Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.

<h4>Objective</h4>Biochanin A (BCA) is an isoflavone found in red clover and peanuts. Recently, it drew much attention as a promising anticancer and antioxidant. Due to its diversity in pharmacological actions, we were encouraged to investigate its potential as an antifibrotic, elucidati...

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Autores principales:	Randa M Breikaa, Mardi M Algandaby, Ebtehal El-Demerdash, Ashraf B Abdel-Naim
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9f057c2072d948ec82c9f7771ca029fe
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spelling	oai:doaj.org-article:9f057c2072d948ec82c9f7771ca029fe2021-11-18T07:37:29ZMultimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.1932-620310.1371/journal.pone.0069276https://doaj.org/article/9f057c2072d948ec82c9f7771ca029fe2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23874933/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Objective</h4>Biochanin A (BCA) is an isoflavone found in red clover and peanuts. Recently, it drew much attention as a promising anticancer and antioxidant. Due to its diversity in pharmacological actions, we were encouraged to investigate its potential as an antifibrotic, elucidating the different molecular mechanisms involved.<h4>Design</h4>Rats were pretreated with BCA, then injected with carbon tetrachloride (CCl4) for 6 weeks. Changes in liver weight and histology were examined and levels of aspartate and alanine aminotransferases, cholesterol, triglycerides, alkaline phosphatase and total bilirubin measured. To assess hepatic efficiency, indocyanine green was injected and its clearance calculated and albumin, total proteins and insulin-like growth factor-1 expression were measured. Cytochrome P4502E1 activity, cytochrome P4501A1 expression, in addition to sulfotransferase1A1 expression were determined to deduce the effect of BCA on hepatic metabolism. As oxidative stress markers, lipid peroxides levels, reduced glutathione, superoxide dismutase and catalase activities, as well as the total antioxidant capacity, were assessed. Nitric oxide, inducible nitric oxide synthase and cyclooxygenase-2 were used as indicators of the inflammatory response. Signaling pathways involving tumor necrosis factor-alpha, nuclear factor-kappa B, transforming growth factor-beta1, matrix metalloproteinase-9 and alpha-smooth muscle actin were investigated accordingly. Extent of fibrosis was examined by Masson's stain and measuring hydroxyproline levels.<h4>Results</h4>BCA pretreatment significantly protected against the chronic damage of CCl4. Liver injury, oxidative stress, inflammation and fibrosis markers decreased, while hepatic efficiency improved.<h4>Conclusion</h4>Our findings suggested that BCA administration protects against fibrotic complications, a property that can be contributed to the multimechanistic approach of the drug.Randa M BreikaaMardi M AlgandabyEbtehal El-DemerdashAshraf B Abdel-NaimPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 7, p e69276 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Randa M Breikaa Mardi M Algandaby Ebtehal El-Demerdash Ashraf B Abdel-Naim Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
description	<h4>Objective</h4>Biochanin A (BCA) is an isoflavone found in red clover and peanuts. Recently, it drew much attention as a promising anticancer and antioxidant. Due to its diversity in pharmacological actions, we were encouraged to investigate its potential as an antifibrotic, elucidating the different molecular mechanisms involved.<h4>Design</h4>Rats were pretreated with BCA, then injected with carbon tetrachloride (CCl4) for 6 weeks. Changes in liver weight and histology were examined and levels of aspartate and alanine aminotransferases, cholesterol, triglycerides, alkaline phosphatase and total bilirubin measured. To assess hepatic efficiency, indocyanine green was injected and its clearance calculated and albumin, total proteins and insulin-like growth factor-1 expression were measured. Cytochrome P4502E1 activity, cytochrome P4501A1 expression, in addition to sulfotransferase1A1 expression were determined to deduce the effect of BCA on hepatic metabolism. As oxidative stress markers, lipid peroxides levels, reduced glutathione, superoxide dismutase and catalase activities, as well as the total antioxidant capacity, were assessed. Nitric oxide, inducible nitric oxide synthase and cyclooxygenase-2 were used as indicators of the inflammatory response. Signaling pathways involving tumor necrosis factor-alpha, nuclear factor-kappa B, transforming growth factor-beta1, matrix metalloproteinase-9 and alpha-smooth muscle actin were investigated accordingly. Extent of fibrosis was examined by Masson's stain and measuring hydroxyproline levels.<h4>Results</h4>BCA pretreatment significantly protected against the chronic damage of CCl4. Liver injury, oxidative stress, inflammation and fibrosis markers decreased, while hepatic efficiency improved.<h4>Conclusion</h4>Our findings suggested that BCA administration protects against fibrotic complications, a property that can be contributed to the multimechanistic approach of the drug.
format	article
author	Randa M Breikaa Mardi M Algandaby Ebtehal El-Demerdash Ashraf B Abdel-Naim
author_facet	Randa M Breikaa Mardi M Algandaby Ebtehal El-Demerdash Ashraf B Abdel-Naim
author_sort	Randa M Breikaa
title	Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
title_short	Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
title_full	Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
title_fullStr	Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
title_full_unstemmed	Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
title_sort	multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/9f057c2072d948ec82c9f7771ca029fe
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Multimechanistic antifibrotic effect of biochanin a in rats: implications of proinflammatory and profibrogenic mediators.

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