Traditional Chinese medicine in the treatment of diabetic kidney disease: the mechanisms of signaling pathways regulations

Diabetic kidney disease (DKD) represents a diabetes-driven microvascular complication characterized by renal physiological and metabolic disorders and is considered a top-ranking trigger of progression to end-stage renal disease and death in diabetic patients. Although the drugs commonly used in clinical practice for DKD provide some renal protection, their toxic side effects and limited ability to halt further progression of the disease remain unsatisfactory. Traditional Chinese medicine (TCM) brings centuries of accumulated practice and distinct therapeutic strengths to the management of chronic diseases with complex pathogenesis such as DKD. Its characteristics of multi-target and multi-pathway intervention establish a solid material basis for DKD therapy, while its low toxicity profile aligns well with the chronic nature of DKD. This review elaborates on the therapeutic potential of examining TCM's impact on DKD through the prism of cellular signaling pathways and reveals that the Nrf2, TGF-β/Smad, NF-κB/NLRP3, MAPK, and PI3K/AKT signaling pathways warrant particular attention in the TCM treatment of DKD. The TCM agents involved include astragaloside IV, Shengqing Jiangzhuo formula, Huangkui capsule, Fuxin granules, Liuwei Dihuang pill, <i>Taxus chinensis</i>, Burdock fructooligosaccharide, baicalin, hirudin, rutin, and fermented seaweed extracts. This review aims to refresh and consolidate the signaling pathways engaged by TCM in DKD, sift for promising targets and drugs, and supply both conceptual and experimental scaffolding for future anti-DKD therapeutics.