| 1. |
- Benchoula, Khaled, et al.
(författare)
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Optimization of Hyperglycemic Induction in Zebrafish and Evaluation of Its Blood Glucose Level and Metabolite Fingerprint Treated with Psychotria malayana Jack Leaf Extract
- 2019
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 24:8
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Tidskriftsartikel (refereegranskat)abstract
- A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
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| 2. |
- Murugesu, Suganya, et al.
(författare)
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Characterization of alpha-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation
- 2018
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 23:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clinacanthus nutans (C. nutans) is an Acanthaceae herbal shrub traditionally consumed to treat various diseases including diabetes in Malaysia. This study was designed to evaluate the alpha-glucosidase inhibitory activity of C. nutans leaves extracts, and to identify the metabolites responsible for the bioactivity. Methods: Crude extract obtained from the dried leaves using 80% methanolic solution was further partitioned using different polarity solvents. The resultant extracts were investigated for their alpha-glucosidase inhibitory potential followed by metabolites profiling using the gas chromatography tandem with mass spectrometry (GC-MS). Results: Multivariate data analysis was developed by correlating the bioactivity, and GC-MS data generated a suitable partial least square (PLS) model resulting in 11 bioactive compounds, namely, palmitic acid, phytol, hexadecanoic acid (methyl ester), 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol, glycerol monostearate, alpha-tocospiro B, and stigmasterol. In-silico study via molecular docking was carried out using the crystal structure Saccharomyces cerevisiae isomaltase (PDB code: 3A4A). Interactions between the inhibitors and the protein were predicted involving residues, namely LYS156, THR310, PRO312, LEU313, GLU411, and ASN415 with hydrogen bond, while PHE314 and ARG315 with hydrophobic bonding. Conclusion: The study provides informative data on the potential alpha-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.
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| 3. |
- Murugesu, Suganya, et al.
(författare)
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Toxicity study on Clinacanthus nutans leaf hexane fraction using Danio rerio embryos
- 2019
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Ingår i: Toxicology reports. - : ELSEVIER. - 2214-7500. ; 6, s. 1148-1154
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Tidskriftsartikel (refereegranskat)abstract
- Clinacanthus nutans, an herbal shrub belonging to the Acanthaceae family, is traditionally used as a functional food to treat various ailments in Malaysia and Indonesia. Although the polar fraction of this plant shows nontoxic effect, the toxicity of the non-polar extract is not reported so far. The present study aimed to assess the toxic effect and determine the lethal concentration of this non-polar fraction using zebrafish embryos. The n-hexane fraction was partitioned from the crude extract of C. nutans obtained using 80% methanolic solution. After spawning of the adult male and female zebrafish, the eggs were collected, transferred into a 96-well plate and incubated with the n-hexane fraction at concentrations of 15.63 mu g/ml, 31.25 mu g/ml, 62.5 mu g/ml, 125 mu g/ml, 250 mu g/ml and 500 mu g/ml in 2% DMSO. The survival and sublethal endpoint were assessed, the mortality and hatchability rates were calculated based on microscopic observation, while the heartbeat rate was measured using DanioScope software. The median lethal concentration (LC50) of the C. nutans n-hexane fraction, which was determined using probit analysis, was calculated to be 75.49 mu g/mL, which is harmful. Moreover, gas chromatography-mass spectrometry (GC-MS) analysis revealed the presence of palmitic acid, phytol, hexadecanoic acid, 1-monopalmitin, stigmast-5-ene, pentadecanoic acid, heptadecanoic acid, 1-linolenoylglycerol and stigmasterol in the n-hexane fraction.
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| 4. |
- Nipun, Tanzina Sharmin, et al.
(författare)
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Alpha-Glucosidase Inhibitory Effect of Psychotria malayana Jack Leaf : A Rapid Analysis Using Infrared Fingerprinting
- 2020
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Ingår i: Molecules. - : MDPI AG. - 1431-5157 .- 1420-3049. ; 25:18
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Tidskriftsartikel (refereegranskat)abstract
- The plant Psychotria malayana Jack belongs to the Rubiaceae family and is known in Malaysia as “meroyan sakat/salung”. A rapid analytical technique to facilitate the evaluation of the P. malayana leaves’ quality has not been well-established yet. This work aimed therefore to develop a validated analytical technique in order to predict the alpha-glucosidase inhibitory action (AGI) of P. malayana leaves, applying a Fourier Transform Infrared Spectroscopy (FTIR) fingerprint and utilizing an orthogonal partial least square (OPLS). The dried leaf extracts were prepared by sonication of different ratios of methanol-water solvent (0, 25, 50, 75, and 100% v/v) prior to the assessment of alpha-glucosidase inhibition (AGI) and the following infrared spectroscopy. The correlation between the biological activity and the spectral data was evaluated using multivariate data analysis (MVDA). The 100% methanol extract possessed the highest inhibitory activity against the alpha-glucosidase (IC50 2.83 ± 0.32 μg/mL). Different bioactive functional groups, including hydroxyl (O-H), alkenyl (C=C), methylene (C-H), carbonyl (C=O), and secondary amine (N-H) groups, were detected by the multivariate analysis. These functional groups actively induced the alpha-glucosidase inhibition effect. This finding demonstrated the spectrum profile of the FTIR for the natural herb P. malayana Jack, further confirming its medicinal value. The developed validated model can be used to predict the AGI of P. malayana, which will be useful as a tool in the plant’s quality control.
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| 5. |
- Nipun, Tanzina Sharmin, et al.
(författare)
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Characterization of alpha-Glucosidase Inhibitors from Psychotria malayana Jack Leaves Extract Using LC-MS-Based Multivariate Data Analysis and In-Silico Molecular Docking
- 2020
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Ingår i: Molecules. - : MDPI. - 1431-5157 .- 1420-3049. ; 25:24
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Tidskriftsartikel (refereegranskat)abstract
- Psychotria malayana Jack has traditionally been used to treat diabetes. Despite its potential, the scientific proof in relation to this plant is still lacking. Thus, the present study aimed to investigate the alpha-glucosidase inhibitors in P. malayana leaf extracts using a metabolomics approach and to elucidate the ligand-protein interactions through in silico techniques. The plant leaves were extracted with methanol and water at five various ratios (100, 75, 50, 25 and 0% v/v; water-methanol). Each extract was tested for alpha-glucosidase inhibition, followed by analysis using liquid chromatography tandem to mass spectrometry. The data were further subjected to multivariate data analysis by means of an orthogonal partial least square in order to correlate the chemical profile and the bioactivity. The loading plots revealed that the m/z signals correspond to the activity of alpha-glucosidase inhibitors, which led to the identification of three putative bioactive compounds, namely 5 '-hydroxymethyl-1 '-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1 '-one (1), alpha-terpinyl-beta-glucoside (2), and machaeridiol-A (3). Molecular docking of the identified inhibitors was performed using Auto Dock Vina software against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A). Four hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, and GLU411. Compound 1, 2, and 3 showed binding affinity values of -8.3, -7.6, and -10.0 kcal/mol, respectively, which indicate the good binding ability of the compounds towards the enzyme when compared to that of quercetin, a known alpha-glucosidase inhibitor. The three identified compounds that showed potential binding affinity towards the enzymatic protein in molecular docking interactions could be the bioactive compounds associated with the traditional use of this plant.
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| 6. |
- Nipun, Tanzina Sharmin, et al.
(författare)
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GC-MS- and NMR-Based Metabolomics and Molecular Docking Reveal the Potential Alpha-Glucosidase Inhibitors from Psychotria malayana Jack Leaves
- 2021
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Ingår i: Pharmaceuticals. - : MDPI. - 1424-8247. ; 14:10
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Tidskriftsartikel (refereegranskat)abstract
- Psychotria malayana Jack leaf, known in Indonesia as "daun salung ", is traditionally used for the treatment of diabetes and other diseases. Despite its potential, the phytochemical study related to its anti-diabetic activity is still lacking. Thus, this study aimed to identify putative inhibitors of alpha-glucosidase, a prominent enzyme contributing to diabetes type 2 in P. malayana leaf extract using gas chromatography-mass spectrometry (GC-MS)- and nuclear magnetic resonance (NMR)-based metabolomics, and to investigate the molecular interaction between those inhibitors and the enzyme through in silico approach. Twenty samples were extracted with different solvent ratios of methanol-water (0, 25, 50, 75, and 100% v/v). All extracts were tested on the alpha-glucosidase inhibition (AGI) assay and analyzed using GC-MS and NMR. Multivariate data analysis through a partial least square (PLS) and orthogonal partial square (OPLS) models were developed in order to correlate the metabolite profile and the bioactivity leading to the annotation of the putative bioactive compounds in the plant extracts. A total of ten putative bioactive compounds were identified and some of them reported in this plant for the first time, namely 1,3,5-benzenetriol (1); palmitic acid (2); cholesta-7,9(11)-diene-3-ol (3); 1-monopalmitin (4); beta-tocopherol (5); alpha-tocopherol (6); 24-epicampesterol (7); stigmast-5-ene (8); 4-hydroxyphenylpyruvic acid (10); and glutamine (11). For the evaluation of the potential binding modes between the inhibitors and protein, the in silico study via molecular docking was performed where the crystal structure of Saccharomyces cerevisiae isomaltase (PDB code: 3A4A) was used. Ten amino acid residues, namely ASP352, HIE351, GLN182, ARG442, ASH215, SER311, ARG213, GLH277, GLN279, and PRO312 established hydrogen bond in the docked complex, as well as hydrophobic interaction of other amino acid residues with the putative compounds. The alpha-glucosidase inhibitors showed moderate to high binding affinities (-5.5 to -9.4 kcal/mol) towards the active site of the enzymatic protein, where compounds 3, 5, and 8 showed higher binding affinity compared to both quercetin and control ligand.
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| 7. |
- Perumal, Vikneswari, et al.
(författare)
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Antioxidants profile of Momordica charantia fruit extract analyzed using LC-MS-QTOF-based metabolomics
- 2021
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Ingår i: FOOD CHEMISTRY: MOLECULAR SCIENCES. - : Elsevier. - 2666-5662. ; 2
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Tidskriftsartikel (refereegranskat)abstract
- Momordica charantia fruit is claimed to have healthy benefit. Despite this potential claim, the phytochemical study of this fruit is still lacking. Thus, this study aimed to evaluate the antioxidants profile of Momordica charantia (Cucurbitaceae) fruit. The antioxidant activity of the ethanolic extracts of various polarities was evaluated and the metabolites that are responsible for its activity were identified using metabolomics approach. Six different mixture of ethanol in water that are 0%, 20%, 40%, 60%, 80%, and 100% (v/v) was extracted using dveseeded fruit sample. Liquid chromatography-mass spectrometry-quadrupole time of flight and multivariate data analysis was used to identify the metabolites that were either antioxidants or pro-oxidants. The 80% ethanol extract exhibited the most antioxidant activity when tested in both 2, 2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) antioxidant assays. This extract showed the most intense LC-MS signals represented to ascorbic acid, margarolic acid, brevifolincarboxylic acid, quercetin 3-O-glycoside, kuguacin H, cucurbitacin E, 3-malonylmomordicin I, and goyaglycoside G correlating to the anti-oxidant activity. This study reports for the first time the existence of brevifolincarboxylic acid in this fruit, and the antioxidant activity of 3-malonylmomordicin I and goyaglycoside G. In addition, the loading plots revealed the unknown compounds possessing the antioxidant activity which are potential to be isolated in the future study.
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