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IJCRR - 13(21), November, 2021

Pages: 53-59

Date of Publication: 09-Nov-2021


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Herbal Medicinal based Approach for Alzheimer Disease - A Mathematical Model

Author: Arora Komal, Khurana Pooja, Kumar Deepak

Category: Healthcare

Abstract:Introduction: Due to the cases of more than 1 million (in India) and more than 80 million (worldwide) of Alzheimer disease, there is an immediate need of finding a cure for Alzheimer. Alzheimer disease, a type of dementia, is a neurodegenerative, progressive disease that gives rise to troubles and issues related to cognitive functions. It is not a normal part of ageing; though the greatest known risk factor is increasing age. Aim: Many treatments and many medications have been found but their efficacy to reach Blood-Brain Barrier and rate of beta-amyloid clearance is very low. Moreover, drawbacks like cost, drug resistance and side effects bringing down their success rate. Methodology: Considering the problem, this entry focuses on the alternate ways (herbal medicine) for Alzheimer cure by generalizing the mathematical model to investigate the effect of selected medicinal plants on the levels of amyloid-beta peptides, the characteristic hallmark of Alzheimer. Results: We have analyzed the effect of active compounds of five potent medicinal plants at different dosages i.e. 250 mg/ day, 500 mg/day, 750 mg/day and 1000 mg/day concerning time and found Withania somnifera as the best plant amongst five as it showed an effective decline in the beta-amyloid levels at 500 mg/day. We have also examined the ADME ( Absorption, Distribution, Metabolism and Excretion) profile of the selected plants using the Swiss ADME server which revealed no violation of Lipinski's rule. Conclusion: This model can act as a utility model for formulating herbal-based compounds that increase the rate of amyloid-beta clearance from the brain by inhibiting aggregation of amyloid-beta with least/no side effects.

Keywords: Alzheimer disease, Amyloid-beta, Mathematical model, Herbal approach, Medicinal plant, Dosage

Full Text:

Introduction

The brain, the central part of our body, controller of all the activities, is made of 100 billion nerves. All the nerves have their specialized functions to perform. Some are involved in thinking, behaviour and memory while others are involved in hearing, audition, gustation, vision and other activities forming a communicating network between different cells. Nerves that are involved in cognitive activities, when starts degenerate lead to the loss of memory. Deteriorative association between the brain cells which decrease the acetylcholine neurotransmitter is the main cause of memory loss, and leads to dementia.1Synapses (the connection between the different neurons), a major expressway or a site of communication for memories, emotions, sensations, thoughts, and movements permit information to pass via chemical pulses between different neurons.

Alzheimer’s disease (AD) is a neurodegenerative, inevitable, progressive disorder that affects memory, thinking behavior and other potential activities.2 Worldwide, more than 25 million people are suffering from dementia, which more of them are from AD. It has been estimated that approximately about 5 million fresh/ new cases happening each year and this figure is expected to become two-fold after every two decades (20 years).

The underlying and foremost step of the disease is to strike the brain’s memory centre leading to individuals of AD being more forgetful and distracted. The initial stage of AD is difficult to be diagnosed as its symptoms are noticeable usually at an advanced stage. The sequential cleavage of APP (Amyloid Precursor protein), results in the formation of peptide Amyloid-beta by beta-secretase followed by gamma-secretase. This is known as the Amyloidogenic pathway. The enzyme alpha-secretase competes with gamma-secretase to stop this amyloidogenic pathway. Competition of alpha-secretase with gamma-secretase is the non-amyloidogenic pathway.3,4 According to the amyloid cascade hypothesis, imbalances between the formation and removal of amyloid beta results in the dysfunction of neurons and ultimately cell death. Different forms of amyloid-beta in terms of structure can occur such as oligomeric, proto fibrillar, and fibrils.5Accumulation of deposits of beta-amyloid protein outside nerve cells results in the formation of hard plaque. Simultaneously, the accumulation of malformed versions of tau proteins inside the neurons results in the collapsing of neuron’s transport microtubules.6 As time passes, the functioning of neurons become less efficient or die, ultimately fail to communicate with one another causing the shrinkage of brain tissue. One’s judgment becomes awful as the disease spreads to the outer layer of the brain. Age and genetic factors are the known risks associated with Alzheimer. Other factors such as gender, awareness, previous head injury, family history, exposure to heavy metals, down’s syndrome contribute greatly to the development of AD. Individuals having down’s syndrome, after 40 years of age, develop almost the same neuropathological symptoms of AD and thus the strong evidence for the genetic premise of Alzheimer disorder.7 2-3% of early-onset AD cases are associated with the mutation caused on chromosome number 21 (the chromosome that encodes the amyloid-beta peptide precursor i.e. APP) whereas 70-80% of AD cases (early onset) are associated with the mutations in presenilin 1 (PS1) gene present on chromosome number 14 and 20-25% of the early cases are linked to the mutations in presenilin 2 (PS2) present on chromosome number 1. APP, PS1 and PS2 alter the processing mechanism of APP that leads to increased amyloid-beta production. APP cleavage by enzyme beta-secretase followed by cleavage by gamma-secretase results in the formation of amyloid-beta. Deposition of these amyloid-beta peptides is a first step in the aetiology and pathogenesis of Alzheimer disease followed by other characteristics of AD such as microtubule misfolding (neurofibrillary tangles), loss of synaptic connection, and dementia. Apo E gene encoded on chromosome number 19 increases the 50% risk of developing Alzheimer.

According to the computed value, it has been reported that around 5.4 million Americans are suffering from Alzheimer dementia in 2017 in which 5.3 million are having late-onset Alzheimer (65 years of age or more). It ranks fifth in terms of causing death.8

The main cause of Alzheimer is the deterioration and death of neurons that are responsible for thinking, learning and behaviour and as the neurons degenerate it affects the entire brain. It is differentiated from the normal brain as the accumulation of deposits of beta-amyloid plaques and neurofibrillary tangles causes shrinkage of the brain.9

 There is a conformational change in the soluble beta monomers to form the beta-sheet rich misfolded structure and hence aggregates to form amyloid fibrils. Deposition of these fibrils outside the neurons, called senile plaques lead to neurodegeneration.9 Amyloid beta, a short peptide cleaved by enzymes β (beta) secretase and γ (gamma) secretase, is derived from the amyloid precursor protein (APP), a gene which is found on chromosome number 21q21.10 Around 40 and 42 peptides of amino acids (beta-amyloid 40 and beta-amyloid 42) are obtained by cleavage by β secretase and then γ secretase.

Tau, a protein associated with microtubules found in cell bodies and mainly in the axons of nerve cells in the CNS. Around 6 isoforms of human tau protein have been expressed by the phenomenon of alternate mRNA splicing from a single gene that contains 16 exons and is present on chromosome 17q21. Twisted fibres of the protein tau, called neurofibrillary tangles (intracytoplasmic structures) build up inside cells because collapsing of neuron’s transport microtubules.11

Also, a decrease in the levels of acetylcholine due to its breakdown by an enzyme called acetylcholinesterase results in memory loss and hence Alzheimer.

Thus, amyloid accumulation, microtubules misfolding, dysfunction of cholinergic mechanism, oxidative stresses are some of the factors involved in the pathophysiology of Alzheimer disease.10

The distinguishing features of the brain describing the characteristic change that arises due to AD usually happen around 20 years before the emergence of symptoms and therapeutic remedy can be identified and accomplished. The phase where the slightest or suggestive symptoms appears offers a likely possibility for curative intercession that can decelerate the progression of the disease. There are four stages in the progression of dementia (starting from cognitively normal to dementia). The stage Mild cognitive impairment (MCI) appears before AD and for the early detection of Alzheimer, the transformation of stage MCI to stage AD is of agreeable concern. Assessment of significant biomarkers can be overriding to early (preclinical) diagnosing, monitoring, treating, and continuing phases of AD analysis.11 However, there is a requirement for standardizing such biomarkers for accurate and early diagnose of AD. This includes amyloid-beta, tat and phosphorylated tau, glucose, Positron emission tomography (PET), Cerebrospinal fluid (CSF), Apo E and telomere length, Magnetic Resonance Imaging (MRI), RNA interference.12-17

Food and drugs administration (FDA) approved drugs to treat symptoms related to Alzheimer’s disease, that includes the class of drugs called “cholinesterase inhibitors”. The cholinesterase inhibitors halt the process of disintegration and breakdown of a chemical messenger in the brain that is important for learning and memory. Examples of such drugs are donepezil, galantamine and rivastigmine approved for the treatment of mild to moderate Alzheimer disease. Other classes of drugs include M drugs (Memantine, melatonin, minocycline, modafinil). Memantine is an uncompetitive NMDA (N-methyl-d-aspartic acid receptor antagonist) and is approved for the management of moderate-to-severe AD, Melatonin is a neuroprotector and antioxidant and anti-inflammatory in nature, Minocycline reduces neuroinflammation and CNS pathology and prevents cell death and Modafinil is a wake-promoting agent is approved for use in narcolepsy and obstructive sleep apnea. It improves global mental status, hippocampal neurogenesis, attention, and cognition. Amyloid-beta degrading enzymes such as an insulin-degrading enzyme, neprilysin, endothelin-converting enzyme decrease the levels of amyloid-beta is also one of the medications approved for Alzheimer treatment.18

Though numerous treatments and medications such as acetylcholinesterase inhibitors, M-drugs, amyloid degrading enzymes are already on the market, their results not indicating the complete clearance of amyloid-beta from the brain. Moreover, some of the downsides of these medications like toxicity, drug resistance, side effects, and cost urge the need to have a transition from these chemical medications towards the natural traditional medications in a form of herbal treatment. Plants are utilized as an essential source for various drugs in Indian medicinal history. The complete description of all the curative properties of the medicinal plants has been listed in Rigveda. After a while, various synthetic drugs developed and commenced which due to their drawbacks failed. Recently, the trend of using plants is again rising and is being utilized confidently.

Medicinal plants such as Curcuma longa, Withania somnifera, Bacopa monnieri, Centella Asiatica, Convolvulus pluricaulis have been reviewed, researched and documented to show potent responses in Alzheimer cure. These plants consist of active compounds like tannins, lignans, triterpenes, alkaloids, flavonoids, sterols and polyphenols and work by inhibiting fibrillation, relaxing CNS, promoting memory.19,20

Material and Methods

Mathematical model

Alzheimer, a neurodegenerative disorder, affects the thinking, memory, behaviour and other activities of an individual. In addition to the effect on an individual’s memory, it produces a considerable stretch to the society also and hence several medications like cholinesterase inhibitors, M drugs, NMDA antagonist, antioxidants, statins, PPAR gamma antagonist and some combinational approaches of these drugs were developed for the treatment of Alzheimer but despite all these treatments, condition of Alzheimer’s patients and hence its influence on society is not improved. Herbal therapy is an alternative for the drugs available in the market that failed due to their drawbacks.

Various mathematical models have been made representing the role of amyloid-beta aggregation, tau phosphorylation, microglia’s, astrocytes, macrophages, in the development and management of Alzheimer disease.32 Puri and Li describe the pathogenesis of Alzheimer in the form of a mathematical model.33 Also, the mathematical model symbolizing the death of neurons in Alzheimer has also been constructed.34

This mathematical model acts as a template to determine the dosage of active constituents of medicinal plants in lowering the levels of amyloid-beta in the brain and helps in their clearance.

The extracellular amyloid beta-peptide satisfies the following equation:

To investigate the effective dosage of medicinal plants to clear the amyloid-beta levels from the brain, extract of five plants have been analyzed in four different doses (250 mg/day, 500 mg/day, 750 mg/day and 1000 mg/day) for about 5 months.

The dosage equation is as follows:

Parametric description

Proteolytic degradation of APP by beta and gamma-secretase releasing Amyloid beta.

 Release of amyloid-beta by activated astrocytes.

 Reference density of the astrocyte cells in the brain.

  Release of amyloid-beta by dendritic cells.

 Reference density of the dendritic cells in the brain.

 Clearance of amyloid-beta by microglia.

 Clearance of amyloid-beta by amyloid-beta degrading enzymes.

H: Dosage quantity

k: Michael’s-Menten coefficient

2.2General solution of first-order differential equations-Euler’s Method.

The general case for the solution of a first-order differential equation can be computed numerically approximations. The differential equation  is replaced with the following approximation 

For sufficiently small. This can be arranged to 

So given step size and initial condition. 

2.3 ADME (Absorption, Distribution, Metabolism, Excretion) Profile analysis

The exploration of pharmacokinetics and physio-chemical characterization is an important step in the identification of any drug to cure the disease effectively. Here, we have used the swiss ADME server to investigate the drug-likeness properties of the plants selected for reducing the amyloid-beta concentration from the brain [35]. Various parameters like molecular weight, lipophilicity, water-solubility, gastrointestinal absorption, CYP inhibitors, bioavailability score have been calculated using swiss ADME and listed in table 2. Also, the violations of Lipinski’s rule (if any) have been reported.

Results and Discussions

Amyloid beta forms in the brain of every individual by the cleavage of APP by the action of enzyme beta-secretase followed by gamma-secretase. However, it excretes out of the brain, meaning the production and removal of amyloid-beta is a simultaneous process. The imbalances between the formation and removal of amyloid-beta from the brain lead to its accumulation.

The alternative for synthetic drugs is herbal medicine. Medicinal plants due to the presence of active constituents have potential in the treatment of various disorders. Active constituents such as curcumin, steroids, glycosides, anthocyanins, terpenoids, Asiatic acid, alkaloids have been reported and documented for the potent purpose of reducing beta-amyloid levels. To find an effective cure, it is very important to explore pharmacokinetics and physicochemical properties such as water solubility, gastrointestinal absorption, lipophilicity, bioavailability score and many more. The Lipinski’s rule is a standardized rule for drug development that determines the drug-likeness properties of a molecule and according to the rule drug molecule having MW > 500 g/mol, hydrogen-bond-donating atoms > 5, Hydrogen-bond-accepting atoms > 10, or log p > 5 is not considered as a good pharmaceutical agent in terms of oral activity. The natural molecules we have selected for the cure of Alzheimer showed good pharmacokinetics and Physico-chemical properties and no violation of Lipinski’s rule except for active compounds bacoside and asiaticoside present in Bacopa monniera and Centella Asiatica. In addition to this, the dosage of different plants has also been investigated at 250 mg/day, 500 mg/day, 750 mg/day and 1000 mg/day for five months where Curcuma longa showed the best results at 1000 mg/day dose, Bacapo monnieri at 750 mg/day, Convolvulus pluricaulis at 1000 mg/day dose, Withania somnifera at 500 mg/day, and Centella Asiatica at 750 mg/day; the results of which are interpreted well in the graphs viz Figure 2, 3, 4, 5, and 6. Our inference from the results implies that Withania somnifera is the best amongst five plants as it is effective in clearing amyloid-beta at a lower dose i.e., 500 mg/day as compared to others.

Conclusion

Due to the challenges faced by the pharmaceutical industries, the treatment of neurodegenerative diseases is becoming expensive, inefficient and riskier. This caused a transition from these chemical medications towards the natural traditional medications in a form of herbal treatment. Considering the effects of memory, thinking and other essential activities on Alzheimer’s patients and its stress to society, this research involves the formation of a mathematical model that acts as a template to represent the change in the levels of beta-amyloid protein (the defining feature of Alzheimer disease) upon intake of herbal formulation in form of active constituents present in the medicinal plant. The potential ability of plants in inhibiting fibrillation and hence reducing the amyloid-beta levels is due to the presence of active constituents like tannins, lignans, triterpenes, alkaloids, flavonoids, sterols and polyphenols. For different doses, the active component of the selected plant was analyzed where information from the graph reveals that all selected plants showed reduced amyloid beta levels, however, Withania somnifera showed the best results at a lower dose (50 mg/day) concerning time as compared to others. Also, the results of ADME analysis showed good bioavailability score, solubility, lipophilicity

Acknowledgement:

The authors thank the Dept. of Biotechnology, MRIIRS LAB to provide data sets on lifestyle disorders to provide facts that motivate authors to do research work.

Conflict of interests: The authors declare no conflict of interest, financial or otherwise.

Funding Agency: None

Contribution of Individual Authors

Arora K. developed the theoretical formalism, performed the analytic calculations and performed the numerical simulations. Both Khurana P. and Kumar D. authors contributed to the final version of the manuscript.

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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
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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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