Department of Biomedical Engineering, Mokwon University, Daejeon 35349, Republic of Korea.
Genome Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea.
J Ethnopharmacol. 2018 Oct 28;225:31-41. doi: 10.1016/j.jep.2018.06.034. Epub 2018 Jun 26.
The herbal composition Gyeongshingangjeehwan 18 (GGEx18), composed of Rheum palmatum L. (Polygonaceae), Laminaria japonica Aresch (Laminariaceae), and Ephedra sinica Stapf (Ephedraceae), is used as an antiobesity drug in Korean clinics. The constituents of GGEx18 have traditionally been reported to inhibit obesity and related metabolic diseases such as insulin resistance and dyslipidemia.
This study investigated the effects of GGEx18 on nonalcoholic fatty liver disease (NAFLD) in mice fed a high-fat diet (HFD) and the underlying cellular and molecular mechanisms involved.
C57BL/6 J mice were fed either a low-fat diet (LFD), an HFD, or an HFD supplemented with GGEx18 (125, 250, or 500 mg/kg of body weight/day). After 13 weeks, blood analyses, histology, immunohistochemistry, and real-time PCR were performed to assess NAFLD development in these mice.
Mice fed an HFD had increases in body weight, epididymal adipose tissue mass, adipocyte size, and adipose expression of inflammation-related genes compared with those fed an LFD. These increases were ameliorated in mice treated with 500 mg/kg/day GGEx18 without affecting food consumption profiles. GGEx18 not only decreased serum levels of triglycerides, free fatty acids, and alanine aminotransferase, but also decreased hepatic lipid accumulation, numbers of mast cells and α-smooth muscle actin-positive cells, and collagen levels induced by an HFD. Consistent with the histological data, the hepatic expression of lipogenesis-, inflammation-, and fibrosis-related genes was lower, while hepatic fatty acid β-oxidation-related gene expression was higher, in mice receiving GGEx18 compared to mice fed only the HFD.
These results indicate that GGEx18 attenuates visceral obesity and NAFLD, in part by altering the expression of genes involved in hepatic steatosis and fibroinflammation in HFD-induced obese mice. These findings suggest that GGEx18 may be effective for preventing and treating NAFLD associated with visceral obesity.
草药组合物 Gyeongshingangjeehwan 18（GGEx18）由大黄（蓼科）、海带（马尾藻科）和麻黄（麻黄科）组成，在韩国诊所用作减肥药。GGEx18 的成分传统上被报道具有抑制肥胖和相关代谢疾病的作用，如胰岛素抵抗和血脂异常。
本研究调查了 GGEx18 对高脂肪饮食（HFD）喂养的非酒精性脂肪肝（NAFLD）小鼠的影响及其潜在的细胞和分子机制。
C57BL/6J 小鼠分别喂食低脂肪饮食（LFD）、高脂肪饮食（HFD）或 HFD 补充 GGEx18（125、250 或 500mg/kg 体重/天）。13 周后，进行血液分析、组织学、免疫组织化学和实时 PCR 以评估这些小鼠的 NAFLD 发展情况。
与喂食 LFD 的小鼠相比，喂食 HFD 的小鼠体重增加、附睾脂肪组织质量增加、脂肪细胞大小增加、脂肪组织炎症相关基因表达增加。用 500mg/kg/天 GGEx18 治疗可改善这些增加，而不影响食物消耗模式。GGEx18 不仅降低了血清甘油三酯、游离脂肪酸和丙氨酸转氨酶水平，还降低了 HFD 诱导的肝脂质堆积、肥大细胞和α-平滑肌肌动蛋白阳性细胞数量以及胶原水平。与组织学数据一致，与仅喂食 HFD 的小鼠相比，接受 GGEx18 的小鼠肝脏中与脂肪生成、炎症和纤维化相关的基因表达降低，而脂肪酸β-氧化相关基因表达升高。
这些结果表明，GGEx18 通过改变 HFD 诱导肥胖小鼠肝脏脂肪变性和纤维化相关基因的表达，减轻内脏肥胖和 NAFLD。这些发现表明，GGEx18 可能对预防和治疗与内脏肥胖相关的 NAFLD 有效。
