{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:14:18Z","timestamp":1787318058895,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cyclophosphamide (CP)\u2010induced hepatotoxic manifestations are major concern for patients undergoing chemotherapy, which often limit its therapeutic utility. Nerolidol (NER) is a natural bioactive molecule having potent gonadoprotective, neuroprotective, and cardioprotective properties but has not been explored for its hepatoprotective effect and underlying mechanism. Therefore, in the current study hepatoprotective potential of nerolidol was studied in CP\u2010induced hepatic oxidative stress, inflammation, apoptosis, and fibrosis via modulation of Nrf2, NF\u2010\u03baB p65, caspase\u20103, TGF\u2010\u03b21, and associated biochemical status in Swiss albino mice. NER (200, 400\u2009mg\/kg, p.o) and fenofibrate (FF) 80\u2009mg\/kg, p.o. were administered from first to fourteenth day and CP was administered at the dose of 200\u2009mg\/kg, i.p on seventh day. On fifteenth day, animals were sacrificed and estimation of oxidative stress, inflammation, apoptosis, fibrosis, histopathology (H E and MT staining), and immunohistochemistry was performed in the liver tissue. Administration of NER effectively normalized the elevated level of hepatic injury markers (alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase), marker of oxidative stress that is, malondialdehyde, inflammatory cytokines (TNF\u2010\u03b1, IL\u20106, IL\u20101\u03b2, and IL\u201010), NF\u2010\u03baB p65, apoptotic marker (cleaved caspase 3) and increased the level of Nrf2 and antioxidant enzymes (superoxide dismutase, CAT, and glutathione). Treatment with NER further reduced the structural damage of hepatocytes and markers of hepatic fibrosis such as TGF\u2010\u03b21, hyaluronic acid, 4\u2010hydroxyproline and collagen\u2010rich stained area, estimated by MT staining. Findings of the current study showed that nerolidol exhibited potent antioxidant, anti\u2010inflammatory, anti\u2010apoptotic, and anti\u2010fibrotic potential and thus acted as hepatoprotective agent. Present study represents novel mechanism of nerolidol against CP\u2010induced hepatotoxicity. However, further studies are needed to use nerolidol as an adjuvant in chemotherapeutically treated patients.<\/jats:p>","DOI":"10.1002\/biof.1679","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T15:08:30Z","timestamp":1600355310000},"page":"963-973","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Nerolidol protects the liver against cyclophosphamide\u2010induced hepatic inflammation, apoptosis, and fibrosis via modulation of Nrf2,\n                    <scp>NF\u2010\u03baB<\/scp>\n                    p65, and caspase\u20103 signaling molecules in Swiss albino mice"],"prefix":"10.1002","volume":"46","author":[{"given":"Ashif","family":"Iqubal","sequence":"first","affiliation":[{"name":"Department of Pharmacology School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2697-7832","authenticated-orcid":false,"given":"Mansoor Ali","family":"Syed","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Jamia Millia Islamia  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Ali","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abul Kalam","family":"Najmi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Mahfuzul","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Biotechnology Jamia Millia Islamia  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2333-1577","authenticated-orcid":false,"given":"Syed Ehtaishamul","family":"Haque","sequence":"additional","affiliation":[{"name":"Department of Pharmacology School of Pharmaceutical Education and Research, Jamia Hamdard  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-80-4-531"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/iju.13474"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00296-018-4189-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs-2019-0093"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.4103\/2008-7802.177898"},{"key":"e_1_2_10_7_1","first-page":"12","article-title":"Molecular mechanism involved in cyclophosphamide\u2010induced cardiotoxicity: Old drug with a new vision","volume":"1","author":"Iqubal A","year":"2018","journal-title":"Life Sci"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22271"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI88881"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhbp.245"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/4016209"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/373295"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-016-0293-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12166"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2019.172666"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2019.116867"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13535"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.4103\/pm.pm_469_17"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2019.07.011"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2018.09.017"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.09.025"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-2242-5"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00795-019-00216-7"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3923\/ijp.2016.644.654"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50018"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12012-014-9247-1"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.06.118"},{"key":"e_1_2_10_29_1","first-page":"265","volume-title":"Extracellular matrix remodeling with focus on biochemical markers in liver fibrosis: Limitations and possibilities, the human gut\u2010liver\u2010Axis in health and disease","author":"Nielsen MJ","year":"2019"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.12.006"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.27656"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1080\/15321810701454649"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1142\/S0192415X15500159"}],"container-title":["BioFactors"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.1679","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/biof.1679","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/biof.1679","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T23:29:20Z","timestamp":1692574160000},"score":1,"resource":{"primary":{"URL":"https:\/\/iubmb.onlinelibrary.wiley.com\/doi\/10.1002\/biof.1679"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,17]]},"references-count":32,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1002\/biof.1679"],"URL":"https:\/\/doi.org\/10.1002\/biof.1679","archive":["Portico"],"relation":{},"ISSN":["0951-6433","1872-8081"],"issn-type":[{"value":"0951-6433","type":"print"},{"value":"1872-8081","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,17]]},"assertion":[{"value":"2020-03-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}