{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T11:41:54Z","timestamp":1788176514807,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"The Italian Ministry of Universities and Research","doi-asserted-by":"publisher","award":["PRIN 20204YRYS5_004"],"award-info":[{"award-number":["PRIN 20204YRYS5_004"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003407","name":"The Italian Ministry of Universities and Research","doi-asserted-by":"publisher","award":["RILO_2022"],"award-info":[{"award-number":["RILO_2022"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["PRIN 20204YRYS5_004"],"award-info":[{"award-number":["PRIN 20204YRYS5_004"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006692","name":"University of Turin","doi-asserted-by":"publisher","award":["RILO_2022"],"award-info":[{"award-number":["RILO_2022"]}],"id":[{"id":"10.13039\/501100006692","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease; however, no specific pharmacological therapy has yet been approved for this condition. Plant-derived extracts can be an important source for the development of new drugs. The aim of this study was to investigate the effects of (E)-\u03b2-caryophyllene (BCP), a phytocannabinoid recently found to be beneficial against metabolic diseases, on HepG2 steatotic hepatocytes. Using a fluorescence-based lipid quantification assay and GC-MS analysis, we show that BCP is able to decrease lipid accumulation in steatotic conditions and to change the typical steatotic lipid profile by primarily reducing saturated fatty acids. By employing specific antagonists, we demonstrate that BCP action is mediated by multiple receptors: CB2 cannabinoid receptor, peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) and \u03b3 (PPAR\u03b3). Interestingly, BCP was able to counteract the increase in CB2 and the reduction in PPAR\u03b1 receptor expression observed in steatotic conditions. Moreover, through immunofluorescence and confocal microscopy, we demonstrate that CB2 receptors are mainly intracellularly localized and that BCP is internalized in HepG2 cells with a maximum peak at 2 h, suggesting a direct interaction with intracellular receptors. The results obtained with BCP in normal and steatotic hepatocytes encourage future applications in the treatment of NAFLD.<\/jats:p>","DOI":"10.3390\/ijms24076060","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T03:50:21Z","timestamp":1679629821000},"page":"6060","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Beta-Caryophyllene Modifies Intracellular Lipid Composition in a Cell Model of Hepatic Steatosis by Acting through CB2 and PPAR Receptors"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4307-8313","authenticated-orcid":false,"given":"Rosaria","family":"Scandiffio","sequence":"first","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"},{"name":"Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15\/a, 10135 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8067-8561","authenticated-orcid":false,"given":"Sara","family":"Bonzano","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"},{"name":"Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4921-1453","authenticated-orcid":false,"given":"Erika","family":"Cottone","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3646-851X","authenticated-orcid":false,"given":"Sujata","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Bossi","sequence":"additional","affiliation":[{"name":"Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15\/a, 10135 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"De Marchis","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"},{"name":"Neuroscience Institute Cavalieri Ottolenghi (NICO), Regione Gonzole 10, Orbassano, 10043 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6814-2353","authenticated-orcid":false,"given":"Massimo E.","family":"Maffei","sequence":"additional","affiliation":[{"name":"Plant Physiology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Quarello 15\/a, 10135 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3746-8542","authenticated-orcid":false,"given":"Patrizia","family":"Bovolin","sequence":"additional","affiliation":[{"name":"Cell Biology Unit, Department of Life Sciences and Systems Biology, University of Turin, Via Accademia Albertina 13, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0140-6736(20)32511-3","article-title":"Non-Alcoholic Fatty Liver Disease","volume":"397","author":"Powell","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1038\/s41591-018-0104-9","article-title":"Mechanisms of NAFLD Development and Therapeutic Strategies","volume":"24","author":"Friedman","year":"2018","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Mantovani, A., and Dalbeni, A. (2021). Treatments for NAFLD: State of Art. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22052350"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Geethangili, M., Lin, C.-W., Mersmann, H.J., and Ding, S.-T. (2021). Methyl Brevifolincarboxylate Attenuates Free Fatty Acid-Induced Lipid Metabolism and Inflammation in Hepatocytes through AMPK\/NF-\u039aB Signaling Pathway. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms221810062"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.freeradbiomed.2019.06.019","article-title":"Berberine Attenuates Nonalcoholic Hepatic Steatosis through the AMPK-SREBP-1c-SCD1 Pathway","volume":"141","author":"Zhu","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Maffei, M.E. (2020). Plant Natural Sources of the Endocannabinoid (E)-\u03b2-Caryophyllene: A Systematic Quantitative Analysis of Published Literature. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21186540"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Scandiffio, R., Geddo, F., Cottone, E., Querio, G., Antoniotti, S., Gallo, M.P., Maffei, M.E., and Bovolin, P. (2020). Protective Effects of (E)-\u03b2-Caryophyllene (BCP) in Chronic Inflammation. Nutrients, 12.","DOI":"10.3390\/nu12113273"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mannino, F., Pallio, G., Corsaro, R., Minutoli, L., Altavilla, D., Vermiglio, G., Allegra, A., Eid, A.H., Bitto, A., and Squadrito, F. (2021). Beta-Caryophyllene Exhibits Anti-Proliferative Effects through Apoptosis Induction and Cell Cycle Modulation in Multiple Myeloma Cells. Cancers, 13.","DOI":"10.3390\/cancers13225741"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"175181","DOI":"10.1016\/j.ejphar.2022.175181","article-title":"\u03b2-Caryophyllene Modulates B-Cell Lymphoma Gene-2 Family Genes and Inhibits the Intrinsic Pathway of Apoptosis in Isoproterenol-Induced Myocardial Infarcted Rats; A Molecular Mechanism","volume":"932","author":"Yovas","year":"2022","journal-title":"Eur. J. Pharmacol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Picciolo, G., Pallio, G., Altavilla, D., Vaccaro, M., Oteri, G., Irrera, N., and Squadrito, F. (2020). \u03b2-Caryophyllene Reduces the Inflammatory Phenotype of Periodontal Cells by Targeting CB2 Receptors. Biomedicines, 8.","DOI":"10.3390\/biomedicines8060164"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9099","DOI":"10.1073\/pnas.0803601105","article-title":"Beta-Caryophyllene Is a Dietary Cannabinoid","volume":"105","author":"Gertsch","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Geddo, F., Antoniotti, S., Querio, G., Salaroglio, I.C., Costamagna, C., Riganti, C., and Gallo, M.P. (2021). Plant-Derived Trans-\u03b2-Caryophyllene Boosts Glucose Metabolism and ATP Synthesis in Skeletal Muscle Cells through Cannabinoid Type 2 Receptor Stimulation. Nutrients, 13.","DOI":"10.3390\/nu13030916"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3168","DOI":"10.1016\/j.bmcl.2014.04.112","article-title":"Trans-Caryophyllene Is a Natural Agonistic Ligand for Peroxisome Proliferator-Activated Receptor-\u03b1","volume":"24","author":"Wu","year":"2014","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Irrera, N., D\u2019ascola, A., Pallio, G., Bitto, A., Mazzon, E., Mannino, F., Squadrito, V., Arcoraci, V., Minutoli, L., and Campo, G.M. (2019). \u03b2-Caryophyllene Mitigates Collagen Antibody Induced Arthritis (CAIA) in Mice Through a Cross-Talk between CB2 and PPAR-\u03b3 Receptors. Biomolecules, 9.","DOI":"10.3390\/biom9080326"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Charytoniuk, T., Zywno, H., Berk, K., Bzdega, W., Kolakowski, A., Chabowski, A., and Konstantynowicz-Nowicka, K. (2022). The Endocannabinoid System and Physical Activity\u2014A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23063083"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lowe, H., Toyang, N., Steele, B., Bryant, J., and Ngwa, W. (2021). The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179472"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Machado, K.d.C., Islam, M.T., Ali, E.S., Rouf, R., Uddin, S.J., Dev, S., Shilpi, J.A., Shill, M.C., Reza, H.M., and Das, A.K. (2018). A Systematic Review on the Neuroprotective Perspectives of Beta-Caryophyllene, John Wiley and Sons Ltd.","DOI":"10.1002\/ptr.6199"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.phrs.2019.02.029","article-title":"Role of Endocannabinoid System in Dopamine Signalling within the Reward Circuits Affected by Chronic Pain","volume":"143","author":"Mlost","year":"2019","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). \u03b2-Caryophyllene: A Sesquiterpene with Countless Biological Properties. Appl. Sci., 9.","DOI":"10.3390\/app9245420"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"166097","DOI":"10.1016\/j.bbadis.2021.166097","article-title":"PPARs in Liver Physiology","volume":"1867","author":"Berthier","year":"2021","journal-title":"Biochim. Biophys. Acta Mol. Basis Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2736","DOI":"10.1111\/jcmm.15028","article-title":"Therapeutic Potential of PPAR\u03b3 Natural Agonists in Liver Diseases","volume":"24","author":"Wu","year":"2020","journal-title":"J. Cell. Mol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.cbi.2018.10.010","article-title":"Beta-Caryophyllene Protects against Diet-Induced Dyslipidemia and Vascular Inflammation in Rats: Involvement of CB2 and PPAR-\u03b3 Receptors","volume":"297","author":"Youssef","year":"2019","journal-title":"Chem. -Biol. Interact."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.cbi.2006.11.004","article-title":"A Human Hepatocellular in Vitro Model to Investigate Steatosis","volume":"165","author":"Donato","year":"2007","journal-title":"Chem.-Biol. Interact."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2228","DOI":"10.1002\/mnfr.201600197","article-title":"\u03b2-Caryophyllene Attenuates Palmitate-Induced Lipid Accumulation through AMPK Signaling by Activating CB2 Receptor in Human HepG2 Hepatocytes","volume":"60","author":"Kamikubo","year":"2016","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.ebiom.2017.03.021","article-title":"Piperine Attenuates Pathological Cardiac Fibrosis Via PPAR-\u03b3\/AKT Pathways","volume":"18","author":"Ma","year":"2017","journal-title":"EBioMedicine"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1038\/s41573-020-00114-z","article-title":"Natural Products in Drug Discovery: Advances and Opportunities","volume":"20","author":"Atanasov","year":"2021","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Saraswathi, V., Kumar, N., Ai, W., Gopal, T., Bhatt, S., Harris, E.N., Talmon, G.A., and Desouza, C.V. (2022). Myristic Acid Supplementation Aggravates High Fat Diet-Induced Adipose Inflammation and Systemic Insulin Resistance in Mice. Biomolecules, 12.","DOI":"10.3390\/biom12060739"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2275","DOI":"10.2337\/db20-1079","article-title":"Inhibition of LncRNA TCONS_00077866 Ameliorates the High Stearic Acid Diet-Induced Mouse Pancreatic \u03b2-Cell Inflammatory Response by Increasing MiR-297b-5p to Downregulate SAA3 Expression","volume":"70","author":"Lu","year":"2021","journal-title":"Diabetes"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Sim\u00e3o, J.J., Cruz, M.M., Abdala, F.M., Bolsoni-Lopes, A., Armelin-Correa, L., and Alonso-Vale, M.I.C. (2022). Palmitoleic Acid Acts on Adipose-Derived Stromal Cells and Promotes Anti-Hypertrophic and Anti-Inflammatory Effects in Obese Mice. Pharmaceuticals, 15.","DOI":"10.3390\/ph15101194"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1136\/gutjnl-2015-310798","article-title":"Liver PPAR\u03b1 Is Crucial for Whole-Body Fatty Acid Homeostasis and Is Protective against NAFLD","volume":"65","author":"Montagner","year":"2016","journal-title":"Gut"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1074\/jbc.M210062200","article-title":"Adipocyte-Specific Gene Expression and Adipogenic Steatosis in the Mouse Liver Due to Peroxisome Proliferator-Activated Receptor Gamma1 (PPARgamma1) Overexpression","volume":"278","author":"Yu","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_32","first-page":"159246","article-title":"A Diet-Independent Zebrafish Model for NAFLD Recapitulates Patient Lipid Profiles and Offers a System for Small Molecule Screening","volume":"1868","author":"Singh","year":"2023","journal-title":"Biochim. et Biophys. Acta (BBA)\u2014Mol. Cell. Biol. Lipids"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Wang, Y., Nakajima, T., Gonzalez, F.J., and Tanaka, N. (2020). PPARs as Metabolic Regulators in the Liver: Lessons from Liver-Specific PPAR-Null Mice. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21062061"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"9555","DOI":"10.1039\/C8RA10178G","article-title":"GVS-12 Attenuates Non-Alcoholic Steatohepatitis by Suppressing Inflammatory Responses via PPAR\u03b3\/STAT3 Signaling Pathways","volume":"9","author":"Wang","year":"2019","journal-title":"RSC Adv."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1084","DOI":"10.1111\/liv.13634","article-title":"Dual PPAR\u03b1\/\u03b3 Agonist Saroglitazar Improves Liver Histopathology and Biochemistry in Experimental NASH Models","volume":"38","author":"Jain","year":"2018","journal-title":"Liver Int."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/s41575-020-00366-5","article-title":"Nonalcoholic Steatohepatitis: The Role of Peroxisome Proliferator-Activated Receptors","volume":"18","author":"Francque","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000362689","article-title":"\u03b2-Caryophyllene Ameliorates the Alzheimer-like Phenotype in APP\/PS1 Mice through CB2 Receptor Activation and the PPAR\u03b3 Pathway","volume":"94","author":"Cheng","year":"2014","journal-title":"Pharmacology"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1038\/s41386-020-00885-4","article-title":"Beta-Caryophyllene Inhibits Cocaine Addiction-Related Behavior by Activation of PPAR\u03b1 and PPAR\u03b3: Repurposing a FDA-Approved Food Additive for Cocaine Use Disorder","volume":"46","author":"Galaj","year":"2021","journal-title":"Neuropsychopharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/bs.podrm.2020.07.005","article-title":"Chapter Six\u2014Validation of in-Vitro Bioassay Methods: Application in Herbal Drug Research","volume":"Volume 46","year":"2021","journal-title":"Profiles of Drug Substances, Excipients and Related Methodology"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Songtrai, S., Pratchayasakul, W., Arunsak, B., Chunchai, T., Kongkaew, A., Chattipakorn, N., Chattipakorn, S.C., and Kaewsuwan, S. (2022). Cyclosorus Terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats. Nutrients, 14.","DOI":"10.3390\/nu14224895"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1111\/apt.12673","article-title":"Review Article: The Endocannabinoid System in Liver Disease, a Potential Therapeutic Target","volume":"39","author":"Basu","year":"2014","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Mboumba Bouassa, R.-S., Sebastiani, G., Di Marzo, V., Jenabian, M.-A., and Costiniuk, C.T. (2022). Cannabinoids and Chronic Liver Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23169423"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1242\/dev.121731","article-title":"Cannabinoid Receptor Signaling Regulates Liver Development and Metabolism","volume":"143","author":"Liu","year":"2016","journal-title":"Development"},{"key":"ref_44","first-page":"169","article-title":"The Effect of CB1 Antagonism on Hepatic Oxidative\/Nitrosative Stress and Inflammation in Nonalcoholic Fatty Liver Disease","volume":"28","year":"2021","journal-title":"Curr. Med. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1053\/j.gastro.2004.12.050","article-title":"Antifibrogenic Role of the Cannabinoid Receptor CB2 in the Liver","volume":"128","author":"Julien","year":"2005","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1482","DOI":"10.1111\/j.1478-3231.2010.02298.x","article-title":"Cannabinoid Receptor 1 and 2 Agonists Increase Lipid Accumulation in Hepatocytes","volume":"30","author":"Spahr","year":"2010","journal-title":"Liver Int."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Deveaux, V., Cadoudal, T., Ichigotani, Y., Teixeira-Clerc, F., Louvet, A., Manin, S., Nhieu, J.T.-V., Belot, M.P., Zimmer, A., and Even, P. (2009). Cannabinoid CB2 Receptor Potentiates Obesity-Associated Inflammation, Insulin Resistance and Hepatic Steatosis. PLoS ONE, 4.","DOI":"10.1371\/journal.pone.0005844"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Bazwinsky-Wutschke, I., Zipprich, A., and Dehghani, F. (2019). Endocannabinoid System in Hepatic Glucose Metabolism, Fatty Liver Disease, and Cirrhosis. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20102516"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1298","DOI":"10.1111\/liv.12263","article-title":"The Endocannabinoid System in Advanced Liver Cirrhosis: Pathophysiological Implication and Future Perspectives","volume":"33","author":"Baldassarre","year":"2013","journal-title":"Liver Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3309","DOI":"10.1111\/bph.15051","article-title":"Differential Hepatoprotective Role of the Cannabinoid CB1 and CB2 Receptors in Paracetamol-Induced Liver Injury","volume":"177","author":"Rivera","year":"2020","journal-title":"Br. J. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1111\/j.1478-3231.2006.01401.x","article-title":"Endocannabinoid Receptor CB2 in Nonalcoholic Fatty Liver Disease","volume":"27","author":"Uribe","year":"2007","journal-title":"Liver Int."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1007\/s11481-017-9744-7","article-title":"Regulation of Cell Surface CB2 Receptor during Human B Cell Activation and Differentiation","volume":"12","author":"Castaneda","year":"2017","journal-title":"J. Neuroimmune Pharm."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Geddo, F., Scandiffio, R., Antoniotti, S., Cottone, E., Querio, G., Maffei, M.E., Bovolin, P., and Gallo, M.P. (2019). Pipenig\u00ae-FL, a Fluid Extract of Black Pepper (Piper Nigrum L.) with a High Standardized Content of Trans-\u03b2-Caryophyllene, Reduces Lipid Accumulation in 3T3-L1 Preadipocytes and Improves Glucose Uptake in C2C12 Myotubes. Nutrients, 11.","DOI":"10.3390\/nu11112788"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/bs.apha.2021.10.006","article-title":"Receptor Mechanisms Underlying the CNS Effects of Cannabinoids: CB1 Receptor and Beyond","volume":"93","author":"Hempel","year":"2022","journal-title":"Adv. Pharm."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3440","DOI":"10.2174\/1381612824666180912151412","article-title":"\u03b2-Caryophyllene Delivery Systems: Enhancing the Oral Pharmacokinetic and Stability","volume":"24","author":"Santos","year":"2018","journal-title":"Curr. Pharm. Des."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"M\u00f6dinger, Y., Knaub, K., Dharsono, T., Wacker, R., Meyrat, R., Land, M.H., Petraglia, A.L., and Sch\u00f6n, C. (2022). Enhanced Oral Bioavailability of \u03b2-Caryophyllene in Healthy Subjects Using the VESIsorb\u00ae Formulation Technology, a Novel Self-Emulsifying Drug Delivery System (SEDDS). Molecules, 27.","DOI":"10.3390\/molecules27092860"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6060\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:01:26Z","timestamp":1760122886000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/7\/6060"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":56,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,4]]}},"alternative-id":["ijms24076060"],"URL":"https:\/\/doi.org\/10.3390\/ijms24076060","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]}}}