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Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats
This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given in...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184875/ https://www.ncbi.nlm.nih.gov/pubmed/25280007 http://dx.doi.org/10.1371/journal.pone.0109424 |
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author | Bardi, Daleya Abdulaziz Halabi, Mohammed Farouq Hassandarvish, Pouya Rouhollahi, Elham Paydar, Mohammadjavad Moghadamtousi, Soheil Zorofchian Al-Wajeeh, Nahla Saeed Ablat, Abdulwali Abdullah, Nor Azizan Abdulla, Mahmood Ameen |
author_facet | Bardi, Daleya Abdulaziz Halabi, Mohammed Farouq Hassandarvish, Pouya Rouhollahi, Elham Paydar, Mohammadjavad Moghadamtousi, Soheil Zorofchian Al-Wajeeh, Nahla Saeed Ablat, Abdulwali Abdullah, Nor Azizan Abdulla, Mahmood Ameen |
author_sort | Bardi, Daleya Abdulaziz |
collection | PubMed |
description | This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson’s Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells. |
format | Online Article Text |
id | pubmed-4184875 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-41848752014-10-07 Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats Bardi, Daleya Abdulaziz Halabi, Mohammed Farouq Hassandarvish, Pouya Rouhollahi, Elham Paydar, Mohammadjavad Moghadamtousi, Soheil Zorofchian Al-Wajeeh, Nahla Saeed Ablat, Abdulwali Abdullah, Nor Azizan Abdulla, Mahmood Ameen PLoS One Research Article This study investigated the hepatoprotective effects of ethanolic Andrographis paniculata leaf extract (ELAP) on thioacetamide-induced hepatotoxicity in rats. An acute toxicity study proved that ELAP is not toxic in rats. To examine the effects of ELAP in vivo, male Sprague Dawley rats were given intraperitoneal injections of vehicle 10% Tween-20, 5 mL/kg (normal control) or 200 mg/kg TAA thioacetamide (to induce liver cirrhosis) three times per week. Three additional groups were treated with thioacetamide plus daily oral silymarin (50 mg/kg) or ELAP (250 or 500 mg/kg). Liver injury was assessed using biochemical tests, macroscopic and microscopic tissue analysis, histopathology, and immunohistochemistry. In addition, HepG2 and WRL-68 cells were treated in vitro with ELAP fractions to test cytotoxicity. Rats treated with ELAP exhibited significantly lower liver/body weight ratios and smoother, more normal liver surfaces compared with the cirrhosis group. Histopathology using Hematoxylin and Eosin along with Masson’s Trichrome stain showed minimal disruption of hepatic cellular structure, minor fibrotic septa, a low degree of lymphocyte infiltration, and minimal collagen deposition after ELAP treatment. Immunohistochemistry indicated that ELAP induced down regulation of proliferating cell nuclear antigen. Also, hepatic antioxidant enzymes and oxidative stress parameters in ELAP-treated rats were comparable to silymarin-treated rats. ELAP administration reduced levels of altered serum liver biomarkers. ELAP fractions were non-cytotoxic to WRL-68 cells, but possessed anti-proliferative activity on HepG2 cells, which was confirmed by a significant elevation of lactate dehydrogenase, reactive oxygen species, cell membrane permeability, cytochrome c, and caspase-8,-9, and, -3/7 activity in HepG2 cells. A reduction of mitochondrial membrane potential was also detected in ELAP-treated HepG2 cells. The hepatoprotective effect of 500 mg/kg of ELAP is proposed to result from the reduction of thioacetamide-induced toxicity, normalizing reactive oxygen species levels, inhibiting cellular proliferation, and inducing apoptosis in HepG2 cells. Public Library of Science 2014-10-03 /pmc/articles/PMC4184875/ /pubmed/25280007 http://dx.doi.org/10.1371/journal.pone.0109424 Text en © 2014 Bardi et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bardi, Daleya Abdulaziz Halabi, Mohammed Farouq Hassandarvish, Pouya Rouhollahi, Elham Paydar, Mohammadjavad Moghadamtousi, Soheil Zorofchian Al-Wajeeh, Nahla Saeed Ablat, Abdulwali Abdullah, Nor Azizan Abdulla, Mahmood Ameen Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title |
Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title_full |
Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title_fullStr |
Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title_full_unstemmed |
Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title_short |
Andrographis paniculata Leaf Extract Prevents Thioacetamide-Induced Liver Cirrhosis in Rats |
title_sort | andrographis paniculata leaf extract prevents thioacetamide-induced liver cirrhosis in rats |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4184875/ https://www.ncbi.nlm.nih.gov/pubmed/25280007 http://dx.doi.org/10.1371/journal.pone.0109424 |
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