Proanthocyanidin offers protection against diabetic nephropathy: elucidation of its mechanism of action using animal models.

Context: Diabetic nephropathy (DN) is a major complication of diabetes mellitus and is the leading cause of kidney disease in patients undergoing renal replacement therapy. DN is associated with an increased risk of death in patients with diabetes. Conventional therapy for DN includes intensive control of blood glucose level and blood pressure and renin-angiotensin system blockade. However, this approach has limited treatment effects on DN. Therefore, identifying novel drugs to delay the progression of DN is urgently needed. Proanthocyanidin (PA) has been shown to exert potentially beneficial effects on DN. However, the protective mechanism and efficacy are yet to be elucidated.

Objective: This study evaluates the efficacy and potential mechanisms of PA in animal models of DN.

Methods: Preclinical studies were searched from Chinese National Knowledge Infrastructure, PubMed, Web of Science, Embase, and Google Scholar databases, with the search deadline of August 2023. Keywords ('diabetic nephropathies', 'nephropathies, diabetic', 'diabetic kidney diseases', 'proanthocyanidin', 'anthocyanidin polymers', 'procyanidins', 'animal*', 'rat', and 'mice') were used to search the databases. RevMan 5.3 was used for statistical analysis.

Results: A total of 22 studies involving 538 animals were included in this analysis. The pooled results indicated that PA therapy significantly improved kidney function and reduced proteinuria and blood glucose levels. The protective mechanism of PA was associated with anti-inflammatory, antioxidant, antifibrotic, and antiapoptotic effects; inhibition of endoplasmic reticulum stress; and alleviation of mitochondrial dysfunction and dyslipidemia.

Conclusion: These findings suggest that PA alleviates DN by mediating multiple targets and pathways.