Nodakenin represses obesity and its complications via the inhibition of the VLDLR signalling pathway in vivo and in vitro

Abstract

Objectives Nodakenin (NK) is a coumarin glucoside that is found in the roots of Angelicae gigas. A limited number of studies have been conducted on the pharmacological activities of NK. Although NK is an important natural resource having anti-inflammatory and antioxidant effects, no investigation has been conducted to examine the effects of NK on obesity and obesity-induced inflammation. Materials and Methods The present study investigated the therapeutic effects of NK treatment on obesity and its complications, and its mechanism of action using differentiated 3T3-L1 adipocytes and high-fat diet (HFD)-induced obese mice. Oil red O staining, western blot assay, qRT-PCR assay, siRNA transfection, enzyme-linked immunosorbent assay, H&E staining, immunohistochemistry, molecular docking and immunofluorescence staining were utilized. Results Treatment with NK demonstrated anti-adipogenesis effects via the regulation of adipogenic transcription factors and genes associated with triglyceride synthesis in differentiated 3T3-L1 adipocytes. Compared with the control group, the group administered NK showed a suppression in weight gain, dyslipidaemia and the development of fatty liver in HFD-induced obese mice. In addition, NK administration inhibited adipogenic differentiation and obesity-induced inflammation and oxidative stress via the suppression of the VLDLR and MEK/ERK1/2 pathways. This is the first study that has documented the interaction between NK and VLDLR structure. Conclusion These results demonstrate the potential of NK as a natural product-based therapeutic candidate for the treatment of obesity and its complications by targeting adipogenesis and adipose tissue inflammation-associated markers.