Wei Xiang-Lan, Fang Ru-Tang, Yang Yong-Hua, Bi Xue-Yuan, Ren Guo-Xia, Luo A-Li, Zhao Ming, Zang Wei-Jin
Department of Pharmacology, Xi'an Jiaotong University Health Science Center, P.O. Box 77#, No.76 Yanta West Road, Xi'an, 710061, People's Republic of China.
Department of Pharmacy, Xi'an Chest Hospital, Xi'an, 710061, People's Republic of China.
BMC Complement Altern Med. 2015 Oct 27;15:389. doi: 10.1186/s12906-015-0916-9.
Liver fibrosis is a feature in the majority of chronic liver diseases and oxidative stress is considered to be its main pathogenic mechanism. Antioxidants including vitamin E, are effective in preventing liver fibrogenesis. Several plant-drived antioxidants, such as silymarin, baicalin, beicalein, quercetin, apigenin, were shown to interfere with liver fibrogenesis. The antioxidans above are polyphenols, flavonoids or structurally related compounds which are the main chemical components of Pomegranate peels and seeds, and the antioxidant activity of Pomegranate peels and seeds have been verified. Here we investigated whether the extracts of pomegranate peels (EPP) and seeds (EPS) have preventive efficacy on liver fibrosis induced by carbon tetrachloride (CCl4) in rats and explored its possible mechanisms.
The animal model was established by injection with 50 % CCl4 subcutaneously in male wistar rats twice a week for four weeks. Meanwhile, EPP and EPS were administered orally every day for 4 weeks, respectively. The protective effects of EPP and EPS on biochemical metabolic parameters, liver function, oxidative markers, activities of antioxidant enzymes and liver fibrosis were determined in CCl4-induced liver toxicity in rats.
Compared with the sham group, the liver function was worse in CCl4 group, manifested as increased levels of serum alanine aminotransferase, aspartate aminotransferase and total bilirubin. EPP and EPS treatment significantly ameliorated these effects of CCl4. EPP and EPS attenuated CCl4-induced increase in the levels of TGF-β1, hydroxyproline, hyaluronic acid laminin and procollagen type III. They also restored the decreased superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) activities and inhibited the formation of lipid peroxidized products in rats treated with CCl4.
The EPP and EPS have protective effects against liver fibrosis induced by CCl4, and its mechanisms might be associated with their antioxidant activity, the ability of decreasing the level of TGF-β1 and inhibition of collagen synthesis.
肝纤维化是大多数慢性肝病的一个特征,氧化应激被认为是其主要致病机制。包括维生素E在内的抗氧化剂对预防肝纤维化有效。几种植物源性抗氧化剂,如水飞蓟宾、黄芩苷、黄芩素、槲皮素、芹菜素,已被证明可干扰肝纤维化形成。上述抗氧化剂均为多酚、黄酮类或结构相关化合物,它们是石榴皮和石榴籽的主要化学成分,且石榴皮和石榴籽的抗氧化活性已得到验证。在此,我们研究了石榴皮提取物(EPP)和石榴籽提取物(EPS)对四氯化碳(CCl4)诱导的大鼠肝纤维化是否具有预防作用,并探讨其可能的机制。
通过每周两次皮下注射50% CCl4,持续四周,在雄性Wistar大鼠中建立动物模型。同时,分别每天口服EPP和EPS,持续4周。在CCl4诱导的大鼠肝毒性中,测定EPP和EPS对生化代谢参数、肝功能、氧化标志物、抗氧化酶活性和肝纤维化的保护作用。
与假手术组相比,CCl4组肝功能较差,表现为血清丙氨酸转氨酶、天冬氨酸转氨酶和总胆红素水平升高。EPP和EPS治疗显著改善了CCl4的这些作用。EPP和EPS减轻了CCl4诱导的转化生长因子-β1、羟脯氨酸、透明质酸层粘连蛋白和III型前胶原水平的升高。它们还恢复了CCl4处理大鼠中降低的超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性,并抑制了脂质过氧化产物的形成。
EPP和EPS对CCl4诱导的肝纤维化具有保护作用,其机制可能与其抗氧化活性、降低转化生长因子-β1水平的能力以及抑制胶原合成有关。