Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13

Abstract

AIM: This study was aimed to determine the antifibrotic activity of Phaleria macrocarpa (PM) extract in liver fibrosis (LF) and its possible mechanism in the rat model.
 METHODS: Sprague Dawley male rats were injected with 2 mL/kg BW of carbon tetrachloride intraperitoneally twice a week for 2 weeks, followed by 1 mL/kg BW for 6 weeks. Afterward, the treatments began from the 3rd week: Silymarin 100 mg/kg BW/day, standardized PM extract (Proliverenol) 75 or 150 mg/kg BW/day orally. Rats were sacrificed in the 8th week. Blood and liver were collected to analyze liver function, liver damage and fibrosis marker, oxidative stress markers, pro-fibrogenic cytokine, and antifibrotic marker.
 RESULTS: Our study showed that the treatment of silymarin and PM resulted in the normalized activity of liver function, followed by the amelioration of oxidative stress, demonstrated by the decreased malondialdehyde levels and an increased ratio of glutathione and glutathione disulfide. All markers examined showed that PM extract has antioxidant activity due to decreased hepatic stellate cell activation. We also found a decrease in tumor growth factors-β1 and protein expressions of matrix metalloproteinases-13 in all treatment groups compared to the carbon tetrachloride group. There were tendencies of the decreased fibrotic area following improvements of biochemical parameters.
 CONCLUSION: PM extracts ameliorate carbon tetrachloride-induced LF. The proposed mechanism is by overcoming oxidative stress and regulating pro-fibrogenic cytokine and antifibrotic markers.

Toxicity Effect of Phaleria macrocarpa (Mahkota Dewa) on Liver Function in Sprague Dawley Rats

“…22 The results with Phaleria macrocarpa fruit extract are in agreement with results obtained by two studies that found hepatoprotective effect of phaleria macrocarpa against ethanolinduced hepatotoxicity and carbon-tetrachloride induced hepatotoxicity. 23,24 The total mean of plasma ALP level was within the normal range (125.93 U/L). Following supplementation with Phaleria macrocarpa fruit extract (750, 1500, 3000 mg/kg bw) the total mean value of plasma ALP level was significantly higher than total mean in control group.…”

“…The findings are consistent with results from the previous study, in which proven Phaleria macrocarpa extract have improved liver function test markers through decreased ALT, AST, GGT and ALP activity. 27…”

Adenine Combined with Cisplatin Promotes Anticancer Activity against Hepatocellular Cancer Cells through AMPK-Mediated p53/p21 and p38 MAPK Cascades

“…As a result, apoptosis, oxidative stress, and inflammation pathways play important roles in both hepatic tumorigenesis and anticancer activity against HCC in response to natural bioactives. Phaleria macrocarpa extract has been reported to exert antifibrotic activity via reducing oxidative stress and pro-fibrogenic TGF-β1 and MMP-13 expression [ 24 ]. Safranal, a small molecule from saffron, has shown anticancer activity against HepG2 cells via oxidative stress-triggered protein destabilization and DNA damage apoptosis [ 25 ].…”

Effect of 12 Months of Exercise With Stachys Lavandulifolia Consumption on Anxiety, Metabolic Syndrome Profiles and Antioxidant Defense and Lipid Peroxidation in Women With Metabolic Syndrome

“…The rate can be determined from the absorbance change over time. Metaphosphoric acid is provided to remove interfering proteins or enzymes from samples (23).…”