Anti-adipogenic Effects and Mechanisms of Ginsenoside Rg3 in Pre-adipocytes and Obese Mice

Abstract

Red or black ginseng has been reported more powerful than white/fresh ginseng in dealing with various diseases/conditions including obesity. The major reason is that heating/steaming, the process of making red or black ginseng, produces large amount of bioactive compounds including ginsenoside Rg3 (Rg3), which are trace in fresh or white ginseng. In the present study, Rg3 was applied both in pre-adipocytes and obese mice to investigate the anti-adipogenic effects and relevant mechanisms. Our results show that Rg3 dose-dependently inhibited cell differentiation both in 3T3-L1 cells (30, 50, and 100 μM) and human primary pre-adipocytes (10, 20, and 30 μM). This inhibitory effect is accompanied by the attenuation of the expressions of adipogenic markers including peroxisome proliferator-activated receptor gamma (PPAR-γ), CCAAT/enhancer binding protein alpha (C/EBP-α), fatty acid synthase (FAS), fatty acid binding protein 4 (FABP4) and perilipin. Although dietary intake of Rg3 (0.1 mg Rg3/kg diet, 8 weeks) did not significantly affect body weight gain, fat pads and food intake as well as of PPAR-γ expression in fat tissues, we found that hepatic PPAR-γ and C/EBP-α protein expressions and hepatic glutathione reductase and glutathione S-transferase, two major antioxidants molecules were significantly reduced by Rg3. These results suggest that ginsenoside Rg3 may be a potential agent in reducing/preventing obesity.

Ginsenoside Rg3 Induces Browning of 3T3-L1 Adipocytes by Activating AMPK Signaling

“…Previous studies regarding anti-obesity effects of Rg3 have suggested that Rg3 inhibits adipogenic differentiation through AMPK activation [12,16]. We also investigated whether Rg3 activates AMPK signaling in differentiated 3T3-L1 adipocytes and found that AMPK phosphorylation was increased dose-dependently following Rg3 treatment for 24 h ( Figure 3A).…”

“…However, processing to red ginseng and black ginseng significantly increases the Rg3 content in both American ginseng [26] and Asian ginseng [27]. Previous studies on Rg3 effects during 3T3-L1 differentiation have reported that Rg3 attenuates differentiation in 3T3-L1 cells by reducing PPAR-γ, C/EBP-α, FAS, and perilipin [12], or in regulating AMPK and PPAR-γ [16]. In this context, our results suggest the role of Rg3 in browning of mature adipocytes.…”

“…Firstly, we evaluated the browning effects of Rg3 on mature 3T3-L1 adipocytes. We differentiated 3T3-L1 cells into mature adipocytes using the adipogenic cocktails for 8 days and then treated the cells with different concentrations of Rg3 for 24 h. As Rg3 with a concentration of more than 100 µM is known to have cytotoxic effects on 3T3-L1 adipocytes [12], we treated the cells with 20 and 40 uM of Rg3. Using RT-qPCR analysis, we found that Rg3 treatment dose-dependently increased the mRNA levels of BAT-specific gene markers Ucp1 and Prdm16 ( Figure 1B).…”

“…Like other ginsenosides, Rg3 has been shown to have multiple therapeutic benefits in antagonizing Adriamycin-induced cardiotoxicity [13], mitigating anxiety in chronic stress [14], and alleviating diabetic complications [15]. Anti-adipogenic effects of Rg3 have also been demonstrated in some studies; however, the effects have been observed in differentiating adipocytes instead of in matured adipocytes [12,16,17].…”

Cooperated biotransformation of ginsenoside extracts into ginsenoside 20( S )‐Rg3 by three thermostable glycosidases

“…The PPD-type minor ginsenoside Rg3, a kind of saponin triterpene, shows significant anticancer properties against, for example lung cancer (Xie et al 2017;Wang et al 2019), colon cancer ), ovarian cancer (Xu et al 2007;Xu et al 2008;Zhao et al 2019) and prostate cancer (Kim et al 2010;Peng et al 2019). In addition, it has remarkable neuroprotection (Tian et al 2005;Tian et al 2009), liver protection (Lee et al 2005), antiobesity (Hwang et al 2009;Zhang et al 2017), antidiabetic (Sun and Zhou 2010;Niu et al 2012;Guo et al 2018) and vasodilatation (Kim and Nah 2005;Kim et al 2006;Jeong et al 2017) activities. Thus, ginsenoside Rg3 has a potential application in the field of medicine and food additive.…”