URAT1/OAT1/XOD regulation

Background Simiao Pill (SP) is a traditional Chinese medicine used to treat hyperuricemia (HUA). Microbial fermentation can enhance the effectiveness of herbal medicines. Objectives This study aimed to evaluate the effects of composite lactic acid bacteria fermentation on the chemical components of SP and its anti-HUA effect. Methods This study revealed the contents of fermented Simiao Pill (FSP), and optimized the optimal fermentation conditions. The anti-HUA effects were evaluated by testing the biochemical indicators of liver and kidney function, and the histology of liver and kidney. Immunohistochemistry, Western blot and RT-qPCR analysis were applied to investigate key proteins and mRNAs. Results After fermentation with composite lactic acid bacteria, the contents of ferulic acid and berberine in fermented Simiao Pill (FSP) were increased by 40.0% and 20.7%, respectively, compared with those in SP. The optimal fermentation conditions were: time of 24 h, temperature of 35 °C, and inoculation of 1%. FSP significantly reduced the serum levels of uric acid, blood urea nitrogen, creatinine. FSP ameliorated the damage of the kidney and the degree of renal interstitial fibrosis. FSP downregulated the protein expressions of URAT1, upregulated that of OAT1, and inhibited the expression of XOD activity and protein, with its efficacy being superior to that of SP. Conclusion Fermentation with composite lactic acid bacteria increased the contents of ferulic acid and berberine in SP. FSP lowered uric acid by increasing OAT1 to promote uric acid excretion, decreasing URAT1 to reduce uric acid reabsorption, and inhibiting XOD to reduce uric acid production.