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Protopanaxatriol, a novel PPARγ antagonist from Panax ginseng, alleviates steatosis in mice.

Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C - Sci Rep (2014)

Bottom Line: Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis.TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study.Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.

ABSTRACT
Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis. Ginseng has been used as food and traditional herbal medicine for the treatment of various metabolic diseases. However, the molecular mechanisms how ginseng and its components participate in the regulation of lipogenesis are still largely unclear. Here, we identified that protopanaxatriol (PPT), a major ginseng constituent, inhibited rosiglitazone-supported adipocyte differentiation of 3T3-L1 cells by repressing the expression of lipogenesis-related gene expression. In high-fat diet-induced obesity (DIO) mice, PPT reduced body weight and serum lipid levels, improved insulin resistance, as well as morphology and lipid accumulation, particular macrovesicular steatosis, in the livers. These effects were confirmed with genetically obese ob/ob mice. A reporter gene assay showed that PPT specifically inhibited the transactivity of PPARγ, but not PPAR α, β/δ and LXR α, β. TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. Our data demonstrate that PPT is a novel PPARγ antagonist. The inhibition of PPARγ activity could be a promising therapy for obesity and steatosis. Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

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PPT ameliorates hepatic steatosis in ob/ob mice.(a) H&E and Oil red O staining of liver sections (×200). (b) Liver TG level. (c) Liver TC level. (d) Serum AST level. (e) Serum ALT level. (f) Liver LPO content. (g) Liver glutathione content. (h) Mitochondrial respiratory chain level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01vs. ob/ob mice.
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f5: PPT ameliorates hepatic steatosis in ob/ob mice.(a) H&E and Oil red O staining of liver sections (×200). (b) Liver TG level. (c) Liver TC level. (d) Serum AST level. (e) Serum ALT level. (f) Liver LPO content. (g) Liver glutathione content. (h) Mitochondrial respiratory chain level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01vs. ob/ob mice.

Mentions: Next, the liver morphology of the mice was examined by using H&E staining. As shown in Fig. 5a, severe macrovesicular steatosis was detected in the liver of the control ob/ob mice, and all of them exhibited grade 3 steatosis. Fat was observed as macrovesicular droplets in 80% to 90% of hepatocytes. After PPT treatment, macrovesicular droplets were notably attenuated to 40%–50% of hepatocytes, though only 3 mice were improved to grade 2 steatosis. Oil Red O staining was also performed with the liver sections. Consistently, lipid accumulation was observed in the liver sections of the control ob/ob mice, whereas PPT ameliorated the lipid accumulation (Fig. 5a). Liver chemistry analysis showed that TG and TC contents in the control ob/ob mice were increased, and PPT treatment reduced TG and TC contents (Fig. 5b and 5c). Consistent with the observations in the DIO mouse model, PPT treatment reduced the levels of AST and ALT, compared with the control ob/ob mice (Fig. 5d and 5e). PPT did not change the hepatic lipid peroxide and glutathione levels (Fig. 5f and 5g), whereas PPT increased MRC complex II level in the liver of ob/ob mice. (Fig. 5h).


Protopanaxatriol, a novel PPARγ antagonist from Panax ginseng, alleviates steatosis in mice.

Zhang Y, Yu L, Cai W, Fan S, Feng L, Ji G, Huang C - Sci Rep (2014)

PPT ameliorates hepatic steatosis in ob/ob mice.(a) H&E and Oil red O staining of liver sections (×200). (b) Liver TG level. (c) Liver TC level. (d) Serum AST level. (e) Serum ALT level. (f) Liver LPO content. (g) Liver glutathione content. (h) Mitochondrial respiratory chain level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01vs. ob/ob mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4260220&req=5

f5: PPT ameliorates hepatic steatosis in ob/ob mice.(a) H&E and Oil red O staining of liver sections (×200). (b) Liver TG level. (c) Liver TC level. (d) Serum AST level. (e) Serum ALT level. (f) Liver LPO content. (g) Liver glutathione content. (h) Mitochondrial respiratory chain level. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01vs. ob/ob mice.
Mentions: Next, the liver morphology of the mice was examined by using H&E staining. As shown in Fig. 5a, severe macrovesicular steatosis was detected in the liver of the control ob/ob mice, and all of them exhibited grade 3 steatosis. Fat was observed as macrovesicular droplets in 80% to 90% of hepatocytes. After PPT treatment, macrovesicular droplets were notably attenuated to 40%–50% of hepatocytes, though only 3 mice were improved to grade 2 steatosis. Oil Red O staining was also performed with the liver sections. Consistently, lipid accumulation was observed in the liver sections of the control ob/ob mice, whereas PPT ameliorated the lipid accumulation (Fig. 5a). Liver chemistry analysis showed that TG and TC contents in the control ob/ob mice were increased, and PPT treatment reduced TG and TC contents (Fig. 5b and 5c). Consistent with the observations in the DIO mouse model, PPT treatment reduced the levels of AST and ALT, compared with the control ob/ob mice (Fig. 5d and 5e). PPT did not change the hepatic lipid peroxide and glutathione levels (Fig. 5f and 5g), whereas PPT increased MRC complex II level in the liver of ob/ob mice. (Fig. 5h).

Bottom Line: Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis.TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study.Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai 201203, China.

ABSTRACT
Obesity is prevalent worldwide, and is highly associated with metabolic disorders, such as insulin resistance, hyperlipidemia and steatosis. Ginseng has been used as food and traditional herbal medicine for the treatment of various metabolic diseases. However, the molecular mechanisms how ginseng and its components participate in the regulation of lipogenesis are still largely unclear. Here, we identified that protopanaxatriol (PPT), a major ginseng constituent, inhibited rosiglitazone-supported adipocyte differentiation of 3T3-L1 cells by repressing the expression of lipogenesis-related gene expression. In high-fat diet-induced obesity (DIO) mice, PPT reduced body weight and serum lipid levels, improved insulin resistance, as well as morphology and lipid accumulation, particular macrovesicular steatosis, in the livers. These effects were confirmed with genetically obese ob/ob mice. A reporter gene assay showed that PPT specifically inhibited the transactivity of PPARγ, but not PPAR α, β/δ and LXR α, β. TR-FRET assay revealed that PPT was specifically bound to PPARγ LBD, which was further confirmed by the molecular docking study. Our data demonstrate that PPT is a novel PPARγ antagonist. The inhibition of PPARγ activity could be a promising therapy for obesity and steatosis. Our findings shed new light on the mechanism of ginseng in the treatment of metabolic syndrome.

Show MeSH
Related in: MedlinePlus