Multi-Target Regulation of Diabetic Nephropathy by Alkaloids: Molecular Targets, Signaling Pathways and Therapeutic...

In the context of the global diabetes epidemic, diabetic nephropathy (DN)-a condition directly associated with diabetes-has become the primary cause of end-stage renal disease, significantly impacting patients' quality of life and placing substantial demands on public healthcare resources. The pathogenesis of DN is characterized by metabolic disturbances induced by high glucose levels, hemodynamic abnormalities, and the synergistic amplification of various stress signals. These factors collectively contribute to the progressive loss of nephrons and irreversible renal dysfunction. Although current standard treatments can partially slow disease progression, they significantly fail to meet clinical needs. Therefore, there is an urgent necessity to identify multi-target intervention strategies that utilize novel mechanisms of action. Alkaloids, a class of natural nitrogen-containing compounds known for their significant structural diversity, have recently demonstrated multiple renoprotective effects in experimental models of DN. This review is based on a search of the PubMed, Web of Science and CNKI databases. The keywords alkaloids, diabetic nephropathy, diabetic nephropathies, diabetic kidney disease, inflammation, oxidative stress, fibrosis, autophagy and apoptosis were used to search for original research articles in both Chinese and English, published between 2010 and 2026, which investigated the mechanisms by which alkaloid compounds exert their anti-DN effects. Focusing on anti-inflammatory effects, anti-oxidative stress, anti-renal fibrosis, autophagy modulation, apoptosis regulation and ferroptosis inhibition, the review then summarized the relevant literature by systematizing the experimental models, intervention protocols, dosages and key results. This provided a new theoretical perspective and experimental basis for the clinical translation and new drug development of alkaloid compounds for the treatment of DN. The review provides a new theoretical perspective and an experimental basis for the clinical translation of, and new drug development based on, alkaloid compounds for the treatment of DN.