TY - JOUR
T1 - Antifibrotic activity of phaleria macrocarpa extract in rat liver-fibrosis model
T2 - Focus on oxidative stress markers, TGF-β1 and MMP-13
AU - Wardhani, Bantari W.K.
AU - Sundari, Nanik
AU - Tjandrawinata, Raymond R.
AU - Jusuf, Ahmad Aulia
AU - Soetikno, Vivian
AU - Louisa, Melva
N1 - Funding Information:
The authors would like to thank PT Dexa Medica (Jakarta, Indonesia) for funding this study, Universitas Indonesia for International Publication grant and drh. Vetnizah Juaniantito, Ph.D. from Bogor Agricultural University, Faculty of Veterinary Medicine, Bogor, Indonesia, for helping us in immunohistochemistry work.
Publisher Copyright:
© 2020 Bantari W. K. Wardhani, Nanik Sundari, Raymond R. Tjandrawinata, Ahmad Aulia Jusuf, Vivian Soetikno, Melva Louisa.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/1/2
Y1 - 2020/1/2
N2 - 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.
AB - 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.
KW - Liver fibrosis
KW - MMP-13
KW - Oxidative stress
KW - Phaleria macrocarpa
KW - TGF-β1
UR - http://www.scopus.com/inward/record.url?scp=85094642452&partnerID=8YFLogxK
U2 - 10.3889/oamjms.2020.4929
DO - 10.3889/oamjms.2020.4929
M3 - Article
AN - SCOPUS:85094642452
VL - 8
SP - 555
EP - 562
JO - Open Access Macedonian Journal of Medical Sciences
JF - Open Access Macedonian Journal of Medical Sciences
SN - 1857-5749
ER -