Lipid Autophagy: An Idea for the Treatment of Diabetic Nephropathy With Ginseng and Its Active Compounds

ABSTRACT Diabetic nephropathy (DN) is a major microvascular complication of diabetes, and its prevalence is increasing as the number of diabetes cases rises. It is a leading cause of chronic renal failure worldwide. Edible ginseng is widely used in the management of diabetes and has demonstrated preventive and therapeutic effects on DN, partly through regulating lipids. However, its impact on lipid autophagy in DN remains unclear. This article reviews the pathogenesis of DN and, for the first time, summarises research into the effects of ginseng and specific ginsenosides (Rg1, Rg3, Rk3, Rb2, Rc, Rb1, Rg5 and Rd) on lipid autophagy in DN, as well as their involvement in related signaling pathways. We have organized the current mechanistic insights into two clinically relevant tiers. Tier 1 delineates direct lipophagy‐targeting pathways: Rg1‐activated AMPK/mTOR and AMPK/mTOR/PI3K cascades, alongside Nrf2‐mediated antioxidant responses; Rg3‐driven PPAR‐γ transcriptional programmes; Rk3‐directed PI3K/AKT signaling; Rb2‐coordinated IRS‐1/PI3K/AKT and NF‐κB axes; and Rc‐facilitated C/EBPα/PPAR‐γ crosstalk. Tier 2 examines adjunctive reno‐protective circuits: Rb1‐induced AMPK/Nrf2/HO‐1/11β‐HSD1 network; Rg5‐suppressed p38 MAPK/NLRP3/NF‐κB inflammasome; and Rd‐mediated AKT and AMPK/SIRT1 pathways. This study will help us gain a more comprehensive understanding and explore the role of edible ginseng and ginsenosides in the early prevention and treatment of DN in clinical practice.