Formononetin-Vitamin E Conjugate Synergistically Supports Adipogenesis, Attenuates Oxidative Stress, and Restores Insulin Sensitization in Differentiated Preadipocytes

In this study, a hybrid conjugate of formononetin (FMN) and vitamin E (VESylated-FMN) was synthesized through succinic acid linker and investigated for its synergistic effect in diabetes. The conjugate was characterized through Ultra Performance Liquid Chromatography - Mass Spectrometry (UPLC-MS), High-Resolution Mass Spectrometry (HRMS), Nuclear Magnetic Resonance (NMR), and Differential Scanning Calorimetry (DSC). The ability of VESylated-FMN to promote adipogenesis and ameliorate insulin resistance brought on by oxidative stress was evaluated in differentiated preadipocytes. Interestingly, VESylated-FMN promoted intracellular glucose absorption, which in turn increased lipid and triglyceride accumulation and thereby encouraged adipogenesis. VESylated-FMN attenuated oxidative stress and promoted cell survival by reducing reactive oxygen species (ROS) generation and reversing apoptosis. Additionally, VESylated-FMN improved insulin sensitization by upregulating the gene and protein expression of insulin-sensitizing markers. Overall, FMN in conjugation with vitamin E can effectively augment prior insulin sensitivity by reducing oxidative stress for efficient glycemic control in hyperglycemia. In this work, VESylated-FMN (a hybrid molecule formononetin and vitamin E) is synthesized to improve its therapeutic efficacy for diabetes. The synthesized conjugate encourages adipogenesis, maintains redox homeostasis, and also restores the insulin sensitivity in differentiated preadipocytes when compared to its native molecules. Considering this, VESylated-FMN possess an attribute to reduce insulin resistance and manages the hyperglycaemic conditions.+image