Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST—Decreasing HMG‐CoA Reductase Expression Via AMP‐Activated Protein Kinase

Han, Joon-Seung; Sung, Jong Hwan; Lee, Seung Kwon

doi:10.1111/1750-3841.13828

Cited by 17 publications

(10 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…AMPK is a key molecule involved in the regulation of biological metabolism, and it has been reported to be associated with diabetes and other metabolic diseases. Accumulating evidence has shown that statins can activate the AMPK pathway (25,26). Therefore, the present study aimed to determine whether Ato exerts its protective roles by regulating AMPK (Fig.…”

Section: Ato Inhibits Lipid Accumulation Via the Ampk-dependent Upregmentioning

confidence: 99%

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

Zhang

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is characterized by diffuse fatty acid degeneration and excess fat accumulation in the liver. Notably, the currently available medications used to treat NAFLD remain limited. The aim of the present study was to investigate the protective role of atorvastatin (Ato) against NAFLD in golden hamsters fed a high fat diet (HFD) and in HepG2 cells treated with palmitate, and identify the underlying molecular mechanism. Ato (3 mg/kg) was administered orally every day for 8 weeks to the hamsters during HFD administration. Hamsters in the model group developed hepatic steatosis with high serum levels of triglyceride, cholesterol, insulin and C-reactive protein, which were effectively reduced by treatment with Ato. Additionally, the relative liver weight of hamsters treated with Ato was markedly lower compared with that of the model group. Hematoxylin and eosin, and oil red O staining indicated that the livers of the animals in the model group exhibited large and numerous lipid droplets, which were markedly decreased after Ato treatment. Western blot analysis indicated that Ato inhibited fat accumulation in the liver through the AMP-activated protein kinase (AMPK)-dependent activation of peroxisome proliferator activated receptor α (PPARα), peroxisome proliferator-activated receptor-γ coactivator 1 α and their target genes. Furthermore, in vitro, Ato inhibited PA-induced lipid accumulation in HepG2 cells. This inhibitory effect was attenuated following Compound C treatment, indicating that AMPK may be a potential target of Ato. In conclusion, the increase in AMPK-mediated PPARα and its target genes may represent a novel molecular mechanism by which Ato prevents NAFLD.

show abstract

Section: Ato Inhibits Lipid Accumulation Via the Ampk-dependent Upregmentioning

confidence: 99%

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

Zhang

et al. 2020

Exp Ther Med

View full text Add to dashboard Cite

show abstract

“…AMPK stimulation leads to the inhibition of HMGCR [34], which is the major regulators of the mevalonate pathway. Mevalonate metabolism are required for RHO function, which in turn is required for YAP activity [16,35,36].…”

Section: Discussionmentioning

confidence: 99%

YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine

et al. 2019

View full text Add to dashboard Cite

Nuciferine, a major aporphine alkaloid constituent of lotus leaves, is a raw material for obesity treatment. Extensive studies have revealed that obesity is associated with pancreatic cancer (PC). However, it has not been clarified whether nuciferine could be used in PC treatment or prevention. Here, we show that nuciferine could enhance the sensitivity of PC cells to gemcitabine in both cultured cells and the xenograft mouse model. The mechanism study demonstrated that nuciferine induced YAP Ser127 phosphorylation [pYAP(Ser127)] through AMPK-mediated 3-hydroxy-3-methyl-glutaryl-coA reductase (HMGCR) downregulation. Remarkably, wild-type YAP overexpression or YAP Ser127 mutant could resist to nuciferine and no longer sensitize PC cells to gemcitabine. Knockdown of AMPK attenuated pYAP(Ser127) induced by nuciferine. Moreover, knockdown of AMPK reversed nuciferine-mediated HMGCR downregulation. Notably, HMGCR inhibiting could restrain YAP by phosphorylation Ser 127, and therefore enhance the efficiency of gemcitabine in PC cells. In line with this consistent, overexpression of HMGCR reduced growth inhibition caused by nuciferine and/or gemcitabine treatment in PC cells. In summary, these results provide an effective supplementary agent and suggest a therapeutic strategy to reduce gemcitabine resistance in PC.

show abstract

“…A phenol-enriched extract of Moringa oleifera leaf significantly increased the expression of both HMGCR and LDL-R in HepG2 cells [ 29 ]. GINST, a hydrolysed ginseng extract, also decreased the expression of HMGCR via AMPKα activation in HepG2 cells [ 30 ]. In addition, hydrolic extract of lemongrass [ Cymbopogon citratus (DC) Stapf.]…”

Section: Discussionmentioning

confidence: 99%

Regulatory effect of Phikud Navakot extract on HMG-CoA reductase and LDL-R: potential and alternate agents for lowering blood cholesterol

Tirawanchai

Supapornhemin

Somkasetrin

et al. 2018

BMC Complement Altern Med

View full text Add to dashboard Cite

BackgroundFor decades, various cardiovascular symptoms have been relieved by the use of Ya-Hom Navakot, which is a formulation comprising 54 herbal medicines. The Thailand Ministry of Public Health listed Ya-Hom Navakot’s nine active principle and nomenclative herbal ingredients and termed them ‘Phikud Navakot’ (PN). Several reports have confirmed that PN has cardiovascular benefits similar to Ya-Hom Navakot. However, whether PN facilitates lipid-lowering activity remains unclear.MethodsThe present study investigated an in vitro model for examining the gene expression levels of 3-hydroxyl-3-methylglutaryl-CoA reductase (HMGCR) and low-density lipoprotein receptor (LDL-R) in HepG2 cells using qRT-PCR. The ethanol and water extractions of Ya-Hom Navakot, PN and Ya-Hom Navakot without PN were compared.ResultsOne mg/ml of both NYEF and NYWF were found to significantly lower cholesterol by either the up-regulation of LDL-R or down-regulation of HMGCR compared with negative controls and 1 mg/ml simvastatin (p < 0.05). PNEF also up-regulated LDL-R gene expression, even more than NYEF (p < 0.05). In addition, the ethanol and water extracts of PN significantly down-regulated HMGCR gene expression compared with those of Ya-Hom Navakot without PN (p < 0.05).ConclusionThe use of Ya-Hom Navakot or PN may provide an alternative treatment to lower cholesterol through HMGCR gene inhibition and LDL-R gene enhancement.

show abstract

Inhibition of Cholesterol Synthesis in HepG2 Cells by GINST—Decreasing HMG‐CoA Reductase Expression Via AMP‐Activated Protein Kinase

Cited by 17 publications

References 23 publications

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

Atorvastatin promotes AMPK signaling to protect against high fat diet‑induced non‑alcoholic fatty liver in golden hamsters

YAP Inhibition by Nuciferine via AMPK-Mediated Downregulation of HMGCR Sensitizes Pancreatic Cancer Cells to Gemcitabine

Regulatory effect of Phikud Navakot extract on HMG-CoA reductase and LDL-R: potential and alternate agents for lowering blood cholesterol

Contact Info

Product

Resources

About