Current advances and future perspectives of Astragalus membranaceus active components in regulating diabetic microvascular complications

BACKGROUND: Diabetic microvascular complications (DMCs) mainly consist of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN). Current therapeutic options for DMCs are often suboptimal and frequently accompanied by a range of adverse effects. By contrast, traditional Chinese medicine (TCM) offers a promising comprehensive approach for DMC management, characterized by multi‑target actions, fewer side effects, the ability to intervene in complications, potential for combined effect with western drugs, and cost advantages, thereby meriting further promotion and investigation. PURPOSE: This review comprehensively assesses the pharmacological actions, potential mechanisms, and current clinical evidence of Astragalus membranaceus (AM) and its active components in DMCs, which could provide novel therapeutic insights for DMCs, and future research directions. STUDY DESIGN AND METHODS: We conducted precise searches in PubMed using the keywords ("Astragalus membranaceus" OR "Huangqi" OR "astragaloside") AND ("diabetic kidney disease" OR "diabetic nephropathy"), ("Astragalus membranaceus" OR "Huangqi" OR "astragaloside") AND ("diabetic peripheral neuropathy"), ("Astragalus" OR "Huangqi" OR "astragaloside") AND ("diabetic retinopathy"), "astragaloside IV (AS-IV)", "Astragalus polysaccharide (APS)", "flavonoids", "formononetin (FMN)" and "calycosin" to accurately retrieve research reports on AM, its active components, and AM-based preparations in DMCs. The retrieved data followed PRISMA criteria. RESULTS: AM has protective effects on the kidneys, retinal blood vessels, and peripheral nerve myelin sheaths. Its mechanisms of action mainly include anti-oxidation, anti-inflammatory effects, and the inhibition of ferroptosis. Especially, AS-IV, flavonoids, APS, FMN and calycosin, these active components of AM have therapeutic potentials for preventing and treating DMCs. The existing clinical data initially indicate that AM can reduce proteinuria, improve metabolic disorders and regulate blood glucose, thereby playing a role in the prevention and treatment of DMCs. CONCLUSION: AM is a promising candidate of TCM for DMCs. Most researches focus on the protective effect of AM on DKD, with the lack of the studies of AM against DPN and DR. Moreover, clinical research of AM in DMCs remains markedly inadequate compared to its basic research. Therefore, future research efforts should prioritize conducting high-quality basic and clinical trials to verify the therapeutic effects of AM against DMCs.