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IJCRR - Vol 13 Issue 07, April, 2021

Pages: 142-148

Date of Publication: 12-Apr-2021


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Anti-inflammatory Activity of Aerial and Root Extracts of Withania somnifera: A Comparative Experimental Evidence

Author: Satyajyoti Kanjilal, Ashok Kumar Gupta, Ranjana Saksena Patnaik, Amitabha Dey

Category: Healthcare

Abstract:Introduction: Withania somnifera Dunal (Ashwagandha) root is recognized as one of the medicinally important herbs for its antiinflammatory properties. Comparative study on both the parts i.e. aerial and root has not been studied yet from the perspectives of its anti-inflammatory activities. Objective: The present study aimed to evaluate the comparative anti-inflammatory activity of standardized methanolic and hydro-methanolic extract of both the roots and the aerial part of the plant in in-vitro models of TNF-\a, Interleukin-1 beta and IL-6. Methods: Hydroalcoholic and methanolic extracts of Withania somnifera aerial part and root part were prepared. Respective assays were performed to estimate the cytokines by using Elisa Kit and absorbance was noted in the Multimode Microplate reader. Results: Both the methanolic and hydroalcoholic extracts from the aerial part was found to have more potential compared to that of roots in inhibiting the TNF \?alpha cytokines and Interleukin 6 inhibition assay. Root Hydroalcoholic extract was better than aerial methanolic extract. In the interleukin beta inhibition assay, both root extracts were better than aerial extract. Conclusion: Both root and aerial parts of Withania somnifera possess anti-inflammatory properties. The aerial part has shown a promising activity vis-à-vis the roots. Therefore, this can be an alternative renewable resource as raw material for preparing medicines for arthritis.

Keywords: Ashwagandha, Inflammation, Interleukin, TNF alpha, Withania somnifera

Full Text:

Introduction

Cytokines are small-secreted proteins referred inconsistently as interleukins, growth factors or chemokines. Physiologically, they activate the inflammatory mechanisms and help repair damaged tissue. During the inflammatory process, a sudden release of cytokines (cytokine storm) occurs via a cascade of activation process.1,2 The uncontrolled expression of these macrophage-derived cytokines (inflammatory mediators) tumour necrosis factor (TNF), interleukins (IL-1, IL-6, IL-8), colony-stimulating factors (CSFs) and growth factors govern the pro-inflammatory signalling pathways in the pathogenesis of rheumatoid arthritis (RA).2,3 The activated macrophages produce TNF-α in the inflamed synovial membrane tissue. This is having the capacity of induction and production of other pro-inflammatory cytokines, including Interleukin-1 beta (IL-1β) and IL-6. Combined facilitation of signalling pathways and cytokines, in turn, release chemokines that attract leukocytes to the inflamed site from the blood. The induction of proteolytic and metalloproteinase enzymes further results in the destruction of the underlying articular cartilage and bone tissue.4-10

The mainstay of the treatment of RA is to control these pro-inflammatory mediators. At therapeutics of Disease-Modifying Antirheumatic Drugs (DMARDs) such as Sulfasalazine, Methotrexate, Leflunomide, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and biologics such as Infliximab, Adalimumab (TNF –blocker), Anakinra (IL-1 blocker), Tocilizumab (IL-6 blocker) are been looked upon for the management.4,11

The drug regimen offers efficient management, however, the chance of suboptimal control, the inability to complete remission and emerging adverse effects in long-term usage often lead to a search for more alternatives.12-16 The need-gap analysis and increasing popularity of plant or herb-based medicine often push for innovations and research which lead to the discovery of many new phytomedicines or enriched extracts or drugs.17 Many plants and formulations are reported to have anti-inflammatory and analgesic properties.18-20

Withania somnifera Dunal (Ashwagandha) or Indian ginseng has been recognized as one of the medicinally important herbs having anti-inflammatory and Rasayana (adaptogen and rejuvenator) properties. Among the other phytoconstituents, the biologically active steroidal lactones Withaferin A and Withanolides were reported to have anti-inflammatory and immunomodulatory properties contributing to their use in painful arthritic conditions.21 Roots are researched for their potent inhibitory effect on inflammatory markers and used in traditional system of medicine.21-23 The aerial part especially the leaves of the plant are also studied for its role as anticancer, antimicrobial, diabetes etc. However, a comparative study on both parts especially the commercially viable extracts are not been studied in the anti-inflammatory perspectives. Therefore, the present study was conducted to evaluate the comparative anti-inflammatory activity of standardized methanolic and hydro-methanolic extract of both the roots and the aerial part of the plant in in-vitro models of TNF-α, Interleukin-1 beta (IL-1β) and IL-6.

Materials and Methods

Plant Material

Withania somnifera raw material of aerial part Lot No.:ASHW/PLPLR30/NOV19 and Aswagandha aerial part hydroalcoholic extract 5%, Lot No: ASHW/PLPL30/NOV were procured from Phyto Life sciences Pvt Ltd, Ahmedabad, Gujarat. The root powder was obtained from Emami Ltd, Research and Development Centre, Kolkata. Both the raw material of aerial and root were further used to get the methanolic and hydroalcoholic extracts in the phytochemistry laboratory of Emami Research and Development Centre.

Chemical and Reagents, Kits, Drugs and Cell line

Reagents and Kits: The TNF alpha Human ELISA Kit (Abcam; Cat. No. ab100654), ab46052 IL-1 beta Human ELISA Kit and ab46042 IL-6 (Interleukin-6) High Sensitivity Human ELISA Kit of Abcam. Drugs: The Anti-arthritic drugs were purchased from the local pharmacist - Methotrexate 25 mg (Folitrax) Batch No. At 071110, Sulfasalazine (Saaz) Batch No. ECL079007AS marketed by IPCA Laboratories Ltd, Mumbai and Diclofenac (Voveran 50) Batch No. 195009MB of Novartis India Ltd were also used. Cell culture mediums and Solutions: Dulbecco's Modified Eagle's medium (DMEM), Fetal Bovine Serum (FBS) & 1% Antibiotic/anti-mitotic solution. MTT (3-(4, 5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) reagent (HiMedia). Dulbecco's phosphate-buffered saline (DPBS - HiMedia). Dimethyl sulfoxide (DMSO). All the chemical and drugs are procured from Local vendor. Cell line: MG 62 and Hep was procured from National Centre for Cell Science, Pune, India.

Preparation of W somnifera extracts

Alcoholic and hydroalcoholic extracts of roots and leaf part of Withania somnifera were evaporated using a rotary vacuum evaporator, whereas aqueous extracts were dried by lyophilization. HPTLC (high-performance thin-layer chromatography) qualitative studies showed that the aqueous-methanolic extracts of both plant parts contain higher amounts of withanolides than all other extracts concerning withaferin A and withanolide A. Accurately weighed 1.0 g of leaf and root powder was soaked separately in 50 ml conical flask with 20 ml of 50% aq-methanol. Both the samples were sonicated at 60 C for 30 minutes and samples were filtered. 

For preparing the reference standard solution, 10.0 mg of withaferin A and withanolide A were dissolved with methanol in 5 ml volumetric flasks which were further made 10-fold dilution. Silica gel aluminium sheet plate 60 F254 (Germany) was used to perform the chromatographic estimation. Linear ascending development was carried out in a twin-trough glass chamber (CAMAG) equilibrated with the mobile phase. The length of the chromatogram run was 6.0 cm. Concentrations of the compound were determined from the intensity of absorbance. The evaluation was made via peak areas versus withanolides amount in linear regression. The withanolides present in the extracts were identified by comparing the HPTLC spectrum of the standards

Cell Line and Culture Condition

The monolayer of the cells was maintained at sub-confluent conditions in growth media containing DMEM with 0.045 g/ml glucose, 1mM sodium pyruvate, L-glutamine, 1.5 g/L sodium bicarbonate, 100 U/ml penicillin, 100 μg/ml streptomycin, and 10% fetal bovine serum (FBS). Cells were maintained in a humidified incubator with ambient oxygen and 5% CO2 at 37°C. Cells from passages 3–15 were used in the experiment, and cells were not allowed to grow to more than 60%–70% confluence.

Prepare the cell culture

100 μl of differentiated cell suspension (1 × 106 cells/ml) were seeded in a 96-well culture plate with 100 μl of DMEM – differentiated cell culture medium. The cells were incubated in an FBS-free medium for 4 to 18 hr before the examination.

Effect of test samples on cell viability and proliferation: MTT assay24

Measurement of cell viability and proliferation forms the basis for numerous in vitro assays of a cell population’s response to external factors. The yellow tetrazolium MTT is reduced by metabolically active cells, in part by the action of dehydrogenase enzymes, to generate reducing equivalents such as NADH (nicotinamide adenine dinucleotide hydrogen) and NADPH (nicotinamide adenine dinucleotide phosphate hydrogen). This reduction takes place only when mitochondrial reductase enzymes are active, and therefore conversion can be directly related to the number of viable (living) cells.  Sample extracts were prepared in the concentration of 100 to 1000 µg/ml. MTT reagent was prepared aseptically by adding 6 ml of cell-based assay buffer (DPBS) in a vial containing 30 mg of MTT reagent and dissolved completely by vigorous vortexing.

Assay Procedure

The wells for control, samples and blank were designated in 96 well plates. The culture medium from each well was removed and washed the cells twice with DPBS. The test samples were added to the 96 well plate containing cells and incubated in a 5% CO2 incubator at 37°C for 18-20 hrs. (The volume of the test sample solution is 100 μl). After the incubation period, the plates from the incubator were removed and 10 µl of MTT reagent (5 mg/ml) were added to all the wells except blank wells. The culture plates were wrapped with aluminium foil to avoid exposure to light.  The plates were returned to the CO2 incubator and incubated for 3 to 4 hours. The culture medium was carefully removed from each well after the process of incubation was over and 100 µl of DMSO were added to each well to solubilize the Formazan crystals.  Absorbance was noted on Multimode Microplate reader: SpectraMax i3X [Molecular Devices] at 570nm. The average 570 nm absorbance values of the control wells were subtracted from the average 570 nm absorbance values of corresponding experimental wells.

For optimization of the process, the cell suspension was serially diluted from 1 × 106 to 1 × 103 cells/ml using the appropriate culture medium. 100 µl of each dilution were seeded in a 96-well plate and a curve of absorbance against cell density was plotted. The optimal number of viable cells after treatment with samples are measured from the linear graph.

Estimation of Cytokines – TNF-α

TNF alpha Human ELISA (Enzyme-Linked Immunosorbent Assay) kit is an in vitro enzyme-linked immunosorbent assay for the quantitative measurement of Human TNF alpha in serum, plasma and cell culture supernatants. This assay employs an antibody specific for Human TNF alpha coated on a 96-well plate. All reagents, samples and standards are prepared as per the instructions on the manual of the kit. Standards and samples 100 μL each are pipetted into the wells and TNF alpha present in a sample is bound to the wells by the immobilized antibody. At each well, the following sequence is followed with incubation at room temperature in between after each addition. The wells are washed and 100 μL of 1X Biotinylated TNF alpha Detection Antibody is added. After washing away the unbound biotinylated antibody, 100 μL of 1X HRP-Streptavidin solution is pipetted to the wells. The wells are again washed, and 100 μL of TMB One-Step Substrate Reagent is added to the wells and colour develops in proportion to the amount of TNF alpha bound. 50 μL of Stop Solution is added to each well which changes the colour from blue to yellow, and the intensity of the colour is measured at 450 nm on Multimode Microplate reader: SpectraMax i3X [Molecular Devices, USA]. The calculations were performed as per the Kit protocol.

Estimation of Cytokines - IL-1β

The ELISA (Enzyme-linked Immunosorbent Assay) kit for estimation of human IL 1β is intended to quantify the enzyme in blood components or culture medium. For experimentation, samples 100µL each is pipetted into the specific antibody-coated wells of microtiter strip microplates. To begin the experimental process, samples, as well as standards and 50 µL of 1X Biotinylated monoclonal anti-IL-1 beta antibody, are simultaneously incubated. After washing, the enzyme 100 μL of 1X Streptavidin- HRP, that binds the biotinylated antibody is added, incubated and washed. A 100 μL of Chromogen TMB substrate solution is added which acts on the bound enzyme to induce a coloured reaction product. Direct exposure to light is avoided by wrapping the plate in aluminium foil. 100 μL of Stop Reagent is added into each well and results are taken immediately after the addition of Stop Reagent, or within one hour, if the microplate is stored at 2-8°C in the dark.

The absorbance of each well is read on a spectrophotometer (SpectraMax i3X) using 450 nm as the primary wavelength and optionally 620 nm (610 nm to 650 nm is acceptable) as the reference wavelength. The more is the concentration of the interleukin beta in the sample, the more is the strength of the coloured product. The standardized protocol mentioned in the kit is followed to calculate during experimentation and analysis.

Estimation of Cytokines - IL-6

ELISA kit for Interleukin-6 in-vitro testing is intended to quantify the enzyme in different blood components, body fluids and experimental solutions. The assay method identifies natural as well as recombinant human IL-6. The coating of interleukin-6 monoclonal antibody was done before the experiment in the specified number of microtiter strips well-plates. Each well was filled with standards and control samples in the quantity of 100 μL respectively. The experiment was started with the incubation of 50 μL of 1 X Biotinylated monoclonal anti-IL-6 antibody along with either samples or standard. After washing, 100 μL of 1X Streptavidin-HRP solution, that binds the biotinylated antibody is added into all wells, incubated at room temperature for 30 minutes and washed.

100 μL of Chromogen TMB (3,3',5,5'-tetramethylbenzidine) substrate solution is added which acts on the bound enzyme to induce a coloured reaction product and incubated in the dark for 12-15 minutes at room temperature. The intensity of this coloured product is directly proportional to the concentration of IL-6 present in the samples 100 μL of Stop Reagent is added into each well and results are taken immediately after the addition of Stop Reagent, The absorbance of each well was noted on a spectrophotometer (SpectraMax i3X ) using 450 nm as the primary wavelength and optionally 620 nm (610 nm to 650 nm is acceptable) as the reference wavelength. The calculations were performed as per the Kit protocol.

Statistical Analysis

Mean ± standard error of the mean (SEM) were calculated from the observed individual values Statistical analysis was performed by one-way analysis of variance (ANOVA) followed by Student-Newman-Keuls multiple comparison test. GraphPad Prism- 5 (GraphPad Software Inc., La Jolla, California, USA) was used for statistical analysis. P-values less than 0.05 were considered statistically significant.

Results and Discussion

The phytochemical analysis of W. somnifera has revealed several groups of bioactive compounds such as flavonoids, tannin, alkaloids, sitoindosides, glycosides, withanicil, steroidal lactones, and alkaloids.25,26 The most therapeutically important chemicals are withanolides especially withaferin A and withanolide D for its antiarthritic effects.27,28 Compounds in sample chromatograms were determined from the intensity of absorbance at 232 nm and identified invalidate High-performance thin-layer chromatography (HPTLC) analysis, which is an efficient tool for quantitative analysis of compounds and yields superior separation efficiency. The withanolides present in the extracts were identified by comparing the HPTLC spectrum of the standards. The quantities of withanolides were present more in 50% aq-methanolic extracts of the root part of Ashwagandha.

The inflammatory mediator Tumour Necrosis Factor-alpha (TNF-α) may lead to the release of other inflammatory cytokines such as IL-1β and IL-629, which promotes synovitis causing cartilage destruction and bone erosion in RA.30,31 W. somnifera is a herb known to have multiple benefits to keep the body healthy. The roots of the plant have known usage for having anti-inflammatory properties.  Both the Leaf and root extracts of W. somnifera has been studied for analysis and standardization of Phyto-constituents and in efficacy models.32-34

The present study gave a preliminary research lead on the most effective part extract in inflammations in-vitro cytokine models. Many researchers in experimental (in-vitro and in-vivo) anti-inflammatory models have studied the leaf part. W. somnifera leaf aqueous extract and one of its active chloroform fractions studied in microglial cell lines was found to inhibit the microglial activation and migration by attenuating the pro-inflammatory markers of TNF-α, IL-1β, IL-6 and others suggesting its role in suppression of neuroinflammation.35 New withanolide glycosides and withanolide isolated from the leaves were studied for their inhibition of cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The majority of compounds showed selective COX-2 enzyme inhibition suggesting their anti-inflammatory activity.36 The hydro-methanolic extract in stainless steel implant induced inflammation in zebrafish in-vivo model has shown an inhibitory effect of TNF α.37

The root part of W. somnifera finds its usage more in experimental models as well as in clinical practice. Hydroalcoholic root extract showed anti-inflammatory effect by inhibition of protein (albumin) denaturation in the in-vitro model.38 Ethanolic extract was effective in acute and chronic in-vivo carrageenan-induced anti-inflammatory model.39 Aqueous extracts in gel dosage form has shown anti-inflammatory activity in trinitrobenzene sulfonic acid-induced in-vivo models for inflammatory bowel disease.40 Root powder41 and aqueous extract 42 decreased the arthritis effects in collagen-induced arthritis in-vivo model suggestive its anti-inflammatory activity. Attenuation of the pro-inflammatory markers (TNF-α, IL-1β, IL-6 and IL-10) were observed in the study by khan et.al. Root powder showed inhibitory effect on pro-inflammatory markers, proteinuria, nephritis in pristane-induced Lupus model.43 Root power exhibited anti-inflammatory activity by decreasing the pro-inflammatory markers TNF-α and IL-6 in fructose-fed rats44 and showed potent analgesic and antipyretic effect by retarding amplification and propagation of the inflammatory response in monosodium urate crystal-induced (Gout) model.45 Root powder had potent inhibitory activity towards the complement system, mitogen-induced lymphocyte proliferation and delayed-type hypersensitivity reaction suggestive usefulness in immunosuppression for the inflammatory diseases.46

Aqueous root extract showed anti?inflammatory activity on human osteoarthritic cartilage47 and in the human keratinocyte cell line by inhibiting expression of inflammatory cytokines IL?8, IL?6, TNF?α, IL?1β and IL?12, and promoting the expression of the anti?inflammatory cytokine transforming growth factor (TGF)?β1.48

The MTT method of cell determination is useful in the measurement of cell growth in response to mitogens, antigenic stimuli, growth factors and other cell growth-promoting reagents, cytotoxicity studies, and in the derivation of cell growth curves (Sigma). In the present study, the MTT assay was performed in MG 63 and Hep G2 cell line. Methotrexate confirmed the authenticity of the study by showing a decreasing trend in cell viability. All the four extracts from the concentration of 100 µg/ml up to 1000 µg/ml have shown a considerable cell survival count (Cells/ml) contributing towards its safety profile (Figures 1 & 2).

Levels of inflammatory cytokine, TNF-α were measured as a marker of inflammation. Both the methanolic and hydroalcoholic extracts from the aerial part was found to have more potential compared to that of roots in inhibiting the TNF –alpha cytokines (Figure 3).  Cytokine IL-1β is reported to play critical roles in the pathogenesis of RA. The inflammatory cytokine IL-6 was measured as a marker of inflammation. In the Interleukin 6 inhibition assay, the extracts of the aerial part were better compared to their respective roots extracts. Root Hydroalcoholic extract was better than aerial methanolic extract. However, among the four, the aerial hydro-alcoholic part is the most potential. In the interleukin beta inhibition assay, both root extracts were better than aerial extract (Figure 4 and 5).

Conclusion

Both parts of W. somnifera possess anti-inflammatory properties however, the aerial part has shown a promising activity vis-à-vis the roots. Therefore, this can be an alternative renewable resource as raw material for preparing medicines for arthritis. Moreover, both the methanolic and hydroalcoholic extracts can be considered for Phyto-pharmaceutical drug development.

Acknowledgements: The authors would like to express their gratitude to the Research and Development centre of Emami Limited, Kolkata, India for providing support for this work. The authors acknowledge the immense help and the knowledge received from the scholars whose articles are cited and included in references to this manuscript. The authors are also grateful to authors/editors/publishers of all those articles, journals and books from where the literature for this article has been reviewed and discussed.

Conflict of interests: Authors declare no conflict of interests.

Funding Source: Nil

Author’s Contribution: SJK and AB have experimented and analysed the data. SJK has prepared the initial manuscript, AKG and RKP have reviewed and modified the manuscript. The manuscript was finalized by SJK and AB after the incorporation of the comments. AKG and RKP has approved the final manuscript.

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One article from every issue is selected for the ‘Best Article Award’. Authors of selected ‘Best Article’ are rewarded with a certificate. IJCRR Editorial Board members select one ‘Best Article’ from the published issue based on originality, novelty, social usefulness of the work. The corresponding author of selected ‘Best Article Award’ is communicated and information of award is displayed on IJCRR’s website. Drop a mail to editor@ijcrr.com for more details.

Women Researcher Award:

This award is instituted to encourage women researchers to publish her work in IJCRR. Women researcher, who intends to publish her research work in IJCRR as the first author is eligible to apply for this award. Editorial Board members decide on the selection of women researchers based on the originality, novelty, and social contribution of the research work. The corresponding author of the selected manuscript is communicated and information is displayed on IJCRR’s website. Under this award selected women, the author is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.

Emerging Researcher Award:

‘Emerging Researcher Award’ is instituted to encourage student researchers to publish their work in IJCRR. Student researchers, who intend to publish their research or review work in IJCRR as the first author are eligible to apply for this award. Editorial Board members decide on the selection of student researchers for the said award based on originality, novelty, and social applicability of the research work. Under this award selected student researcher is eligible for publication incentives. Drop a mail to editor@ijcrr.com for more details.


Best Article Award

A Study by Humaira Tahir et al. entitled "Comparison of First Analgesic Demand after Major Surgeries of Obstetrics and Gynecology between Pre-Emptive Versus Intra-Operative Groups by Using Intravenous Paracetamol: A Cross-Sectional Study" is awarded Best Article for Vol 14 issue 14
A Study by Monica K. entitled "Risk Predictors for Lymphoma Development in Sjogren Syndrome - A Systematic Review" is awarded Best Article for Vol 14 issue 13
A Study by Mokhtar M Sh et al. entitled "Prevalence of Hospital Mortality of Critically Ill Elderly Patients" is awarded Best Article for Vol 14 issue 12
A Study by Vidya S. Bhat et al. entitled "Effect of an Indigenous Cleanser on the Microbial Biofilm on Acrylic Denture Base - A Pilot Study" is awarded Best Article for Vol 14 issue 11
A Study by Pandya S. et al. entitled "Acute and 28-Day Repeated Dose Subacute Toxicological Evaluation of Coroprotect Tablet in Rodents" is awarded Best Article for Vol 14 issue 10
A Study by Muhammad Zaki et al. entitled "Effect of Hemoglobin Level on the Severity of Acute Bronchiolitis in Children: A Case-Control Study" is awarded Best Article for Vol 14 issue 09
A Study by Vinita S & Ayushi S entitled "Role of Colour Doppler and Transvaginal Sonography for diagnosis of endometrial pathology in women presenting with Abnormal Uterine Bleeding" is awarded Best Article for Vol 14 issue 08
A Study by Prabhu A et al. entitled "Awareness of Common Eye Conditions among the ASHA (Accredited Social Health Activist) Workers in the Rural Communities of Udupi District- A Pilot Study" is awarded Best Article for Vol 14 issue 07
A Study by Divya MP et al. entitled "Non-Echoplanar Diffusion-Weighted Imaging and 3D Fiesta Magnetic Resonance Imaging Sequences with High Resolution Computed Tomography Temporal Bone in Assessment and Predicting the Outcome of Chronic Suppurative Otitis Media with Cholesteatoma" is awarded Best Article for Vol 14 issue 06
A Study by Zahoor Illahi Soomro et al. entitled "Functional Outcomes of Fracture Distal Radius after Fixation with Two Different Plates: A Retrospective Comparative Study" is awarded Best Article for Vol 14 issue 05
A Study by Ajai KG & Athira KN entitled "Patients’ Gratification Towards Service Delivery Among Government Hospitals with Particular Orientation Towards Primary Health Centres" is awarded Best Article for Vol 14 issue 04
A Study by Mbungu Mulaila AP et al. entitled "Ovarian Pregnancy in Kindu City, D.R. Congo - A Case Report" is awarded Best Article for Vol 14 issue 03
A Study by Maryam MJ et al. entitled "Evaluation Serum Chemerin and Visfatin Levels with Rheumatoid Arthritis: Possible Diagnostic Biomarkers" is awarded Best Article for Vol 14 issue 02
A Study by Shanthan KR et al. entitled "Comparison of Ultrasound Guided Versus Nerve Stimulator Guided Technique of Supraclavicular Brachial Plexus Block in Patients Undergoing Upper Limb Surgeries" is awarded Best Article for Vol 14 issue 01
A Study by Amol Sanap et al. entitled "The Outcome of Coxofemoral Bypass Using Cemented Bipolar Hemiarthroplasty in the Treatment of Unstable Intertrochanteric Fracture of Femur in a Rural Setup" is awarded Best Article Award of Vol 13 issue 24
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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Disclaimer: 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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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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