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.
Saponins of Panax notoginseng (Burk.) F.H. Chen have been classified as a type of composition in functional foods for numerous diseases. However, its mild effects and other characteristics limited clinical applications in diseases. Inspired by "nine steaming and nine processing" of P. notoginseng in traditional Chinese medicine, we developed a "steaming"-mimic protocol, which significantly changed the composition of saponins of P. notoginseng from the original, R1, Rg1, Re, Rb1, and Rd (raw-PNS), to the products after steaming, 20S/R-Rh1, Rk3, Rh4, 20S/R-Rg3, Rk1, and Rg5 (N-PNS). Surprisingly, N-PNS demonstrated promising activities in improving hyperlipidemia and reducing body weight and weight of white adipose tissue and the inhibition of adipogenesis in obese mice. In accordance with the results in vivo, N-PNS remarkably blunted adipogenesis at the early stage of differentiation dose-dependently in vitro. Moreover, we demonstrated that the activity may involve the adenosine monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway by promoting phosphorylation of AMPK T172 and downregulating its downstream factors: sterol regulatory element binding protein 1c, stearoyl-CoA desaturase 1, and fatty acid synthase. Taken together, the steaming-induced eight compositions of saponins showed a very promising function in improving hyperlipidemia and obesity both in vivo and in vitro, providing fundamental evidence for future study and application in treatment of hyperlipidemia, obesity, and other lipid-related metabolic syndromes.
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