Antihyperuricemic, hepatoprotective and nephroprotective roles of Benincasae Exocarpium in hyperuricemia rats.

ETHNOPHARMACOLOGICAL RELEVANCE

Benincasae Exocarpium (BE) is the outer peel of the herbaceous plant Benincasa hispida Cogn., belonging to the Cucurbitaceae family. BE has a long-standing history in medicinal applications for its capabilities to relieve thirst, promote diuresis, eliminate dampness, and clear heart fire, which suggest its potential for the intervention of hyperuricemia (HUA).

AIM OF THE STUDY

This study aimed to clarify how BE exerts its anti-HUA effect in HUA rats, especially its protective function on liver and kidney damage.

MATERIALS AND METHODS

UPLC-MS/MS analysis was employed to identify the components of BE, HUA rats were established by potassium oxonate and hypoxanthine, and the biochemical parameters and transcriptomics analyses of liver and kidney in BE-treated HUA rats were carried out with further verification by Western Blot.

RESULTS

BE mainly consisted of amino acids, flavonoids, alkaloids, and terpenoids with a moderate inhibitory effect on xanthine oxidase (XOD, IC = 720.6 μg/mL) in vitro and reduced serum levels of uric acid (UA), TC, TG, IL-1β, IL-6 and TNF-α, as well as lowered AST, CRE, and BUN levels in vivo, which supported the efficacy of BE in improving liver and kidney function in HUA rats. In addition, BE inhibited UA synthesis and facilitated UA excretion by regulating the expressions of XOD in liver and URAT1, GLUT9, ABCG2 and OAT1 in kidney. Moreover, BE regulated HUA-induced renal inflammation and glomerular swelling through TLR4/NF-κB/NLRP3 signaling pathway, as evidenced by validation experiments combining transcriptomics with Western Blot analysis. Notably, liver transcriptome analysis and further molecular data indicated that BE alleviated metabolic disorders caused by HUA through regulation of IRS2/FoxO1/AMPK/ACC signaling pathway.

CONCLUSIONS

Above results suggest that BE primarily promotes UA excretion and is effective in both reducing UA reabsorption and inhibiting UA production. Notably, BE exerts protective effect on liver and kidney of HUA rats by reducing glomerular swelling and alleviating hepatic metabolic disorders. Therefore, BE can act as a dietary supplement with anti-HUA property.