Plant Biochemistry Department, National Research Centre (NRC), 33 El Buhouth St. (Former El-Tahrir St.), 12622 Dokki, Cairo, Egypt.
Pharmacology Department, National Research Centre (NRC), 33 El Buhouth St. (Former El-Tahrir St.), 12622 Dokki, Cairo, Egypt.
Biomed Res Int. 2021 Feb 11;2021:6631415. doi: 10.1155/2021/6631415. eCollection 2021.
Hepatic fibrosis is a consequence of chronic liver diseases. Metalloproteinase and its inhibitor have crucial roles in the resolution of liver fibrosis. The current relevant study is aimed to evaluate the therapeutic effect of ( extract, astaxanthin-rich fraction, astaxanthin ester-rich fraction, and -carotene-rich fraction as well as their mechanisms of action in curing hepatic fibrosis induced by thioacetamide (TAA). Liver fibrosis was induced using TAA (intraperitoneal injection, two times a week for 6 weeks), in a rat model and extract (200 mg/kg), and other fractions (30 mg/kg) were orally administered daily for 4 weeks after the last TAA injection. Based on HPLC analysis, extract contains -carotene (12.95 mg/g, extract) and free astaxanthin (10.85 mg/g, extract), while HPLC/ESI-MS analysis revealed that extract contains 28 carotenoid compounds including three isomers of free astaxanthin, or -carotene, lutein, 14 astaxanthin mono-esters, 5 astaxanthin di-esters, and other carotenoids. and its fractions reduced liver enzymes, nitric oxide, collagen 1, alpha-smooth muscle actin, and transforming growth factor-beta as well as elevated catalase antioxidant activity compared to the TAA group. Also, extract and its fractions exceedingly controlled the balance between metalloproteinase and its inhibitor, activated Kupffer cells proliferation, and suppressed liver apoptosis, necrobiosis, and fibrosis. These findings conclude that extract and its fractions have an antifibrotic effect against TAA-induced liver fibrosis by regulating the oxidative stress and proinflammatory mediators, suppressing multiple profibrogenic factors, and modulating the metalloproteinase and its inhibitor pathway, recommending extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.
肝纤维化是慢性肝病的后果。金属蛋白酶及其抑制剂在肝纤维化的消退中起着至关重要的作用。目前的相关研究旨在评估（提取物、虾青素丰富的部分、虾青素酯丰富的部分和β-胡萝卜素丰富的部分）治疗硫代乙酰胺（TAA）诱导的肝纤维化的疗效及其作用机制。采用 TAA（腹腔注射，每周两次，共 6 周）诱导肝纤维化大鼠模型，在最后一次 TAA 注射后，每日口服 提取物（200mg/kg）和其他部分（30mg/kg），共 4 周。基于 HPLC 分析，提取物含有β-胡萝卜素（12.95mg/g，提取物）和游离虾青素（10.85mg/g，提取物），而 HPLC/ESI-MS 分析表明，提取物含有 28 种类胡萝卜素化合物，包括三种游离虾青素的异构体、β-胡萝卜素、叶黄素、14 种虾青素单酯、5 种虾青素二酯和其他类胡萝卜素。与 TAA 组相比，提取物及其部分降低了肝酶、一氧化氮、胶原 1、α-平滑肌肌动蛋白和转化生长因子-β，并提高了过氧化氢酶抗氧化活性。此外，提取物及其部分还极好地控制了金属蛋白酶及其抑制剂之间的平衡，激活了库普弗细胞的增殖，并抑制了肝凋亡、坏死和纤维化。这些发现表明，提取物及其部分通过调节氧化应激和促炎介质、抑制多种促纤维化因子以及调节金属蛋白酶及其抑制剂途径，对 TAA 诱导的肝纤维化具有抗纤维化作用，为治疗肝纤维化疾病开发新的有效药物推荐了提取物及其部分。
