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Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse

View Article: PubMed Central - PubMed

ABSTRACT

Aristolochia manshuriensis Kom (AMK) is an herb used as a traditional medicine; however, it causes side effects such as nephrotoxicity and carcinogenicity. Nevertheless, AMK can be applied in specific ways medicinally, including via ingestion of low doses for short periods of time. Non-alcoholic steatohepatitis (NASH) induced the hepatocyte injury and inflammation. The protective effects of AMK against NASH are unclear; therefore, in this study, the protective effects of AMK ethyl acetate extract were investigated in a high-fat diet (HFD)-induced NASH model. We found decreased hepatic steatosis and inflammation, as well as increased levels of lipoproteins during AMK extract treatment. We also observed decreased hepatic lipid peroxidation and triglycerides, as well as suppressed hepatic expression of lipogenic genes in extract-treated livers. Treatment with extract decreased the activation of c-jun N-terminal kinase 1/2 (JNK1/2) and increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). These results demonstrate that the protective effect of the extract against HFD-induced NASH occurred via reductions in reactive oxygen species production, inflammation suppression, and apoptosis related to the suppression of JNK1/2 activation and increased ERK1/2 phosphorylation. Taken together, these results indicate that that ethyl acetate extract of AMK has potential therapeutic effects in the HFD-induced NASH mouse model.

No MeSH data available.


Related in: MedlinePlus

Effects of HFD and treatment with EtOAc extract of AMK on hepatic mRNA expression. Expression of regulation genes such as (A) hepatic fatty acid, (B) adiopogenesis and (C) inflammation was measured in the hepatocytes of mice fed ND, HFD, or HFD plus EtOAc extract of AMK (2.5 mg/kg) for 15 weeks. Data are the means ± SD of 10 mice in each group. *p < 0.05, **p < 0.01 vs. HFD-fed mice.
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Figure 4: Effects of HFD and treatment with EtOAc extract of AMK on hepatic mRNA expression. Expression of regulation genes such as (A) hepatic fatty acid, (B) adiopogenesis and (C) inflammation was measured in the hepatocytes of mice fed ND, HFD, or HFD plus EtOAc extract of AMK (2.5 mg/kg) for 15 weeks. Data are the means ± SD of 10 mice in each group. *p < 0.05, **p < 0.01 vs. HFD-fed mice.

Mentions: In this study, the hepatic levels of lipogenic genes including PPAR-γ, FAS, SCD1, and C/EBPβ, as well as the lipolytic genes PPAR-α, CYP4A10, and CYP4A14, which are known to be PPAR-α downstream target molecules (panels A and B in Fig. 4), were measured to evaluate the hepatic TG-reducing effects of AMK. Administration of EtOAc extract greatly increased the expression of PPAR-α, which was reduced by HFD (panel A in Fig. 4). However, HFD-induced C/EBP-β was significantly decreased following treatment with the EtOAc extract (panel B in Fig. 4). The other lipogenic genes were altered compared to the HFD-fed mice, but these changes were not significant (panels A and B in Fig. 4). CYP2E1, which is a major mediator of lipid peroxidation, was promoted by HFD. The expression of CYPE21 mRNA was markedly increased by HFD, but was significantly reduced following treatment with the EtOAc extract (panel B in Fig. 4). The expression of CYPE21 protein was strongly increased by EtOAc extract (panel A in Fig. 5).


Aristolochia manshuriensis Kom ethyl acetate extract protects against high-fat diet-induced non-alcoholic steatohepatitis by regulating kinase phosphorylation in mouse
Effects of HFD and treatment with EtOAc extract of AMK on hepatic mRNA expression. Expression of regulation genes such as (A) hepatic fatty acid, (B) adiopogenesis and (C) inflammation was measured in the hepatocytes of mice fed ND, HFD, or HFD plus EtOAc extract of AMK (2.5 mg/kg) for 15 weeks. Data are the means ± SD of 10 mice in each group. *p < 0.05, **p < 0.01 vs. HFD-fed mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037294&req=5

Figure 4: Effects of HFD and treatment with EtOAc extract of AMK on hepatic mRNA expression. Expression of regulation genes such as (A) hepatic fatty acid, (B) adiopogenesis and (C) inflammation was measured in the hepatocytes of mice fed ND, HFD, or HFD plus EtOAc extract of AMK (2.5 mg/kg) for 15 weeks. Data are the means ± SD of 10 mice in each group. *p < 0.05, **p < 0.01 vs. HFD-fed mice.
Mentions: In this study, the hepatic levels of lipogenic genes including PPAR-γ, FAS, SCD1, and C/EBPβ, as well as the lipolytic genes PPAR-α, CYP4A10, and CYP4A14, which are known to be PPAR-α downstream target molecules (panels A and B in Fig. 4), were measured to evaluate the hepatic TG-reducing effects of AMK. Administration of EtOAc extract greatly increased the expression of PPAR-α, which was reduced by HFD (panel A in Fig. 4). However, HFD-induced C/EBP-β was significantly decreased following treatment with the EtOAc extract (panel B in Fig. 4). The other lipogenic genes were altered compared to the HFD-fed mice, but these changes were not significant (panels A and B in Fig. 4). CYP2E1, which is a major mediator of lipid peroxidation, was promoted by HFD. The expression of CYPE21 mRNA was markedly increased by HFD, but was significantly reduced following treatment with the EtOAc extract (panel B in Fig. 4). The expression of CYPE21 protein was strongly increased by EtOAc extract (panel A in Fig. 5).

View Article: PubMed Central - PubMed

ABSTRACT

Aristolochia manshuriensis Kom (AMK) is an herb used as a traditional medicine; however, it causes side effects such as nephrotoxicity and carcinogenicity. Nevertheless, AMK can be applied in specific ways medicinally, including via ingestion of low doses for short periods of time. Non-alcoholic steatohepatitis (NASH) induced the hepatocyte injury and inflammation. The protective effects of AMK against NASH are unclear; therefore, in this study, the protective effects of AMK ethyl acetate extract were investigated in a high-fat diet (HFD)-induced NASH model. We found decreased hepatic steatosis and inflammation, as well as increased levels of lipoproteins during AMK extract treatment. We also observed decreased hepatic lipid peroxidation and triglycerides, as well as suppressed hepatic expression of lipogenic genes in extract-treated livers. Treatment with extract decreased the activation of c-jun N-terminal kinase 1/2 (JNK1/2) and increased the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). These results demonstrate that the protective effect of the extract against HFD-induced NASH occurred via reductions in reactive oxygen species production, inflammation suppression, and apoptosis related to the suppression of JNK1/2 activation and increased ERK1/2 phosphorylation. Taken together, these results indicate that that ethyl acetate extract of AMK has potential therapeutic effects in the HFD-induced NASH mouse model.

No MeSH data available.


Related in: MedlinePlus