Limits...
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.

Show MeSH

Related in: MedlinePlus

PPT ameliorates metabolic disorders in ob/ob mice.(a) Body weight gain. (b) Food intake amount. (c) Fasting glucose level. (d) Glucose tolerance test (GTT) in ob/ob mice. (e) Serum TC, TG, LDL-c, and HDL-c levels. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. ob/ob mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4260220&req=5

f4: PPT ameliorates metabolic disorders in ob/ob mice.(a) Body weight gain. (b) Food intake amount. (c) Fasting glucose level. (d) Glucose tolerance test (GTT) in ob/ob mice. (e) Serum TC, TG, LDL-c, and HDL-c levels. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. ob/ob mice.

Mentions: To further confirm the effects of PPT on metabolic disorders, the ob/ob mouse, which is a model for obesity, insulin resistance, hyperlipidemia and steatosis, was fed with PPT. After treatment with PPT for two weeks, the body weight and food intake of ob/ob mice were not altered (Fig. 4a and 4b). However, the fasting blood glucose levels (Fig. 4c) were lower in the PPT-treated group compared to that in control ob/ob mice. The glucose tolerance test showed that the blood glucose levels of the PPT-treated mice were decreased at 60 and 90 min, compared with that of control ob/ob mice (Fig. 4d). PPT treatment also significantly attenuated serum TG levels, while serum TC, LDL-c and HDL-c levels remained unchanged (Fig. 4e).


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 metabolic disorders in ob/ob mice.(a) Body weight gain. (b) Food intake amount. (c) Fasting glucose level. (d) Glucose tolerance test (GTT) in ob/ob mice. (e) Serum TC, TG, LDL-c, and HDL-c levels. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. ob/ob mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f4: PPT ameliorates metabolic disorders in ob/ob mice.(a) Body weight gain. (b) Food intake amount. (c) Fasting glucose level. (d) Glucose tolerance test (GTT) in ob/ob mice. (e) Serum TC, TG, LDL-c, and HDL-c levels. Data are presented as means ± SEM (n = 8). *P<0.05, **P<0.01 vs. ob/ob mice.
Mentions: To further confirm the effects of PPT on metabolic disorders, the ob/ob mouse, which is a model for obesity, insulin resistance, hyperlipidemia and steatosis, was fed with PPT. After treatment with PPT for two weeks, the body weight and food intake of ob/ob mice were not altered (Fig. 4a and 4b). However, the fasting blood glucose levels (Fig. 4c) were lower in the PPT-treated group compared to that in control ob/ob mice. The glucose tolerance test showed that the blood glucose levels of the PPT-treated mice were decreased at 60 and 90 min, compared with that of control ob/ob mice (Fig. 4d). PPT treatment also significantly attenuated serum TG levels, while serum TC, LDL-c and HDL-c levels remained unchanged (Fig. 4e).

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