Identification of Benzoxazolinone Derivatives Based Inhibitors for Depression and Pain Related Disorders Using Human Serotonin and Norepinephrine Transporter as Dual Therapeutic Target: A Computational Approach

Pain is commonly associated with depression. Both pain and depression share common biological pathways and neurotransmitters, which has implications for the treatment of both disorders. A drug that could ameliorate both pain and depression could be beneficial in the development of new therapeutics in the management of disorders associated with pain/depression dyad. Alterations in the neurotransmitters namely, serotonin and norepinephrine in the central nervous system (CNS) have been implicated in the pathophysiology of pain and depression. Serotonin and norepinephrine reuptake inhibitors (SNRIs) have been implicated as a novel therapeutic target for a wide range of biological functions, including pain, anxiety and depression. 2-benzoxazolinone (2-BOA) from the mangrove Acanthus ilicifolius and its derivatives have been reported for its analgesic and antidepressant activities. In the present work, docking studies were done on the crystal structure of human transporters of serotonin (hSERT) and on homology modeled human transporters of norepinephrine (hNET) as therapeutic targets of depression and pain related disorders using 2-BOA and its derivatives as potential candidates. A homology model for hNET was constructed using MODELLER and validated. Further docking studies were done on hSERT and hNET using 2-BOA and its structural analogs. The result of the study proposes the possible potential candidate among 2-BOA derivatives that may be further developed as a therapeutic lead compound for use in disorders associated with depression and pain

Identification of Nephelium lappaceum leaves phenolic and flavonoid component with radical scavenging, antidiabetic and antibacterial potential

360-365Nephelium lappaceum Linn. (Rambutan) is traditionally claimed, as a source of natural antioxidants and for its use in the treatment of diabetes and bacterial infections. The present study investigates the in vitro effect of ethanolic Rambutan leaves extract (NL) for its antioxidant effect, α-glucosidase, α-amylase enzyme inhibition, and antibacterial potentials. The total phenolic, total flavonoid content of NL was quantified and were expressed in terms of gallic acid (19.6±0.04 mg GAE/g) and rutin equivalents (16.7±0.01 mg RUE/g) respectively. The antioxidant assay revealed that NL exhibited significant inhibition of DPPH (IC50±SEM: 1.52±0.03 μg/mL) and ABTS (IC50±SEM: 1.295±0.05 μg/mL) radicals. NL also inhibited both α-amylase (IC50±SEM: 2.624±0.07 μg/mL), α-glucosidase (IC50±SEM: 2.416±0.06 μg/mL) enzyme activities, supported by its antioxidant potential and its phenolic and flavonoid content. The antibacterial activity was screened against seven human pathogenic ATCC strains for which the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were recorded. The selected MIC dose was tested, confirmed by Kirby-Bauer agar well diffusion method. NL exhibited MIC and MBC of 62.5 μg/mL and 125 μg/mL against B.subtilis and E.coli respectively. The results support the scientific claim of NL for its antioxidant, antidiabetic and antibacterial potential

Identification of Nephelium lappaceum leaves phenolic and flavonoid component with radical scavenging, antidiabetic and antibacterial potential

360-365Nephelium lappaceum Linn. (Rambutan) is traditionally claimed, as a source of natural antioxidants and for its use in the treatment of diabetes and bacterial infections. The present study investigates the in vitro effect of ethanolic Rambutan leaves extract (NL) for its antioxidant effect, α-glucosidase, α-amylase enzyme inhibition, and antibacterial potentials. The total phenolic, total flavonoid content of NL was quantified and were expressed in terms of gallic acid (19.6±0.04 mg GAE/g) and rutin equivalents (16.7±0.01 mg RUE/g) respectively. The antioxidant assay revealed that NL exhibited significant inhibition of DPPH (IC50±SEM: 1.52±0.03 μg/mL) and ABTS (IC50±SEM: 1.295±0.05 μg/mL) radicals. NL also inhibited both α-amylase (IC50±SEM: 2.624±0.07 μg/mL), α-glucosidase (IC50±SEM: 2.416±0.06 μg/mL) enzyme activities, supported by its antioxidant potential and its phenolic and flavonoid content. The antibacterial activity was screened against seven human pathogenic ATCC strains for which the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were recorded. The selected MIC dose was tested, confirmed by Kirby-Bauer agar well diffusion method. NL exhibited MIC and MBC of 62.5 μg/mL and 125 μg/mL against B.subtilis and E.coli respectively. The results support the scientific claim of NL for its antioxidant, antidiabetic and antibacterial potential

Design of Peptide Models for β-Hairpins and Equilibrating Helix-Hairpin Structures

It is well established that synthetic peptides containing a centrally positioned Type-I or Type-II β-turn can form well folded peptide hairpins (1). Earlier studies from this laboratory have established that D-Pro-Xxx segments nucleate β-hairpin structures, with formation of a central Type-II β-turn (2). The octapeptide (Boc-Leu-Phe-Val-Aib-D-Ala-Leu-Phe- Val-OMe) is a rare example of a synthetic peptide hairpin, containing a central Type-I β-turn. Hairpins with Type-I turns are considerably more twisted than their Type-II counterparts. The Aib-Xxx segment has also been shown to adopt a Type-I β-turn structure, resulting in incorporation into the centre of a long synthetic, helical peptide (3) (Figures 1,2).&nbsp;</p

New Distant TeV Blazars: Pushing the VHE gamma-ray Horizon

The discovery of several distant TeV blazars (redshift up to z~0.2 and possibly z~0.5) with the new generation Cherenkov telescopes HESS and MAGIC enables to set strong limits on the extragalactic background light (EBL) in the near to mid-infrared region. These upper limits are only a factor of two to three higher than the lower limits derived from source counts and several theoretical models could already be excluded. Such a low level of the EBL implies that the universe is much more transparent to VHE gamma-rays than previously anticipated. Here we summarize the recent results and discuss future prospects

Apoptosis Induction by Polygonum minus Is Related to Antioxidant Capacity, Alterations in Expression of Apoptotic-Related Genes, and S-Phase Cell Cycle Arrest in HepG2 Cell Line

Polygonum minus (Polygonaceae) is a medicinal herb distributed throughout eastern Asia. The present study investigated antiproliferative effect of P. minus and its possible mechanisms. Four extracts (petroleum ether, methanol, ethyl acetate, and water) were prepared by cold maceration. Extracts were subjected to phytochemical screening, antioxidant, and antiproliferative assays; the most bioactive was fractionated using vacuum liquid chromatography into seven fractions (F1–F7). Antioxidant activity was measured via total phenolic content (TPC), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing antioxidant power (FRAP) assays. Antiproliferative activity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Most active fraction was tested for apoptosis induction and cell cycle arrest in HepG2 cells using flow cytometry and confocal microscopy. Apoptotic-related gene expression was studied by RT-PCR. Ethyl acetate extract was bioactive in initial assays. Its fraction, F7, exhibited highest antioxidant capacity (TPC; 113.16±6.2 mg GAE/g extract, DPPH; EC50: 30.5±3.2 μg/mL, FRAP; 1169±20.3 μmol Fe (II)/mg extract) and selective antiproliferative effect (IC50: 25.75±1.5 μg/mL). F7 induced apoptosis in concentration- and time-dependent manner and caused cell cycle arrest at S-phase. Upregulation of proapoptotic genes (Bax, p53, and caspase-3) and downregulation of antiapoptotic gene, Bcl-2, were observed. In conclusion, F7 was antiproliferative to HepG2 cells by inducing apoptosis, cell cycle arrest, and via antioxidative effects

Antidiabetic, antioxidant and in silico studies of bacterial endosymbiont inhabiting Nephelium lappaceum L.

Endophytes, notably obtaining attention, have been abided by potential origins of bioactive metabolites. In the acquaint study, endophyte was isolated from the leaves of Nephelium lappaceum L. The chosen endosymbiont was identified by 16s rRNA partial genome sequencing and investigated for their antioxidant and antidiabetic activities. A preliminary phytochemical test was comported for the affirmation of phytoconstituents in endophytic crude extract (NLM). Antioxidant activities were conducted by using 2-diphenyl-1-picrylhydrazyl (DPPH) method and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid (ABTS) method to screen the radical scavenging potential. The evaluation of antidiabetic activities was done by using α-amylase and α-glucosidase inhibition assay. Qualitative phytochemical test on NLM affirmed the presence of phenols, carbohydrates, alkaloids, flavonoids, steroids, mucilage and glycosides. In silico parameters were also specified for antidiabetic activities. The antioxidant assay of NLM expressed proficient antioxidant activity of IC50±SEM 1.35±0.03 µg/mL and IC50±SEM 1.47±0.03 µg/mL, for ABTS and DPPH respectively. Antidiabetic assay results evidenced dose dependent percentage inhibition of the enzyme. The results testified estimable inhibition of α-amylase (IC50±SEM 2.549±0.08 µg/mL) and α-glucosidase inhibition (IC50±SEM 2.29±0.03µg/mL) compared to the standard drug (Acarbose). In silico study divulged that the ellagic acid component present in the plant was responsible for antidiabetic activity. Thus, the study shows that NLM has a wellspring of natural source of antioxidants and antidiabetic agents and furtherance of studies on its mechanism is recommended to know detailed facts

QUANTITATIVE ESTIMATION AND ANTIMICROBIAL POTENTIAL OF ETHANOL EXTRACT OF DURIO ZIBETHINUS MURR. LEAVES

Objectives: Current research is aimed to investigate the natural antimicrobial potential of Durio zibethinus murr. ethanol leaves extract (DZL).Methods: DZL was subjected to the preliminary phytochemical screening along with quantitative analysis of phenols and flavonoids. Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) were recorded. The agar well diffusion method was used to measure the antibacterial activity against gram positive and gram negative bacteria. The microorganisms used for the study were the ATCC strains of Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus, Streptococcus pyogenes, Neisseria gonorrhoeae, Pseudomonas aeruginosa and Escherichia coli.Results: DZL exhibited the highest MIC of 0.1mg/mL and MBC of 0.25 mg/mL against gram negative bacteria, Pseudomonas aeruginosa and Escherichia coli. At MIC of 0.1mg/mL, DZL displayed significant zone of inhibition against Pseudomonas aeruginosa and Escherichia coli compared to gentamycin.Conclusion: This research has shown that DZL has natural antibacterial properties against gram negative human pathogens

A Simple HPLC-UV Method for the Determination of Glutathione in PC-12 Cells

A highly sensitive and simple HPLC-UV method was developed and validated for the assay of glutathione (GSH) in PC-12 cells. Glutathione is a major intracellular antioxidant having multiple biological effects, best known for its cytoprotective effects against cell damage from reactive oxygen species and toxic reactive metabolites and regulating the cellular redox homeostasis. Due to its own sulfhydryl (SH) group, GSH readily reacts with Ellman’s reagent to form a stable dimer which allows for quantitative estimation of GSH in biological systems by UV detection. The separation was achieved using a C8 column with a mobile phase consisting of phosphate buffer adjusted to pH 2.5 (mobile phase A) and acetonitrile (mobile phase B), running in a segmented gradient manner at a flow rate of 0.8 mL/min, and UV detection was performed at 280 nm. The developed HPLC-UV method was validated with respect to precision, accuracy, robustness, and linearity within a range of 1–20 μg/mL. Limit of detection (LOD) and limit of quantification (LOQ) were 0.05 and 0.1 μg/mL, respectively. Furthermore, the method shows the applicability for monitoring the oxidative stress in PC-12 cells

SCREENING ANTIMICROBIAL POTENTIAL FOR MALAYSIAN ORIGINATED TAMARINDUS INDICA ETHANOLIC LEAVES EXTRACT

 Objective: The aim of the research is to study the antimicrobial potential of Tamarindus indica leaves extract (Malaysian origin).Methods: T. indica leaves extraction was carried out by maceration (TIME) and Soxhlet extraction methods (TISE). The phytochemical test was conducted for the confirmation of various phytoconstituents present in the leaves extract. Antimicrobial assays were carried out by minimum bactericidal concentration (MBC), minimum inhibitory concentration (MIC), and agar well diffusion method against ATCC bacterial strains.Results: Ethanolic extraction of T. indica leaves by maceration method showed better yield (70.38%) compared to Soxhlet extraction method (60.55%). The qualitative phytochemical test on TISE and TIME were confirmed the presence of alkaloids, flavonoids, phenols, mucilage, tannins, steroids, proteins, and carbohydrates. TIME was selected for antimicrobial studies, and it was found to have MBC value of 500 μg/mL and MIC value of 250 μg/mL among various test bacteria, and it was also found to exhibit good zone of inhibition against Gram-negative bacteria such as Escherichia coli and Neisseria gonorrhoeae. Conclusion: These findings deduced that T. indica leaves have various phytochemical constituents which could be responsible for their natural antibacterial activity especially against Gram-negative bacteria