State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
Chin J Nat Med. 2018 Jun;16(6):436-445. doi: 10.1016/S1875-5364(18)30077-3.
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.
心血管疾病 (CVD) 是非酒精性脂肪性肝病 (NAFLD) 患者死亡的最常见原因。迫切需要新的治疗策略，这些策略有可能减缓 NAFLD 的发展并降低与 CVD 相关的死亡率。他汀类药物在治疗血脂异常方面得到了广泛认可，但由于安全性问题，其在 NAFLD 治疗中的应用受到限制。冬凌草甲素 (IA) 是中国常用草药“山绿茶”中的主要生物活性化合物之一。在本研究中，我们研究了冬凌草甲素和辛伐他汀 (SV) 联合治疗 NAFLD 的可能协同治疗效果。IA 或 SV 通过降低肝重、肝指数和丙氨酸氨基转移酶和天冬氨酸氨基转移酶的血浆水平，调节脂质异常代谢，改善肝脏脂肪变性，对 NAFLD 大鼠有有益作用。IA 显著增强了 SV 的降血脂和抗炎作用。此外，还开发了一种灵敏、准确、方便和重现性好的 LC-MS 方法来研究 IA 对 SV 药代动力学的影响。与单独使用 SV 治疗组相比，IA 加 SV 合用组 SV 和辛伐他汀羟酸的药代动力学参数没有明显变化。IA 不改变 CYP3A1 的 mRNA 水平和活性。总之，本研究结果有助于进一步临床应用 SV 和 IA 单独或联合应用。
