Abstract
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 Haematococcus pluvialis (H. pluvialis) extract, astaxanthin-rich fraction, astaxanthin ester-rich fraction, and β-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 H. pluvialis 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, H. pluvialis extract contains β-carotene (12.95 mg/g, extract) and free astaxanthin (10.85 mg/g, extract), while HPLC/ESI-MS analysis revealed that H. pluvialis extract contains 28 carotenoid compounds including three isomers of free astaxanthin, α or β-carotene, lutein, 14 astaxanthin mono-esters, 5 astaxanthin di-esters, and other carotenoids. H. pluvialis 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, H. pluvialis 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 H. pluvialis 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 H. pluvialis extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders.
Highlights
Liver fibrosis is induced by a chronic hepatic insult and associated with liver dysfunction and life-threatening complications [1]
These findings conclude that H. pluvialis 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 H. pluvialis extract and its fractions for the development of new effective medicine for treating hepatic fibrosis disorders
We evaluated the therapeutic effect of H. pluvialis extract and its astaxanthin-rich fraction, astaxanthin esterrich fraction, and β-carotene-rich fraction and their mechanisms of action in curing hepatic fibrosis induced by TAA in rats via modulation of matrix metalloproteinase (MMPs) and its inhibitor as a target to ameliorate liver fibrosis
Summary
Liver fibrosis is induced by a chronic hepatic insult and associated with liver dysfunction and life-threatening complications [1]. Chronic liver diseases affected millions of patients worldwide; 30% of patients are likely to develop fibrosis and cirrhosis. This condition is evolved towards liver cancer and an elevation in the mortality rate [2, 3]. In fibrosis and chronic liver diseases, there is an accumulation of fibrillar extracellular matrix (ECM) [4] and stimulation of sinusoidal endothelial cells releasing cytokines and activating hepatic stellate cells (HSCs) [5]. Kupffer cells, hepatic macrophages, play an important role in the resolution of liver fibrosis [6] via the production of a large spectrum of matrix metalloproteinase (MMPs) expression [7].
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