[Potential pathways for traditional Chinese medicine intervention in diabetic kidney disease: macrophage polarization]

Abstract

Diabetic kidney disease(DKD) is a prevalent and severe microvascular complication of type 2 diabetes mellitus(T2DM). Chronic microinflammation is an important factor exacerbating renal tissue damage in DKD individuals. Macrophages play a crucial role in immune-inflammatory responses, and they can transiently and reversibly polarize into the pro-inflammatory M1 phenotype and anti-inflammatory M2 phenotype based on microenvironmental differences. The imbalance in M1/M2 macrophage polarization can exacerbate DKD progression by fostering inflammatory cytokine aggregation in the glomeruli and renal interstitium. Therefore, restoring the balance of macrophage is a pivotal avenue to ameliorate the chronic microinflammation state in DKD. Macrophage polarization is a complex and dynamic process. Various information molecules and cytokines involved in the polarization process play important roles in regulating phenotypes during the progression of DKD. They are closely related to various mechanisms such as metabolism, inflammation, fibrosis, and mitochondrial autophagy in DKD. By coordinating the inflammatory responses through polarization, they play a key role in regulating inflammation in metabolic-related diseases. The complex network of pathways involved in macrophage polarization corresponds well with the multi-pathway, multi-target treatment model of traditional Chinese medicine(TCM). Active ingredients and formulas of TCM can intervene in DKD by regulating macrophage polarization. Studies on relieving renal inflammation, repairing renal tissues, and promoting renal function recovery through macrophage polarization modulation are not uncommon. Therefore, based on exis-ting evidence, this study reviews TCM in targeting M1/M2 macrophage polarization balance to improve DKD, aiming to explore the potential of macrophage polarization in regulating DKD, which is expected to provide evidence support for the clinical diagnosis and treatment of DKD with TCM as well as the exploration of its biological mechanisms.

Keywords: active ingredients; diabetic kidney disease; herbal compound; inflammatory microenvironment; macrophage polarization.