Rapid investigation of Αlpha-Glucosidase inhibitory activity of Psychotria Malayana Jack leaf using infrared fingerprinting

Background: Psychotria malayana Jack is the plant belongs to Rubiaceae family and known in Malaysia as “meroyan sakat/salung”. The analytical approach used in the quality control of Psychotria malayana leaves has not been developed yet. Objectives: Therefore, this research was aimed to evaluate the α-glucosidase inhibitory activity of Psychotria malayana Jack leave extracts in correlation to its Fourier transform infrared spectroscopy (FT-IR) fingerprint, utilizing orthogonal partial least square. Methodology: The dried extracts prepared by sonication of different solvents ratios of methanol-water (0, 25, 50, 75, and 100% v/v), were evaluated for the α-glucosidase inhibitory activity and analyzed via infrared spectroscopy. Multivariate data analysis was done through correlating the bioactivity and infrared spectra of every extract using orthogonal partial least square (OPLS) method. Results: The 100% methanol extract of the leave is more effective against α-glucosidase activity. The loading plot from multivariate data analysis identified several functional groups which actively induced α- -glucosidase inhibitory activity. Discussion and Conclusion: The results of the present study developed the FT-IR spectrum profile for the medicinally important plant Psychotria malayana Jack that further confirms its medicinal values. Therefore, Psychotria malayana Jack leaves extract is medicinally potent that assist to develop this plant as an alternative anti-diabetic natural plant-based medicine

LC-MS-based metabolomics and molecular docking to characterize α-glucosidase inhibitors from Psychotria Malayana Jack leaves extract

The plant Psychotria malayana Jack belongs to the Rubiaceae family and is locally referred to as "meroyan sakat/salung" in Malaysia. Diabetes has traditionally been treated with P. malayana Jack. Despite its potential, scientific evidence for this plant is still lacking. Thus, the current study sought to investigate α�glucosidase inhibitors in P. malayana leaf extracts using a metabolomics approach, as well as to illuminate ligand-protein interactions using in-silico techniques (molecular docking). The plant leaves were extracted in five different ratios with methanol and water (100, 75, 50, 25 and 0% v/v; water–methanol). After testing for α-glucosidase inhibition activity, each extract was analyzed using liquid chromatography tandem to mass spectrometry. Additionally, the data were subjected to multivariate data analysis by developing an orthogonal partial least squares method in order to establish a correlation between the chemical profile and the bioactivity. The loading plots demonstrated that the m/z signals correspond to the activity of α-glucosidase inhibitors, allowing five putative bioactive compounds to be identified, namely 1-monopalmitin (1), 5′-hydroxymethyl-1′-(1, 2, 3, 9-tetrahydro-pyrrolo (2, 1-b) quinazolin-1-yl)-heptan-1′-one (2), α-terpinyl-β-glucoside (3), machaeridiol-A (4), and 4-hydroxyphenylpyruvic acid (5). The discovered inhibitors were docked against the crystal structure of Saccharomyces cerevisiae isomaltase (Protein Data Bank code: 3A4A) using the Auto Dock Vina software. Nine hydrogen bonds were detected in the docked complex, involving several residues, namely ASP352, ARG213, ARG442, GLU277, GLN279, HIE280, HIE351, ASH215, and GLU411. Compound 1, 2, 3, 4, and 5 showed binding affinity values of −6.1, −8.3, −7.6, −10.0, and −6.5 kcal/mol, respectively, indicating the moderate to the good binding affinity of the compounds towards the active site of the enzyme when compared to that of a known α-glucosidase inhibitor, quercetin (−8.4 kcal/mol). The five identified compounds showing potential binding affinity towards the α-glucosidase enzyme in in-silico study could be the bioactive compounds associated with this plant's traditional use

Alpha-glucosidase inhibitory effect of psychotria malayana jack leaf: A rapid analysis using infrared fingerprinting

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

Synthesis of flavone-based compounds as ros-dependent apoptosis inducers in colorectal cancer

Apoptosis is essential for maintaining cell homeostasis. It hinders the cancer cells survival and excessive ROS can induce DNA damage in cancer cells, which lead to apoptosis. Therefore, targeting apoptosis may be a universal cancer therapeutic technique. Twelve flavone-based compounds were synthesised and characterised. All compounds were evaluated for cytotoxicity against four human cancer cell lines: kidney, breast, colorectal, and bladder cancer cells. Only compound 8 exhibited excellent cytotoxicity against all investigated cancer cell lines, with notably potent cytotoxicity against colorectal (SW620) cells (IC50: 3.2 μM) and higher cytotoxicity than control (IC50: 4.2 μM). Mechanistic analyses such as colony formation, cell cycle arrests and flow cytometry analyses demonstrated an increase in intracellular ROS-induced apoptosis in SW620 cells, which is a potential mode of action for compound 8. Western blot research confirmed the apoptotic mechanism of 8 by showing overexpression of c-PARP, BAD, BAK, and AMPK and downregulation of BCL-2 and AKT. Taken together, the data showed that 8 induces apoptosis by increasing ROS. According to this study, a 4-chloromethyl substituent at the C3-phenyl group may be required for 8's cytotoxicity since other para substituents are inactive. Therefore, structure-activity analysis of 8 in related proteins can be studied

Characterization of alpha-Glucosidase Inhibitors from Psychotria malayana Jack Leaves Extract Using LC-MS-Based Multivariate Data Analysis and In-Silico Molecular Docking

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

Alpha-Glucosidase Inhibitory Effect of Psychotria malayana Jack Leaf: A Rapid Analysis Using Infrared Fingerprinting

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

GC-MS- and NMR-Based Metabolomics and Molecular Docking Reveal the Potential Alpha-Glucosidase Inhibitors from Psychotria malayana Jack Leaves

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.</p&gt