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Table 1.

Primers used for analysis of the expression of AMPK pathway and lipid metabolism-related genes.

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Fig 1.

Cytotoxicity and lipid accumulation in UME-treated HepG2 cells.

(A) Cell viability was determined with an MTT assay. HepG2 cells were treated with various concentrations of UME (25, 50, 100, and 200 μg/mL). (B) Intracellular lipid droplets in HepG2 cells were stained with oil red O and observed at 200× magnification. HepG2 cells were treated with compound C (10 μM) for 1h and then incubated with or without UME (25, 50 and 100 μg/mL) and ATO (10 μM) for an additional 1 h. Cells were then incubated with OA for 1 h. Lipid droplets were quantified by measuring the resultant absorbance at 540 nm. Data are expressed as the mean ± SEM (n = 10). **p < 0.01, compared to the control. #p < 0.05, compared to the OA-only treated group. ##p < 0.01, compared to the OA-only treated group. UME: Ulmus macrocarpa Hance extracts, CC: compound C, ATO: atorvastatin, OA: oleic acid.

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Fig 2.

The expression levels of the lipogenic genes AMPK, SREBP1c, HMGCR, and ACC in HepG2 cells were examined by real-time RT-PCR.

Data are expressed as the mean ± SEM (n = 10). *p < 0.05, compared to the control. **p < 0.01, compared to the control. #p < 0.05, compared to the OA-only treated group. ##p < 0.01, compared to the OA-only treated group. UME: Ulmus macrocarpa Hance extracts, CC: compound C, ATO: atorvastatin, OA: oleic acid.

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Table 2.

Body weight gain, feed intake, feed efficiency ratio (FER) and liver weight/body weight in rats fed HCD with UME.

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Table 2 Expand

Fig 3.

Levels of AST and ALT in UME-treated HCD-fed rats.

The levels of ALT and AST in serum were measured according to the kit manufacturer’s instructions. Data are expressed as the mean ± SEM (n = 10). AST: aspartate aminotransferase, ALT: alanine aminotransferase. **p < 0.01, compared to normal. #p < 0.05, compared to the control. ##p < 0.01, compared to the control. N: normal, C: high-cholesterol diet (HCD), UME 25–100: HCD + UME (25, 50, 100 mg/kg), ATO: HCD + atorvastatin, O3: HCD + omega-3.

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Fig 4.

Lipid biomarkers in the serum of UME-treated HCD-fed rats.

(A-D) Serum concentrations of total cholesterol, triglyceride, HDL cholesterol and LDL cholesterol were measured by a commercial analysis kit. Data are expressed as the mean ± SEM (n = 10). **p < 0.01, compared to normal. ***p < 0.001, compared to normal. #p < 0.05, compared to the control. ##p < 0.01, compared to the control. N: normal, C: high-cholesterol diet (HCD), UME 25–100: HCD + UME (25, 50, 100 mg/kg), ATO: HCD + atorvastatin, O3: HCD + omega-3.

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Table 3.

Cardiac risk factor (CRF) and atherogenic index (AI) in the serum of rats.

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Table 3 Expand

Fig 5.

Levels of total cholesterol and triglyceride in the livers of UME-treated HCD-fed rats.

Liver concentrations of total cholesterol and triglyceride were measured by a commercial analysis kit. Data are expressed as the mean ± SEM (n = 10). **p < 0.01, compared to normal. #p < 0.05, compared to the control. N: normal, C: high-cholesterol diet (HCD), UME 25–100: HCD + UME (25, 50, 100 mg/kg), ATO: HCD + atorvastatin, O3: HCD + omega-3.

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Fig 6.

Activation of AMPK pathway in the liver of UME-treated HCD-fed rats.

(A) The protein expression levels of p-AMPK, AMPK, p-ACC, ACC, SREBP1 and HMGCR in liver tissue were measured by western blot. (B) The bar graphs indicate the average p-AMPK/AMPK, p-ACC/ACC, SREBP1, and HMGCR activity. Data are expressed as the mean ± SEM (n = 10). ***p < 0.001, compared to normal. #p < 0.05, compared to the control. ##p < 0.01, compared to the control. ###p < 0.001, compared to the control. N: normal, C: high-cholesterol diet (HCD), UME 25–100: HCD + UME (25, 50, 100 mg/kg), ATO: HCD + atorvastatin, O3: HCD + omega-3.

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Fig 7.

Hepatic lipid accumulation in UME-treated HCD-fed rats.

H&E staining (magnification 200×) was quantified by determining the stained area, in pixels, in each image using the Image Pro analysis program. Data are expressed as the mean ± SEM (n = 10). **p < 0.01, compared to normal. #p < 0.05, compared to the control. ##p < 0.01, compared to the control. N: normal, C: high-cholesterol diet (HCD), UME 25–100: HCD + UME (25, 50, 100 mg/kg), ATO: HCD + atorvastatin, O3: HCD + omega-3.

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Fig 8.

Predictable mechanism in hepatic tissues of UME-treated HCD-fed rats.

UME prevented hyperlipidemia by up-regulating the AMPK pathway and regulation of lipid metabolism. SREBP1: sterol regulatory element binding protein-1, ACC: acetyl CoA carboxylase, HMGCR: 3-hydroxy-3-methylglutaryl-CoA reductase, AST: aspartate aminotransferase, ALT: alanine aminotransferase, TC: total cholesterol, TG: triglyceride, LDL: low-density lipoprotein cholesterol, HDL: high-density lipoprotein cholesterol.

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