{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T05:13:17Z","timestamp":1778649197184,"version":"3.51.4"},"reference-count":44,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,5,1]],"date-time":"2021-05-01T00:00:00Z","timestamp":1619827200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["0020"],"award-info":[{"award-number":["0020"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmacology"],"published-print":{"date-parts":[[2021,5]]},"DOI":"10.1016\/j.ejphar.2021.174056","type":"journal-article","created":{"date-parts":[[2021,3,20]],"date-time":"2021-03-20T12:09:49Z","timestamp":1616242189000},"page":"174056","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":6,"special_numbering":"C","title":["Hepatoprotective effect of selected isoandrographolide derivatives on steatotic HepG2 cells and High Fat Diet fed rats"],"prefix":"10.1016","volume":"899","author":[{"given":"Erenius","family":"Toppo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naif Abdullah","family":"Al-Dhabi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chinnakulandai","family":"Sankar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sanmugapriya Nagul","family":"Kumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kanniappan","family":"Buvanesvaragurunathan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Santhanam Sylvester","family":"Darvin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antony","family":"Stalin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kedeke","family":"Balakrishna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stanislaus Antony","family":"Ceasar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Perumal","family":"Pandikumar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Savarimuthu","family":"Ignacimuthu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuppusamy","family":"Sivasankaran","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul","family":"Agastian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib1","first-page":"66","article-title":"Andrographis paniculata: a review of pharmacological activities and clinical effects","volume":"16","author":"Akbar","year":"2011","journal-title":"Alternative Med. Rev."},{"key":"10.1016\/j.ejphar.2021.174056_bib2","unstructured":"Al-Dhabi, N.A., Ignacimuthu, S., Pandikumar, P., Toppo, E., Darvin, S.S., 2019. Isoandrographolide-19-propionate for Treatment of Non-alcoholic Fatty Liver Disease (NAFLD). US patent No. 10064841."},{"issue":"10","key":"10.1016\/j.ejphar.2021.174056_bib3","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1517\/13543776.2014.956084","article-title":"Andrographolide: progression in its modifications and applications - a patent review (2012\u20132014)","volume":"24","author":"Aromdee","year":"2014","journal-title":"Expert Opin. Ther. Pat."},{"issue":"16","key":"10.1016\/j.ejphar.2021.174056_bib4","doi-asserted-by":"crossref","first-page":"715","DOI":"10.4254\/wjh.v9.i16.715","article-title":"Non-alcoholic fatty liver disease: an expanded review","volume":"9","author":"Benedict","year":"2017","journal-title":"World J. Hepatol."},{"key":"10.1016\/j.ejphar.2021.174056_bib5","first-page":"1592","article-title":"The diagnosis and management of non-alcoholic fatty liver disease: practice guideline by the American Gastroenterological Association","volume":"142","author":"Brunt","year":"2012","journal-title":"American Association for the Study of Liver Diseases, and American College of Gastroenterology, Gastroenterology"},{"key":"10.1016\/j.ejphar.2021.174056_bib6","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1111\/liv.14354","article-title":"New drugs for non-alcoholic steatohepatitis","volume":"40","author":"Cardoso","year":"2020","journal-title":"Liver Int."},{"issue":"11","key":"10.1016\/j.ejphar.2021.174056_bib7","doi-asserted-by":"crossref","first-page":"1589","DOI":"10.1002\/ptr.5193","article-title":"Review on liver inflammation and antiinflammatory activity of Andrographis paniculata for hepatoprotection","volume":"28","author":"Chua","year":"2014","journal-title":"Phytother Res."},{"key":"10.1016\/j.ejphar.2021.174056_bib8","doi-asserted-by":"crossref","first-page":"42717","DOI":"10.1038\/srep42717","article-title":"Swiss ADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules","volume":"7","author":"Daina","year":"2017","journal-title":"Sci. Rep."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174056_bib9","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1124\/jpet.114.217968","article-title":"Andrographolide prevents high-fat diet\u2013induced obesity in C57BL\/6 mice by suppressing the sterol regulatory element-binding protein pathway","volume":"351","author":"Ding","year":"2014","journal-title":"J. Pharmacol. Exp. Therapeut."},{"issue":"S2","key":"10.1016\/j.ejphar.2021.174056_bib10","doi-asserted-by":"crossref","first-page":"W116","DOI":"10.1093\/nar\/gkl282","article-title":"CASTp: computed atlas of surface topography of proteins with structural and topographical mapping of functionally annotated residues","volume":"34","author":"Dundas","year":"2006","journal-title":"Nucleic Acids Res."},{"issue":"6","key":"10.1016\/j.ejphar.2021.174056_bib11","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1007\/s00125-016-3912-9","article-title":"Bavachinin, as a novel natural pan-PPAR agonist, exhibits unique synergistic effects with synthetic PPAR-\u03b3 and PPAR-\u03b1 agonists on carbohydrate and lipid metabolism in db\/db and diet-induced obese mice","volume":"59","author":"Feng","year":"2016","journal-title":"Diabetologia"},{"key":"10.1016\/j.ejphar.2021.174056_bib12","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1159\/000447866","article-title":"Differential lipotoxic effects of palmitate and oleate in activated human hepatic stellate cells and epithelial hepatoma cells","volume":"39","author":"Hetherington","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"issue":"6","key":"10.1016\/j.ejphar.2021.174056_bib13","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1002\/jcc.20634","article-title":"A semiempirical free energy force field with charge-based desolvation","volume":"28","author":"Huey","year":"2007","journal-title":"J. Comput. Chem."},{"issue":"12","key":"10.1016\/j.ejphar.2021.174056_bib14","first-page":"2683","article-title":"Morphological and functional characterization of non-alcoholic fatty liver disease induced by a methionine-choline-deficient diet in C57BL\/6 mice","volume":"6","author":"Itagaki","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"issue":"26","key":"10.1016\/j.ejphar.2021.174056_bib15","doi-asserted-by":"crossref","first-page":"8364","DOI":"10.3748\/wjg.v20.i26.8364","article-title":"Experimental models of non-alcoholic fatty liver disease in rats","volume":"20","author":"Kucera","year":"2014","journal-title":"World J. Gastroenterol."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174056_bib16","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0173499","article-title":"Prevalence of non-alcoholic fatty liver disease and risk factors for advanced fibrosis and mortality in the United States","volume":"12","author":"Le","year":"2017","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2021.174056_bib17","first-page":"1","article-title":"Overview of drug product development","volume":"7","author":"Lee","year":"2001","journal-title":"Current Protocols in Pharmacology"},{"issue":"24","key":"10.1016\/j.ejphar.2021.174056_bib18","doi-asserted-by":"crossref","first-page":"6891","DOI":"10.1016\/j.bmcl.2007.10.009","article-title":"Synthesis of andrographolide derivatives and their TNF-\u03b1 and IL-6 expression inhibitory activities","volume":"17","author":"Li","year":"2007","journal-title":"Bioorg. Med. Chem. Lett"},{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib19","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0086724","article-title":"Therapeutic role of ursolic acid on ameliorating hepatic steatosis and improving metabolic disorders in high-fat diet-induced non-alcoholic fatty liver disease rats","volume":"9","author":"Li","year":"2014","journal-title":"PloS One"},{"key":"10.1016\/j.ejphar.2021.174056_bib20","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.biochi.2016.11.009","article-title":"PPARs and nonalcoholic fatty liver disease","volume":"136","author":"Liss","year":"2017","journal-title":"Biochimie"},{"issue":"3","key":"10.1016\/j.ejphar.2021.174056_bib21","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/ptr.2948","article-title":"Oleanolic acid is a selective Farnesoid X Receptor modulator","volume":"24","author":"Liu","year":"2010","journal-title":"Phytother Res."},{"issue":"4","key":"10.1016\/j.ejphar.2021.174056_bib22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0093567","article-title":"GPBAR1\/TGR5 mediates bile acid-induced cytokine expression in murine Kupffer cells","volume":"9","author":"Lou","year":"2014","journal-title":"PloS One"},{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib23","first-page":"1","article-title":"Therapeutic potentials of andrographolide from Andrographis paniculata: a review","volume":"6","author":"Maiti","year":"2006","journal-title":"J. Nat. Remedies"},{"issue":"16","key":"10.1016\/j.ejphar.2021.174056_bib24","doi-asserted-by":"crossref","first-page":"2785","DOI":"10.1002\/jcc.21256","article-title":"AutoDock 4 and AutoDock tools 4: automated docking with selective receptor flexibility","volume":"30","author":"Morris","year":"2009","journal-title":"J. Comput. Chem."},{"key":"10.1016\/j.ejphar.2021.174056_bib25","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J. Immunol. Methods"},{"key":"10.1016\/j.ejphar.2021.174056_bib26","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.ejmech.2013.09.002","article-title":"Synthesis of new andrographolide derivatives and evaluation of their antidyslipidemic, LDL-oxidation and antioxidant activity","volume":"69","author":"Pandeti","year":"2013","journal-title":"Eur. J. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejphar.2021.174056_bib27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1007\/BF00316069","article-title":"Quantitation of adipose conversion and triglycerides by staining intracytoplasmic lipids with Oil red O","volume":"97","author":"Ramirez-Zacarias","year":"1992","journal-title":"Histochemistry"},{"issue":"2","key":"10.1016\/j.ejphar.2021.174056_bib28","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1021\/ci500588j","article-title":"DataWarrior: an open-source program for chemistry aware data visualization and analysis","volume":"55","author":"Sander","year":"2015","journal-title":"J. Chem. Inf. Model."},{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib29","first-page":"57","article-title":"Python: a programming language for software integration and development","volume":"17","author":"Sanner","year":"1999","journal-title":"J. Mol. Graph. Model."},{"issue":"10","key":"10.1016\/j.ejphar.2021.174056_bib30","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1054\/bjoc.2000.1457","article-title":"Expression of peroxisome proliferator-activated receptor (PPAR) \u03b3 in gastric cancer and inhibitory effects of PPAR\u03b3 agonists","volume":"83","author":"Sato","year":"2000","journal-title":"Br. J. Canc."},{"issue":"8","key":"10.1016\/j.ejphar.2021.174056_bib31","doi-asserted-by":"crossref","first-page":"1355","DOI":"10.1107\/S0907444904011679","article-title":"PRODRG: a tool for high-throughput crystallography of protein\u2013ligand complexes","volume":"60","author":"Sch\u00fcttelkopf","year":"2004","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"issue":"5","key":"10.1016\/j.ejphar.2021.174056_bib32","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.jhep.2006.11.019","article-title":"The Interleukin-1 receptor antagonist is a direct target gene of PPAR\u03b1 in liver","volume":"46","author":"Stienstra","year":"2007","journal-title":"J. Hepatol."},{"issue":"9","key":"10.1016\/j.ejphar.2021.174056_bib33","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1021\/ml100164p","article-title":"Drawing the PDB: protein\u2212 ligand complexes in two dimensions","volume":"1","author":"Stierand","year":"2010","journal-title":"ACS Med. Chem. Lett."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174056_bib34","doi-asserted-by":"crossref","first-page":"846","DOI":"10.2353\/ajpath.2006.050953","article-title":"A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-\u03b1 and n-3 polyunsaturated fatty acid treatment on liver injury","volume":"169","author":"Svegliati-Baroni","year":"2006","journal-title":"Am. J. Pathol."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174056_bib35","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1111\/cbdd.12246","article-title":"Design, synthesis, and biological evaluation of andrographolide derivatives as potent hepatoprotective agents","volume":"83","author":"Tang","year":"2014","journal-title":"Chem. Biol. Drug Des."},{"issue":"3","key":"10.1016\/j.ejphar.2021.174056_bib36","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.jep.2010.01.044","article-title":"Regulation effects on abnormal glucose and lipid metabolism of TZQ-F, a new kind of Traditional Chinese Medicine","volume":"128","author":"Tao","year":"2010","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.ejphar.2021.174056_bib37","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.biopha.2017.08.071","article-title":"Effect of two andrographolide derivatives on cellular and rodent models of non-alcoholic fatty liver disease","volume":"95","author":"Toppo","year":"2017","journal-title":"Biomed. Pharmacother."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174056_bib38","doi-asserted-by":"crossref","first-page":"293","DOI":"10.2174\/157340612800493629","article-title":"Synthesis and preliminary antihyperlipidaemic activities evaluation of andrographolide derivatives","volume":"8","author":"Wang","year":"2012","journal-title":"Med. Chem."},{"issue":"6","key":"10.1016\/j.ejphar.2021.174056_bib39","first-page":"504","article-title":"Synthesis and antitumor activity of isoandrographolide compounds","volume":"36","author":"Wang","year":"2005","journal-title":"J. China Pharm. Univ."},{"issue":"6","key":"10.1016\/j.ejphar.2021.174056_bib40","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0099245","article-title":"Peroxisome proliferator-activated receptor \u03b1 activation induces hepatic steatosis suggesting an adverse effect","volume":"9","author":"Yan","year":"2014","journal-title":"PloS One"},{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib41","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease: meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"issue":"3\u20134","key":"10.1016\/j.ejphar.2021.174056_bib42","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1159\/000452560","article-title":"Alisol A 24-acetate prevents hepatic steatosis and metabolic disorders in HepG2 cells","volume":"40","author":"Zeng","year":"2016","journal-title":"Cell. Physiol. Biochem."},{"issue":"1","key":"10.1016\/j.ejphar.2021.174056_bib43","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1186\/1479-5876-7-62","article-title":"Hypoglycemic and beta cell protective effects of andrographolide analogue for diabetes treatment","volume":"7","author":"Zhang","year":"2009","journal-title":"J. Transl. Med."},{"issue":"2","key":"10.1016\/j.ejphar.2021.174056_bib44","first-page":"298","article-title":"Biological activities and corresponding SARs of andrographolide and its derivatives","volume":"13","author":"Zhou","year":"2013","journal-title":"Mini Rev. Med. Chem."}],"container-title":["European Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921002090?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0014299921002090?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T04:46:31Z","timestamp":1778647591000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0014299921002090"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5]]},"references-count":44,"alternative-id":["S0014299921002090"],"URL":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174056","relation":{},"ISSN":["0014-2999"],"issn-type":[{"value":"0014-2999","type":"print"}],"subject":[],"published":{"date-parts":[[2021,5]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Hepatoprotective effect of selected isoandrographolide derivatives on steatotic HepG2 cells and High Fat Diet fed rats","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejphar.2021.174056","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"174056"}}