Effects of Ginsenoside Rg3 on Inhibiting Differentiation, Adipogenesis, and ER Stress-Mediated Cell Death in Brown Adipocytes

Abstract

Objectives. Ginsenoside Rg3 (Rg3), a main active component of Panax ginseng, has various therapeutic properties in literatures, and it has been studied for its potential use in obesity control due to its antiadipogenic effects in white adipocytes. However, little is known about its effects on brown adipocytes. Methods. The mechanisms through which Rg3 inhibits differentiation, adipogenesis, and ER stress-mediated cell death in mouse primary brown adipocytes (MPBAs) are explored. Results. Rg3 significantly induced cytotoxicity in differentiated MPBAs but not in undifferentiated MPBAs. Rg3 treatment downregulated the expression of differentiation and adipogenesis markers and the level of perilipin in MPBAs while upregulating the expression of lipolytic Kruppel-like factor genes. Rg3 also induced lipolysis and efflux of triglycerides from MPBAs and subsequently increased proinflammatory cytokine levels. Notably, Rg3 treatment resulted in elevation of ER stress and proapoptotic markers in MPBAs. Conclusions. Our results demonstrate that Rg3 is able to selectively exert cytotoxicity in differentiated MPBAs while leaving undifferentiated MPBAs intact, resulting in the induction of ER stress and subsequent cell death in MPBAs via regulation of various genes related to adipocyte differentiation, adipogenesis, lipolysis, and inflammation. These results indicate that further studies on the potential therapeutic applications of Rg3 are warranted.

Ginsenoside Rg3, enriched in red ginseng extract, improves lipopolysaccharides-induced suppression of brown and beige adipose thermogenesis with mitochondrial activation

“…Rg3 significantly reverses the inflammation-induced inhibition of BAT and/or beige fat thermogenesis both in in vitro and in vivo models induced by cAMP or CL via mitochondrial activation. While there is considerable research on RGE and/or ginsenoside Rg3 in metabolic disorders 26 , 50 – 52 , our study introduces novelty by specifically examining Rg3's impact on brown adipose tissue (BAT) and beige adipocytes during inflammation. Furthermore, we employed the STRING database for the visualization of the protein–protein interaction network under Rg3 treatment, as depicted in Fig.…”

Combination of Panax ginseng and Diospyros kaki Leaf Inhibits White Adipocyte Differentiation and Browning Process through AMP-Activated Protein Kinase (AMPK) Activation In Vitro and In Vivo

“…The efficacy of PG against obesity has been extensively studied and reported [ 23 ]. Previously, ginsenosides like Rb1, Rg1, and Rg3 were reported in PG, which inhibited adipogenesis by downregulating several adipogenic factors, including leptin and aP2, and transcription factors like C/EBPα, PPARγ, SREBP-1c, and Glut4 and by modulating the histone deacetylase sirtuin 1 [ 24 , 25 , 26 ]. Similarly, the present study was designed to evaluate the impact of PG.…”

Panax notoginseng extract and total saponin suppress diet-induced obesity and endoplasmic reticulum stress in epididymal white adipose tissue in mice

“…Ginsenoside Re exhibits anti-inflammatory role through inhibition of p38/JNK activation in 3T3-L1 cell, as well as relieving the insulin resistance [ 46 ]. Ginsenoside Rg3 inhibits ER stress-mediated adipocyte death [ 47 ]. In other cell type like cardiomyocytes, PNS [ 48 ] and notoginsenoside R1 [ 49 ] protect against ER stress-related signaling pathways.…”