In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression

Phaleria macrocarpa.iPm) fruit is traditionally used to treat high cholesterol level. .However itsanti-hypercholesterolemic property is still unknown. LDL receptor is a ligand that involves in the cholesterol metabolism by taking in LDL which has -high proportion of cholesterol whereas PCSK9 i...

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Main Author:	Chong, Soo Ching
Format:	Thesis
Language:	English
Published:	2011
Subjects:	Proteins - pharmacology Rats
Online Access:	http://psasir.upm.edu.my/id/eprint/69655/1/fpsk%202011%2057%20ir.pdf
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spelling	my-upm-ir.696552019-11-11T08:35:42Z In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression 2011-12 Chong, Soo Ching Phaleria macrocarpa.iPm) fruit is traditionally used to treat high cholesterol level. .However itsanti-hypercholesterolemic property is still unknown. LDL receptor is a ligand that involves in the cholesterol metabolism by taking in LDL which has -high proportion of cholesterol whereas PCSK9 is a protein that mediates the degradation of LDL receptor. This study investigat-ed the effects of Pm fruit aqueous extract on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro conditions. In vivo study, 36 male Sprague dawley rats were randomized to 6 groups. 5 groups were given 3% (v/v) cholesterol enriched-diet for 52 days to induced to become hypercholesterolemia, followed by Pm fruit aqueous extract (0, 20, 30 and 40 mg -extract/kg bw) or .simvastatin (40 mg/kg) treatment for 84 days. The sixth group was used as a negative controL The effects of Pm fruit aqueous extr-acttreatment were determined on the following parameters: 1) body weight, 2) liver weight 3) liver weight-to-body weight ratio 4) blood lipid profiles (TC, TG: HDL and LDL) and 5) expression level of hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. Pm fruit aqueous extract significantly (p<0.05) reduced body weight gain but tends to reduce liver weight and liver weight-to-body weight ratio. As for the blood lipid profiles, 20 mgextract! kg bw of Pm significantly (P<0.05) reduced TC (1.54 mmol/L), TG (0.38 mmol/L), HDL (0.68 mmol/L) and LDL (0.94 mmollL) -whereas 30 mg extract! kg bw of Pm significantly (p<0.05) reduced TC (1-.55 mmol/L), TG (0.33 mmol/L) and LDL (0.93 mmol/L) as compared I to the untreated hypercholesterolemic group [TC (2.4 mmol/L), TG (1.13 mmol/L), HDL JO.94 mmollL) and LDL-(1.51 mmol/Lj], 40 mg. extract! kg bw of Pm signiIicantly-(p<0.05) reduced TC (1.85 mmol/L) and LDL (1.03 mmol/L). On the other hand, 20 mg extract! kg bw of Pm significantly (P<0.05Y increased LDL receptor and PCSK9 proteins by l-fold whereas 30 and 40 mg extract! kg bw of Pm had no effect on LDL receptor and PCSK9. Effect of Pm fruit aqueous extract in- in vivo model was then further analyzed in in vitro study. In vitro study, HepG2 cells were cultured in serum-free RPM! 1640, supplemented with 0.2% BSA with or without LDL (200 llM) and in the presence of Pm fruit aqueous extract (0, 0.1,2,40 and 1000 ug/ml) or simvastatin (10 llM) for 24 hours. The abundance of both LDL receptor (1-60 kDa) and -PCSK9 proteins and mRNA were then investigated. Similar to the in vivo study, Pm fruit aqueous extract was found to have increased -LDL receptor and PCSK9 proteins by l-fold in HepG2 cells with significant increment (P<0.05) at the concentration of 0.1 ug/ml. Besides that, Pm fruit aqueous extract at the concentration of 0.1 ug/ml also significantly (P<0.05) increased both LDL receptor and PCSK9 mRNA transcripts, comparable to simvastatin treated group. These study indicated that Pm fruit aqueous extract reduces body weight gain, liver weight, liver weight-to-body weight ratio and exhibited anti-hypercholesterolemic effect by reducing blood lipid profile of hypercholesterolemic rats and upregulating LDL receptor and PCSK9 at both protein and rnRNA level. Proteins - pharmacology Rats 2011-12 Thesis http://psasir.upm.edu.my/id/eprint/69655/ http://psasir.upm.edu.my/id/eprint/69655/1/fpsk%202011%2057%20ir.pdf text en public masters Universiti Putra Malaysia Proteins - pharmacology Rats
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Proteins - pharmacology Rats
spellingShingle	Proteins - pharmacology Rats Chong, Soo Ching In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
description	Phaleria macrocarpa.iPm) fruit is traditionally used to treat high cholesterol level. .However itsanti-hypercholesterolemic property is still unknown. LDL receptor is a ligand that involves in the cholesterol metabolism by taking in LDL which has -high proportion of cholesterol whereas PCSK9 is a protein that mediates the degradation of LDL receptor. This study investigat-ed the effects of Pm fruit aqueous extract on weight control and mechanistic basis of its anti-hypercholesterolemic effect in both in vivo and in vitro conditions. In vivo study, 36 male Sprague dawley rats were randomized to 6 groups. 5 groups were given 3% (v/v) cholesterol enriched-diet for 52 days to induced to become hypercholesterolemia, followed by Pm fruit aqueous extract (0, 20, 30 and 40 mg -extract/kg bw) or .simvastatin (40 mg/kg) treatment for 84 days. The sixth group was used as a negative controL The effects of Pm fruit aqueous extr-acttreatment were determined on the following parameters: 1) body weight, 2) liver weight 3) liver weight-to-body weight ratio 4) blood lipid profiles (TC, TG: HDL and LDL) and 5) expression level of hepatic LDL receptor (160 kDa and 120 kDa) and PCSK9 proteins. Pm fruit aqueous extract significantly (p<0.05) reduced body weight gain but tends to reduce liver weight and liver weight-to-body weight ratio. As for the blood lipid profiles, 20 mgextract! kg bw of Pm significantly (P<0.05) reduced TC (1.54 mmol/L), TG (0.38 mmol/L), HDL (0.68 mmol/L) and LDL (0.94 mmollL) -whereas 30 mg extract! kg bw of Pm significantly (p<0.05) reduced TC (1-.55 mmol/L), TG (0.33 mmol/L) and LDL (0.93 mmol/L) as compared I to the untreated hypercholesterolemic group [TC (2.4 mmol/L), TG (1.13 mmol/L), HDL JO.94 mmollL) and LDL-(1.51 mmol/Lj], 40 mg. extract! kg bw of Pm signiIicantly-(p<0.05) reduced TC (1.85 mmol/L) and LDL (1.03 mmol/L). On the other hand, 20 mg extract! kg bw of Pm significantly (P<0.05Y increased LDL receptor and PCSK9 proteins by l-fold whereas 30 and 40 mg extract! kg bw of Pm had no effect on LDL receptor and PCSK9. Effect of Pm fruit aqueous extract in- in vivo model was then further analyzed in in vitro study. In vitro study, HepG2 cells were cultured in serum-free RPM! 1640, supplemented with 0.2% BSA with or without LDL (200 llM) and in the presence of Pm fruit aqueous extract (0, 0.1,2,40 and 1000 ug/ml) or simvastatin (10 llM) for 24 hours. The abundance of both LDL receptor (1-60 kDa) and -PCSK9 proteins and mRNA were then investigated. Similar to the in vivo study, Pm fruit aqueous extract was found to have increased -LDL receptor and PCSK9 proteins by l-fold in HepG2 cells with significant increment (P<0.05) at the concentration of 0.1 ug/ml. Besides that, Pm fruit aqueous extract at the concentration of 0.1 ug/ml also significantly (P<0.05) increased both LDL receptor and PCSK9 mRNA transcripts, comparable to simvastatin treated group. These study indicated that Pm fruit aqueous extract reduces body weight gain, liver weight, liver weight-to-body weight ratio and exhibited anti-hypercholesterolemic effect by reducing blood lipid profile of hypercholesterolemic rats and upregulating LDL receptor and PCSK9 at both protein and rnRNA level.
format	Thesis
qualification_level	Master's degree
author	Chong, Soo Ching
author_facet	Chong, Soo Ching
author_sort	Chong, Soo Ching
title	In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
title_short	In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
title_full	In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
title_fullStr	In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
title_full_unstemmed	In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
title_sort	in vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression
granting_institution	Universiti Putra Malaysia
publishDate	2011
url	http://psasir.upm.edu.my/id/eprint/69655/1/fpsk%202011%2057%20ir.pdf
_version_	1747812717455998976

In vivo and in vitro effects of phaleria macrocarpa (scheff.) boerl on low density lipoprotein and pcsk9 expression

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