Anti-Diabetic Activity of Partially Purified Santalin A from the Heartwood of Pterocarpus santalinus L.f. in Alloxan-induced Diabetic Wistar Rat

The ever-increasing use of plant-based pharmaceuticals as alternatives to conventional drugs for disease management demands identification, isolation, and characterization of novel compounds. Despite the potential of plant extracts to mitigate the morbidity of diseases, several active principles are preferred to avoid the interference of other compounds. The promising health benefits of the extracts and isolated compounds of Pterocarpus santalinus in the treatment of diabetes, cardiovascular disease, cancer, and infections have been described. However, such studies on the active principle, namely, santalins, are not reported. In this study, we standardized the isolation of a mixture of santalins A and B from the heartwood of P. santalinus by column chromatography followed by preparative TLC and HPLC. The partially purified santalins were characterized by LC-MS, HR-MS, and ¹H NMR analyses. The isolated combination of santalins displayed higher total antioxidant and DPPH free radical scavenging activity in vitro than the crude heartwood extracts. Administration of the mixture of santalins A and B did not exhibit any antihyperglycemic activity in the liver, kidney, and pancreas of alloxan-induced diabetic rats. However, pretreatment of rats with a mixture of santalins at a dose of 1.0 mg/kg body weight prevented alloxan-induced diabetes as indicated by the normal blood glucose levels. Hyperglycemia-associated lipid peroxidation was abrogated in santalin-pretreated rats that did not develop alloxan-induced diabetes. Furthermore, the alterations in catalase, glutathione peroxidase, and glutathione-S-transferase activities in the pancreas of santalinpretreated rats could be responsible for preventing damage to the pancreas and thus non-induction of diabetes following alloxan treatment. Therefore, for the first time, we report the simplified procedure for isolating a mixture of santalins, including their ability to prevent the induction of diabetes in Wistar rats. The outcome of our study has significant clinical importance to the fact that supplementation of santalins may potentially avoid or delay the onset of diabetes in high-risk individuals.