Cargando…
Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity
OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl(4))-induced injury. MATERIALS AND METHODS: Hepatotoxicity was induced by a single dose...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Medknow Publications & Media Pvt Ltd
2016
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971954/ https://www.ncbi.nlm.nih.gov/pubmed/27563222 http://dx.doi.org/10.4103/0973-1296.185765 |
_version_ | 1782446187903713280 |
---|---|
author | Al-Rasheed, Nouf Faddah, Laila Al-Rasheed, Nawal Bassiouni, Yieldez A. Hasan, Iman H. Mahmoud, Ayman M. Mohamad, Raeesa A. Yacoub, Hazar I. |
author_facet | Al-Rasheed, Nouf Faddah, Laila Al-Rasheed, Nawal Bassiouni, Yieldez A. Hasan, Iman H. Mahmoud, Ayman M. Mohamad, Raeesa A. Yacoub, Hazar I. |
author_sort | Al-Rasheed, Nouf |
collection | PubMed |
description | OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl(4))-induced injury. MATERIALS AND METHODS: Hepatotoxicity was induced by a single dose of CCl(4) (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/kg) and/or ME (20 mg/kg) for 21 days. RESULTS: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase-3 activity were significantly attenuated in SIL treated CCl(4)-intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl(4)-intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. CONCLUSIONS: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl(4)-induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies. SUMMARY: Silymarin, chlorogenic acid and melatonin possess in vivo hepatoprotective activity. Silymarin, chlorogenic acid and melatonin attenuate fibrogenesis, oxidative DNA damage, inflammation and apoptosis. Chlorogenic acid and melatonin enhance the hepatoprotective effect of silymarin. Abbreviations used: SIL: silymarin, CA: chlorogenic acid, ME: melatonin, CCl4: carbon tetrachloride, CYP2E1, cytochrome P450 2E1, ALT: alanine aminotransferase, IL-6: interleukin 6, IFN-γ: interferon gamma, VEGF: vascular endothelial growth factor, TNF-α: tumor necrosis factor alpha, CRP: C-reactive protein, 8-OxodG: 8-Oxo-2’-deoxyguanosine, TGF-B1: transforming growth factor beta 1, HSCs: hepatic stellate cells. |
format | Online Article Text |
id | pubmed-4971954 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Medknow Publications & Media Pvt Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-49719542016-08-25 Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity Al-Rasheed, Nouf Faddah, Laila Al-Rasheed, Nawal Bassiouni, Yieldez A. Hasan, Iman H. Mahmoud, Ayman M. Mohamad, Raeesa A. Yacoub, Hazar I. Pharmacogn Mag Original Article OBJECTIVE: The aim of this study was to evaluate the hepatoprotective effects of silymarin (SIL), alone and combined with chlorogenic acid (CA) and/or melatonin (ME), using a rat model of carbon tetrachloride (CCl(4))-induced injury. MATERIALS AND METHODS: Hepatotoxicity was induced by a single dose of CCl(4) (1 ml/kg, IP). One day after, rats were received SIL (200 mg/kg) alone or in combination with CA (60 mg/kg) and/or ME (20 mg/kg) for 21 days. RESULTS: SIL significantly decreased serum alanine aminotransferase, inflammatory cytokines, and vascular endothelial growth factor levels. Histological alterations, fibrogenesis, oxidative DNA damage, inflammatory mediators, and caspase-3 activity were significantly attenuated in SIL treated CCl(4)-intoxicated rats. On the other hand, cytochrome P450 2E1 activity showed a significant decrease in the liver of CCl(4)-intoxicated rats, an effect that was reversed following treatment with SIL. All beneficial effects of SIL were markedly potentiated when combined with CA and/or ME. CONCLUSIONS: These data indicate that SIL, alone and combined with CA and/or ME, protected the liver against CCl(4)-induced hepatotoxicity via attenuating inflammation, oxidative DNA damage, apoptosis, and fibrotic changes. The significantly intensified hepatoprotective effects of SIL when combined with both CA and ME suggest a possible synergism. These synergistic effects need to be further confirmed using detailed studies. SUMMARY: Silymarin, chlorogenic acid and melatonin possess in vivo hepatoprotective activity. Silymarin, chlorogenic acid and melatonin attenuate fibrogenesis, oxidative DNA damage, inflammation and apoptosis. Chlorogenic acid and melatonin enhance the hepatoprotective effect of silymarin. Abbreviations used: SIL: silymarin, CA: chlorogenic acid, ME: melatonin, CCl4: carbon tetrachloride, CYP2E1, cytochrome P450 2E1, ALT: alanine aminotransferase, IL-6: interleukin 6, IFN-γ: interferon gamma, VEGF: vascular endothelial growth factor, TNF-α: tumor necrosis factor alpha, CRP: C-reactive protein, 8-OxodG: 8-Oxo-2’-deoxyguanosine, TGF-B1: transforming growth factor beta 1, HSCs: hepatic stellate cells. Medknow Publications & Media Pvt Ltd 2016-05 /pmc/articles/PMC4971954/ /pubmed/27563222 http://dx.doi.org/10.4103/0973-1296.185765 Text en Copyright: © Pharmacognosy Magazine http://creativecommons.org/licenses/by-nc-sa/3.0 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms. |
spellingShingle | Original Article Al-Rasheed, Nouf Faddah, Laila Al-Rasheed, Nawal Bassiouni, Yieldez A. Hasan, Iman H. Mahmoud, Ayman M. Mohamad, Raeesa A. Yacoub, Hazar I. Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title | Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title_full | Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title_fullStr | Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title_full_unstemmed | Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title_short | Protective Effects of Silymarin, Alone or in Combination with Chlorogenic Acid and/or Melatonin, Against Carbon Tetrachloride-induced Hepatotoxicity |
title_sort | protective effects of silymarin, alone or in combination with chlorogenic acid and/or melatonin, against carbon tetrachloride-induced hepatotoxicity |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4971954/ https://www.ncbi.nlm.nih.gov/pubmed/27563222 http://dx.doi.org/10.4103/0973-1296.185765 |
work_keys_str_mv | AT alrasheednouf protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT faddahlaila protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT alrasheednawal protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT bassiouniyieldeza protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT hasanimanh protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT mahmoudaymanm protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT mohamadraeesaa protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity AT yacoubhazari protectiveeffectsofsilymarinaloneorincombinationwithchlorogenicacidandormelatoninagainstcarbontetrachlorideinducedhepatotoxicity |