New insights into anti-diabetes effects and molecular mechanisms of dietary saponins

Diabetes mellitus (DM) is a long-term metabolic disorder that manifests as chronic hyperglycemia and impaired insulin, bringing a heavy load on the global health care system. Considering the inevitable side effects of conventional anti-diabetic drugs, saponins-rich natural products exert promising therapeutic properties to serve as safer and more cost-effective alternatives for DM management. Herein, this review systematically summarized the research progress on the anti-diabetic properties of dietary saponins and their underlying molecular mechanisms in the past 20 years. Dietary saponins possessed the multidirectional anti-diabetic capabilities by concurrent regulation of various signaling pathways, such as IRS-1/PI3K/Akt, AMPK, Nrf2/ARE, NF-κB-NLRP3, SREBP-1c, and PPARγ, in liver, pancreas, gut, and skeletal muscle. However, the industrialization and commercialization of dietary saponin-based drugs are confronted with a significant challenge due to the low bioavailability and lack of the standardization. Hence, in-depth evaluations in pharmacological profile, function-structure interaction, drug-signal pathway interrelation are essential for developing dietary saponins-based anti-diabetic treatments in the future.