Attenuation of lipid synthesis and improved insulin sensitivity by a bifunctional molecule from costus speciosus and understanding its mechanism of action

Abstract

Metabolic syndrome is a collection of conditions of obesity, hyperglycemia, high blood pressure, high serum triglycerides and a lower high-density lipoprotein. Metabolic syndrome is linked with an increased risk of developing type 2 diabetes, cardio vascular disease and nonalcoholic fatty liver disease. The currently available oral anti-diabetic drugs such as Metformin, Pioglitazone and few insulin secretagogues exhibit severe side effects such as lactic acidosis, edema, body weight gain, cardiovascular risk, bone fracture and even hypoglycemia due to prolonged use. With the existing number of therapeutic drugs for metabolic syndrome being limited, search for bioactive components from botanical sources are of immediate interest due to their potential in simplifying the drug development. Drugs of botanical origin are less toxic with fewer side effects compared to synthetic origin. In this paradigm, many of the antidiabetic strategies have focused on either sensitizing the Insulin signaling (Metformin) or activating PPARand#534; (rosiglitazone) to regain the loss in glucose uptake and adipogenesis. Recently, selective modulators of PPARand#534; have been identified from synthetic and natural products which reduced transactivation of PPARand#534; or exhibited partial PPARand#534; agonism without side effects, which could serve as novel therapeutics for T2DM and related disorders. The present study was carried out with the rhizome of Costus speciosus Linn, which belongs to family Zingiberaceae. Differentiated 3T3-L1 cells treated with Costus speciosus ethanolic water extract (CSEW) showed a dose dependent increase in glucose uptake with 50% increase at 1 µg/mL concentration compared to untreated cells without any cytotoxicity. Investigation of the antiadipogenic activity of CSEW using Nile red assa revealed a 50% decrease in lipid accumulation at 1 µg/mL treatment compared to control. Considering the anti-diabetic and antiadipogenic potential of the extract, the fractionation for the bifunctional molecule from CSEW was carried out.