The Ethanol Extract from Lonicera japonica Thunb. Regresses Nonalcoholic Steatohepatitis in a Methionine- and Choline-Deficient Diet-Fed Animal Model.
Nonalcoholic steatohepatitis (NASH) is characterized as fat accumulation in the hepatic tissue associated with various degrees of inflammation and progressive fibrosis. The potent anti-inflammatory and ethnopharmacological properties of Lonicera japonica Thunb. (Caprifoliaceae) make it an excellent source of novel medicinal targets for the treatment of NASH. The aim of the study was to investigate the effects of L. japonica ethanol extract (LJEE) on NASH in mice. C57BL/6J mice were fed with methionine-choline-deficient diet (MCDD) for eight weeks to promote the development of NASH. After development of the model, the mice were administered LJEE once daily via oral gavage at doses of 100, 200, or 300 mg/kg for another four weeks. Simultaneous treatments with LJEE (300 mg/kg/day) resulted in pronounced improvements in liver steatosis, ballooning degeneration, and inflammation. LJEE prevented MCDD-induced plasma level increases in aspartate aminotransferase and alanine aminotransferase. LJEE significantly reduced hepatic malondialdehyde level and ameliorated hepatic inflammation and fibrosis in MCDD-fed mice, which were associated with down-regulation of cytochrome P450 2E1 suppression of multiple proinflammatory and profibrotic genes. LJEE can prevent hepatic steatosis by reducing hepatic peroxisome acyl-CoA:diacylglycerol acyltransferase 2 expression, as well as by inducing proliferator-activated receptor α expression. In addition, the LJEE treatments caused significant reduction in the phosphorylated form of Jun N-terminal kinase along with an increase in the phosphorylated level of extra cellular signal-regulated kinase 1/2. Our study demonstrated the protective role of LJEE in ameliorating nutritional steatohepatitis.
Department of Pharmacy and Master Program, Tajen University, Pingtung, 90741, Taiwan. d850084@yahoo.com.tw.
Thing-Fong
TF
Tzeng
St. Dominic's Catholic High School, Kaohsiung, 80288, Taiwan. 2770727@yahoo.com.tw.
Yu-Cheng
YC
Tzeng
Department of Pharmacy and Master Program, Tajen University, Pingtung, 90741, Taiwan. azyl2032@gmail.com.
Yu-Jou
YJ
Cheng
Department of Pharmacy and Master Program, Tajen University, Pingtung, 90741, Taiwan. ssliou@tajen.edu.tw.
Shorong-Shii
SS
Liou
Department of Pharmacy and Master Program, Tajen University, Pingtung, 90741, Taiwan. iml@tajen.edu.tw.
I-Min
IM
Liu
D000818:Animals; D002796:Choline Deficiency / Q000150:complications; D004032:Diet / Q000009:adverse effects; D004195:Disease Models, Animal; D007249:Inflammation / Q000188:drug therapy; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy; D031239:Lonicera; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D015398:Signal Transduction
D010936:Plant Extracts; D008715:Methionine
Jun N-terminal kinase; Lonicera japonica Thunb; and choline-deficient diet (MCDD); extra cellular signal-regulated kinase 1/2; methionine; non-alcoholic steatohepatitis (NASH)