scholarly journals Anti-inflammatory Effects of S. cumini Seed Extract on Gelatinase-B (MMP-9) Regulation against Hyperglycemic Cardiomyocyte Stress

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Neha Atale ◽  
Chandra Bhushan Mishra ◽  
Shrey Kohli ◽  
Raj Kumar Mongre ◽  
Amresh Prakash ◽  
...  

Black berry (Syzygium cumini) fruit is useful in curing diabetic complications; however, its role in diabetes-induced cardiomyopathy is not yet known. In this study, we investigated the regulation of gelatinase-B (MMP-9) by S. cumini methanol seed extract (MSE) in diabetic cardiomyopathy using real-time PCR, RT-PCR, immunocytochemistry, gel diffusion assay, and substrate zymography. The regulatory effects of MSE on NF-κB, TNF-α, and IL-6 were also examined. Identification and estimation of polyphenol constituents present in S. cumini extract were carried out using reverse-phase HPLC. Further, in silico docking studies of identified polyphenols with gelatinase-B were performed to elucidate molecular level interaction in the active site of gelatinase-B. Docking studies showed strong interaction of S. cumini polyphenols with gelatinase-B. Our findings indicate that MSE significantly suppresses gelatinase-B expression and activity in high-glucose- (HG-) stimulated cardiomyopathy. Further, HG-induced activation of NF-κB, TNF-α, and IL-6 was also remarkably reduced by MSE. Our results suggest that S. cumini MSE may be useful as an effective functional food and dietary supplement to regulate HG-induced cardiac stress through gelatinase.

Author(s):  
Muhammad Asif ◽  
Hafiz Muhammad Yousaf ◽  
Mohammed Saleem ◽  
Malik Saadullah ◽  
Tahir Ali Chohan ◽  
...  

Introduction: Inflammation is a vital reaction of the natural immune system that protects against encroaching agents. However, uncontrolled inflammation can lead to complications. Trigonella foenum-graecum is traditionally used as an anti-inflammatory herb. Objectives: The current study was conducted to explore the antioxidant, anti-inflammatory, and antiangiogenic potentials of Trigonella foenum-graecum seeds oil. Methods: Oil was extracted from seeds of Trigonella foenum-graecum by cold press method and labelled as TgSO. Phytochemical (GCMS, Folin-Ciocalteu method) and metal analyses were conducted to evaluate the metalo-chemical profile of TgSO. In vitro antioxidant assays (2,2-diphenyl-1-picrylhydrazyl, 2,2'-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid and ferric reducing antioxidant power) were performed to assess its antioxidant potential. In vitro antimicrobial property was evaluated using the agar disc diffusion method and the safety profile of TgSO was assessed following OECD 425 guidelines. In vivo anti-inflammatory activity of TgSO was assessed in carrageenan, serotonin, histamine, formalin, and cotton pellet-induced oedema models. Serum TNF-α, superoxide dismutase (SOD) and, catalases (CAT) levels were assessed by ELISA kit while the effects on angiogenesis were assessed by chick chorioallantoic membrane (CAM) assay. Histopathological studies using excised paws were conducted to observe the effect of TgSO treatment at the tissue level. In silico docking studies were conducted to screen binding potential of identified compounds towards TNF- α. Results: Extraction by cold press yielded 16% of TgSO. Phytochemical analysis of TgSO through GC-MS showed the presence of eugenol, dihydrocoumairn, and heptadecanoic acid, tri- and tetradecanoic acid and hexadecanoic acid respectively. Total phenolic contents of TgSO were found to be 37.1 ± 0.91 mg/g gallic acid equivalent in Folin-Ciocalteu method. Metal analysis indicated the presence of different metals in TgSO. Findings of antioxidant models showed moderate antioxidant potential of TgSO. Findings of antimicrobial assays showed that TgSO was active against S. aureus, S.epidermidis, C. albicans, and A. niger. In vivo toxicity study data showed that TgSO was safe up to the dose of 5000 mg/kg. Data of oedema models showed significant (p < 0.05) reduction in oedema development in TgSO treated animals in both acute and chronic models. Histopathological evaluations of paws showed minimal infiltration with inflammatory cells in TgSO-treated animals. Treatment also significantly (p < 0.05) down-regulated TNF-α in serum and while levels of SOD and CAT were upregulated. CAM assay findings revealed antiangiogenic activity of TgSO. Findings of in silico docking studies showed that identified phytoconstituents have potential to bind with culprit cytokine. Conclusion: Data of that current study conclude that TgSO has antioxidant, anti-inflammatory, and antiangiogenic effects that validate its traditional uses. Moreover, the synergistic actions of different phytoconstituents are proposed to be responsible for the observed effects.


Author(s):  
Suman Rohilla ◽  
Ranju Bansal ◽  
Puneet Chauhan ◽  
Sonja Kachler ◽  
Karl-Norbert Klotz

Background: Adenosine receptors (AR) have emerged as competent and innovative nondopaminergic targets for the development of potential drug candidates and thus constitute an effective and safer treatment approach for Parkinson’s disease (PD). Xanthine derivatives are considered as potential candidates for the treatment Parkinson’s disease due to their potent A2A AR antagonistic properties. Objective: The objectives of the work are to study the impact of substituting N7-position of 8-m/pchloropropoxyphenylxanthine structure on in vitro binding affinity of compounds with various AR subtypes, in vivo antiparkinsonian activity and binding modes of newly synthesized xanthines with A2A AR in molecular docking studies. Methods: Several new 7-substituted 8-m/p-chloropropoxyphenylxanthine analogues have been prepared. Adenosine receptor binding assays were performed to study the binding interactions with various subtypes and perphenazine induced rat catatonia model was used for antiparkinsonian activity. Molecular docking studies were performed using Schrödinger molecular modeling interface. Results: 8-para-substituted xanthine 9b bearing an N7-propyl substituent displayed the highest affinity towards A2A AR (Ki = 0.75 µM) with moderate selectivity versus other AR subtypes. 7-Propargyl analogue 9d produced significantly longlasting antiparkinsonian effects and also produced potent and selective binding affinity towards A2A AR. In silico docking studies further highlighted the crucial structural components required to develop xanthine derived potential A2A AR ligands as antiparkinsonian agents. Conclusion: A new series of 7-substituted 8-m/p-chloropropoxyphenylxanthines having good affinity for A2A AR and potent antiparkinsonian activity has been developed.


2020 ◽  
Vol 17 (7) ◽  
pp. 840-849
Author(s):  
Mahendra Gowdru Srinivas ◽  
Prabitha Prabhakaran ◽  
Subhankar Probhat Mandal ◽  
Yuvaraj Sivamani ◽  
Pranesh Guddur ◽  
...  

Background: Thiazolidinediones and its bioisostere, namely, rhodanines have become ubiquitous class of heterocyclic compounds in drug design and discovery. In the present study, as part of molecular design, a series of novel glitazones that are feasible to synthesize in our laboratory were subjected to docking studies against PPAR-γ receptor for their selection. Methods and Results: As part of the synthesis of selected twelve glitazones, the core moiety, pyridine incorporated rhodanine was synthesized via dithiocarbamate. Later, a series of glitazones were prepared via Knovenageal condensation. In silico docking studies were performed against PPARγ protein (2PRG). The titled compounds were investigated for their cytotoxic activity against 3T3-L1 cells to identify the cytotoxicity window of the glitazones. Further, within the cytotoxicity window, glitazones were screened for glucose uptake activity against L6 cells to assess their possible antidiabetic activity. Conclusion: Based on the glucose uptake results, structure activity relationships are drawn for the title compounds.


2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.


2019 ◽  
Vol 15 (4) ◽  
pp. 318-333
Author(s):  
Dipak P. Mali ◽  
Neela M. Bhatia

Objective:To screen the phytochemicals for phosphodiesterase 5A (PDE5A) inhibitory potential and identify lead scaffolds of antihypertensive phytochemicals using in silico docking studies.Methods:In this perspective, reported 269 antihypertensive phytochemicals were selected. Sildenafil, a PDE5A inhibitor was used as the standard. In silico docking study was carried out to screen and identify the inhibiting potential of the selected phytochemicals against PDE5A enzyme using vLife MDS 4.4 software.Results:Based on docking score, π-stacking, H-bond and ionic interactions, 237 out of 269 molecules were selected which have shown one or more interactions. Protein residue Gln817A was involved in H-boding whereas Val782A, Phe820A and Leu804A were involved in π-stacking interaction with ligand. The selected 237 phytochemicals were structurally diverse, therefore 82 out of 237 molecules with one or more tricycles were filtered out for further analysis. Amongst tricyclic molecules, 14 molecules containing nitrogen heteroatom were selected for lead scaffold identification which finally resulted in three different basic chemical backbones like pyridoindole, tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline as lead scaffolds.Conclusion:In silico docking studies revealed that nitrogen-containing tetrahydro-pyridonaphthyridine and dihydro-pyridoquinazoline tricyclic lead scaffolds have emerged as novel PDE5A inhibitors for antihypertensive activity. The identified lead scaffolds may provide antihypertensive lead molecules after its optimization.


2021 ◽  
Vol 183 ◽  
pp. 112598
Author(s):  
Duaa Eliwa ◽  
Mohamed A. Albadry ◽  
Abdel-Rahim S. Ibrahim ◽  
Amal Kabbash ◽  
Kumudini Meepagala ◽  
...  

Toxins ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 152 ◽  
Author(s):  
Boris Zhang ◽  
Feng Li ◽  
Zhengyao Chen ◽  
Indira Shrivastava ◽  
Edward Gasanoff ◽  
...  

Cobra venom cardiotoxins (CVCs) can translocate to mitochondria to promote apoptosis by eliciting mitochondrial dysfunction. However, the molecular mechanism(s) by which CVCs are selectively targeted to the mitochondrion to disrupt mitochondrial function remains to be elucidated. By studying cardiotoxin from Naja mossambica mossambica cobra (cardiotoxin VII4), a basic three-fingered S-type cardiotoxin, we hypothesized that cardiotoxin VII4 binds to cardiolipin (CL) in mitochondria to alter mitochondrial structure/function and promote neurotoxicity. By performing confocal analysis, we observed that red-fluorescently tagged cardiotoxin rapidly translocates to mitochondria in mouse primary cortical neurons and in human SH-SY5Y neuroblastoma cells to promote aberrant mitochondrial fragmentation, a decline in oxidative phosphorylation, and decreased energy production. In addition, by employing electron paramagnetic resonance (EPR) and protein nuclear magnetic resonance (1H-NMR) spectroscopy and phosphorescence quenching of erythrosine in model membranes, our compiled biophysical data show that cardiotoxin VII4 binds to anionic CL, but not to zwitterionic phosphatidylcholine (PC), to increase the permeability and formation of non-bilayer structures in CL-enriched membranes that biochemically mimic the outer and inner mitochondrial membranes. Finally, molecular dynamics simulations and in silico docking studies identified CL binding sites in cardiotoxin VII4 and revealed a molecular mechanism by which cardiotoxin VII4 interacts with CL and PC to bind and penetrate mitochondrial membranes.


2012 ◽  
Vol 12 (2) ◽  
pp. 157-161 ◽  
Author(s):  
Arumugam Madeswaran ◽  
Muthuswamy Umamaheswari ◽  
Kuppusamy Asokkumar ◽  
Thirumalaisamy Sivashanmugam ◽  
Varadharajan Subhadradevi ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1191
Author(s):  
Christian R. Gomez ◽  
Ingrid Espinoza ◽  
Fazlay S. Faruke ◽  
Mahbub Hasan ◽  
Khondaker Miraz Rahman ◽  
...  

To date very few promising leads from natural products (NP) secondary metabolites with antiviral and immunomodulatory properties have been identified for promising/potential intervention for COVID-19. Using in-silico docking studies and genome based various molecular targets, and their in vitro anti-SARS CoV-2 activities against whole cell and/or selected protein targets, we select a few compounds of interest, which can be used as potential leads to counteract effects of uncontrolled innate immune responses, in particular those related to the cytokine storm. A critical factor for prevention and treatment of SARS-CoV-2 infection relates to factors independent of viral infection or host response. They include population-related variables such as concurrent comorbidities and genetic factors critically relevant to COVID-19 health disparities. We discuss population risk factors related to SARS-CoV-2. In addition, we focus on virulence related to glucose-6-phosphate dehydrogenase deficiency (G6PDd), the most common human enzymopathy. Review of data on the response of individuals and communities with high prevalence of G6PDd to NP, prompts us to propose the rationale for a population-specific management approach to rationalize design of therapeutic interventions of SARS-CoV-2 infection, based on use of NP. This strategy may lead to personalized approaches and improve disease-related outcomes.


2021 ◽  
Vol 19 (3) ◽  
pp. 355-363
Author(s):  
Jung-Wook Kang ◽  
In-Chul Lee

Purpose: This study aimed to investigate the effects of the Cassia obtusifolia L. seed extract (CSE) on particulate matter (PM)-induced skin.Methods: The effects of CSE on cell viability were evaluated using a skin cell line. To determine the anti-inflammatory effects and matrix metallopeptidase-1 (MMP-1)-inhibitory effects of CSE on PM-induced skin, NO and MMP-1 expressions were measured using an enzyme-linked immunosorbent assay (ELISA) kit. Also, the effects of CSE was investigated the induction of IL-8 and TNF-α treated PM on reconstructed human full thickness skin models.Results: It was observed that CSE decreased NO production in PM-induced RAW 264.7 cells without cytotoxicity. In addition, CSE decreased the expression of MMP-1 in PM-induced cells in a dose-dependent manner. CSE decreased IL-8 and TNF-α production in a PM-reconstructed human skin model.Conclusion: These results indicate that CSE could be used as a cosmetic material to induce anti-inflammation and inhibition of MMP-1 in PM-induced skin.


Sign in / Sign up

Export Citation Format

Share Document