{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T14:07:11Z","timestamp":1791986831020,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2014,4,6]],"date-time":"2014-04-06T00:00:00Z","timestamp":1396742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81173462"],"award-info":[{"award-number":["81173462"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Open Research Fund of State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Phytotherapy Research"],"published-print":{"date-parts":[[2014,10]]},"abstract":"<jats:p>Hypertrophic scarring is characterized by collagen overproduction and excessive deposition of extracellular matrix. No consensus arises currently about the best therapeutics to produce complete and permanent improvement of scars with few side effects. In the present study, the mechanism of oleanolic acid (OA)\u2010induced apoptosis in hypertrophic scar fibroblasts (HSFs) was investigated for the first time. OA activated the protein phosphorylation of p38 MAPK and JNK but not ERK. OA did not antagonize the inhibitory effects of SB203580 on p38 MAPK pathway activity but sharply enhanced JNK phosphorylation when HSFs were pretreated with SB203580. Similarly, the inhibition of JNK signal pathway activation by pretreatment with SP600125 facilitated the protein phosphorylation of p38 MAPK caused by OA. Inhibition of p38 MAPK and\/or JNK by inhibitors significantly enhanced cell viability and OA only partially depressed the increased cell viability. Moreover, OA increased Bax translocation, MMP loss, mitochondrial cytochrome c and AIF release, Bax and caspase\u20103 protein expression and the ratio of Bax to Bcl\u20102, decreased Bcl\u20102 protein expression, and elevated the mRNA expression of Apaf\u20101, caspase\u20109, and capase\u20103. These results suggest that OA elicits apoptosis through triggering of p38 MAPK and JNK signaling and activation of the mitochondrial death pathway. OA might be a good and useful natural drug against hypertrophic scars. Copyright \u00a9 2014 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/ptr.5150","type":"journal-article","created":{"date-parts":[[2014,4,7]],"date-time":"2014-04-07T03:32:50Z","timestamp":1396841570000},"page":"1468-1478","source":"Crossref","is-referenced-by-count":28,"title":["Triggering of p38 MAPK and JNK Signaling is Important for Oleanolic Acid\u2010Induced Apoptosis via the Mitochondrial Death Pathway in Hypertrophic Scar Fibroblasts"],"prefix":"10.1002","volume":"28","author":[{"given":"Jian\u2010Yu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"},{"name":"Department of Pharmaceutical Botany, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Botany, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Botany, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"Pharmaceutical Analysis Center, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu\u2010Ping","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, School of Pharmacy Second Military Medical University  Shanghai 200433 PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,4,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.0040234"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401166"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2008.07.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00403-006-0651-7"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2008.03.011"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4020-6554-5_3"},{"key":"e_1_2_7_8_1","first-page":"379","article-title":"Characteristics of P38 mitogen\u2010activated protein kinase and c\u2010Jun expression in hypertrophic scar and their effects on scar formation","volume":"17","author":"Chen W","year":"2003","journal-title":"Chinese J Repar Reconstr Surg"},{"key":"e_1_2_7_9_1","first-page":"188","article-title":"Connective tissue growth factor stimulates hypertrophic scar derived fibroblasts primarily by ERK\/MAPK signal pathway","volume":"15","author":"Dai X","year":"2009","journal-title":"Chin J Med Aesth Cosmet"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.4744"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2008.10.001"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006527-200604000-00010"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.03.016"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7859rev"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12272-011-0817-5"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0111-7"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.24158"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/18715206113139990144"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/BCR.0B013E318031A151"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar2567"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006534-199910000-00031"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phytochem.2011.12.022"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2007.02636.x"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejs.6161681002"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.burns.2005.08.004"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2007.11.022"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2008.12.028"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mito.2010.08.005"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(97)80541-2"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.4757"},{"key":"e_1_2_7_31_1","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1002\/ptr.4616","article-title":"3\u2010O\u2010acetyloleanolic acid induces apoptosis in human colon carcinoma HCT\u2010116 cells","volume":"26","author":"Yoo KH","year":"2012","journal-title":"Phytother Res"},{"key":"e_1_2_7_32_1","first-page":"271","article-title":"Silencing of insulin receptor substrate\u20101 increases cell death in retinal M\u00fcller cells","volume":"18","author":"Walker RJ","year":"2012","journal-title":"Mol Vis"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-genet-102108-134850"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2010.01.034"},{"key":"e_1_2_7_35_1","first-page":"29","article-title":"Clinical observation of Ba\u2010Hen\u2010Zhi\u2010Yang\u2010Ruan\u2010Hua ointment in the treatment of hypertrophic scars","volume":"22","author":"Wei JJ","year":"1981","journal-title":"J tradit Chin Med"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2230.2010.04012.x"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2010.499517"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2008.06.035"},{"key":"e_1_2_7_39_1","first-page":"46","article-title":"Bao WH. The role of cell pathway in apoptosis of fibroblasts from proliferative scar induced by steroid or IFN","volume":"24","author":"Xu SJ","year":"2008","journal-title":"Chinese J Plast Surg"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M411902200"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.maturitas.2008.09.023"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0046574"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/837581"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.3736\/jintegrmed2013035"}],"container-title":["Phytotherapy Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.5150","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fptr.5150","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ptr.5150","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T14:32:47Z","timestamp":1696516367000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ptr.5150"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,4,6]]},"references-count":43,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2014,10]]}},"alternative-id":["10.1002\/ptr.5150"],"URL":"https:\/\/doi.org\/10.1002\/ptr.5150","archive":["Portico"],"relation":{},"ISSN":["0951-418X","1099-1573"],"issn-type":[{"value":"0951-418X","type":"print"},{"value":"1099-1573","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,4,6]]}}}