In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee

Muntingia calabura /Muntingiaceae,! is known as kerukup siam’ or 'pokok buah ceri’ locally. It has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the safety and the metabolic pathways involved i...

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Main Author:	Rofiee, Mohd Salleh
Format:	Thesis
Language:	English
Published:	2016
Subjects:	Diseases of the digestive system Gastroenterology
Online Access:	https://ir.uitm.edu.my/id/eprint/41509/1/41509.pdf
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id	my-uitm-ir.41509
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spelling	my-uitm-ir.415092022-11-30T07:35:23Z In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee 2016 Rofiee, Mohd Salleh Diseases of the digestive system. Gastroenterology Pharmacognosy. Pharmaceutical substances (Plant, animal, and inorganic) Muntingia calabura /Muntingiaceae,! is known as kerukup siam’ or 'pokok buah ceri’ locally. It has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the safety and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura. Phytochemical analysis of the extract was carried out. The standardization of the extracts was done using LCMS Q-TOF. The standardized extract was subjected to acute and repeated doses of 28-day oral toxicity study. Three different in-vim hepatotoxic models which are CCU-induced, PCM-induced and alcohol-induced were developed and a dose dependent hepatoprotective effect of M calabura (100 mg/kg, 200 mg/kg and 400 mg/kg) was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment for CCU and PCM induced hepatotoxic rats while samples were collected at the end of 22-days for alcohol-induced hepatotoxic rats. Histopathological study of the liver slice was carried out to confirm the hepatoprotective activity of the extract. Liquid chromatography-mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with hepatoxicant and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of the pathways involved. This study shows that the body weight, food and water consumption were significantly decreased and histopathological study revealed liver damage in all In-vivo models of hepatotoxic rats. PCA score plots of the hepatotoxic rats clustered separately from the control, while groups given pre-treatment with the extract clustered closely with the control. This indicates that the metabolic profiles from the groups which were given pre-treatment with the extract were almost similar to those of the control. Several candidate biomarkers were identified and they were associated with perturbations of major pathways involve in inflammation. Interestingly, all the potential biomarkers were reversed to almost normal level in the group given pre-treatment with the extract. This study has successfully isolated major pathways involved in the hepatoprotective effects of MCME using LCMS Q-TOF metabolomics approach. Several biomarkers and their pathways in hepatoprotection have not been reported previously and may provide potential therapeutic targets and/or options for protection from chemical induced liver injury. 2016 Thesis https://ir.uitm.edu.my/id/eprint/41509/ https://ir.uitm.edu.my/id/eprint/41509/1/41509.pdf text en public phd doctoral Universiti Teknologi MARA (UiTM) Faculty of Pharmacy Teh, Lay Kek
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Teh, Lay Kek
topic	Diseases of the digestive system Gastroenterology Diseases of the digestive system Gastroenterology
spellingShingle	Diseases of the digestive system Gastroenterology Diseases of the digestive system Gastroenterology Rofiee, Mohd Salleh In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
description	Muntingia calabura /Muntingiaceae,! is known as kerukup siam’ or 'pokok buah ceri’ locally. It has been used in Southeast Asia and tropical America as antipyretic, antiseptic, analgesic, antispasmodic and liver tonic. This study aims to determine the safety and the metabolic pathways involved in the hepatoprotective mechanism of M. calabura. Phytochemical analysis of the extract was carried out. The standardization of the extracts was done using LCMS Q-TOF. The standardized extract was subjected to acute and repeated doses of 28-day oral toxicity study. Three different in-vim hepatotoxic models which are CCU-induced, PCM-induced and alcohol-induced were developed and a dose dependent hepatoprotective effect of M calabura (100 mg/kg, 200 mg/kg and 400 mg/kg) was conducted. Body weight, food and water consumption were measured every day and rats were sacrificed to collect the serum samples at the end of the 10-days treatment for CCU and PCM induced hepatotoxic rats while samples were collected at the end of 22-days for alcohol-induced hepatotoxic rats. Histopathological study of the liver slice was carried out to confirm the hepatoprotective activity of the extract. Liquid chromatography-mass spectrometry quadrapole time of flight (LC/MS-QTOF) combined with principal component analysis (PCA) were used to determine differentially expressed metabolites due to treatment with hepatoxicant and M. calabura extracts. Metabolomics Pathway Analysis (MetPA) was used for analysis and visualization of the pathways involved. This study shows that the body weight, food and water consumption were significantly decreased and histopathological study revealed liver damage in all In-vivo models of hepatotoxic rats. PCA score plots of the hepatotoxic rats clustered separately from the control, while groups given pre-treatment with the extract clustered closely with the control. This indicates that the metabolic profiles from the groups which were given pre-treatment with the extract were almost similar to those of the control. Several candidate biomarkers were identified and they were associated with perturbations of major pathways involve in inflammation. Interestingly, all the potential biomarkers were reversed to almost normal level in the group given pre-treatment with the extract. This study has successfully isolated major pathways involved in the hepatoprotective effects of MCME using LCMS Q-TOF metabolomics approach. Several biomarkers and their pathways in hepatoprotection have not been reported previously and may provide potential therapeutic targets and/or options for protection from chemical induced liver injury.
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Rofiee, Mohd Salleh
author_facet	Rofiee, Mohd Salleh
author_sort	Rofiee, Mohd Salleh
title	In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
title_short	In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
title_full	In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
title_fullStr	In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
title_full_unstemmed	In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee
title_sort	in vivo hepatoprotective activity of muntingia calabura leaves extract: a metabolomics analysis / mohd salleh rofiee
granting_institution	Universiti Teknologi MARA (UiTM)
granting_department	Faculty of Pharmacy
publishDate	2016
url	https://ir.uitm.edu.my/id/eprint/41509/1/41509.pdf
_version_	1783734643291324416

In vivo hepatoprotective activity of Muntingia calabura leaves extract: a metabolomics analysis / Mohd Salleh Rofiee

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