Antidiabetic action of Cleome droserifolia through direct interaction with pancreatic islet beta cell FABP3

Cleome droserifolia (Forssk.) Delile (Cleomaceae) is traditionally used in Egypt and other countries to manage a variety of diseases, including diabetes. Its antihyperglycemic effect is unconvincingly linked to its general antioxidant and anti-inflammatory effect. More specific antidiabetic mechanisms remain unexplored. In this context, fatty acid binding protein 3 (FABP3) is expressed by pancreatic islet beta cells; suppression of this protein has been shown to shield beta cells from lipotoxicity. This work investigates the possible relation of C. droserifolia bioactive components to FABP3 and its direct effects on pancreatic islets of a type 2 diabetes animal model. Here, fractionated constituents of C. droserifolia were evaluated for their possible binding to FABP3 by in silico molecular docking. Four-week-old rats were fed a high-fat/high-fructose diet (HFHFD) mixed with aqueous or ethanolic extract of C. droserifolia for 16 weeks to investigate the effect on the glycemic and lipidemic states during the development of the diabetic model. Cleome droserifolia inhibited the progression of HFHFD-induced obesity, hyperglycemia, hyperinsulinemia, impaired glucose tolerance test, insulin resistance, and dyslipidemia. Molecular docking results showed that many compounds of C. droserifolia , such as cleomaldeic acid, cleomeolide, luteolin, kaempferol, amblyone, and brachycarpone, can strongly bind onto FABP3 and occupy its binding pocket. In beta cells of rats, which concurrently fed HFHFD and C. droserifolia , fewer lipid droplets, immune cell infiltration, inflammatory, and apoptotic responses were observed. Components of C. droserifolia competitively inhibit the binding of FABP3 with native fatty ligands, limiting lipid-induced deterioration of beta cells. The antidiabetic action of C. droserifolia can be attributed to this direct beneficial effect on pancreatic islet beta cells. Not applicable.