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: | |
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| Format: | Thesis |
| Language: | English |
| Published: |
2016
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/69460/1/FSTM%202016%2026%20IR.pdf |
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| Summary: | 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. |
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