Ameliorative effects of Wiryeongtang (herbal medicine) on cardiorenal complications via modulation of inflammatory and fibrotic responses in diabetic mice

: Diabetes-induced cardiorenal complications are characterized by chronic inflammation, fibrosis, and metabolic dysfunction, contributing to both renal and cardiac impairments. Although current therapeutic strategies focus on managing hyperglycemia and minimizing organ damage, complementary approaches are still needed. Wiryeongtang (WRT), a traditional herbal formula provided by Hanpung Pharm & Foods Co. Ltd. (Jeonju, Korea), has shown potential in alleviating metabolic disorder-related complications. This study aimed to investigate the protective effects of WRT on cardiorenal complications in db/db diabetic mice. : This study involved four experimental groups to evaluate the therapeutic effects of WRT. The control group consisted of db/m mice (non-diabetic), while the diabetes group included untreated db/db mice. The positive control group was treated with vildagliptin at 50 mg/kg/day, and the WRT group received WRT at 200 mg/kg/day. Mice were randomly assigned to the groups and treated for the designated period. To assess metabolic improvements, plasma blood glucose levels, lipid accumulation, and oral glucose tolerance were measured. Insulin resistance was evaluated using glucose tolerance tests. Renal outcomes were assessed through histological examinations, focusing on glomerulosclerosis, mesangial matrix expansion, and fibrosis biomarkers. Cardiac tissues were examined for structural and functional changes, including hypertrophy, fibrosis, and inflammation. Apoptotic signaling pathways were also analyzed by measuring the expression levels of caspase-3, caspase-9, Bcl-2, and Bax. : WRT administration significantly reduced plasma blood glucose levels and attenuated lipid accumulation in db/db mice. The WRT group showed marked improvements in oral glucose tolerance and insulin resistance. In the kidneys, WRT treatment reduced glomerulosclerosis, mesangial matrix expansion, and fibrosis markers, demonstrating renal protective effects. In the heart, WRT mitigated diabetes-induced cardiac dysfunction and histopathological changes, including hypertrophy, fibrosis, and inflammation. Mechanistically, WRT downregulated the expression of apoptotic markers (caspase-3 and caspase-9) while upregulating the Bcl-2/Bax ratio, suggesting anti-apoptotic effects. : The findings of this study suggest that WRT may serve as a potential therapeutic agent for managing cardiorenal complications associated with type II diabetes. WRT effectively alleviated hyperglycemia, improved insulin sensitivity, and reduced inflammation and fibrosis in both the heart and kidneys. These results highlight the therapeutic potential of WRT in addressing diabetes-induced cardiorenal dysfunction through its anti-apoptotic and anti-fibrotic mechanisms.