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


  • Bantari W. K. Wardhani Doctoral Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
  • Nanik Sundari Master Program in Biomedical Sciences, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
  • Raymond R. Tjandrawinata Dexa Laboratories of Biomolecular Sciences Unit, Dexa Medica Group, Cikarang, West Java, Indonesia
  • Ahmad Aulia Jusuf Department of Histology, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
  • Vivian Soetikno Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia
  • Melva Louisa Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Indonesia, Depok, Indonesia



Liver fibrosis, Phaleria macrocarpa, TGF-Beta1, MMP-13, oxidative stress


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.


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How to Cite

Wardhani BWK, Sundari N, Tjandrawinata RR, Jusuf AA, Soetikno V, Louisa M. Antifibrotic Activity of Phaleria macrocarpa Extract in Rat Liver-fibrosis Model: Focus on Oxidative Stress Markers, TGF-β1 and MMP-13. Open Access Maced J Med Sci [Internet]. 2020 Sep. 10 [cited 2022 May 19];8(A):555-62. Available from: