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Fulltext Characterization of α-Glucosidase Inhibitors from Clinacanthus nutans Lindau Leaves by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Simulation

Murugesu S, Ibrahim Z, Ahmed QU, Nik Yusoff NI, Uzir BF, Perumal V, et al.

Molecules, 2018 Sep 19;23(9).
PMID: 30235889 DOI: 10.3390/molecules23092402

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 α-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 α-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 α-glucosidase inhibitors identified in C. nutans leaves, indicating the plant's therapeutic effect to manage hyperglycemia.
Fulltext Characterization of Gold-Sputtered Zinc Oxide Nanorods-a Potential Hybrid Material

Perumal V, Hashim U, Gopinath SC, Rajintra Prasad H, Wei-Wen L, Balakrishnan SR, et al.

Nanoscale Res Lett, 2016 Dec;11(1):31.
PMID: 26787050 DOI: 10.1186/s11671-016-1245-8

Generation of hybrid nanostructures has been attested as a promising approach to develop high-performance sensing substrates. Herein, hybrid zinc oxide (ZnO) nanorod dopants with different gold (Au) thicknesses were grown on silicon wafer and studied for their impact on physical, optical and electrical characteristics. Structural patterns displayed that ZnO crystal lattice is in preferred c-axis orientation and proved the higher purities. Observations under field emission scanning electron microscopy revealed the coverage of ZnO nanorods by Au-spots having diameters in the average ranges of 5-10 nm, as determined under transmission electron microscopy. Impedance spectroscopic analysis of Au-sputtered ZnO nanorods was carried out in the frequency range of 1 to 100 MHz with applied AC amplitude of 1 V RMS. The obtained results showed significant changes in the electrical properties (conductance and dielectric constant) with nanostructures. A clear demonstration with 30-nm thickness of Au-sputtering was apparent to be ideal for downstream applications, due to the lowest variation in resistance value of grain boundary, which has dynamic and superior characteristics.
Fulltext Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study

Sarian MN, Ahmed QU, Mat So'ad SZ, Alhassan AM, Murugesu S, Perumal V, et al.

Biomed Res Int, 2017;2017:8386065.
PMID: 29318154 DOI: 10.1155/2017/8386065

The best described pharmacological property of flavonoids is their capacity to act as potent antioxidant that has been reported to play an important role in the alleviation of diabetes mellitus. Flavonoids biochemical properties are structure dependent; however, they are yet to be thoroughly understood. Hence, the main aim of this work was to investigate the antioxidant and antidiabetic properties of some structurally related flavonoids to identify key positions responsible, their correlation, and the effect of methylation and acetylation on the same properties. Antioxidant potential was evaluated through dot blot, 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, ABTS+ radical scavenging, ferric reducing antioxidant power (FRAP), and xanthine oxidase inhibitory (XOI) assays. Antidiabetic effect was investigated through α-glucosidase and dipeptidyl peptidase-4 (DPP-4) assays. Results showed that the total number and the configuration of hydroxyl groups played an important role in regulating antioxidant and antidiabetic properties in scavenging DPPH radical, ABTS+ radical, and FRAP assays and improved both α-glucosidase and DPP-4 activities. Presence of C-2-C-3 double bond and C-4 ketonic group are two essential structural features in the bioactivity of flavonoids especially for antidiabetic property. Methylation and acetylation of hydroxyl groups were found to diminish the in vitro antioxidant and antidiabetic properties of the flavonoids.
Fulltext Antidiabetic and antioxidants activities of clinacanthus nutans (burm f.) lindau leaves extracts

Murugesu, S., Khatib, A., Ibrahim, Z., Ahmed, Q. U., Uzir, B.F., Nik-Yusoff, N.I., et al.

International Food Research Journal, 2019;26(1):319-327.
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Clinacanthus nutans (Acanthaceae) is a local plant consumed as tisane in Indonesia and ‘ulam’ in Malaysia. This plant has been claimed for its ability to prevent many diseases including diabetes. However, the scientific proof on this claim is still lacking. Therefore, the present work study was designed to evaluate the antidiabetic potential and antioxidant capacity of C. nutans leaves extracts using in vitro bioassay tests. The 80% methanolic crude extract of this plant was further partitioned using different polarity solvents namely hexane, hexane:ethyl acetate (1:1, v/v), ethyl acetate, ethyl acetate:methanol (1:1, v/v), and methanol. All the sub-fractions were analysed for antioxidant effect via 2, 2-diphenyl-2-picrylhydrazil (DPPH) scavenging activity, ferric reducing power (FRAP) and xanthine oxidase (XO) assays followed by antidiabetic evaluation via α-glucosidase and dipeptidyl peptidase-IV (DPP-IV) inhibitory assays and glucose uptake experiment. The ethyl acetate fraction showed a good antioxidant potential while the hexane fraction exhibited high α-glucosidase and DPP-IV enzyme inhibition. The hexane fraction also improved glucose uptake in a dose-dependent manner. The present work thus provides an informative data on the potential of C. nutans to be developed as a functional food in preventing diabetes.
A quadruplet 3-D laser scribed graphene/MoS2, functionalised N2-doped graphene quantum dots and lignin-based Ag-nanoparticles for biosensing

Vasudevan M, Perumal V, Raja PB, Ibrahim MNM, Lee HL, Gopinath SCB, et al.

Int J Biol Macromol, 2023 Dec 31;253(Pt 2):126620.
PMID: 37683754 DOI: 10.1016/j.ijbiomac.2023.126620

Troponin I is a protein released into the human blood circulation and a commonly used biomarker due to its sensitivity and specificity in diagnosing myocardial injury. When heart injury occurs, elevated troponin Troponin I levels are released into the bloodstream. The biomarker is a strong and reliable indicator of myocardial injury in a person, with immediate treatment required. For electrochemical sensing of Troponin I, a quadruplet 3D laser-scribed graphene/molybdenum disulphide functionalised N2-doped graphene quantum dots hybrid with lignin-based Ag-nanoparticles (3D LSG/MoS2/N-GQDs/L-Ag NPs) was fabricated using a hydrothermal process as an enhanced quadruplet substrate. Hybrid MoS2 nanoflower (H3 NF) and nanosphere (H3 NS) were formed independently by varying MoS2 precursors and were grown on 3D LSG uniformly without severe stacking and restacking issues, and characterized by morphological, physical, and structural analyses with the N-GQDs and Ag NPs evenly distributed on 3D LSG/MoS2 surface by covalent bonding. The selective capture of and specific interaction with Troponin I by the biotinylated aptamer probe on the bio-electrode, resulted in an increment in the charge transfer resistance. The limit of detection, based on impedance spectroscopy, is 100 aM for both H3 NF and H3 NS hybrids, with the H3 NF hybrid biosensor having better analytical performance in terms of linearity, selectivity, repeatability, and stability.
A new nano-worm structure from gold-nanoparticle mediated random curving of zinc oxide nanorods

Perumal V, Hashim U, Gopinath SC, Haarindraprasad R, Poopalan P, Liu WW, et al.

Biosens Bioelectron, 2016 Apr 15;78:14-22.
PMID: 26584078 DOI: 10.1016/j.bios.2015.10.083

Creating novel nanostructures is a primary step for high-performance analytical sensing. Herein, a new worm like nanostructure with Zinc Oxide-gold (ZnO/Au) hybrid was fabricated through an aqueous hydrothermal method, by doping Au-nanoparticle (AuNP) on the growing ZnO lattice. During ZnO growth, fine tuning the solution temperature expedites random curving of ZnO nanorods and forms nano-worms. The nano-worms which were evidenced by morphological, physical and structural analyses, revealed elongated structures protruding from the surface (length: 1 µm; diameter: ~100 nm). The appropriate peaks for the face centred cubic gold were (111) and (200), as seen from X-ray diffractogram. The strong interrelation between Au and ZnO was manifested by X-ray photoelectron spectroscopy. The combined surface area increment from the nanoparticle radii and ZnO nanorod random curving gives raise an enhancement in detection sensitivity by increasing bio-loading. 'Au-decorated hybrid nano-worm' was immobilized with a probe DNA from Vibrio Cholera and duplexed with a target which was revealed by Fourier Transform Infrared Spectroscopy. Our novel Au-decorated hybrid nano-worm is suitable for high-performance bio-sensing, as evidenced by impedance spectroscopy, having higher-specificity and attained femtomolar (10 fM) sensitivity. Further, higher stability, reproducibility and regeneration on this sensing surface were demonstrated.
A Comprehensive Review on Biopolymer Mediated Nanomaterial Composites and Their Applications in Electrochemical Sensors

Vasudevan M, Perumal V, Karuppanan S, Ovinis M, Bothi Raja P, Gopinath SCB, et al.

Crit Rev Anal Chem, 2022 Oct 26.
PMID: 36288094 DOI: 10.1080/10408347.2022.2135090

Biopolymers are an attractive green alternative to conventional polymers, owing to their excellent biocompatibility and biodegradability. However, their amorphous and nonconductive nature limits their potential as active biosensor material/substrate. To enhance their bio-analytical performance, biopolymers are combined with conductive materials to improve their physical and chemical characteristics. We review the main advances in the field of electrochemical biosensors, specifically the structure, approach, and application of biopolymers, as well as their conjugation with conductive nanoparticles, polymers and metal oxides in green-based noninvasive analytical biosensors. In addition, we reviewed signal measurement, substrate bio-functionality, biochemical reaction, sensitivity, and limit of detection (LOD) of different biopolymers on various transducers. To date, pectin biopolymer, when conjugated with either gold nanoparticles, polypyrrole, reduced graphene oxide, or multiwall carbon nanotubes forming nanocomposites on glass carbon electrode transducer, tends to give the best LOD, highest sensitivity and can detect multiple analytes/targets. This review will spur new possibilities for the use of biosensors for medical diagnostic tests.
Fulltext 1,1'-Carbonyldiimidazole-copper nanoflower enhanced collapsible laser scribed graphene engraved microgap capacitive aptasensor for the detection of milk allergen

Subramani IG, Perumal V, Gopinath SCB, Mohamed NM, Ovinis M, Sze LL

Sci Rep, 2021 10 21;11(1):20825.
PMID: 34675227 DOI: 10.1038/s41598-021-00057-4

The bovine milk allergenic protein, 'β-lactoglobulin' is one of the leading causes of milk allergic reaction. In this research, a novel label-free non-faradaic capacitive aptasensor was designed to detect β-lactoglobulin using a Laser Scribed Graphene (LSG) electrode. The graphene was directly engraved into a microgapped (~ 95 µm) capacitor-electrode pattern on a flexible polyimide (PI) film via a simple one-step CO2 laser irradiation. The novel hybrid nanoflower (NF) was synthesized using 1,1'-carbonyldiimidazole (CDI) as the organic molecule and copper (Cu) as the inorganic molecule via one-pot biomineralization by tuning the reaction time and concentration. NF was fixed on the pre-modified PI film at the triangular junction of the LSG microgap specifically for bio-capturing β-lactoglobulin. The fine-tuned CDI-Cu NF revealed the flower-like structures was viewed through field emission scanning electron microscopy. Fourier-transform infrared spectroscopy showed the interactions with PI film, CDI-Cu NF, oligoaptamer and β-lactoglobulin. The non-faradaic sensing of milk allergen β-lactoglobulin corresponds to a higher loading of oligoaptamer on 3D-structured CDI-Cu NF, with a linear range detection from 1 ag/ml to 100 fg/ml and attomolar (1 ag/ml) detection limit (S/N = 3:1). This novel CDI-Cu NF/LSG microgap aptasensor has a great potential for the detection of milk allergen with high-specificity and sensitivity.
Fulltext 'Spotted Nanoflowers': Gold-seeded Zinc Oxide Nanohybrid for Selective Bio-capture

Perumal V, Hashim U, Gopinath SC, Haarindraprasad R, Foo KL, Balakrishnan SR, et al.

Sci Rep, 2015 Jul 16;5:12231.
PMID: 26178973 DOI: 10.1038/srep12231

Hybrid gold nanostructures seeded into nanotextured zinc oxide (ZnO) nanoflowers (NFs) were created for novel biosensing applications. The selected 'spotted NFs' had a 30-nm-thick gold nanoparticle (AuNP) layer, chosen from a range of AuNP thicknesses, sputtered onto the surface. The generated nanohybrids, characterized by morphological, physical and structural analyses, were uniformly AuNP-seeded onto the ZnO NFs with an average length of 2-3 μm. Selective capture of molecular probes onto the seeded AuNPs was evidence for the specific interaction with DNA from pathogenic Leptospirosis-causing strains via hybridization and mis-match analyses. The attained detection limit was 100 fM as determined via impedance spectroscopy. High levels of stability, reproducibility and regeneration of the sensor were obtained. Selective DNA immobilization and hybridization were confirmed by nitrogen and phosphorus peaks in an X-ray photoelectron spectroscopy analysis. The created nanostructure hybrids illuminate the mechanism of generating multiple-target, high-performance detection on a single NF platform, which opens a new avenue for array-based medical diagnostics.