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IJCRR - 13(16), August, 2021

Pages: 198-206

Date of Publication: 30-Aug-2021


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In Silico Screening of Phytochemicals of Styrax Benzoin Against the Inflammatory Mediators

Author: Swathy B, Menaka M, Kiran G, Prabhakar Reddy V

Category: Healthcare

Abstract:Introduction: Inflammatory mediators are up-regulated during SARS-CoV-2 infection and also during injury and surgery. The wound is categorized as break down or opening of the skin, which could lead to malfunctioning of skin. Many physiological processes, protein targets, and cellular signalling pathways are involved in wound healing. Many inflammatory mediators are produced during injury and inhibition of the negative inflammatory mediators like 1RAK4 and NLRP3 inflammasome plays a key role in the wound healing process. Therefore, it could essential to find therapeutics for inhibiting the signalling pathways responsible for the release of negative inflammatory mediators. However, the conventional approaches to drug development are time-consuming and expensive. Objective: In the present study, we have adopted a computational approach to identify lead molecules from Styrax Benzoinagainst the inflammatory mediators. Method: We have screened ligands from Styrax Benzoin library for their ability to bind and inhibit the two potential inflammatory targets such as IRAK4 (Interleukin-1 Receptor Associated Kinase-4) with Protein Data Bank (6F3I) and innate immune signalling receptor NLRP3 (NOD-, LRR-, and pyrin domain-containing-3) inflammasome with Protein Data Bank (6NPY). Results: We found that p-coumarin cinnamate 6 and coniferyl benzoate 12 could bind at the substrate-binding pocket of inflammatory targets with high binding affinity. Bioavailability properties and Pharmacophore features were also studied. Conclusion: The results suggest that the Phytoconstituents of Styrax Benzoin have the potential to be developed as novel inhibitors of inflammatory mediators. These inflammatory mediators are upregulated during SARS-CoV-2 infections. However, their clinical usage on wound healing is a subject of further investigations and clinical trials.

Keywords: Styrax Benzoin, Inflammatory Mediators, SARS-CoV-2, Wound, 1RAK4, NLRP3 inflammasome

Full Text:

INTRODUCTION

Inflammatory mediators are upregulated during SARS-CoV2 infections and also during injury and surgery. Viruses can affect the wound healing process by causing physiological changes. As per WHS (Wound Healing Society), wound is categorized as break down or opening of the skin, which could lead to malfunctioning of skin.1 The physiology stages of wound healing are primary and secondary interventions, smaller wounds heal by primary interventions and larger wound are heal by secondary interventions.2, 3 Among the different stages in wound healing the first stage is the inflammatory stage and is very essential phase in wound healing process.2, 4. These clots release monocytes and forms macrophages and further produce the cytokines.5When the tissue is injury that going to release inflammatory cytokines from the damaged tissue cells.6, 7 Neutrophils, also contribute in wound healing by releasing the cytokines and growth factors and also has phagocytosis functions which protect the wound against bacterial infections.8, 9. Therefore, it could essential to find therapeutics for inhibiting the signaling pathways responsible for release of negative inflammatory mediators. Inflammatory mediators like cytokines, chemokines and growth factors play the key role in wound healing by releasing fibroblasts and keratinocytes from cells and replace or restore the skin integrity.10, 11 NLRP3 (Nod-like receptor protein) inflammasome cellular pathway is involved in wound healing and various inflammatory skin diseases.12, 13Yimin Chai group have studied role NLRP3 expression in diabetic wounds in humans and the results demonstrates the higher expression of caspase1, NLRP3, IL-1β inflammatory mediators.14 These mediators could be the potential targets for the diabetic wound healing process. IRAK4 (interleukin-1 receptor-associated kinase 4) is an important molecular target for the release of inflammatory substances.15, 16 IRAK inhibitors could be useful in the prophylaxis treatment of psoriasis, sclerosis, myocardial infarction, lupus erythematous, and arthritis.17, 18

Styrax Benzoin (Latin: Benzoinum) is a balsamic resin and other species are Sumatra Benzoin and Siam Benzoin and belongs to family Styraceae.19 It is grown highly in tropical rain forests of South-Eastern Asia Countries like Indonesia, Thailand, China and Vietnam. (20) The plants grow up to 14 cm long and flowers are white in color and bell-shaped. Sumatra benzoin resin contains chemical constituents are balsamic acid which esters of benzoic and cinnamic acids.21 They also contains Triterpenoid acids like summaresinolic and siaresinolic acids are present.22 Whereas, Siam Benzoin about 76% of coniferyl benzoate is present as chief active constituent.23  The sytrax benzoin resin is prepared as tincture and used as expectorant, carminative, disinfectant and diuretic.24-27 It also has the biological uses in throat infection and upper respiratory tract infections.28 The aim of this study is to investigate the In Silico computational study of 22 Phytoconstituents of Styrax Benzoin against the inflammatory mediators 1RAK4 and NLRP3 inflammasome.

EXPERIMENTAL

Protein Preparation:

The present study is aimed to perform the computational studies of phytochemical analogs of Styrax Benzoin against COVID-19 negative immune regulators such as IRAK4 (Interleukin-1 Receptor Associated Kinase 4) with PDB ID: 6F3I and innate immune signaling receptor NLRP3 (NOD-, LRR-, and pyrin domain-containing 3) inflammasome with PDB ID: 6NPY.29,30The X-ray crystal structures of IRAK4 in complex with pyrrolotriazine inhibitor and NLRP3 bound to NEK7 were retrieved from Protein Data Bank (https://www.rcsb.org/structure/6F3I; https://www.rcsb.org/structure/6NPY). The protein targets were downloaded in PDB format and protein structural preparation in Macromolecule protocol was carried out in Discovery Studio software with default settings. Protein structures were cleaned and missing residues, Hydrogen’s were added and 3D protonation were carried out to the target protein and minimized for the selected active residues.

Ligand Preparation:

The important phytochemicals of Styrax Benzoin were collected from the literature survey and also from TCIM database. The canonical smiles were saved in .csv format and structures were generated by using Data warrior software and all the 22 Phytoconstituents were saved in SD file. All the ligand structures were energy minimized using CHARMm force field in Small-molecule Protocol and different conformers were generated.

Molecular Docking Studies:

Molecular docking were carried out for the 18 Phytoconstituents of Styrax Benzoin (1-22) to identify the molecular interactions between inflammatory targets 1RAK4 (PDB ID: 6F3I) and NLRP3 inflammasome (PDB ID: 6NPY).29, 30All the ligands were docked with by using Accelrys Discovery Studio version 3.5 with Libdocker and CDocker software. The protein structures were retrieved form protein data bank and the protein preparation and minimization were carried out with the default settings in Discovery Studio.  The active site sphere generated from by ligand binding sites with current selection of Define and Edit Binding site in Receptor-Ligand Interaction tools. The binding site sphere specified based on the binding interactions of co-crystal ligand against the target protein, Docking Tolerance as 0.25, Docking Preferences as High Quality.  The results were analysed and 3D and 2D interactions were obtained with Discovery studio Visualizer.

Pharmacophore Modelling.

            Pharmacophores features are generated between receptor-ligand using Interaction Pharmcophore generations in DS Protocol.  Different molecular interactions like HBA (hydrogen bond acceptor), HBD (hydrogen bond donor), HY (hydrophobic center) and PI (Positive ionisable) were generated for receptor-ligand complex. The study was done for best docked pose of p-coumaryl cinnamate6 and coniferyl benzoate12 for 1RAK4 and NLRP3 complex proteins.

In Silico Absorption Distribution Metabolism Excretion (ADME) and Toxicity Prediction:

All the Phytoconstituents of Styrax Benzoin(1-22) were predicted In silico ADME properties and Toxicity analysis were carried out using Discovery Studio, pKCSM web server and Data Warrior Software.31,32

RESULTS AND DISCUSSION

Molecular Docking Studies

The molecular docking studies were carried out in Discovery Studio Docking software. The 3-dimensional proteins (PDB: 6F3I and 6NPY) were retrieved from the protein data bank. All the proteins were prepared and their energies were minimized by the protein preparation wizard. The receptor sphere around their co-crystal ligands were generated using current selection of co-crystal ligand interactions. All the selected 22 Phytoconstituents of Styrax Benzoinwere downloaded from Pubmed (Figure-1). The molecular docking using normal mode was carried out and results were analyzed.

The initial rationale molecular docking studies of all 22 Phytoconstituents of Styrax Benzoin (1-22) in the active site of 1RAK4 (PDB ID: 6F3I) and NLRP3 inflammasome (PDB ID: 6NPY)were carried out in order to predict the binding efficiencies. The molecular docking scores are summarized in (Table:1-3). Initially the docking studies were carried out for all ligands with Libdock which High Throughput Screen-based software and best ligand poses were further docked with CDocker.

Molecular Docking Studies with 1RAK4 (PDB ID: 6F3I):

            The molecular docking study was carried out for 22 phytoconstituents of Styrax Benzoin (1-22) into the active site of 1RAK4 (PDB ID: 6F3I). IRAK family (IRAK1-4) plays a central role in positive and negative inflammatory responses by regulating the expression of genes in immune cells.33 These signals which stimulus the various inflammatory mediators and plays key role for elimination of pathogens like virus, bacteria and carcinogenic cells, as well as for wound healing.

Among the ligands docked against IRAK-4, coniferyl benzoate (12) has showed excellent free energy binding with Lib dock score 99.36 and with Cdock score -20.73 and with binding energy value of -78.73 kcal/mol. Coniferyl benzoate(12) exerted H-bond interactions and bond distance in Å with Glu194(2.43), Met265(1.91), Val263(2.84) Tyr264(2.63) amino acid residues and hydrophobic interactions with Val200, Met192, Tyr262, Ala211, Leu318 residues. Similarly, p-coumaryl cinnamate has exhibited H-bond interactions with Met265(2.01), Asn316(2.23), Tyr264(2.86) residues and hydrophobic interactions with Val200, Ala211, Leu318, Met192 amino acid residues with Libdock Score 105.19and Cdock score -20.90and binding energy value of -36.49 kcal/mol. (Table-1 & 2)

Whereas, Crystal ligand CKN (Pyrrolotriazine) has involved key interactions with residues forming H-bond with Arg273(1.87), Arg273(2.88), Asn316(2.38), Asp329(2.48), Asp272(2.81), Asp272(2.37), and hydrophobic interactions with Met192, Val200, Lys213, Ala211, Val246, Met265, Leu318, residues with Libdock Score 130.28 and Cdock score 30.24 and binding energy value of -82.79 kcal/mol. It signifies that Coniferyl benzoate(12) is occupying the same residues of active site of crystal ligand. (Figure: 2 & 3)

Molecular Docking Studies with NLRP3 inflammasome (PDB ID: 6NPY):

            The molecular docking study was carried out for 22 phytoconstituents of Styrax Benzoin (1-22) into the active site of NLRP3 inflammasome (PDB ID: 6NPY). NLRP3 inflammatory signalling pathway plays a key role in release of inflammatory mediators, on activation of NLRP3 abrupt the cytochrome storms viz Interlukins (IL-1β, IL-6) and TNF-αand causes inflammatory in lower respiratory tract.34  On inhibition of NLRP3 will stops the release of negative inflammatory mediators.

Among the ligands docked against IRAK-4, coniferyl benzoate (12) has showed excellent free energy binding with Lib dock score 119.99and with Cdock score -27.54 and with binding energy value of -63.66 kcal/mol. Coniferyl benzoate(12) exerted H-bond interactions and bond distance in Å with Thr167(2.22), Thr167(3.03), Arg165(2.40), Gly229(2.45), Gly227(2.95), amino acid residues and hydrophobic interactions with Phe371, Pro410, Ile232, Leu411, and Leu162 residues. Similarly, p-coumaryl cinnamate(6) has exhibited H-bond interactions with Thr167(1.98), His520(2.17), Thr167(2.02), Gly229(2.41) residues and hydrophobic interactions with Pro410, Ile232, Arg235 amino acid residues. (Table 1 & 3)

Whereas, Crystal ligand CKN has involved key interactions with residues forming H-bond with His163 and Glu166 with a bond distance 2.06 Ao and 2.18 Ao, respectively and hydrophobic interactions with His41, Met49 and Met165 residues. It signifies that p-coumaryl cinnamate(6) and Coniferyl benzoate(12) is occupying the same residues of active site of crystal ligand. (Figure: 4-6)

Structure-Based Pharmacophore: The best protein-ligand pose of docking were further analysed for Pharmacophore features using Interaction Pharmacophore Generation Protocol.  Table-4 give the details about Common Pharmacophore Feature for ligand p-coumaryl cinnamate 6 has HHDA pharmacophore feature and fit value 3.99 and rank 9.13 and whereas, coniferyl benzoate 12 has HHHDA pharmacophore features with fit value 4.99 and rank 11.50 which shows better features. The interaction pharmacophore features for receptor-ligand complex among the result coniferyl benzoate-6F3I complex has 10 pharmacophore models with H-bond interactions Glu194, Val263, Tyr264, Met265 and with hydrophobic interactions Met192, Val200, Ala211, Tyr262, Leu318. Similarly, with coniferyl benzoate-6NPY complex has 10 pharmacophore models with H-bond interactions Arg165, Thr167, Gly227 and hydrophobic interactions Leu162, Ile232, Phe371, Pro410, Leu411. The interaction pharmacophore features are shown in Figure-7.

In Silico ADMET Prediction:

            In Silico Prediction of ADME and Toxicity parameters were analysed for the Phytoconstituents of Stryax Benzoin by using Discovery Studio, pKCSM webserver and Data Warrior Software.  All the phytochemicals has obeyed Lipinski’s rule of 5 in which the Mol. Wt is below 500, logP <5, No of Hydrogen Bond Donors is <5 and Acceptors < 10 and Molar refractivity (2) between 40-130. Almost all the phytochemicals have not deviated the rule of 5 and hence they potential for oral absorption and less toxicity.  (Figure-8).

Some of the potential Phytochemicals (1-7, 9, 11-16, 20) which have shown good binding affinity with the docking studies were analysed for ADMET using pKCSM webserver(Table-5). Absorption properties of the compounds are studied by Caco-2 permeability, human intestinal absorption, skin permeability, and p-gp substrate or inhibitor. Predicted value >0.90 indicates high Caco-2 permeability. Vanillin 1, vanillic acid 2, ursolic acid 3, resorcinol 4, p-OHcinnamic acid5, p-coumaryl cinnamate 6, oleanonic acid 7, masilinic acid9, corosolic acid 11, coniferyl benzoate12, cinnamyl alcohol13, cinnamic acid14, benzyl cinnamate15, benzyl benzoate16, 4-hydroxy-benzenepropanol20 were predicted to have highCaco-2 permeability. All phytochemicals have good intestinal absorption. In terms of skin permeability if the compounds has logKp > -2.5 consider to be low skin permeability. Among analysed compounds, cinnamyl alcohol13 was consider to have low skin permeability with logKp = -1.70.

None of the phytochemicals are substrate for p-glycoprotein which is an efflux transporter which excretes chemicals or drugs from the cells. All phytochemicals have apparent volume of distribution the limits are VDss is low if log VDss <-0.15 and high if logVDss >0.45. For Blood-Brain Barrier permeability, compound with logBB > 0.3 consider to cross the BBB and logBB < -1 are impermeable to brain. Phytoconstituents 12-16 & 20 will cross the BBB as predicted values are logBB>0.3. Regarding CNS permeability, phytochemicals 6, 7, 9, 11, 13, 14, 15, 16 & 20 have high CNS permeability (logPS > -2).

Cytochrome P450 is important enzyme for biotransformation of drugs in liver and inhibitors of CYP450 will affect the pharmacokinetic properties of drug. All phytochemicals are not substrate for CYP2D6, Compound 12, 13,

16 & 20 are substrate for CYP3A4. Compound 6, 12 & 13 are inhibitors for CYP1A2 inhibitor.

Regarding toxicity compound 6 has Ames toxicity, and compounds 3, 9, 11 have hepatoxicity, 4, 13, & 20 has skin sensitisation problems. All phytochemicals have hERG toxicity and are free form cardiotoxicity. From these observations it could revealed that all phytochemicals of Styrax Benzoin have shown good drug-like properties viz., no toxicity, good oral absorption, metabolism and excretion and no interaction with cytochrome P450 enzymes and free from cardiotoxicity.

Conclusion:

InSilico computational studies like molecular docking, pharmacophore mode, ADMET prediction could provide helpful information for rapid design of drugs. Wound infection causes cytokine storm and release negative inflammatory mediators such as 1RAK4 and NRLP3. Therefore, it could essential to find therapeutics for inhibiting the signaling pathways responsible for release of negative inflammatory mediators. To find potent inhibitors for inflammatory targets 1RAK4 and NRLP3 inflammasome we performed molecular docking studies for 22 Phytoconstituents of Styrax Benzoin using Libdocker and Cdocker. The results shown p-coumaryl benzoate 6 and coniferyl benzoate 12 have high binding affinity against the protein targets. A detail pharmacophore features were also generated against these docked complexes. ADMET prediction studies indicate that all the Phytoconstituents are having good oral absorption and less toxicity. The results suggest that the Phytoconstituents of Styrax Benzoin have the potential to be developed as novel inhibitors of inflammatory mediators. These inflammatory mediators are upregulated during SARS-CoV-2 infections. However, their clinical usage against inflammatory mediators is a subject of further investigations and clinical trials.

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A study by Dorothy Ebere Adimora et al. entitled \"Remediation for Effects of Domestic Violence on Psychological well-being, Depression and Suicide among Women During COVID-19 Pandemic: A Cross-cultural Study of Nigeria and Spain\" is awarded Best Article of Vol 14 issue 23
A study by Muhas C. et al. entitled \"Study on Knowledge & Awareness About Pharmacovigilance Among Pharmacists in South India\" is awarded Best article for Vol 14 issue 22
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A Study by Manoj KP et al. entitled "A Randomized Comparative Clinical Trial to Know the Efficacy of Ultrasound-Guided Transversus Abdominis Plane Block Against Multimodal Analgesia for Postoperative Analgesia Following Caesarean Section" is awarded Best Article Award of Vol 13 issue 23
A Study by Karimova II et al. entitled "Changes in the Activity of Intestinal Carbohydrases in Alloxan-Induced Diabetic Rats and Their Correction with Prenalon" is awarded Best Article of Vol 13 issue 22
A Study by Ashish B Roge et al. entitled "Development, Validation of RP-HPLC Method and GC MS Analysis of Desloratadine HCL and It’s Degradation Products" is awarded Best Article of Vol 13 issue 21
A Study by Isha Gaurav et al. entitled "Association of ABO Blood Group with Oral Cancer and Precancer – A Case-control Study" is awarded Best Article for Vol 13 issue 20
A Study by Amr Y. Zakaria et al. entitled "Single Nucleotide Polymorphisms of ATP-Binding Cassette Gene(ABCC3 rs4793665) affect High Dose Methotrexate-Induced Nephrotoxicity in Children with Osteosarcoma" is awarded Best Article for Vol 13 issue 19
A Study by Kholis Ernawati et al. entitled "The Utilization of Mobile-Based Information Technology in the Management of Dengue Fever in the Community Year 2019-2020: Systematic Review" is awarded Best Article for Vol 13 issue 18
A Study by Bhat Asifa et al. entitled "Efficacy of Modified Carbapenem Inactivation Method for Carbapenemase Detection and Comparative Evaluation with Polymerase Chain Reaction for the Identification of Carbapenemase Producing Klebsiella pneumonia Isolates" is awarded Best Article for Vol 13 issue 17
A Study by Gupta R. et al. entitled "A Clinical Study of Paediatric Tracheostomy: Our Experience in a Tertiary Care Hospital in North India" is awarded Best Article for Vol 13 issue 16
A Study by Chandran Anand et al. entitled "A Prospective Study on Assessment of Quality of Life of Patients Receiving Sorafenib for Hepatocellular Carcinoma" is awarded Best article for Vol 13 issue 15
A Study by Rosa PS et al. entitled "Emotional State Due to the Covid – 19 Pandemic in People Residing in a Vulnerable Area in North Lima" is awarded Best Article for Vol 13 issue 14
A Study by Suvarna Sunder J et al. entitled "Endodontic Revascularization of Necrotic Permanent Anterior Tooth with Platelet Rich Fibrin, Platelet Rich Plasma, and Blood Clot - A Comparative Study" is awarded Best Article for Vol 13 issue 13
A Study by Mona Isam Eldin Osman et al. entitled "Psychological Impact and Risk Factors of Sexual Abuse on Sudanese Children in Khartoum State" is awarded Best Article for Vol 13 issue 12
A Study by Khaw Ming Sheng & Sathiapriya Ramiah entitled "Web Based Suicide Prevention Application for Patients Suffering from Depression" is awarded Best Article for Vol 13 issue 11
A Study by Purushottam S. G. et al. entitled "Development of Fenofibrate Solid Dispersions for the Plausible Aqueous Solubility Augmentation of this BCS Class-II Drug" is awarded Best article for Vol 13 issue 10
A Study by Kumar S. et al. entitled "A Study on Clinical Spectrum, Laboratory Profile, Complications and Outcome of Pediatric Scrub Typhus Patients Admitted to an Intensive Care Unit from a Tertiary Care Hospital from Eastern India" is awarded Best Article for Vol 13 issue 09
A Study by Mardhiah Kamaruddin et al. entitled "The Pattern of Creatinine Clearance in Gestational and Chronic Hypertension Women from the Third Trimester to 12 Weeks Postpartum" is awarded Best Article for Vol 13 issue 08
A Study by Sarmila G. B. et al. entitled "Study to Compare the Efficacy of Orally Administered Melatonin and Clonidine for Attenuation of Hemodynamic Response During Laryngoscopy and Endotracheal Intubation in Gastrointestinal Surgeries" is awarded Best Article for Vol 13 issue 07
A Study by M. Muthu Uma Maheswari et al. entitled "A Study on C-reactive Protein and Liver Function Tests in Laboratory RT-PCR Positive Covid-19 Patients in a Tertiary Care Centre – A Retrospective Study" is awarded Best Article of Vol 13 issue 06 Special issue Modern approaches for diagnosis of COVID-19 and current status of awareness
A Study by Gainneos PD et al. entitled "A Comparative Evaluation of the Levels of Salivary IgA in HIV Affected Children and the Children of the General Population within the Age Group of 9 – 12 Years – A Cross-Sectional Study" is awarded Best Article of Vol 13 issue 05 Special issue on Recent Advances in Dentistry for better Oral Health
A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" is awarded Best Article of Vol 13 issue 06
A Study by Chen YY and Ghazali SRB entitled "Lifetime Trauma, posttraumatic stress disorder Symptoms and Early Adolescence Risk Factors for Poor Physical Health Outcome Among Malaysian Adolescents" is awarded Best Article of Vol 13 issue 04 Special issue on Current Updates in Plant Biology to Medicine to Healthcare Awareness in Malaysia
A Study by Kumari PM et al. entitled "Study to Evaluate the Adverse Drug Reactions in a Tertiary Care Teaching Hospital in Tamilnadu - A Cross-Sectional Study" is awarded Best Article for Vol 13 issue 05
A Study by Anu et al. entitled "Effectiveness of Cytological Scoring Systems for Evaluation of Breast Lesion Cytology with its Histopathological Correlation" is awarded Best Article of Vol 13 issue 04
A Study by Sharipov R. Kh. et al. entitled "Interaction of Correction of Lipid Peroxidation Disorders with Oxibral" is awarded Best Article of Vol 13 issue 03
A Study by Tarek Elwakil et al. entitled "Led Light Photobiomodulation Effect on Wound Healing Combined with Phenytoin in Mice Model" is awarded Best Article of Vol 13 issue 02
A Study by Mohita Ray et al. entitled "Accuracy of Intra-Operative Frozen Section Consultation of Gastrointestinal Biopsy Samples in Correlation with the Final Histopathological Diagnosis" is awarded Best Article for Vol 13 issue 01
A Study by Badritdinova MN et al. entitled "Peculiarities of a Pain in Patients with Ischemic Heart Disease in the Presence of Individual Combines of the Metabolic Syndrome" is awarded Best Article for Vol 12 issue 24
A Study by Sindhu Priya E S et al. entitled "Neuroprotective activity of Pyrazolone Derivatives Against Paraquat-induced Oxidative Stress and Locomotor Impairment in Drosophila melanogaster" is awarded Best Article for Vol 12 issue 23
A Study by Habiba Suhail et al. entitled "Effect of Majoon Murmakki in Dysmenorrhoea (Usre Tams): A Standard Controlled Clinical Study" is awarded Best Article for Vol 12 issue 22
A Study by Ghaffar UB et al. entitled "Correlation between Height and Foot Length in Saudi Population in Majmaah, Saudi Arabia" is awarded Best Article for Vol 12 issue 21
A Study by Siti Sarah Binti Maidin entitled "Sleep Well: Mobile Application to Address Sleeping Problems" is awarded Best Article for Vol 12 issue 20
A Study by Avijit Singh"Comparison of Post Operative Clinical Outcomes Between “Made in India” TTK Chitra Mechanical Heart Valve Versus St Jude Mechanical Heart Valve in Valve Replacement Surgery" is awarded Best Article for Vol 12 issue 19
A Study by Sonali Banerjee and Mary Mathews N. entitled "Exploring Quality of Life and Perceived Experiences Among Couples Undergoing Fertility Treatment in Western India: A Mixed Methodology" is awarded Best Article for Vol 12 issue 18
A Study by Jabbar Desai et al. entitled "Prevalence of Obstructive Airway Disease in Patients with Ischemic Heart Disease and Hypertension" is awarded Best Article for Vol 12 issue 17
A Study by Juna Byun et al. entitled "Study on Difference in Coronavirus-19 Related Anxiety between Face-to-face and Non-face-to-face Classes among University Students in South Korea" is awarded Best Article for Vol 12 issue 16
A Study by Sudha Ramachandra & Vinay Chavan entitled "Enhanced-Hybrid-Age Layered Population Structure (E-Hybrid-ALPS): A Genetic Algorithm with Adaptive Crossover for Molecular Docking Studies of Drug Discovery Process" is awarded Best article for Vol 12 issue 15
A Study by Varsha M. Shindhe et al. entitled "A Study on Effect of Smokeless Tobacco on Pulmonary Function Tests in Class IV Workers of USM-KLE (Universiti Sains Malaysia-Karnataka Lingayat Education Society) International Medical Programme, Belagavi" is awarded Best article of Vol 12 issue 14, July 2020
A study by Amruta Choudhary et al. entitled "Family Planning Knowledge, Attitude and Practice Among Women of Reproductive Age from Rural Area of Central India" is awarded Best Article for special issue "Modern Therapeutics Applications"
A study by Raunak Das entitled "Study of Cardiovascular Dysfunctions in Interstitial Lung Diseas epatients by Correlating the Levels of Serum NT PRO BNP and Microalbuminuria (Biomarkers of Cardiovascular Dysfunction) with Echocardiographic, Bronchoscopic and HighResolution Computed Tomography Findings of These ILD Patients" is awarded Best Article of Vol 12 issue 13 
A Study by Kannamani Ramasamy et al. entitled "COVID-19 Situation at Chennai City – Forecasting for the Better Pandemic Management" is awarded best article for  Vol 12 issue 12
A Study by Muhammet Lutfi SELCUK and Fatma entitled "Distinction of Gray and White Matter for Some Histological Staining Methods in New Zealand Rabbit's Brain" is awarded best article for  Vol 12 issue 11
A Study by Anamul Haq et al. entitled "Etiology of Abnormal Uterine Bleeding in Adolescents – Emphasis Upon Polycystic Ovarian Syndrome" is awarded best article for  Vol 12 issue 10
A Study by entitled "Estimation of Reference Interval of Serum Progesterone During Three Trimesters of Normal Pregnancy in a Tertiary Care Hospital of Kolkata" is awarded best article for  Vol 12 issue 09
A Study by Ilona Gracie De Souza & Pavan Kumar G. entitled "Effect of Releasing Myofascial Chain in Patients with Patellofemoral Pain Syndrome - A Randomized Clinical Trial" is awarded best article for  Vol 12 issue 08
A Study by Virendra Atam et. al. entitled "Clinical Profile and Short - Term Mortality Predictors in Acute Stroke with Emphasis on Stress Hyperglycemia and THRIVE Score : An Observational Study" is awarded best article for  Vol 12 issue 07
A Study by K. Krupashree et. al. entitled "Protective Effects of Picrorhizakurroa Against Fumonisin B1 Induced Hepatotoxicity in Mice" is awarded best article for issue Vol 10 issue 20
A study by Mithun K.P. et al "Larvicidal Activity of Crude Solanum Nigrum Leaf and Berries Extract Against Dengue Vector-Aedesaegypti" is awarded Best Article for Vol 10 issue 14 of IJCRR
A study by Asha Menon "Women in Child Care and Early Education: Truly Nontraditional Work" is awarded Best Article for Vol 10 issue 13
A study by Deep J. M. "Prevalence of Molar-Incisor Hypomineralization in 7-13 Years Old Children of Biratnagar, Nepal: A Cross Sectional Study" is awarded Best Article for Vol 10 issue 11 of IJCRR
A review by Chitra et al to analyse relation between Obesity and Type 2 diabetes is awarded 'Best Article' for Vol 10 issue 10 by IJCRR. 
A study by Karanpreet et al "Pregnancy Induced Hypertension: A Study on Its Multisystem Involvement" is given Best Paper Award for Vol 10 issue 09

List of Awardees

A Study by Ese Anibor et al. "Evaluation of Temporomandibular Joint Disorders Among Delta State University Students in Abraka, Nigeria" from Vol 13 issue 16 received Emerging Researcher Award


A Study by Alkhansa Mahmoud et al. entitled "mRNA Expression of Somatostatin Receptors (1-5) in MCF7 and MDA-MB231 Breast Cancer Cells" from Vol 13 issue 06 received Emerging Researcher Award


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International Journal of Current Research and Review (IJCRR) provides platform for researchers to publish and discuss their original research and review work. IJCRR can not be held responsible for views, opinions and written statements of researchers published in this journal

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