Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics

In the present study, antioxidant and antidiabetic activities of different Melicope Lunu-ankenda (ML) ethanolic extracts were evaluated using in vitro and in vivo models. Proton nuclear magnetic resonance (1H NMR) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS...

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Main Author:	Baroor Al-Zuaidy, Mizher Hezam
Format:	Thesis
Language:	English
Published:	2016
Subjects:	Glucose - Synthesis Hypoglycemic agents
Online Access:	http://psasir.upm.edu.my/id/eprint/69460/1/FSTM%202016%2026%20IR.pdf
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id	my-upm-ir.69460
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spelling	my-upm-ir.694602019-09-20T02:19:31Z Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics 2016-12 Baroor Al-Zuaidy, Mizher Hezam In the present study, antioxidant and antidiabetic activities of different Melicope Lunu-ankenda (ML) ethanolic extracts were evaluated using in vitro and in vivo models. Proton nuclear magnetic resonance (1H NMR) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were used to profile the bioactive metabolites in ML leaf extracts. Sixty percent ethanolic ML extract showed the highest inhibitory effect against α-glucosidase, DPPH scavenging activity and ferric reducing antioxidant power. Results based on cell line investigations showed that the leaf extract stimulated the glucose uptake by both 3T3-L1 and HepG2 cells. A discriminatory study on the metabolites responsible for the variation between different ethanolic ML extracts was successfully performed using 1H-NMR-based metabolomics. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) scores revealed clear and distinct separations by PC1 and PC2 with an eigenvalue of 69.9%. The main bioactive compounds found responsible for the separation were isorhamnetin, skimmianine, scopoletin and melicarpinone. The antidiabetic effect was also carried out in vivo using rat models. The extract exerted its effect by decreasing the blood glucose level, insulin resistance, and increasing insulin sensitivity. The treatment of obese diabetic rats with ML extract also resulted in significant decrease in TG, TC, and LDL levels. However, HDL levels were significantly increased. The impact of treatment was also observed in terms of regulation of the renal injury markers and activities of liver enzymes. In addition, NMR-based metabolomics and multivariate data analysis showed clear metabolic differences in the serum and urine samples of healthy, diabetic and treated diabetic Sprague-dawley rats. The metabolomics results demonstrated that the observed metabolic changes were linked with diabetes progression, and metabolic biomarkers were reflected by the perturbed metabolites, hence providing clear understanding regarding the underlying mechanism involved in generation and progression of diabetes. This study presented potent antidiabetic activity of ML and describes its mechanism of action. The NMR based metabolomics approach is supportive for the additional understanding of diabetes-related mechanisms and enhances the metabolic pathways affected in the diabetic rats. These results of the present study may further contribute towards understanding of the underlying molecular mechanism of this medicinal remedy. Glucose - Synthesis Hypoglycemic agents 2016-12 Thesis http://psasir.upm.edu.my/id/eprint/69460/ http://psasir.upm.edu.my/id/eprint/69460/1/FSTM%202016%2026%20IR.pdf text en public doctoral Universiti Putra Malaysia Glucose - Synthesis Hypoglycemic agents
institution	Universiti Putra Malaysia
collection	PSAS Institutional Repository
language	English
topic	Glucose - Synthesis Hypoglycemic agents
spellingShingle	Glucose - Synthesis Hypoglycemic agents Baroor Al-Zuaidy, Mizher Hezam Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
description	In the present study, antioxidant and antidiabetic activities of different Melicope Lunu-ankenda (ML) ethanolic extracts were evaluated using in vitro and in vivo models. Proton nuclear magnetic resonance (1H NMR) and ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) were used to profile the bioactive metabolites in ML leaf extracts. Sixty percent ethanolic ML extract showed the highest inhibitory effect against α-glucosidase, DPPH scavenging activity and ferric reducing antioxidant power. Results based on cell line investigations showed that the leaf extract stimulated the glucose uptake by both 3T3-L1 and HepG2 cells. A discriminatory study on the metabolites responsible for the variation between different ethanolic ML extracts was successfully performed using 1H-NMR-based metabolomics. Principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA) scores revealed clear and distinct separations by PC1 and PC2 with an eigenvalue of 69.9%. The main bioactive compounds found responsible for the separation were isorhamnetin, skimmianine, scopoletin and melicarpinone. The antidiabetic effect was also carried out in vivo using rat models. The extract exerted its effect by decreasing the blood glucose level, insulin resistance, and increasing insulin sensitivity. The treatment of obese diabetic rats with ML extract also resulted in significant decrease in TG, TC, and LDL levels. However, HDL levels were significantly increased. The impact of treatment was also observed in terms of regulation of the renal injury markers and activities of liver enzymes. In addition, NMR-based metabolomics and multivariate data analysis showed clear metabolic differences in the serum and urine samples of healthy, diabetic and treated diabetic Sprague-dawley rats. The metabolomics results demonstrated that the observed metabolic changes were linked with diabetes progression, and metabolic biomarkers were reflected by the perturbed metabolites, hence providing clear understanding regarding the underlying mechanism involved in generation and progression of diabetes. This study presented potent antidiabetic activity of ML and describes its mechanism of action. The NMR based metabolomics approach is supportive for the additional understanding of diabetes-related mechanisms and enhances the metabolic pathways affected in the diabetic rats. These results of the present study may further contribute towards understanding of the underlying molecular mechanism of this medicinal remedy.
format	Thesis
qualification_level	Doctorate
author	Baroor Al-Zuaidy, Mizher Hezam
author_facet	Baroor Al-Zuaidy, Mizher Hezam
author_sort	Baroor Al-Zuaidy, Mizher Hezam
title	Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
title_short	Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
title_full	Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
title_fullStr	Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
title_full_unstemmed	Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics
title_sort	antidiabetic effects of melicope lunu-ankenda (gaertn.) t.g. hartley on obese stz-induced diabetic rats using nmr-based metabolomics
granting_institution	Universiti Putra Malaysia
publishDate	2016
url	http://psasir.upm.edu.my/id/eprint/69460/1/FSTM%202016%2026%20IR.pdf
_version_	1747812702182440960

Antidiabetic effects of Melicope lunu-ankenda (Gaertn.) T.G. Hartley on obese STZ-induced diabetic rats using NMR-based metabolomics

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