{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:47:22Z","timestamp":1792133242259,"version":"4.4.0"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pharmacology Res &amp;amp; Perspec"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\u03b2\u2010Caryophyllene (BCP), a selective agonist of cannabinoid receptor type 2 (CB2), has garnered attention as a promising nutraceutical agent for modulating organ damage. The current study aimed at evaluating the pharmacological role of BCP in Thioacetamide (TAA)\u2010induced liver fibrosis, with particular attention to the involvement of CB2\u2010mediated signaling. Following the induction of fibrosis by TAA, rats were treated with BCP for 6 weeks. In a separate group, AM630, a selective CB2 receptor antagonist, was co\u2010administered with BCP in order to validate CB2\u2010dependent actions. TAA administration triggered significant hepatocellular injury. In addition, TAA activated necroptotic cellular death, shown in the upregulated RIPK1\/RIPK3\/p\u2010MLKL expression. Growth factors' signaling was disrupted and liver regeneration was impaired. On the contrary, BCP treatment ameliorated oxidative stress, mitigated inflammation, and decreased hepatic stellate cells' activation. This was accompanied by reduced collagen deposition and attenuated fibrosis. BCP markedly abrogated necroptosis and decreased the stimulation of fibrogenic and angiogenic signaling. Additionally, BCP potentiated hepatocytes' survival and restored hepatic regenerative capacity. AM630 co\u2010treatment abolished BCP's protective effects, confirming the CB2 receptors\u2010dependent effects. Given findings highlight BCP as a potential therapeutic agent for liver fibrosis and delineate endocannabinoid system's role in modulating organ fibrosis.<\/jats:p>","DOI":"10.1002\/prp2.70311","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:02:22Z","timestamp":1788757342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["\u03b2\u2010Caryophyllene Mitigates Thioacetamide\u2010Induced Liver Fibrosis Through\n                    <scp>CB2<\/scp>\n                    \u2010Mediated Suppression of Necroptosis: A Therapeutic Investigation"],"prefix":"10.1002","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8184-8756","authenticated-orcid":false,"given":"Lujain Bader","family":"Eddin","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seenipandi","family":"Arunachalam","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4166-1847","authenticated-orcid":false,"given":"Loay","family":"Lubbad","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4356-0863","authenticated-orcid":false,"given":"Fayez T.","family":"Hammad","sequence":"additional","affiliation":[{"name":"Department of Surgery, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1439-1562","authenticated-orcid":false,"given":"Ernest","family":"Adeghate","sequence":"additional","affiliation":[{"name":"Department of Anatomy, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4802-500X","authenticated-orcid":false,"given":"Sandeep","family":"Subramanya","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7801-2966","authenticated-orcid":false,"given":"Shreesh","family":"Ojha","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, College of Medicine and Health Sciences United Arab Emirates University  Al Ain UAE"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,6]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c120009"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci24282"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2019.4244"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1042\/cs20140732"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.11.008"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102020\u2010321767"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.04.051"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.14768"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.105.005520"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476\u20105381.2011.01238.x"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0803601105"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750\u20103841.2009.01277.x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu12113273"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.seizure.2018.03.009"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.01.046"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2016.01.029"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13722"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3164\/jcbn.17\u20103"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.38"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40139\u2010015\u20100089\u20108"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986\u2010021\u201000589\u20106"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.08.021"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1293\/tox.2017\u20100018"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26178493"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2024.115069"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575\u2010023\u201000807\u2010x"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2014.10.056"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.783886"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12091653"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1609711"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2020.106556"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jafc.4c03239"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118253"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i35.12526"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2021.07.034"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40001\u2010025\u201002948\u2010y"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900752R"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1267996"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/187152709789824615"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27010064"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018\u2010011\u20100757\u20108"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14329"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2017.7641"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43152\u2010020\u201000013\u2010w"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1177\/0960327120947453"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2008.91"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25020810"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.808855"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120036"},{"key":"e_1_2_10_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25625"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.052"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms26094430"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26761"}],"container-title":["Pharmacology Research &amp; Perspectives"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70311","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/prp2.70311","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/prp2.70311","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T06:14:49Z","timestamp":1792131289000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1002\/prp2.70311"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,6]]},"references-count":53,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/prp2.70311"],"URL":"https:\/\/doi.org\/10.1002\/prp2.70311","archive":["Portico"],"relation":{},"ISSN":["2052-1707","2052-1707"],"issn-type":[{"value":"2052-1707","type":"print"},{"value":"2052-1707","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,6]]},"assertion":[{"value":"2026-04-29","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-06","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70311"}}