Sinapic acid alleviates kidney injury of hyperuricemia mice by inhibiting ERK1/2-mediated apoptosis of renal tubular epithelial cells

Sinapic acid (SA) is a compound widely found in plants, known for its anti-inflammatory, antioxidant, and renal protective effects. This study combined network pharmacology, RNA sequencing, and both in vivo and in vitro experiments to explore the therapeutic effects and mechanisms of SA in hyperuricemia (HUA) mice. SA (50 mg/kg, 100 mg/kg) showed no toxicity in mice. Both SA and U0126–EtOH (MEK1/2 inhibitor) effectively reduced serum uric acid levels in HUA mice, alleviated kidney dysfunction, mitigated renal damage, inhibited ROS production in the kidneys, reduced the expression of MDA, IL-1β, and IL-6, and promoted SOD secretion. Molecular docking showed strong binding of SA to key targets. Western blot and PCR analyses revealed that SA inhibited p-ERK, Bax, and Caspase3 expression, while promoting Bcl-2 expression. Overall, SA alleviates HUA-induced renal injury by inhibiting p-ERK1/2 signaling and apoptosis in renal tubular epithelial cells, offering clinical application for uric acid-lowering therapy. • The protective effect of SA against HUA-induce renal injury. • ERK1/2 pathway is involved in the therapeutic effect of SA on HUA. • SA inhibit apoptosis of renal tubular epithelial in HUA mice. • SA improve renal function and tubular functions in HUA mice.