Berberine in diabetic nephropathy: mechanistic overview

Diabetic nephropathy (DN) represents the most common cause of end-stage renal disease (ESRD) worldwide, affecting 20-40% of diabetic patients. Current therapeutic strategies remain insufficient to halt disease progression, underscoring the need for novel interventions.

This comprehensive review examines the multifaceted pathogenesis of DN and evaluates the therapeutic potential of berberine (BBR) by analyzing molecular, cellular,and epigenetic mechanisms.

We demonstrate that BBR, a bioactive alkaloid derived from Coptidis rhizome, protects the kidneys via multiple interrelated mechanisms. BBR improves glucose metabolism by activating AMPK signaling, reduces inflammatory responses by inhibiting the NF-κB pathway, and alleviates oxidative stress by upregulating the Nrf2 pathway. Furthermore, BBR inhibits renal fibrosis by blocking the TGF-β/Smad3 signaling and preserves podocyte function by promoting autophagy via inhibition of the mTOR pathway. Additionally, BBR modulates metabolism, suppresses the polyol pathway, and influences epigenetic processes, including DNA methylation and miRNA expression.

BBR represents a promising multi-target therapeutic agent for DN, demonstrating potential superior efficacy over traditional single-pathway treatments. These results elucidate the multifaceted mechanisms of action of BBR, providing a robust scientific rationale for its therapeutic application and highlighting its potential as a novel strategy for the of metabolic kidney diseases.