Uncontrolled hyperuricemia often leads to the development
of hyperuricemic
nephropathy (HN), characterized by excessive inflammation and oxidative
stress. Piperine, a cinnamic acid alkaloid, possesses various pharmacological
activities, such as antioxidant and anti-inflammatory effects. In
this study, we intended to investigate the protective effects of piperine
on adenine and potassium oxonate-induced HN mice and a uric-acid-induced
injury model in renal tubular epithelial cells (mRTECs). We observed
that treatment with piperine for 3 weeks significantly reduced serum
uric acid levels and reversed kidney function impairment in mice with
HN. Piperine (5 μM) alleviated uric acid-induced damage in mRTECs.
Moreover, piperine inhibited transporter expression and dose-dependently
inhibited the activity of both transporters. The results revealed
that piperine regulated the AKT/mTOR signaling pathway both in vivo and in vitro. Overall, piperine
inhibits URAT1/GLUT9 and ameliorates HN by inhibiting the AKT/mTOR
pathway, making it a promising candidate for patients with HN.