TCM-based natural products in type 2 diabetes: a comprehensive review of bioactive compounds and molecular mechanisms

Type 2 Diabetes Mellitus (T2DM) is a complex metabolic disorder. It is marked not just by high blood sugar levels but also by insulin resistance, oxidative stress, chronic inflammation, issues with lipids, problems in mitochondria, and ongoing injury to β-cells. Because of this varied set of causes, natural products from Traditional Chinese Medicine (TCM) have gained interest as potential treatments that target multiple areas. This review compares three major TCM-derived classes of plant chemicals that have strong evidence supporting their effectiveness against diabetes: the alkaloid berberine, the polyphenol curcumin, and the saponin ginsenosides. We conducted a structured narrative review using databases like PubMed/MEDLINE, Web of Science, ScienceDirect, Scopus, Google Scholar, and CNKI. We focused on mechanistic in vitro studies, animal experiments, clinical evidence, and practical relevance. The evidence indicates that these compounds help regulate glucose and lipid levels through both common and unique mechanisms. Berberine is mainly linked to activating AMP-activated protein kinase, promoting glucose transport, reducing liver glucose production, and changing gut bacteria. Curcumin shows anti-inflammatory, antioxidant, anti-fibrotic, and protective effects, involving pathways like nuclear factor kappa B, c-Jun N-terminal kinase, transforming growth factor beta/Smad, and protein kinase B/glycogen synthase kinase-3 beta. Ginsenosides are more associated with insulin signaling through phosphoinositide 3-kinase/protein kinase B, protecting β-cells, and reducing kidney damage, while also affecting gut bacteria. Despite strong support from mechanistic and preclinical studies, wider clinical use is limited by issues like poor absorption, differences in formulations, varying doses, and inconsistent human studies. Overall, these compounds should be seen as promising additional treatments for T2DM, rather than primary therapies. Future advancements will hinge on better drug absorption, consistent formulations, and larger long-term clinical trials.