Ilexgenin A enhances the effects of simvastatin on non-alcoholic fatty liver disease without changes in simvastatin pharmacokinetics.
10.1016/S1875-5364(18)30077-3
- Author:
Ya-Wen LU
1
;
Ying-Chao ZHU
1
;
Li ZHANG
1
;
Ping LI
1
;
Jie YANG
2
,
3
;
Xiao-Dong WEN
3
,
4
Author Information
1. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
2. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. Electronic address: cpusyj@
3. com.
4. State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China. Electronic address: cpuwxd@
- Publication Type:Journal Article
- Keywords:
Ilexgenin A;
Non-alcoholic fatty liver;
Pharmacokinetics;
Simvastatin;
Simvastatin acid
- MeSH:
Alanine Transaminase;
metabolism;
Animals;
Aspartate Aminotransferases;
metabolism;
Cytochrome P-450 CYP3A;
genetics;
metabolism;
Diet, High-Fat;
Disease Models, Animal;
Drug Synergism;
Drug Therapy, Combination;
Lipids;
blood;
Liver;
metabolism;
pathology;
physiopathology;
Male;
Molecular Structure;
Non-alcoholic Fatty Liver Disease;
blood;
drug therapy;
Rats;
Rats, Sprague-Dawley;
Simvastatin;
analogs & derivatives;
pharmacokinetics;
therapeutic use;
Transcription, Genetic;
Triterpenes;
chemistry;
therapeutic use
- From:
Chinese Journal of Natural Medicines (English Ed.)
2018;16(6):436-445
- CountryChina
- Language:English
-
Abstract:
Cardiovascular disease (CVD) is the most common cause of death in patients with non-alcoholic fatty liver disease (NAFLD). New therapeutic strategies which have the potential for slowing down the evolution of NAFLD and reducing CVD-related mortality are urgently needed. Statins are well recognized in the treatment of dyslipidemia, but their use in the treatment of NAFLD is limited due to the safety concerns. Ilexgenin A (IA) is one of the main bioactive compounds in 'Shan-lv-cha', an herbal tea commonly used in China. In the present study, we investigated the possible synergistic therapeutic effects of IA and simvastatin (SV) on NAFLD. IA or SV showed beneficial effects on the rats with NAFLD by lowering the liver weight, liver index and plasma levels of alanine aminotransferase and aspartate aminotransferase, regulating abnormal metabolism of lipids and ameliorating steatosis in liver. IA significantly enhanced the hypolipidemic and anti-inflammation effects of SV. Furthermore, a sensitive, accurate, convenient and reproducible LC-MS method was developed to investigate the effects of IA on the pharmacokinetics of SV. No significant changes were observed in pharmacokinetic parameters of SV and simvastatin hydroxy acid in the IA plus SV co-treated group in comparison with those in the group treated with SV alone. The mRNA levels and activity of CYP3A1 were not altered by IA. In conclusion, the results obtained from the present study should be helpful for further clinical application of SV and IA alone or in combination.
