Correlation of the α-glucosidase inhibitory activity to metabolites of tetracera scandens leaves extracts using metabolomics and molecular docking approaches /
α-Glucosidase inhibition is regarded as an efficient mechanism for management of the postprandial hyperglycemia associated with type 2 diabetes mellitus. The severe gastrointestinal adverse effects have been reported to affect patient's compliance towards the synthetic α-glucosidase inhibitor d...
Saved in:
| Main Author: | |
|---|---|
| Format: | Thesis |
| Language: | English |
| Published: |
Kuantan, Pahang :
Kulliyyah of Pharmacy, International Islamic University Malaysia,
2020
|
| Subjects: | |
| Online Access: | Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| LEADER | 058220000a22003970004500 | ||
|---|---|---|---|
| 008 | 200908s2020 my a f m 000 0 eng d | ||
| 040 | |a UIAM |b eng |e rda | ||
| 041 | |a eng | ||
| 043 | |a a-my--- | ||
| 100 | 1 | |a Nokhala, Ahmed Ahmed Mohamed, |e author | |
| 245 | 1 | |a Correlation of the α-glucosidase inhibitory activity to metabolites of tetracera scandens leaves extracts using metabolomics and molecular docking approaches / |c by Ahmed Ahmed Mohamed Nokhala | |
| 264 | 1 | |a Kuantan, Pahang : |b Kulliyyah of Pharmacy, International Islamic University Malaysia, |c 2020 | |
| 300 | |a xiv, 107 leaves : |b colour illustrations ; |c 30cm. | ||
| 336 | |2 rdacontent |a text | ||
| 337 | |2 rdamedia |a unmediated | ||
| 337 | |2 rdamedia |a computer | ||
| 338 | |2 rdacarrier |a volume | ||
| 338 | |2 rdacarrier |a computer disc | ||
| 338 | |2 rdacarrier |a online resource | ||
| 347 | |2 rdaft |a text file |b PDF | ||
| 500 | |a Abstracts in English and Arabic. | ||
| 500 | |a "A thesis submitted in fulfilment of the requirement for the degree of Master in Pharmaceutical Sciences (Pharmaceutical Chemistry)." --On title page. | ||
| 502 | |a Thesis (MSPHC)--International Islamic University Malaysia, 2020. | ||
| 504 | |a Includes bibliographical references (leaves 77-88). | ||
| 520 | |a α-Glucosidase inhibition is regarded as an efficient mechanism for management of the postprandial hyperglycemia associated with type 2 diabetes mellitus. The severe gastrointestinal adverse effects have been reported to affect patient's compliance towards the synthetic α-glucosidase inhibitor drugs and have prompted many studies to discover natural alternatives with comparable efficiency and better tolerability. Tetracera scandens is a traditional medicinal plant, whose leaf has been used for the treatment of diabetes mellitus in Malaysia and other Southeast Asian countries. The α-glucosidase inhibitory potential of T. scandens leaf has not been assessed so far. Hence, this study was aimed to evaluate the α-glucosidase inhibitory potential of T. scandens leaf extracts. Moreover, it aimed to develop and validate a multivariate model to correlate the Fourier transform infrared (FT-IR) spectral fingerprint of the plant extracts to their α-glucosidase inhibitory activity. Another aim of this study was to characterize the putative α-glucosidase inhibitory metabolites of T. scandens extracts using metabolomics approach. Eventually, the affinity of the putative active metabolites towards α-glucosidase was to be predicted through molecular docking study. Different hydromethanolic extracts were prepared and assayed for their α-glucosidase inhibitory potential. The FT-IR spectra of T. scandens extracts were acquired and correlated to their corresponding α-glucosidase inhibitory IC50 values via the orthogonal partial least squares (OPLS) algorithm. Furthermore, the mass spectral data acquired via gas chromatography-mass spectrometry (GC-MS) analysis of the plant extracts was correlated to their α-glucosidase inhibitory IC50 values through an OPLS model, and the putative α-glucosidase inhibitory metabolites were suggested by the loading column plot of the developed model. Moreover, the 3D structures of the putative α-glucosidase inhibitory metabolites were further docked into the active site of Saccharomyces cerevisiae isomaltase in order to predict the ligand-enzyme interactions and affinities. The methanolic extracts of T. scandens leaf showed higher α-glucosidase inhibitory potential as compared to the aqueous ones. The developed OPLS model successfully predicted the α-glucosidase inhibitory potential of new independent T. scandens leaf samples given their fingerprint FT-IR spectra, therefore it can be used as a simple and rapid quality control tool. Moreover, the bands corresponding to the carbon-hydrogen bond (C-H), carbon-carbon double bond (C=C) and carbon-oxygen single bond (C-O) were determined to be positively correlated with the α- glucosidase inhibitory activity of the plant extracts. GC-MS based profiling of the α-glucosidase inhibitory metabolites led to the determination of 6 putative metabolites, namely, palmitic acid, 1-monopalmitin, stearic acid, emodin, catechin and β-sitosterol. Moreover, the metabolites malic acid, 4-hydroxybenzoic acid, xylitol, citric acid, D-fructose, D-glucose, D-mannose and myo-inositol were suggested to induce α-glucosidase activity. The results of the molecular docking study further supported the findings of the metabolite profiling study, since the putative α-glucosidase inhibitory metabolites showed predicted binding energies of -5.9 to -8.8, indicating moderate to high affinities. Conclusively, this study demonstrated the in vitro α-glucosidase inhibitory activity of T. scandens leaf. Furthermore, the metabolomics approach was successfully used to develop a rapid method for quality control of T. scandens leaf and to characterize its putative α-glucosidase inhibitory metabolites. | ||
| 596 | |a 1 6 | ||
| 655 | 7 | |a Theses, IIUM local | |
| 690 | |a Dissertations, Academic |x Department of Pharmaceutical Chemistry |z IIUM | ||
| 700 | 1 | |a Siddiqui, Mohammad Jamshed |e degree supervisor | |
| 700 | 1 | |a Ahmed. Qamar Uddin |e degree supervisor | |
| 710 | 2 | |a International Islamic University Malaysia. |b Department of Pharmaceutical Chemistry | |
| 856 | 4 | |u http://studentrepo.iium.edu.my/handle/123456789/9849 |z Click here to view 1st 24 pages of the thesis. Members can view fulltext at the specified PCs in the library. | |
| 900 | |a sz to aaz | ||
| 999 | |c 439171 |d 470899 | ||
| 952 | |0 0 |6 XX(563485.10) |7 0 |8 THESES |9 762325 |a KIMC |b KIMC |c CLOSEACCES |g 0.00 |o XX(563485.10) |p 11100417987 |r 1900-01-02 |t 1 |v 0.00 |y THESIS | ||
| 952 | |0 0 |6 XX(563485.10) CD |7 7 |8 THESES |9 859234 |a IIUM |b IIUM |c MULTIMEDIA |g 0.00 |o XX(563485.10) CD |p 11100417988 |r 1900-01-02 |t 1 |v 0.00 |y THESISDIG | ||