Multifaceted therapeutic potential of saponins in type 2 diabetes mellitus: mechanisms targeting insulin resistance and diabetic complications

Background: Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder that poses management challenges due to the limited efficacy and adverse effects of current therapies. Saponins, a class of bioactive phytochemicals widely distributed in medicinal plants and other natural sources, exhibit antidiabetic activities through multi-target mechanisms, have emerged as promising therapeutic candidates for T2DM. This review systematically summarizes the pharmacological mechanisms and therapeutic potential of saponins in management of T2DM and its complications. Materials and methods: Studies involving molecular, cellular, animal, and clinical studies of saponins in T2DM and its complications were screened and analyzed to provide a systematic overview. All the literature information in this review was collected from relevant literature published up to 2025 from the scientific databases, including PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI). Results: The pathogenesis of T2DM is characterized by insulin resistance, β-cell dysfunction, genetic susceptibility, gut microbiota dysbiosis, and metabolic disturbances, leading to hyperglycemia and systemic complications. This review demonstrates that saponins exert multifaceted antidiabetic effects through modulating key signaling pathways, including Keap1/Nrf2, AMPK/PI3K/Akt, and NF-κB. Furthermore, saponins demonstrate significant organ-specific protection against major diabetic complications, such as nephropathy, cardiomyopathy, neuropathy, and retinopathy. Conclusion: Saponins represent a potent class of bioactive metabolites with multi-target therapeutic potential for T2DM and its complications. Their ability to simultaneously modulate metabolic, inflammatory, oxidative, mitochondrial, and gut microbiota-related pathways highlights clear advantages over single-target therapies. A growing body of research has underscored its potential clinical significance in T2DM, providing essential evidence for developing effective and safe therapeutic strategies.