International Journal of Current Research and Review
ISSN: 2231-2196 (Print)ISSN: 0975-5241 (Online)
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IJCRR - 11(7), April, 2019

Pages: 05-08

Date of Publication: 12-Apr-2019


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Inhibitory Action Against Alpha Glucosidase by Selected Dihydroxy Flavones

Author: S. Umamaheswari, K. S. Sridevi Sangeetha

Category: Healthcare

Abstract:Background: Diabetes is one of the common metabolic disorder that occurs due to poor secretion of insulin. It is more common among aged people in India. The incidence of diabetes is increasing every day and this indicates the increasing need for the treatment for diabetes.
Objective: The objective of the present study is to screen the effects of selected substituted dihydroxyflavone for its in vitro antidiabetic effect by finding the potential to inhibit the enzymes \a-Glucosidase.
Materials and Methods: The dihydroxy flavones used in the present study includes 2',3'- dihydroxy flavone and 2', 4' dihydroxy flavones. They were synthesized using standard procedures. In vitro \a-glucosidase inhibitory activity was evaluated by Li et al., 2004. The different concentration of the flavonoid ( 0.1, 0.3, 1, 3,10, 30, 100, 300, 1000 (\?M/ml) were used and the experiment was done for triplicate sample. The standard antidiabetic drug used in the study was Acarbose. The inhibitory activity was calculated and tabulated.
Results: The selected Dihydroxy flavones 2',3'- dihydroxy flavone and 2', 4' dihydroxy flavones showed significant invitro anti diabetic activity when compared with standard drug acarbose. The IC50 value of 2',3'- dihydroxy flavones and 2', 4' dihydroxy flavones was found to be 0.47\?M/ml, 46.37 \?M/ml respectively.

Keywords: Diabetes, Dihydroxy flavones, in vitro, Alpha glucosidase, Metabolic disorder

Full Text:

Introduction:

Diabetes is often called the silent killer because people who have it are often unaware they are affected. It is one of the oldest and most prevalent chronic non-communicable disease. Diabetes Mellitus is characterized by hyperglycemia, impaired metabolism of lipids, carbohydrates and proteins with an increased risk of complication related to vascular diseases. The minimum defining feature to identify diabetes mellitus is the chronic and substantiated rise in circulating glucose concentration. The normal level of blood sugar in a fasting person is between 80-120mg percent. If the fasting level of blood sugar is more than 110mg percent or after meals more than 160mg percent, it is called high blood sugar (Diabetes Mellitus). In diabetic patients, sugar can be detected in the urine also. Patients with diabetes have a higher chance of development of coronary blockages. They also get several other diseases like kidney damages as well as damage to the nerves and eyes1-3.

According to an estimation of the International Diabetes Federation, approximately 366 million people are suffering from diabetes and this may double by 2030, in India to be 40.9 million, which is expected to grow to 60.9 million by 20254.

This can also be characterized by a state of chronic hyperglycemia, glucosuria, polyurea, polydipsia, polyphagia sudden weight loss, ketoacidosis and ketonuria. In type 1 diabetes, the pancreas fails to produce insulin. Because insulin transports sugar into cells, when a body lacks insulin, its cells starve for energy. In type 2 diabetes, there is plenty of insulin in the body, but sugar still cannot get inside the cells. In both types of diabetes, sugar in the blood becomes very high. Type 2 is more prevalent than type 1, with more than 90% of the total diabetic patients suffering from it. Postprandial hyperglycemia plays an important role in the development of T2D5.

Number of environmental factors act on genetically susceptible individuals. They includes Sedentary life style, Diet, Malnutrition, Viral Infections, Chemical agents and Stress.

Diabetes is generally accepted as a major challenging health problem all over the world  and especially in the developing countries. India has the dubious distinction of being home to one in five persons with diabetes world. The World Health Organization (WHO) predicts that the number of people with diabetes is to double in the next couple of decades and that the major burnt of this will be borne by the developing countries6.

The management of Diabetes Mellitus is considered as a global problem whose successful treatment is yet to be discovered. Insulin is widely accepted as an ideal choice for treatment of diabetes mellitus but the difficulty of repeated administration led to the search for the hypoglycemic agents.

Chronic hyperglycemia has been considered as one of the principal causes for several diabetic complications. In patients with Type II diabetes, postprandial blood glucose is elevated due to absorption of glucose from the gastrointestinal tract. The major enzyme involved in carbohydrates digestion is α-glucosidase (Figure-1), it is present in the brush borders of small intestine. It plays a vital role in preventing postprandial rise in blood glucose, this is because Inhibition of these enzyme systems helps to reduce the rate of digestion of carbohydrates and reduces the rate of glucose absorption from the gut and finally lowers the postprandial rise in blood glucose level7-9. Therefore, inhibition of α-glucosidase is a key in the management and treatment of Type II diabetes10,11. Alpha glucosidase inhibitors are used as oral anti diabetic drugs for treating type 2 diabetes mellitus12,13

 

Flavonoids are the largest group of naturally occurring poly phenolic compounds present almost in all parts of flowering plants. Flavones have reported to have interesting pharmacological action such as anti-oxidant, anti-inflammatory, antihepatotoxic, anti-microbial, anticarcinogenic The combination of multiple pharmacological properties in a single nucleus is quite interesting.

In a previous study done by the authors, it has been proven that the selected dihydroxyflavones 2’,3’- dihydroxy flavone  and  2’, 4’ dihydroxy   flavones have  potent antinociceptive14 and anti-inflammatory action 15. In the present study an attempt was done to screen the effects of selected substituted dihydroxyflavone for its in vitro antidiabetic effect by finding the potential to inhibit the enzymes α-Glucosidase.

Material and Methods:

α-glucosidase and 3, 5, di-nitro salicylic acid (DNS) were purchased from Sigma-Aldrich, Bangalore. P-nitro-phenyl-α-D-glucopyranoside (p-NPG), sodium carbonate (Na2 CO3), sodium dihydrogen phosphate, di-sodium hydrogen phosphate were purchased from Hi-Media, Mumbai.

The dihydroxy flavones used in the present study includes 2’,3’- dihydroxy flavone  and  2’, 4’ dihydroxy    flavones, they were synthesized using standard procedures at Research Organics, Chennai, India. The authenticities of these compounds were done with melting points and UV method.

In vitro α-glucosidase inhibitory activity was evaluated by Li et al., 2004. α-Glucosidase inhibitory assay is based on the breakdown of maltose to glucose.  200 μl of α -glucosidase solution was pre-incubated with the test and control samples for 5 min. The reaction was started by adding 200 μl of sucrose and it was terminated after 30 min incubation at 370C by heating at 90–1000C. The liberated glucose was determined. The enzyme activity is directly proportional to the liberated glucose and the liberated glucose is measured by GOD-POD method at 546nm using semi auto analyzer. The different concentration of the flavonoid ( 0.1, 0.3, 1, 3,10, 30, 100, 300, 1000 (μM/ml) were used and the experiment was done for triplicate sample. The standard antidiabetic drug used in the study was Acarbose. The inhibitory activity of the compounds was calculated as follows

                             % Inhibition= [(control-test)/control)] X 100

Statistical Analysis:

All the measurements were done in triplicate and results are expressed in terms of mean ± standard deviation and IC50 values were calculated using Graph Pad Prism version 5.01.

Results and discussions:

One of the therapeutic approaches for preventing diabetes mellitus is to decrease the absorption of glucose through inhibition of α-glucosidase, which is a carbohydrates digesting enzymes, located in the brush borders of the small intestine. Determining the In vitro α-glucosidase inhibitory activity was found to be one of the important tool used to examine the antidiabetic effect of any compound. The Percentage α-glucosidase inhibition was calculated for 2’,3’- dihydroxy flavone  and  2’, 4’ dihydroxy   flavone at various concentration 1, 0.3, 1, 3,10, 30, 100, 300, 1000 (μM/ml)and presented in Table 1. Standard drug used here is acarbose. The Inhibitory concentration IC50 was calculate using graph pad prism software. The selected Dihydroxy flavones 2’,3’- dihydroxy flavone  and  2’, 4’ dihydroxy   flavone showed  significant In vitro α-glucosidase inhibitory activity when compared with  standard drug acarbose. The IC50 value of 2’,3’- dihydroxy flavones and  2’, 4’ dihydroxy    flavones was found to be 0.47μM/ml, 46.37 μM/ml respectively.

Table 1: In vitro α-glucosidase inhibitory activity of 2’,3’- dihydroxy flavone ,   2’, 4’ dihydroxy   flavone and the standard drug ( acarbose)

The present study showed that 2’,3’- dihydroxy flavone and   2’, 4’ dihydroxy   flavones moderately inhibit α-glucosidase activity. Out of the two compounds 2’, 3’ dihydroxy   flavones have excellent invitro antidiabetic effect in α-Glucosidase inhibitory model, hence it can be used as oral antidiabetic drug. Further preclinical evaluation studies are needed to confirm its action on postprandial hypoglycemic effect.

Conclusion: The study reveal that 2’, 3’ dihydroxy   flavones have excellent in vitro antidiabetic effect in α-Glucosidase inhibitory assay model.

Source of Funding:   Nil

Conflict of interest: Nil

Authors’ Contribution: First author involved in the experimentation and analysis of work. The second author contributed in writing part of the study.

Acknowledgment:  The author wish to thank the management of Sri Ramachandra Institute of Higher Education and Research for the encouragement and support.

References:

  1. American Diabetes Association. 2. Classification and diagnosis of diabetes: standards of medical care in diabetes—2018. Diabetes care. 2018 Jan 1;41(Supplement 1):S13-27.

  2. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Reviews Endocrinology. 2018 Feb;14(2):88.

  3. Ramachandran A, Snehalatha C. Current scenario of diabetes in India. Journal of diabetes. 2009 Mar;1(1):18-28.

  4. Mitra A, Dewanjee D, Dey B. Mechanistic studies of lifestyle interventions in type 2 diabetes. World journal of diabetes. 2012 Dec 15;3(12):201.

  5. Matyka KA. Type 2 diabetes in childhood: epidemiological and clinical aspects. British medical bulletin. 2008 Jun 1;86(1):59-75.

  6. Tiwari AK, Rao JM. Diabetes mellitus and multiple therapeutic approaches of phytochemicals: Present status and future prospects. Current science. 2002 Jul 10:30-8.

  7.  Matsui T, Tanaka T, Tamura S, Toshima A, Tamaya K, Miyata Y, Tanaka K, Matsumoto K. α-Glucosidase inhibitory profile of catechins and theaflavins. Journal of Agricultural and Food Chemistry. 2007 Jan 10;55(1):99-105.

  8. Kim YM, Jeong YK, Wang MH, Lee WY, Rhee HI. Inhibitory effect of pine extract on α-glucosidase activity and postprandial hyperglycemia. Nutrition. 2005 Jun 1;21(6):756-61.

  9. Chipiti T, Ibrahim MA, Singh M, Islam MS. In vitro α-amylase and α-glucosidase Inhibitory and Cytotoxic Activities of Extracts from Cissus cornifolia Planch Parts. Pharmacognosy magazine. 2017 Jul;13(Suppl 2):S329.

  10. Kumar S, Narwal S, Kumar V, Prakash O. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacognosy reviews. 2011 Jan;5(9):19.

  11. Nair SS, Kavrekar V, Mishra A. In vitro studies on alpha amylase and alpha glucosidase inhibitory activities of selected plant extracts. European Journal of Experimental Biology. 2013;3(1):128-32.

  12. Li Y, Peng G, Li Q, Wen S, Huang TH, Roufogalis BD, Yamahara J. Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese Zucker rats. Life sciences. 2004 Aug 20;75(14):1735-46.

  13. Telagari M, Hullatti K. In-vitro α-amylase and α-glucosidase inhibitory activity of Adiantum caudatum Linn. and Celosia argentea Linn. extracts and fractions. Indian journal of pharmacology. 2015 Jul;47(4):425.

  14. Umamaheswari S, Viswanathan S, Sathiyasekaran BW, Parvathavarthini S, Ramaswamy S. Antinociceptive activity of certain dihydroxy flavones. Indian journal of pharmaceutical sciences. 2006;68(6):749.

  15. Umamaheswari S, Sangeetha KS. Anti-Inflammatory Effect of Selected Dihydroxyflavones. Journal of clinical and diagnostic research: JCDR. 2015 May;9(5):FF05.

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Awards, Research and Publication incentive Schemes by IJCRR

Best Article Award: 

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

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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
A study by Saurabh Suvidha entitled \"A Case of Mucoid Degeneration of Uterine Fibroid with Hydrosalphinx and Ovarian Cyst\" is awarded Best article of Vol 14 issue 21
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A study by Shafaque M. et al. entitled \"A Case-Control Study Performed in Karachi on Inflammatory Markers by Ciprofloxacin and CoAmoxicillin in Patients with Chronic Suppurative Otitis Media\" is awarded Best Article of Vol 14 issue 17
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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
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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
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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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