APMCG-1, a mountain-cultivated ginseng-derived glycopeptide, attenuates hyperglycemia-induced renal inflammation and fibrosis in diabetic kidney disease

Background Mountain-cultivated ginseng (MCG) residues have significant therapeutic potential but are underutilized. We previously isolated a potent glycopeptide, APMCG-1, from MCG residues using alkaline protease-assisted extraction. Methods The effect of APMCG-1 on diabetic kidney disease (DKD) was evaluated using high-glucose (HG)-induced human kidney proximal tubular cells and high-fat diet (HFD)/streptozotocin (STZ)-treated male C57BL/6J mouse models. In vivo experiments involved male C57BL/6J mice that received a single intraperitoneal injection of STZ (100 mg/kg), followed by oral administration of APMCG-1 solution for the next 8 weeks. Results Histological studies revealed that APMCG-1-treated groups recovered from renal injury and fibrosis. In vitro experiments were conducted to evaluate the protective effects and the proteins related to fibrosis and apoptosis. Western blotting showed decreased expression of pro-apoptotic and pro-fibrotic proteins, including Bax and cleaved caspase-3, alongside increased expression of the anti-apoptotic protein Bcl-2. Furthermore, APMCG-1 treatment reversed the STZ-induced changes in apoptotic proteins, decreased Bax expression, and increased Bcl-2 expression compared to the STZ-alone group. Metabolomic analysis revealed that the renoprotective effect of APMCG-1 was associated with the modulation of key metabolites such as phenol sulphate and phenylpyruvic acid. The metabolites represent multiple distinct yet potentially interconnected pathways central to the progression of diabetic nephropathy, which are involved in sulfate/sulfite metabolism, phenylalanine and tyrosine metabolism, ammonia recycling, and glycine and serine metabolism. Conclusion Collectively, our findings demonstrate that APMCG-1 is a promising therapeutic candidate for preventing and treating DKD as it reduces oxidative stress, inhibits cell apoptosis, and restores renal metabolic homeostasis.