Ono Masafumi, Ogasawara Mitsunari, Hirose Akira, Mogami Sachiko, Ootake Nobuhiro, Aritake Kosuke, Higuchi Takuma, Okamoto Nobuto, Sakamoto Shuji, Yamamoto Masahiro, Urade Yoshihiro, Saibara Toshiji, Oben Jude A
Department of Gastroenterology and Hepatology, Kochi Medical School, Kohasu, Nankoku, Kochi, 783-8505, Japan,
J Gastroenterol. 2014 Jun;49(6):1065-73. doi: 10.1007/s00535-013-0852-8. Epub 2013 Jun 26.
Obesity-induced liver disease (nonalcoholic fatty liver disease, NAFLD) is now the commonest cause of chronic liver disease in affluent nations. There are presently no proven treatments for NAFLD or its more severe stage, nonalcoholic steatohepatitis (NASH). Bofutsushosan (BTS), a Japanese herbal (Kampo) medicine, long used as an anti-obesity medicine in Japan and other Asian countries, has been shown to reduce body weight and improve insulin resistance (IR) and hepatic steatosis. The precise mechanism of action of BTS, however, remains unclear. To evaluate the ability of BTS to prevent the development of NASH, and determine the mediators and pathways involved.
C57BL/6 mice were injected intra-peritoneally with gold-thioglucose and fed a high-fat diet (HF) or HF diet admixed with either 2 or 5 % BTS for 12 weeks. The effectiveness of BTS in attenuating features of NASH and the mechanisms through which BTS attenuated NASH were then assayed through an assessment of the anthropometric, radiological, biochemical and histological parameters.
BTS attenuated the progression of NASH through induction of adiponectin and its receptors along with an induction of PPAR-α and PPAR-γ, decreased expression of SREBP-1c, increased hepatic fatty acid oxidation and increased hepatic export of triglycerides. BTS moreover, reduced IR through phosphorylation of the protein kinase, Akt.
BTS through induction of adiponectin signaling and Akt attenuated development of NASH. Identification of the active entity in BTS should allow development of novel treatments for NASH.
肥胖诱导的肝病（非酒精性脂肪性肝病，NAFLD）目前是富裕国家慢性肝病最常见的病因。目前尚无经证实的针对NAFLD或其更严重阶段——非酒精性脂肪性肝炎（NASH）的治疗方法。防己茯苓散（BTS）是一种日本草药（汉方）药，在日本和其他亚洲国家长期用作抗肥胖药物，已显示可减轻体重、改善胰岛素抵抗（IR）和肝脂肪变性。然而，BTS的确切作用机制仍不清楚。为评估BTS预防NASH发生的能力，并确定其中涉及的介质和途径。
给C57BL/6小鼠腹腔注射金硫葡萄糖，并给予高脂饮食（HF）或含2%或5%BTS的HF饮食，持续12周。然后通过评估人体测量学、放射学、生化和组织学参数，测定BTS减轻NASH特征的有效性以及BTS减轻NASH的机制。
BTS通过诱导脂联素及其受体以及诱导PPAR-α和PPAR-γ，减少SREBP-1c的表达，增加肝脏脂肪酸氧化和肝脏甘油三酯输出，从而减轻NASH的进展。此外，BTS通过蛋白激酶Akt的磷酸化降低IR。
BTS通过诱导脂联素信号传导和Akt减轻NASH的发展。鉴定BTS中的活性成分应有助于开发NASH的新型治疗方法。
