Investigating the effects of different ratios of Citrus limon, Citrus sinensis, and Vitis vinifera extracts on insulin resistance in HepG2 cells

This study aimed to investigate the molecular mechanisms by which Lemotrin™, a nutraceutical formulation based on Citrus limon (L.) Osbeck, Citrus sinensis (L.) Osbeck, and Vitis vinifera L. extracts, improves insulin resistance in an in vitro model of insulin-resistant human liver cells (HepG2/IR). Three different blends of these plant extracts (Mix1, Mix2 and Mix3) were tested to evaluate their efficacy. The cellular cytotoxicity of each formulation was first assessed. The hypoglycemic effect of each blend was analyzed by measuring glucose uptake, intracellular glycogen content, and the modulation of IRS1 and pro-inflammatory cytokines expression. Mix 1 and Mix 2 of Lemotrin™ significantly increased glucose uptake and intracellular glycogen content, enhanced IRS1 expression and reduced its inhibitory phosphorylated form at Serine 307. TNF-α and IL6 were reduced following treatment with Lemotrin™. Our findings suggest that Lemotrin™ is a promising nutraceutical candidate for the prevention and management of insulin resistance-related conditions. • Lemotrin™ improves insulin resistance in liver cells in vitro. • Cytotoxicity, glucose uptake, glycogen content, IRS1, and cytokines were analyzed. • Mix 1 and Mix 2 of Lemotrin™ are the most effective. • Lemotrin™ could be a nutraceutical for managing insulin resistance-related issues.