Qian Weibin, Hasegawa Junichi, Tsuno Satoshi, Endo Yusuke, Matsuda Akiko, Miura Norimasa
Division of Pharmacotherapeutics, Department of Pathophysiological and Therapeutic Science, School of Medicine, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
†Department of Fundamental Nursing, School of Health Science, Tottori University Faculty of Medicine, Yonago 683-8503, Japan.
Yonago Acta Med. 2014 Dec;57(4):147-58. Epub 2014 Dec 26.
Bofutsushosan is a well known Kampo, traditional Japanese medicine, based on ancient Chinese medicine mainly used in the treatment of hypercholesterolemia in Japan. We selected two Kampo formulas, Boiogito and Keishibukuryogan mainly used in the treatment of hypercholesterolemia in China to compare with Bofutsushosan and cholesterol absorption inhibitor ezetimibe.
Hypercholesterolemia and fatty liver were induced by high cholesterol (containing 2% cholesterol and 0.5% cholic acid) diet in male Wistar rats for 6 and 12 weeks. Kampo formulas Boiogito, Bofutsushosan, Keishibukuryogan and ezetimibe were added to the high-cholesterol diet, respectively. After 6 and 12 weeks, body and liver weights, blood chemistry, cholesterol concentrations, fat-related and inflammatory-related factors were examined.
High-cholesterol diet increased body and liver weights, and serum cholesterol concentrations. Boiogito and ezetimibe improved them. Serum ICAM-1 and RBP4 were increased in the high cholesterol diet group. Boiogito and ezetimibe improved them too. In the histological examinations of liver and adipose tissues, we observed a significant improvement after treatment. Immunostaining expression of ICAM-1 in aorta was improved by Boiogito, Bofutsushosan, Keishibukuryogan and ezetimibe. The mRNA expression of RBP4, HFABP, CFABP, MCP1 and CCR2 in liver and adipose tissue were decreased by Boiogito and ezetimibe.
Boiogito has a protective effect on the progression of hypercholesterolemia and fatty liver induced by high-cholesterol diet in rats and more effective than Bofutsushosan and Keishibukuryogan. The lipid-lowering effect of Boiogito is not stronger than ezetimibe. But the anti-inflammatory (MCP1, CCR2) and anti-arteriosclerotic (ICAM-1) effects of Boiogito are more potent than ezetimibe.
防己地黄汤是一种著名的汉方,即传统日本医学,它基于古代中医,在日本主要用于治疗高胆固醇血症。我们选择了两种主要用于治疗中国高胆固醇血症的汉方方剂,即补阳还五汤和桂枝茯苓丸,与防己地黄汤和胆固醇吸收抑制剂依泽替米贝进行比较。
通过在雄性Wistar大鼠中喂食高胆固醇(含2%胆固醇和0.5%胆酸)饮食6周和12周来诱导高胆固醇血症和脂肪肝。将汉方方剂补阳还五汤、防己地黄汤、桂枝茯苓丸和依泽替米贝分别添加到高胆固醇饮食中。6周和12周后,检测体重、肝脏重量、血液生化指标、胆固醇浓度、脂肪相关因子和炎症相关因子。
高胆固醇饮食增加了体重、肝脏重量和血清胆固醇浓度。补阳还五汤和依泽替米贝改善了这些指标。高胆固醇饮食组血清细胞间黏附分子-1(ICAM-1)和视黄醇结合蛋白4(RBP4)升高。补阳还五汤和依泽替米贝也改善了这些指标。在肝脏和脂肪组织的组织学检查中,我们观察到治疗后有显著改善。补阳还五汤、防己地黄汤、桂枝茯苓丸和依泽替米贝改善了主动脉中ICAM-1的免疫染色表达。补阳还五汤和依泽替米贝降低了肝脏和脂肪组织中RBP4、心脏型脂肪酸结合蛋白(HFABP)、小肠型脂肪酸结合蛋白(CFABP)、单核细胞趋化蛋白-1(MCP1)和C-C趋化因子受体2(CCR2)的mRNA表达。
补阳还五汤对大鼠高胆固醇饮食诱导的高胆固醇血症和脂肪肝的进展具有保护作用,且比防己地黄汤和桂枝茯苓丸更有效。补阳还五汤的降脂作用不比依泽替米贝强。但补阳还五汤的抗炎(MCP1、CCR2)和抗动脉粥样硬化(ICAM-1)作用比依泽替米贝更强。