Harnessing Nature's Arsenal: The multitarget anticancer and antidiabetic networks of saponins

Saponins from medicinal plants are structurally diverse, naturally occurring amphiphilic glycoside molecules with broad biological activities. They are primarily classified into triterpenoid and steroidal types based on their aglycone scaffolds. This review systematically examines their multi-pathway, multi-target regulatory networks. It highlights their roles in both antitumor and antidiabetic interventions, as well as the miRNA-mediated epigenetic crosstalk between cancer and diabetes. Saponins combat cancer by inducing multiple programmed cell death modalities, causing cell cycle arrest, inhibiting metastasis and angiogenesis, disrupting metabolic reprogramming, and overcoming drug resistance. Their antidiabetic effects involve improving insulin resistance, inhibiting gluconeogenesis, protecting pancreatic β-cells, and preventing and treating diabetic complications. In reviewed studies, individual saponins link to multiple anticancer phenotypes and improved certain antidiabetic endpoints. Yet evidence is mostly compound/model-specific, so shared pathway and miRNA convergence across studies is seen as an indirect link or hypothesis. To address poor solubility and bioavailability, lipid-based nanoparticles are proposed as a delivery platform for improved stability and targeted application in both cancer and diabetes. This review integrates current knowledge to advance mechanistic understanding and promote saponins as multi-targeted therapeutics for cancer and diabetes.