HN242透過抑制氧化壓力減緩高脂飲食所誘導的非酒精性脂肪肝病

Abstract

非酒精性脂肪肝病(Non-alcoholic fatty liver disease, NAFLD)在歐美地區已經成為主要的肝臟疾病病之一，據估計，在美國和其他西方國家高達30％的成年人都有NAFLD。近年來由於飲食及生活習慣的改變，台灣NAFLD病人有逐漸增加的趨勢。NAFLD目前的治療方式有限，除了改變生活習慣外，多種藥物的使用都會有副作用，因此，尋找新的治療藥物刻不容緩。而這個疾病常被報導是由於因為肝臟內氧化壓力過高所引發，若能尋得抗氧化的藥物，也許對於NAFLD的治療能有助益。HN242為一種樹皮萃取出的天然物，已知能提高抗氧化能力，我們試圖了解其是否能保護肝細胞。 本實驗使用高脂飲食引發NAFLD，測量血清中的AST/ALT，高脂組小鼠的肝功能確實降低，切片染色後，觀察到有大量脂肪及纖維化的組織堆積在高脂組的小鼠的肝臟中；本研究證實不同模式的HN242餵食可以經由提升抗氧化能力達到減緩胰島素阻抗與抑制發炎等作用，在肝臟組織達到預防及治療大量脂肪堆積在肝臟的效果，同時也能防止肝臟出現纖維化的現象，對於NAFLD所產生的糖質新生也有抑制的效果，雖然治療效果不如預防顯著，但仍證實HN242能對肝臟產生實質的保護；在細胞實驗中使用HepG2肝細胞處理Palmitic acid來模擬高脂環境，結果發現自由基ROS (H2O2、O2-)的增加且細胞產生胰島素阻抗，胰島素傳訊路徑中的p-IRS及p-Akt均降低，加入HN242的組別可以減緩胰島素阻抗及降低ROS；現階段結果證實HN242具有治療及預防NAFLD極高的潛力。

Non-alcoholic fatty liver disease (NAFLD) has become one of the major liver disease worldwide. It is estimated that up to 30% of adults have NAFLD in the United States and other Western countries. Due to changes in diet and lifestyle in Taiwan in recent years, there has been a dramatic increase number of NAFLD patients. Current treatment for NAFLD is limited. In addition to lifestyle changes developing new drugs for preventing or treating NAFLD is necessary and urgent. Since oxidative stress in the liver is reported to be the main cause of NAFLD, drugs with anti-oxidative ability may have potential to treat NAFLD. HN242 is a natural plant extraction that is known to enhance the antioxidant capacity in organism. We try to understand whether it can protect liver from damages of NAFLD. In the in vivo study, high-fat-diet (HF) was used to induce NAFLD, and serum ALT/AST was measured. The liver function of the mice in HF group was indeed reduced, and a large amount of fat and fibrotic tissue was observed in livers. Two kinds of HN242 feeding were set up: (HF+HN242) HN242 was feed with HF for 70 days, and (HF-HN242) HN242 was feed with HF for 35 days after 35 days of HFD feeding. This study demonstrated that both two kinds of HN242 feeding ways can inhibit insulin resistance and decrease inflammation by increasing antioxidant capacity, thus slow down the fat accumulation and fibrosis in the livers. It also has an inhibitory effect on the gluconeogenesis produced by NAFLD. Although the therapeutic effect is not as obvious as prevention, it is confirmed that HN242 can provide substantial protection to the liver. In the in vitro experiment, Palmitic acid were used to treat HepG2 hepatocytes to mimic the high-fat environment. The results showed that the free radical (reactive oxidative species, ROS: H2O2、O2-) increased and the insulin resistance, also increased, with the insulin signaling pathway decreased. The addition of HN242 reduced ROS and slowed insulin resistance. Current results confirmed that HN242 has great potential as the preventing and treating drug for NAFLD.