Borapetoside E, a Clerodane Diterpenoid Extracted from<i>Tinospora crispa</i>, Improves Hyperglycemia and Hyperlipidemia in High-Fat-Diet-Induced Type 2 Diabetes Mice

Abstract

An insidious increase in the incidence of obesity, insulin resistance, and hyperlipidemia has led to an epidemic of type 2 diabetes worldwide. Tinospora crispa (T. crispa) is a familiar plant traditionally used in herbal medicine for diabetes; however, the major active ingredients of this plant are still unclear. In this study, we identified the therapeutic effects of borapetoside E, a small molecule extracted from T. crispa, in high-fat-diet (HFD)-induced obesity in mice. The therapeutic effects of borapetoside E in HFD-induced obese mice were assessed physiologically, histologically, and biochemically following intraperitoneal injection. Furthermore, we analyzed the expression of glucose and lipid metabolism-related genes and proteins in borapetoside E-treated obese mice. Compared with vehicle-treated mice, borapetoside E markedly improved hyperglycemia, insulin resistance, hepatic steatosis, hyperlipidemia, and oxygen consumption in obese mice, and the effects were comparable to or better than the drug metformin. In addition, borapetoside E suppressed the expression of sterol regulatory element binding proteins (SREBPs) and their downstream target genes related to lipid synthesis in the liver and adipose tissue. Borapetoside E showed beneficial effects in vivo, demonstrating that borapetoside E may be a potential therapy for the treatment of diet-induced type 2 diabetes and related metabolic syndromes.