{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:12:46Z","timestamp":1791313966420,"version":"4.3.1"},"reference-count":48,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T00:00:00Z","timestamp":1407110400000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0104005","type":"journal-article","created":{"date-parts":[[2014,8,4]],"date-time":"2014-08-04T17:11:25Z","timestamp":1407172285000},"page":"e104005","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":111,"title":["Enhanced Biosynthesis of Withanolides by Elicitation and Precursor Feeding in Cell Suspension Culture of Withania somnifera (L.) Dunal in Shake-Flask Culture and Bioreactor"],"prefix":"10.1371","volume":"9","author":[{"given":"Ganeshan","family":"Sivanandhan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natesan","family":"Selvaraj","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andy","family":"Ganapathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markandan","family":"Manickavasagam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2014,8,4]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1021\/np0200515","article-title":"Challenges and opportunities confronting the botanical dietary supplement industry","volume":"65","author":"JH Cardellina","year":"2002","journal-title":"J Nat Prod"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/0141-0229(94)00108-4","article-title":"Strategies for the improvement of secondary metabolite production in plant cell cultures","volume":"17","author":"H D\u00f6rnenburg","year":"1995","journal-title":"Enzym Microb Technol"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1007\/s00449-012-0679-3","article-title":"Evaluation of nutrient uptake and physical parameters on cell biomass growth and production of spilanthol in suspension cultures of <italic>Spilanthes acmella<\/italic> Murr","volume":"35","author":"M Singh","year":"2012","journal-title":"Bioprocess Biosyst Eng"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1007\/s11738-011-0768-y","article-title":"The effect of polyamines on the efficiency of multiplication and rooting of <italic>Withania somnifera<\/italic> (L.) Dunal and content of some withanolides in obtained plants","volume":"33","author":"G Sivanandhan","year":"2011","journal-title":"Acta Physiol Plant"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.indcrop.2011.11.022","article-title":"Chitosan enhances withanolides production in adventitious root cultures of <italic>Withania somnifera<\/italic> (L.) Dunal","volume":"37","author":"G Sivanandhan","year":"2012","journal-title":"Ind Crop Prod"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1038\/sj.bjp.0706122","article-title":"Neuritic regeneration and synaptic reconstruction induced by Withanolide-A","volume":"144","author":"T Kuboyama","year":"2005","journal-title":"Br J Pharmacol"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.lfs.2007.01.029","article-title":"A standardized root extract of <italic>Withania somnifera<\/italic> and its major constituent withanolide-A solicit humoral and cell-mediated immune responses by up regulation of Th1-dominant polarization in BALB\/c mice","volume":"80","author":"F Malik","year":"2007","journal-title":"Life Sci"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"6080","DOI":"10.1016\/j.vaccine.2009.07.011","article-title":"Molecular insight into the immune up-regulatory properties of the leaf extract of Ashwagandha and identification of Th1 immunostimulatory chemical entity","volume":"27","author":"SF Khan","year":"2009","journal-title":"Vaccine"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"2115","DOI":"10.1007\/s10495-007-0129-x","article-title":"Reactive oxygen species generation and mitochondrial dysfunction in the apoptotic cell death of human myeloid leukemia HL-60 cells by a dietary compound withaferin A with concomitant protection by N-acetyl cysteine","volume":"12","author":"F Malik","year":"2007","journal-title":"Apoptosis"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.vph.2014.01.009","article-title":"Antiplatelet, anticoagulant, and profibrinolytic activities of withaferin A","volume":"60","author":"SK Ku","year":"2014","journal-title":"Vascul Pharmacol"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1016\/j.bcp.2012.08.027","article-title":"Molecular insight in the multifunctional activities of Withaferin A","volume":"84","author":"WV Berghe","year":"2012","journal-title":"Biochem Pharmacol"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1007\/s10456-004-1026-3","article-title":"Withaferin A is a potent inhibitor of angiogenesis","volume":"7","author":"R Mohan","year":"2004","journal-title":"Angiogenesis"},{"key":"ref13","first-page":"334","article-title":"Scientific basis for the therapeutic use of <italic>Withania somnifera<\/italic> (ashwagandha): a review","volume":"5","author":"LC Mishra","year":"2000","journal-title":"Alternat Med Rev"},{"key":"ref14","unstructured":"Sharada M, Ahuja A, Vij SP (2008) Applications of biotechnology in Indian ginseng (ashwagandha): progress and prospects. In: Kumar A, Sopory SK (eds) Recent advances in plant biotechnology and its applications. I. K. International Pvt Ltd, New Delhi, pp 645\u2013667."},{"key":"ref15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s12010-012-9809-2","article-title":"Optimization of elicitation conditions with methyl jasmonate and salicylic acid to improve the productivity of withanolides in the adventitious root culture of <italic>Withania somnifera<\/italic> (L.) Dunal","volume":"168","author":"G Sivanandhan","year":"2012","journal-title":"Appl Biochem Biotechnol"},{"key":"ref16","first-page":"461","article-title":"Phytochemical variability in commercial herbal products and preparations of <italic>Withania somnifera<\/italic> (Ashwagandha)","volume":"86","author":"RS Sangwan","year":"2007","journal-title":"Curr Sci"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1016\/S0141-0229(02)00041-8","article-title":"Towards manipulation of postbiosynthetic events in secondary metabolism of plant cell cultures","volume":"30","author":"W Zhang","year":"2002","journal-title":"Enzyme Microb Technol"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1007\/s00344-012-9264-x","article-title":"Salt stress-induced responses in growth and metabolism in callus cultures and differentiating in vitro shoots of Indian ginseng (<italic>Withania somnifera<\/italic> Dunal)","volume":"31","author":"F Sabir","year":"2012","journal-title":"J Plant Growth Regul"},{"key":"ref19","article-title":"Effect of cadmium stress on inductive enzymatic and nonenzymatic responses of ROS and sugar metabolism in multiple shoot cultures of Ashwagandha (<italic>Withania somnifera<\/italic> Dunal)","author":"B Mishra","year":"2014","journal-title":"Protoplasma"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/nprot.2010.144","article-title":"Initiation, growth and cryopreservation of plant cell suspension cultures","volume":"6","author":"NR Mustafa","year":"2011","journal-title":"Nat Protoc"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1023\/A:1005502632053","article-title":"Metabolic engineering of plant secondary metabolite pathways for the production of fine chemicals","volume":"21","author":"R Verpoorte","year":"1999","journal-title":"Biotechnol Lett"},{"key":"ref22","first-page":"1","article-title":"Plant cell cultures, chemical factories of secondary metabolites","volume":"20","author":"RS Rao","year":"2002","journal-title":"Biotechnol Adv"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1016\/S0168-9452(01)00490-3","article-title":"Production of plant secondary metabolites: a historical perspective","volume":"161","author":"F Bourgaud","year":"2001","journal-title":"Plant Sci"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1007\/BF02933747","article-title":"Production of anthocyanins by plant cell cultures","volume":"4","author":"W Zhang","year":"1999","journal-title":"Biotechnol Bioprocess Eng"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1007\/s11240-009-9594-y","article-title":"Ethylene and polyamine production patterns during <italic>in vitro<\/italic> shoot organogenesis of two passion fruit species as affected by polyamines and their inhibitor","volume":"99","author":"LLC Dias","year":"2009","journal-title":"Plant Cell Tiss Organ Cult"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1007\/s11240-010-9688-6","article-title":"Enhanced accumulation of decursin and decursinol angelate in root cultures and intact roots of <italic>Angelica gigas<\/italic> Nakai following elicitation","volume":"101","author":"HS Rhee","year":"2010","journal-title":"Plant Cell Tiss Organ Cult"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1023\/A:1013993403959","article-title":"Alkaloid formation in cell suspension cultures of <italic>Tabernaemontana elegans<\/italic> after feeding of tryptamine and loganin or secologanin","volume":"68","author":"E Lucumi","year":"2002","journal-title":"Plant Cell Tiss Org Cult"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1007\/s00709-012-0471-x","article-title":"A promising approach on biomass accumulation and withanolides production in cell suspension culture of <italic>Withania somnifera<\/italic> (L.) Dunal","volume":"250","author":"G Sivanandhan","year":"2013","journal-title":"Protoplasma"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s11240-013-0297-z","article-title":"Increased production of withanolide A, withanone and withaferin A in hairy root cultures of <italic>Withania somnifera<\/italic> (L.) Dunal elicited with methyl jasmonate and salicylic acid","volume":"114","author":"G Sivanandhan","year":"2013","journal-title":"Plant Cell Tiss Organ Cult"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"490","DOI":"10.4103\/0250-474X.27824","article-title":"Withaferin A from cell cultures of <italic>Withania somnifera<\/italic>","volume":"68","author":"V Ciddi","year":"2006","journal-title":"Indian J Pharm Sci"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1007\/s12010-008-8231-2","article-title":"Dual elicitation for improved production of withaferin A by cell suspension cultures of <italic>Withania somnifera<\/italic>","volume":"151","author":"A Baldi","year":"2008","journal-title":"Appl Biochem Biotechnol"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1016\/j.biortech.2010.03.078","article-title":"Establishment of cell suspension cultures of <italic>Withania somnifera<\/italic> for the production of withanolide A","volume":"101","author":"P Nagella","year":"2010","journal-title":"Bioresour Technol"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1007\/s11240-010-9799-0","article-title":"Effects of macroelements and nitrogen source on biomass accumulation and withanolide-A production from cell suspension cultures of <italic>Withania somnifera<\/italic> (L.) Dunal","volume":"104","author":"P Nagella","year":"2011","journal-title":"Plant Cell Tissue Organ Cult"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s11816-011-0165-4","article-title":"Biotransformation of withanolides by cell suspension cultures of <italic>Withania somnifera<\/italic> (Dunal.)","volume":"5","author":"F Sabir","year":"2011","journal-title":"Plant Biotech Rep"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1111\/j.1399-3054.1962.tb08052.x","article-title":"A revised medium for rapid growth and bioassays with tobacco tissue cultures","volume":"15","author":"T Murashige","year":"1962","journal-title":"Physiol Plant"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"3480","DOI":"10.1016\/j.procbio.2005.02.025","article-title":"Enhanced production of phenylethanoid glycosides by precursor feeding to cell culture of <italic>Cistanche deserticola<\/italic>","volume":"40","author":"J Ouyang","year":"2005","journal-title":"Process Biochem"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.bej.2006.09.002","article-title":"Improved accumulation of phenylethanoid glycosides by precursor feeding to suspension culture of <italic>Cistanche salsa<\/italic>","volume":"33","author":"JY Liu","year":"2007","journal-title":"Biochem Eng J"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"4609","DOI":"10.1016\/j.biortech.2007.06.061","article-title":"Yield enhancement strategies for artemisinin production by suspension cultures of <italic>Artemisia annua<\/italic>","volume":"99","author":"A Baldi","year":"2008","journal-title":"Bioresour Tech"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.plantsci.2006.08.002","article-title":"Enhanced paclitaxel productivity and release capacity of <italic>Taxus chinensis<\/italic> cell suspension cultures adapted to chitosan","volume":"172","author":"CH Zhang","year":"2007","journal-title":"Plant Sci"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/s11240-011-0014-8","article-title":"The effects of jasmonic acid and methyl jasmonate on rosmarinic acid production in <italic>Mentha<\/italic>\u00d7<italic>piperita<\/italic> cell suspension cultures","volume":"108","author":"J Krzyzanowska","year":"2012","journal-title":"Plant Cell Tiss Organ Cult"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.plantsci.2007.01.006","article-title":"Molecular aspects of the early stages of elicitation of secondary metabolites in plants","volume":"172","author":"A Vasconsuelo","year":"2007","journal-title":"Plant Sci"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.biotechadv.2005.01.003","article-title":"Elicitor signal transduction leading to production of plant secondary metabolites","volume":"23","author":"J Zhao","year":"2005","journal-title":"Biotechnol Adv"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1007\/s00253-010-2443-4","article-title":"Effects of biotic and abiotic elicitors on cell growth and tanshinone accumulation in <italic>Salvia miltiorrhiza<\/italic> cell cultures","volume":"87","author":"JL Zhao","year":"2010","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"1502","DOI":"10.1093\/pcp\/pcf181","article-title":"Biosynthesis of sterols and triterpenes in cell suspension cultures of <italic>Uncaria tomentosa<\/italic>","volume":"43","author":"IJ Flores-Sanchez","year":"2002","journal-title":"Plant Cell Physiol"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1007\/s00299-012-1302-4","article-title":"Withanolide biosynthesis recruits both mevalonate and DOXP pathways of isoprenogenesis in Ashwagandha <italic>Withania somnifera<\/italic> L.(Dunal)","volume":"31","author":"ND Chaurasia","year":"2012","journal-title":"Plant Cell Rep"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1111\/j.1399-3054.2008.01076.x","article-title":"Withanolide A is inherently de novo biosynthesized in roots of the medicinal plant Ashwagandha (<italic>Withania somnifera<\/italic>)","volume":"133","author":"RS Sangwan","year":"2008","journal-title":"Physiol Plant"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"2379","DOI":"10.1007\/s00253-012-4489-y","article-title":"<italic>In vitro<\/italic> propagation and production of cardiotonic glycosides in shoot cultures of <italic>Digitalis purpurea<\/italic> L. by elicitation and precursor feeding","volume":"97","author":"JT Patil","year":"2013","journal-title":"Appl Microbiol Biotechnol"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1007\/s002530000568","article-title":"Effects of stress factors, bioregulators and synthetic precursor on indole alkaloid production in compact callus clusters cultures of <italic>Catharanthus roseus<\/italic>","volume":"55","author":"J Zhao","year":"2001","journal-title":"Appl Microbiol Biotechnol"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0104005","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T17:29:41Z","timestamp":1588958981000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0104005"}},"subtitle":[],"editor":[{"given":"Keith R.","family":"Davis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2014,8,4]]},"references-count":48,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2014,8,4]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0104005","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,8,4]]}}}