Paeoniflorin suppresses lipid accumulation and alleviates insulin resistance by regulating the Rho kinase/IRS-1 pathway in palmitate-induced HepG2Cells

Ma, Zhihong; Liu, Hongying; Wang, Weijie; Guan, Shengjiang; Yi, Jianfeng; Chu, Li

doi:10.1016/j.biopha.2017.03.087

Cited by 23 publications

(20 citation statements)

References 33 publications

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“…Increased glycogen storage could be attributed to the upregulated phosphorylation level of AKT (Ser 473) induced by paeoniflorin, which further verified the improvement of insulin signaling. These results are consistent with previous reports [ 10 , 36 ]. It is noticeable that the activation of AMPK will inhibit glycogenesis, whereas AKT promotes it.…”

Section: Discussionsupporting

confidence: 94%

“…Paeoniflorin ( Figure 1 ), a monoterpene glucoside component of Paeonia lactiflora Pall., possesses a variety of pharmacological activities, including antioxidant, hepatoprotection, hypolipidemic, and hypoglycemic properties. Recent studies reported that paeoniflorin can ameliorate high-fat diet–induced steatohepatitis by enhancing insulin signaling, promoting fatty acid oxidation, and inhibiting lipids synthesis in liver [ 9 , 10 , 11 ]. However, it still remains unclear whether paeoniflorin could improve fructose induced insulin resistance and hepatic steatosis.…”

Section: Introductionmentioning

confidence: 99%

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Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Qiao

Wang

et al. 2018

Nutrients

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The present study aimed to evaluate the effects of paeoniflorin on insulin resistance and hepatic steatosis induced by fructose. Male Sprague-Dawley rats were fed 20% fructose drink for eight weeks. The insulin sensitivity, serum lipid profiles, and hepatic lipids contents were measured. The results showed that paeoniflorin significantly decreased serum insulin and glucagon levels, improved insulin sensitivity and serum lipids profiles, and alleviated hepatic steatosis in fructose-fed rats. Moreover, paeoniflorin enhanced the phosphorylation level of AMP-activated protein kinase (AMPK) and protein kinase B (PKB/AKT) and inhibited the phosphorylation of acetyl coenzyme A carboxylase (ACC)1 in liver. Paeoniflorin also increased the hepatic carnitine palmitoyltransferase (CPT)-1 mRNA and protein expression and decreased the mRNA expression of sterol regulatory element-binding protein (SREBP)1c, stearyl coenzyme A decarboxylase (SCD)-1 and fatty acid synthetase (FAS). Furthermore, we found that paeoniflorin significantly increased the heptatic protein expression of tumor suppressor serine/threonine kinase (LKB)1 but not Ca2+/CaM-dependent protein kinase kinase (CaMKK)β. These results suggest that the protective effects of paeoniflorin might be involved in the activation of LKB1/AMPK and insulin signaling, which resulted in the inhibition of lipogenesis, as well as the activation of β-oxidation and glycogenesis, thus ameliorated the insulin resistance and hepatic steatosis. The present study may provide evidence for the beneficial effects of paeoniflorin in the treatment of insulin resistance and non-alcoholic fatty liver.

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Section: Discussionsupporting

confidence: 94%

Section: Introductionmentioning

confidence: 99%

Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Qiao

Wang

et al. 2018

Nutrients

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“… 34 Paeoniflorin inhibited de novo lipid synthesis and prevented lipid accumulation in palmitate-induced HepG2 cells. 35 Elevated PPAR-gamma and glucose transporter 4 proteins contributed to the positive effects of glycyrrhizin on several metabolic diseases, including dyslipidemia, insulin resistance and hyperglycemia. 36 Based on these reports, we suggest that the mechanism of action of the three GSS formulae on lipid accumulation might be related to enhanced fatty acid oxidation or inhibited expression of lipid synthesis related genes, such as sterol response element binding proteins, fatty acid synthase and HMGCR.…”

Section: Discussionmentioning

confidence: 99%

Effects of three different formulae of Gamisoyosan on lipid accumulation induced by oleic acid in HepG2 cells

Ryuk

Hwang

et al. 2017

Integrative Medicine Research

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BackgroundGamisoyosan (GSS) is an herbal formula which has been used to treat women’s diseases for several hundred years in Korea. GSS is one of the three most common prescriptions among women and is used to treat menopausal symptoms. Fatty liver disease is also common in postmenopausal women and can precede more severe diseases, such as steatohepatitis. The present study compared the effects of GSS on fatty liver using three different formulae, Dongui-Bogam (KIOM A), Korean Pharmacopeia (KIOM B) and Korean National Health Insurance (KIOM C).MethodsIn oleic acid-induced HepG2 fatty liver cells, cellular lipid accumulation, triglycerides and total cholesterol were measured after treatment with three GSS formulae and simvastatin as a positive control. To investigate the phytoestrogen activity of GSS, MCF-7 cells were treated with GSS, and hormone levels were quantified. Also, qualitative analysis was performed with UPLC.ResultsAll types of GSS decreased cellular lipid accumulation. KIOM A was slightly less effective than the other two GSS formulae. KIOM B and KIOM C decreased cellular triglycerides more effective than simvastatin, but KIOM A did not affect cellular triglycerides. Cellular total cholesterol was decreased by all GSS and simvastatin. GSS showed phytoestrogen activity in MCF-7 cells. From the UPLC analysis data, geniposide, paeoniflorin and glycyrrhizin were detected form three GSS formulae.ConclusionThese results suggest that all GSS formulae have a beneficial effect on fatty liver disease during menopause and that differences of formula have no effect on the efficacy of the prescription.

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“…Treatment of PA inhibits the glycogen synthesis and activates the gluconeogenesis in HepG2 cells (Ishii et al, 2015;Ma et al, 2017). In this study, we also determined the intracellular glycogen contents and glucose production of HepG2 cells.…”

Section: Effect Of Wee On the Glucose Production The Intracellular Gmentioning

confidence: 96%

“…Penicillin/streptomycin antibiotics (1%) and heat-inactivated FBS (10%) were added into the DMEM medium. To induce IR, 0.3 mM PA (sodium salt of PA, Sigma, Malaysia) was added to HepG2 cells with fatty acid free BSA as supplement in a final concentration of 1% in the culture medium as previously described (Ma et al, 2017). After reaching 70-80% confluence, the cells were washed with PBS twice and incubated with normal glucose (5.5 mM) or high glucose (30 mM) plus PA (0.3 mM) in the absence or presence of WEE or Metformin with various concentrations for 24 h. Cells treated with normal glucose (5.5 mM) were used as the negative control and cells treated with metformin were used as the positive control.…”

Section: Cell Culture and Pa Treatmentmentioning

confidence: 99%

Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes

et al. 2020

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The flower of Edgeworthia gardneri (Wall.) Meisn is commonly used in beverage products in Tibet and has potential health benefits for diabetes. However, the mechanisms underlying anti-insulin resistance (IR) action of the flower of E. gardneri are not fully understood. This study aims to investigate the effects of the water extract of the flower of E. gardneri (WEE) on IR in palmitate (PA)-exposed HepG2 hepatocytes. WEE was characterized by UPLC analysis. PA-treated HepG2 cells were selected as the IR cell model. The cell viability was determined using MTT assay. Moreover, the glucose consumption and production were measured by glucose oxidase method. The glucose uptake and glycogen content were determined by the 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]-D-glucose) glucose uptake assay and anthrone-sulfuric acid assay, respectively. The intracellular triglyceride content was detected by oxidative enzymic method. Protein levels were examined by Western blotting. Nuclear localization of FoxO1 was detected using immunofluorescence analyses and Western blotting. The expression of FoxO1 target genes was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The viability of PA-treated HepG2 cells was concentrationdependently increased by incubation with WEE for 24 h. WEE treatment remarkably increased the consumption and uptake of glucose in PA-exposed HepG2 cells. Moreover, treatment with WEE significantly decreased the PA-induced overproduction of glucose in HepG2 cells. After exposure of HepG2 cells with PA and WEE, the glycogen content was significantly elevated. The phosphorylation and total levels of IRb, IRS1, and Akt were upregulated by WEE treatment in PA-exposed HepG2 cells. The phosphorylation of GSK3b was elevated after WEE treatment in PA-treated cells. WEE treatment also concentration-dependently downregulated the phosphorylated CREB, ERK, c-Jun, p38

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Paeoniflorin suppresses lipid accumulation and alleviates insulin resistance by regulating the Rho kinase/IRS-1 pathway in palmitate-induced HepG2Cells

Cited by 23 publications

References 33 publications

Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Paeoniflorin Ameliorates Fructose-Induced Insulin Resistance and Hepatic Steatosis by Activating LKB1/AMPK and AKT Pathways

Effects of three different formulae of Gamisoyosan on lipid accumulation induced by oleic acid in HepG2 cells

Edgeworthia gardneri (Wall.) Meisn. Water Extract Ameliorates Palmitate Induced Insulin Resistance by Regulating IRS1/GSK3β/FoxO1 Signaling Pathway in Human HepG2 Hepatocytes

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