| Abstract: | 非酒精性脂肪肝(non-alcoholic fatty liver diseases, NAFLD)近年來患病率快速增加影響全球近三成人口，這和飲食習慣西化和靜態的生活方式高度相關，也是NAFLD發生率逐年上升的主因。此外，NAFLD也與罹患心血管疾病風險增加有關。目前證據顯示NAFLD與胰島素阻抗，體重過重、第二型糖尿病及代謝症候群高度相關，但引發非酒精性脂肪肝的機制尚未完全釐清。臨床上NAFLD也被視為未來成為肝臟移植患者的預測指標之一。截至目前，尚未有明確治療NAFLD的方式，多以預防或延緩NAFLD發展為主，其中又以培養良好生活習慣及改善飲食型態為重中之重。紫蘇為傳統常見的中藥草，許多研究發現紫蘇葉提取的精油主要芳香成分—紫蘇醛(Perillaldehyde)具有血管舒張、抗微生物、抗發炎、抗氧化及抗癌等功效，但紫蘇醛改善NAFLD的生物活性卻少被探討，因此本實驗欲探討紫蘇醛對於含膽固醇及膽酸之高油脂飲食所引發的NAFLD是否具有改善功效。C57BL/6J小鼠分為一般飲食組和含膽固醇及膽酸之高油脂飲食(HFHC)組，其中HFHC飲食再分為對照組、經口補充低劑量紫蘇醛組(75 mg/kg)及高劑量紫蘇醛組(150 mg/kg)。實驗結果顯示，相較於HFHC組，餵食紫蘇醛九周後可明顯降低小鼠的體重、血糖及心臟和腎臟的重量相對體重比，肝臟的重量相對體重比雖未達顯著差異，但仍低於HFHC組；另外補充紫蘇醛可降低小鼠紅血球及肝臟丙二醛(Malondialdehyde, MDA)濃度；與HFHC組相比，紫蘇醛顯著降低肝臟NOD-like receptor protein 3 (NLRP3)、caspase-1、pro caspase-1和IL-1β及TNF-α等發炎相關蛋白表現；脂質代謝蛋白表現上，紫蘇醛顯著增加肝臟hormone-sensitive lipase (HSL)蛋白表現，但顯著減少HMG CoA reductase (HMGCR)與sterol regulatory element-binding protein 1c (SREBP-1c)；此外，補充紫蘇醛顯著增加肝臟heme oxygenase-1 (HO-1)抗氧化蛋白的表現，並顯著減少superoxide dismutase 1 (SOD1)、SOD2及glutathione peroxidase 1 (GPx1)蛋白表現。綜合以上結果可知，補充紫蘇醛可減少NAFLD小鼠NLRP3發炎路徑，並藉由改善ROS增加而影響其抗氧化酵素與脂質代謝蛋白表現。
Non-alcoholic fatty liver disease (NAFLD) has affected nearly 30% of the global population in recent years. Westernized diet and secondary lifestyle are the major cause of the increasing incidence of NAFLD year after year. About 20%~30% of the patients with NAFLD would develop liver fibrosis, or even liver cirrhosis and hepatoma. Moreover, NAFLD has shown to be associated with increased risk of cardiovascular disease. However, the mechanism underlying the development of NAFLD has not been clarified. Evidence shows high correlation between NAFLD and insulin resistance, overweight, type 2 diabetes mellitus and metabolite syndrome. Clinically, NAFLD is regarded as one of the predictors of liver transplantation in the future. Up to date, there is no suitable treatment for NAFLD, and the method of NAFLD prevention is based on cultivation of good lifestyle and diets. Perilla frutescens (L.) Britt. is a traditional Chinese herb medicine. The main aromatic component of perilla is called perillaldehyde, which is also extracted as essential oil. Based on previous research results, perillaldehyde exhibits a variety of biological activities, including vasodilation of blood vessels, antifungal activity, anti-inflammation, anti-oxidantion and anticancer. The aim of this study was to investigate the effect of perillaldehyde on high fat-high cholic acid diet-induced NAFLD mice. The C57BL/6J mice were fed a chow diet and were randomly assigned into control, high fat diet containing 1.25% of cholesterol and 0.5% of cholic acid (HFHC) and HFHC with oral administration with perillaldehyde (low dose 75 mg/kg and high dose 150 mg/kg). The results showed significant decrease in the body weight and the blood glucose after oral administration of perillaldehyde for 9 week to HFHC mice. Compare with HFHC mice, the weight of heart and kidney was lower in mice treated with perillaldehyde, while the weight of liver reduced slightly in perillaldehyde-treated mice. The result also showed that treating with perillaldehyde, the concentration of MDA reduced notably in red blood cells and liver tissues. Compared with HFHC mice, the expression of inflammation-related proteins, such as NOD-like receptor protein 3 (NLRP3), caspase-1, pro-caspase 1, IL-1β and TNF-α were remarkably decreased in perillaldehyde-treatedmice. The protein expression of hormone-sensitive lipase (HSL) was higher in perillaldehyde-treated mice, while HMG CoA reductase (HMGCR) and sterol regulatory element-binding protein 1c (SREBP-1c) protein expression was lower. Moreover, the protein expression of anti-oxidant proteins in liver, such heme oxygenase-1 (HO-1) was higher and superoxide dismutase 1 (SOD1), superoxide dismutase 2 (SOD2) as well as glutathione peroxidase 1 (GPx1) was lower in mice treated with perillaldehyde In summary, treatment with perillaldehyde would reduce protein expression of NLRP3 inflammasome and inflammation-related proteins, and also has an improved impact on antioxidant enzyme as well as lipid metabolite-related protein expression in NAFLD mice. |
