{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T02:59:39Z","timestamp":1792897179993,"version":"4.5.0"},"reference-count":56,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"DOI":"10.13039\/501100001843","name":"Department of Science and Technology-Science and Engineering Research Board","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001843","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Engineering Research Council","award":["ECR\/2016\/000415"],"award-info":[{"award-number":["ECR\/2016\/000415"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2020,4]]},"DOI":"10.1016\/j.ejphar.2020.173004","type":"journal-article","created":{"date-parts":[[2020,2,8]],"date-time":"2020-02-08T11:08:14Z","timestamp":1581160094000},"page":"173004","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":107,"special_numbering":"C","title":["Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1\/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats"],"prefix":"10.1016","volume":"873","author":[{"given":"Shyamaladevi","family":"Babu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhan","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ponnulakshmi","family":"Rajagopal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayalakshmi","family":"Periyasamy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vishnupriya","family":"Veeraraghavan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramajayam","family":"Govindan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Selvaraj","family":"Jayaraman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl. 2","key":"10.1016\/j.ejphar.2020.173004_bib1","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/j.1467-789X.2012.01036.x","article-title":"Revisiting the diacylglycerol-induced insulin resistance hypothesis","volume":"13","author":"Amati","year":"2012","journal-title":"Obes. Rev."},{"key":"10.1016\/j.ejphar.2020.173004_bib2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/S2222-1808(14)60429-1","article-title":"Evaluation of antidiabetic property of Andrographis paniculata powder in high fat and sucrose-induced type-2 diabetic adult male rat","volume":"4","author":"Augustine","year":"2014","journal-title":"Asian Pac. J. Trop"},{"issue":"1","key":"10.1016\/j.ejphar.2020.173004_bib3","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1515\/cclm-2012-0490","article-title":"Diabetes as a complication of adipose tissue dysfunction. Is there a role for potential new biomarkers?","volume":"51","author":"Bergmann","year":"2013","journal-title":"Clin. Chem. Lab. Med."},{"key":"10.1016\/j.ejphar.2020.173004_bib4","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s12263-010-0196-4","article-title":"Gene regulation in b-sitosterol-mediated stimulation of adipogenesis, glucose uptake, and lipid mobilization in rat primary adipocytes","volume":"6","author":"Chai","year":"2011","journal-title":"Genes Nutr."},{"key":"10.1016\/j.ejphar.2020.173004_bib5","doi-asserted-by":"crossref","first-page":"1807","DOI":"10.1016\/S0002-8223(02)90388-3","article-title":"Effects of a new soy\/\u03b2 sitosterol supplement on plasma lipids in moderately hypercholesterolemic subjects","volume":"102","author":"Cicero","year":"2002","journal-title":"J. Am. Diet Assoc."},{"issue":"2","key":"10.1016\/j.ejphar.2020.173004_bib6","doi-asserted-by":"crossref","first-page":"191","DOI":"10.5114\/aoms.2013.33181","article-title":"Biochemistry of adipose tissue: an endocrine organ","volume":"9","author":"Coelho","year":"2013","journal-title":"Arch. Med. Sci."},{"issue":"10","key":"10.1016\/j.ejphar.2020.173004_bib7","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1007\/s00125-012-2644-8","article-title":"Regulation of insulin sensitivity by serine\/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2","volume":"55","author":"Copps","year":"2012","journal-title":"Diabetologia"},{"issue":"3","key":"10.1016\/j.ejphar.2020.173004_bib8","doi-asserted-by":"crossref","first-page":"217","DOI":"10.4103\/0250-474X.106063","article-title":"Targeting multidrug resistant mycobacterium tuberculosis htra2 with identical chemical entitiesof fluoroquinolon","volume":"74","author":"Daisy","year":"2012","journal-title":"Indian J. Pharmaceut. Sci."},{"key":"10.1016\/j.ejphar.2020.173004_bib9","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1741-7007-9-71","article-title":"Molecular dynamics simulations and drug discovery","volume":"9","author":"Durrant","year":"2011","journal-title":"BMC Biol."},{"issue":"3","key":"10.1016\/j.ejphar.2020.173004_bib10","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1113\/jphysiol.2006.120006","article-title":"Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation","volume":"577","author":"Eduardo","year":"2006","journal-title":"Physiol."},{"key":"10.1016\/j.ejphar.2020.173004_bib11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1161\/01.CIR.14.1.77","article-title":"The effect of \u03b2 sitosterol on the serum lipids of young men with arteriosclerotic heart disease","volume":"14","author":"Farquhar","year":"1956","journal-title":"Circulation"},{"key":"10.1016\/j.ejphar.2020.173004_bib12","first-page":"5","article-title":"Northern blotting: efficient RNA staining and transfer","volume":"10","author":"Fourney","year":"1988","journal-title":"Focus"},{"key":"10.1016\/j.ejphar.2020.173004_bib13","doi-asserted-by":"crossref","first-page":"1739","DOI":"10.1021\/jm0306430","article-title":"Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy","volume":"47","author":"Friesner","year":"2004","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2020.173004_bib14","doi-asserted-by":"crossref","first-page":"6177","DOI":"10.1021\/jm051256o","article-title":"Extra precision glide: docking and scoring incorporating a model of hydrophobic enclosure for protein-ligand complexes","volume":"49","author":"Friesner","year":"2006","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejphar.2020.173004_bib15","doi-asserted-by":"crossref","first-page":"225","DOI":"10.2174\/157340909789577847","article-title":"Molecular dynamics as a tool in rational drug design: current status and some major applications","volume":"4","author":"Galeazzi","year":"2009","journal-title":"Curr. Comput. Aided Drug Des."},{"issue":"12","key":"10.1016\/j.ejphar.2020.173004_bib16","doi-asserted-by":"crossref","first-page":"4715","DOI":"10.1210\/en.2013-1672","article-title":"\u03b2-Arrestin 1 and 2 and G protein-coupled receptor kinase 2 expression in pituitary adenomas: role in the regulation of response to somatostatin analogue treatment in patients with acromegaly","volume":"154","author":"Gatto","year":"2013","journal-title":"Endocrinology"},{"key":"10.1016\/j.ejphar.2020.173004_bib17","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1080\/gye.16.3.193.205","article-title":"Effects of pregnancy on insulin receptor in liver, skeletal muscle and adipose tissue of rats","volume":"16","author":"Gonzalez","year":"2002","journal-title":"Gynecol. Endocrinol."},{"key":"10.1016\/j.ejphar.2020.173004_bib18","first-page":"187","article-title":"Regulation of insulin receptor substrate-1 in the liver, skeletal muscle and adipose tissue of rats throughout pregnancy","volume":"17","author":"Gonzalez","year":"2003","journal-title":"Gynecol. Endocrinol."},{"key":"10.1016\/j.ejphar.2020.173004_bib19","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1111\/j.1753-0407.2010.00107.x","article-title":"Antidiabetic and antioxidant potential of b-sitosterol in streptozotocin-induced experimental hyperglycemia","volume":"3","author":"Gupta","year":"2011","journal-title":"J. Diabetes"},{"key":"10.1016\/j.ejphar.2020.173004_bib20","doi-asserted-by":"crossref","first-page":"357","DOI":"10.2337\/db07-0706","article-title":"Impaired insulin-stimulated phosphorylation of Akt and AS160 in skeletal muscle of women with polycystic ovary syndrome is reversed by pioglitazone treatment","volume":"57","author":"Hojlund","year":"2008","journal-title":"Diabetes"},{"key":"10.1016\/j.ejphar.2020.173004_bib21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1146\/annurev.biochem.69.1.373","article-title":"Protein tyrosine kinase structure and function","volume":"69","author":"Hubbard","year":"2000","journal-title":"Annu. Rev. Biochem."},{"key":"10.1016\/j.ejphar.2020.173004_bib22","doi-asserted-by":"crossref","first-page":"1253","DOI":"10.1016\/j.bbrc.2008.10.136","article-title":"Beneficial effects of b-sitosterol on glucose and lipid metabolism in L6 myotube cells are mediated by AMP-activated protein kinase","volume":"377","author":"Hwang","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2020.173004_bib23","series-title":"IDF Diabetes Atlas","author":"International Diabetes Federation","year":"2017"},{"key":"10.1016\/j.ejphar.2020.173004_bib24","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1007\/s00125-012-2534-0","article-title":"Management of hyperglycemia in type-2 diabetes: a patient centered approach. Position statement of the american diabetes association (ADA) and the European association for the study of diabetes (EASD)","volume":"55","author":"Inzucchi","year":"2012","journal-title":"Diabetologia"},{"issue":"7","key":"10.1016\/j.ejphar.2020.173004_bib25","doi-asserted-by":"crossref","first-page":"2005","DOI":"10.2337\/diabetes.51.7.2005","article-title":"Lipidinduced insulin resistance in human muscle is associated with changes in diacylglycerol, protein kinase C, and Ikappa B-alpha","volume":"51","author":"Itani","year":"2002","journal-title":"Diabetes"},{"key":"10.1016\/j.ejphar.2020.173004_bib26","first-page":"224","article-title":"Antihyperglycemic and insulin-releasing effects of \u00df-sitosterol 3-\u00df-D-Glucoside and its aglycone, \u00df-sitosterol","volume":"296","author":"Ivorra","year":"1988","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"issue":"4","key":"10.1016\/j.ejphar.2020.173004_bib27","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1111\/j.1747-0285.2008.00707.x","article-title":"Driving forces for ligand migration in the Leucine transporter","volume":"72","author":"J\u00f8rgensen","year":"2008","journal-title":"Chem. Biol. Drug Des."},{"issue":"4","key":"10.1016\/j.ejphar.2020.173004_bib28","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1172\/JCI10842","article-title":"Obesity and insulin resistance","volume":"106","author":"Kahn","year":"2000","journal-title":"J. Clin. Invest."},{"issue":"1","key":"10.1016\/j.ejphar.2020.173004_bib29","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejmech.2009.09.013","article-title":"Three dimensional pharmacophore modelling for c-Kit receptor tyrosine kinase inhibitors","volume":"45","author":"Kansal","year":"2010","journal-title":"Eur. J. Med. Chem."},{"key":"10.1016\/j.ejphar.2020.173004_bib30","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.devcel.2009.09.011","article-title":"Arrestin development: emerging roles for \u03b2 -arrestins in developmental signaling pathways","volume":"17","author":"Kovacs","year":"2009","journal-title":"Dev. Cell"},{"key":"10.1016\/j.ejphar.2020.173004_bib31","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1038\/nrm3351","article-title":"Regulation of glucose transport by insulin: traffic control of GLUT4","volume":"13","author":"Leto","year":"2012","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.ejphar.2020.173004_bib32","series-title":"Schrodinger","author":"Ligprep","year":"2019"},{"key":"10.1016\/j.ejphar.2020.173004_bib33","doi-asserted-by":"crossref","first-page":"701","DOI":"10.1016\/j.bbrc.2005.11.068","article-title":"High-fat diet feeding impairs both the expression and activity of AMPKa in rats' skeletal muscle","volume":"339","author":"Liu","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.ejphar.2020.173004_bib34","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0021-9258(19)52451-6","article-title":"Protein measurement with the Folin phenol reagent","volume":"193","author":"Lowry","year":"1951","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.ejphar.2020.173004_bib35","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1038\/nature07617","article-title":"Deficiency of a \u03b2 arrestin- 2 signal complex contributes to insulin resistance","volume":"457","author":"Luan","year":"2009","journal-title":"Nature"},{"issue":"19","key":"10.1016\/j.ejphar.2020.173004_bib36","doi-asserted-by":"crossref","first-page":"6155","DOI":"10.1021\/jp077018h","article-title":"Microsecond molecular dynamics simula- tion shows elect of slow loop dynamics on backbone amide order parameters of proteins","volume":"112","author":"Maragakis","year":"2008","journal-title":"J. Phys. Chem. B"},{"key":"10.1016\/j.ejphar.2020.173004_bib37","doi-asserted-by":"crossref","first-page":"52","DOI":"10.3389\/fendo.2013.00052","article-title":"Mechanisms of obesity-induced inflammation and insulin resistance: insights into the emerging role of nutritional strategies","volume":"4","author":"McArdle","year":"2013","journal-title":"Front. Endocrinol."},{"issue":"9","key":"10.1016\/j.ejphar.2020.173004_bib38","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1002\/jcp.25632","article-title":"Challenging of AS160\/TBC1D4 alters intracellular lipid milieu in L6 myotubes incubated with palmitate","volume":"232","author":"Miklosz","year":"2017","journal-title":"J. Cell. Physiol."},{"issue":"11","key":"10.1016\/j.ejphar.2020.173004_bib39","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1001\/2012.jama.11132","article-title":"Dysfunctional adiposity and the risk of prediabetes and type 2 diabetes in obese adults","volume":"308","author":"Neeland","year":"2012","journal-title":"J. Am. Med. Assoc."},{"key":"10.1016\/j.ejphar.2020.173004_bib40","first-page":"130","article-title":"Herbal management of benign prostatic hyperplasia","volume":"8","author":"Nyamai","year":"2016","journal-title":"J. Canc. Sci. Ther."},{"key":"10.1016\/j.ejphar.2020.173004_bib41","first-page":"1","article-title":"Rat pro-inflammatory cytokine and cytokine related mRNA quantification by real-time polymerase chain reaction using SYBR green","volume":"3","author":"Peinnequin","year":"2004","journal-title":"BMC Immunol."},{"key":"10.1016\/j.ejphar.2020.173004_bib42","first-page":"1","article-title":"Insilico and in vivo analysis to identify the antidiabetic activity of beta sitosterol in adipose tissue of high fat diet and sucrose induced type-2 diabetic experimental rats","author":"Ponnulakshmi","year":"2018","journal-title":"Toxicol. Mech. Methods"},{"key":"10.1016\/j.ejphar.2020.173004_bib43","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.niox.2013.04.007","article-title":"Nitric oxide mediates the insulin-sensitizing effects of b-sitosterol in high fat diet-fed rats","volume":"32","author":"Radika","year":"2013","journal-title":"Nitric Oxide"},{"issue":"5","key":"10.1016\/j.ejphar.2020.173004_bib44","doi-asserted-by":"crossref","first-page":"590","DOI":"10.9734\/EJMP\/2014\/7764","article-title":"The story of beta-sitosterol- A review","volume":"4","author":"Saeidnia","year":"2014","journal-title":"Eur. J. Med. Plants"},{"issue":"3","key":"10.1016\/j.ejphar.2020.173004_bib45","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.homp.2013.05.002","article-title":"Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic rats","volume":"102","author":"Sampath","year":"2013","journal-title":"Homeopathy"},{"key":"10.1016\/j.ejphar.2020.173004_bib46","article-title":"Effect of troxerutin on insulin signaling molecules in the gastrocnemius muscle of high fat and sucrose-induced type-2 diabetic adult male rat","author":"Sathish","year":"2014","journal-title":"Mol. Cell. Biochem."},{"issue":"7","key":"10.1016\/j.ejphar.2020.173004_bib47","first-page":"1307","article-title":"Docking mode of delvardine and its analogues into the p66 domain of HIV-1 reverse transcriptase: screening using molecular mechanics-generalized born\/surface area and absorption, distribution, metabolism and excretion properties","volume":"32","author":"Sengupta","year":"2007","journal-title":"J. Bio. Sci."},{"key":"10.1016\/j.ejphar.2020.173004_bib48","doi-asserted-by":"crossref","first-page":"71","DOI":"10.33549\/physiolres.931707","article-title":"Rapid reversal of insulinstimulated AS160 phosphorylation in rat skeletal muscle after insulin exposure","volume":"59","author":"Sharma","year":"2010","journal-title":"Physiol. Res."},{"key":"10.1016\/j.ejphar.2020.173004_bib49","series-title":"Schr\u00f6dinger","author":"SiteMap","year":"2019"},{"key":"10.1016\/j.ejphar.2020.173004_bib50","first-page":"1","article-title":"Ectopic fat and insulin resistance: pathophysiology and effect of diet and lifestyle interventions","author":"Snel","year":"2012","journal-title":"Internet J. Endocrinol."},{"key":"10.1016\/j.ejphar.2020.173004_bib51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.ijdm.2009.12.013","article-title":"Biological evaluation of (3b)-STIGMAST-5-EN-3-OL as potent anti-diabetic agent in regulating glucose transport using in vitro model","volume":"2","author":"Sujatha","year":"2010","journal-title":"Int J Diabetes Mellit"},{"key":"10.1016\/j.ejphar.2020.173004_bib52","article-title":"Phytosterols in type 2 diabetes and obesity \u2013 molecular mechanisms of action","volume":"201\u2013219","author":"Szyda","year":"2015","journal-title":"Plant Lipids Science, Technology, Nutritional Value and Benefits to Human Health"},{"key":"10.1016\/j.ejphar.2020.173004_bib53","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.cmet.2006.05.003","article-title":"Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1","volume":"3","author":"Um","year":"2006","journal-title":"Cell Metabol."},{"key":"10.1016\/j.ejphar.2020.173004_bib54","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1007\/s008940050096","article-title":"SCORE: a new empirical method for estimating the binding affinity of a protein-ligand complex","volume":"4","author":"Wang","year":"1998","journal-title":"J. Mol. Model."},{"key":"10.1016\/j.ejphar.2020.173004_bib55","first-page":"265","article-title":"Drug therapy of severe hypercholesterolemia","volume":"2","author":"Weizel","year":"1997","journal-title":"Eur. J. Med. Res."},{"issue":"4","key":"10.1016\/j.ejphar.2020.173004_bib56","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1021\/jm070680h","article-title":"Two-carbon-elongated HIV-1 protease inhibitors with a tertiary-alcohol-containing transition-state mimic","volume":"51","author":"Wu","year":"2008","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920300960?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299920300960?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T04:07:55Z","timestamp":1762142875000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299920300960"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":56,"alternative-id":["S0014299920300960"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173004","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Beta-sitosterol attenuates insulin resistance in adipose tissue via IRS-1\/Akt mediated insulin signaling in high fat diet and sucrose induced type-2 diabetic rats","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2020.173004","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2020 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"173004"}}