Abstract

Cirsium brevicaule A. GRAY is a wild perennial herb, and its roots (CbR) have traditionally been used as both food and medicine on the Japanese islands of Okinawa and Amami. The present study evaluated the antiadipogenic effect of CbR using mouse embryonic fibroblast cell line 3T3-L1 from JCRB cell bank. Dried CbR powder was serially extracted with solvents of various polarities, and these crude extracts were tested for antiadipogenic activity. Treatment with the methanol extract of CbR showed a significant suppression of lipid accumulation in 3T3-L1 cells. Methanol extract of CbR was then fractionated and subjected to further activity analyses. The phenylpropanoid glycosidic molecule syringin was identified as an active compound. Syringin dose dependently suppressed lipid accumulation of 3T3-L1 cells without cytotoxicity, and significantly reduced the expressions of peroxisome proliferator-activated receptor gamma, the master regulator of adipogenesis, and other differentiation markers. It was demonstrated that syringin effectively enhanced the phosphorylation of the AMP-activated protein kinase and acetyl-CoA carboxylase. These results indicate that syringin attenuates adipocyte differentiation, adipogenesis, and promotes lipid metabolism; thus, syringin may potentially serve as a therapeutic candidate for treatment of obesity.

Highlights

  • Obesity is a complex, chronic disease, with its adverse consequences reaching pandemic levels in recent times

  • Differentiation of preadipocytes involves the expression of genes and transcription factors, including CCAAT-enhancer-binding protein (C/EBP) α and peroxisome proliferator-activated receptor (PPAR) γ, which are responsible for the expression of adipogenesis-related genes [5]; during the late stages of differentiation, a momentous increase in lipogenic and lipogenesis-related genes is observed [6]

  • Fr-1 and Fr-2 were profiled by HPLC (Supplementary Figure S1) and Fr-1 was used for the further fractionation on the basis of low polarity

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Summary

Introduction

Chronic disease, with its adverse consequences reaching pandemic levels in recent times. More than 1.9 billion adults worldwide are overweight with over 650 million of them being obese. A significant increase in obese children under the age of five years reached 38 million in 2019 [1]. Obesity represents a major health challenge because it substantially increases risk of noncommunicable diseases, including cardiovascular diseases, cancer, and diabetes mellitus, which account for > 70% of early deaths worldwide, representing the leading cause of mortality and premature disability [2,3]. Obesity can be developed as a result of an increase in the number of adipocytes due to division and differentiation of preadipocytes, or storage of excess energy in the form of glycerol and fatty acids [4]. Inhibition of adipocyte differentiation from preadipocytes and the release of glycerol following the breakdown of triglycerides present in lipids are important for the prevention and management of obesity

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