Abstract
Phaleria macrocarpa is one of the Indonesian herbal plants which has been shown to have a hepatoprotective effect. This study was conducted to evaluate the protective effect of water extract of mahkota dewa (Phaleria macrocarpa) in liver fibrosis and to elucidate its mechanism of action. Male Sprague-Dawley rats were treated with carbon tetrachloride (CCl4) for 8 weeks to induce liver fibrosis. Rats were randomly divided into 6 groups (n=5), i.e., control group, CCl4 group, CCl4 + NAC group, CCl4 + various doses of water extract of Phaleria macrocarpa (50, 100, and 150 mg/kg body weight). Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), liver histopathology, malondialdehyde (MDA), ratio GSH/GSSG, Tumor Necrosis Factor- (TNF-) α, and Transforming Growth Factor- (TGF-) β1 were analyzed. This study demonstrated that water extract of Phaleria macrocarpa and NAC significantly protected CCl4-induced liver injury as demonstrated by reduced AST, ALT, ALP, and fibrosis percentage compared with the CCl4-only group. In addition, water extract of Phaleria macrocarpa and NAC significantly reduced the levels of MDA, TNF-α, and TGF-β1 as well as increasing the ratio of GSH/GSSG. Water extract of Phaleria macrocarpa prevents CCl4-induced fibrosis in rats. The prevention of liver fibrosis was at least in part through its antioxidant and anti-inflammatory activities and through its capacity to inhibit hepatic stellate cells (HSC) activation by reducing fibrogenic cytokine TGF-β1.
Highlights
Liver fibrosis is the accumulation of extracellular matrix, or excess connective tissue, in response to chronic liver injury
This study has demonstrated that intraperitoneal injection of CCl4 to rats for 8 weeks leads to a marked elevation in the activities of plasma ALT, AST, and alkaline phosphatase (ALP) as compared with the control group
Our results were in agreement with the findings of Morsy et al (2012) [6], Chaved E et al (2008) [7], Demiroren et al (2014) [13], and Fu et al (2008) [20], in which they used CCl4 to develop a model of liver fibrosis
Summary
Liver fibrosis is the accumulation of extracellular matrix, or excess connective tissue, in response to chronic liver injury. Carbon tetrachloride (CCl4), a well-known hepatotoxin, is widely used in laboratory animals to induce liver injuries including liver fibrosis. Hepatic stellate cells (HSC), whose main function is to store vitamin A and plays a pivotal role in activating the immune response via secretion of cytokines and chemokines, are activated as a result of liver injury. HSC increase their production of extracellular matrix (ECM) protein leading to liver fibrosis. Mahkota dewa is rich in alkaloid, flavonoid, and polyphenol and these compounds have pharmacological activities such as antiinflammation, antioxidant, anticancer, antidiabetic, antihypertension, and hepatoprotective [8,9,10,11]. Journal of Toxicology in CCl4-induced liver fibrosis in rats and its mechanism of action. For comparison we used N-acetylcysteine (NAC) which has antioxidant and free radical scavenging action [6, 12, 13]
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