{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T06:54:28Z","timestamp":1792306468074,"version":"4.4.0"},"reference-count":98,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,2,4]],"date-time":"2024-02-04T00:00:00Z","timestamp":1707004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Research and Innovation Fund (NSRF)"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application.<\/jats:p>","DOI":"10.3390\/molecules29030713","type":"journal-article","created":{"date-parts":[[2024,2,6]],"date-time":"2024-02-06T05:36:43Z","timestamp":1707197803000},"page":"713","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Bergaptol, a Major Furocoumarin in Citrus: Pharmacological Properties and Toxicity"],"prefix":"10.3390","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8104-722X","authenticated-orcid":false,"given":"Pakkapong","family":"Phucharoenrak","sequence":"first","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6739-6295","authenticated-orcid":false,"given":"Dunyaporn","family":"Trachootham","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Mahidol University, Nakhon Pathom 73170, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1111\/j.1365-313X.2008.03568.x","article-title":"Scopoletin is biosynthesized via ortho-hydroxylation of feruloyl CoA by a 2-oxoglutarate-dependent dioxygenase in Arabidopsis thaliana","volume":"55","author":"Kai","year":"2008","journal-title":"Plant J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1111\/j.1365-313X.2011.04879.x","article-title":"A 2-oxoglutarate-dependent dioxygenase from Ruta graveolens L. exhibits p-coumaroyl CoA 2\u2032-hydroxylase activity (C2\u2032H): A missing step in the synthesis of umbelliferone in plants","volume":"70","author":"Vialart","year":"2012","journal-title":"Plant J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1126\/science.137.3534.977","article-title":"Biosynthesis of Coumarin and Herniarin in Lavender","volume":"137","author":"Brown","year":"1962","journal-title":"Science"},{"key":"ref_4","first-page":"223","article-title":"Umbelliferone: Sources, chemistry and bioactivities review","volume":"55","author":"Mazimba","year":"2017","journal-title":"Bull. Fac. Pharm. Cairo Univ."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1432-1033.1988.tb13800.x","article-title":"Elicitor-induced biosynthesis of psoralens in Ammi majus L. suspension cultures","volume":"171","author":"Hamerski","year":"1988","journal-title":"Eur. J. Biochem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1492","DOI":"10.1007\/s40242-022-2089-7","article-title":"A New Approach to the Synthesis of Bergapten","volume":"38","author":"Cai","year":"2022","journal-title":"Chem. Res. Chin. Univ."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1002\/jlcr.3172","article-title":"Synthesis of [7-14C]bergapten","volume":"57","author":"Filer","year":"2014","journal-title":"J. Label. Compd. Radiopharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1039\/b601096b","article-title":"Design, synthesis and evaluation of furanocoumarin monomers as inhibitors of CYP3A4","volume":"4","author":"Row","year":"2006","journal-title":"Org. Biomol. Chem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1248\/bpb.29.2274","article-title":"The Use of Heat Treatment to Eliminate Drug Interactions Due to Grapefruit Juice","volume":"29","author":"Uesawa","year":"2006","journal-title":"Biol. Pharm. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"D622","DOI":"10.1093\/nar\/gkab1062","article-title":"HMDB 5.0: The Human Metabolome Database for 2022","volume":"50","author":"Wishart","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Duke, J.A. (2001). Handbook of Medicinal Herbs: Herbal Reference Library, Taylor & Francis.","DOI":"10.1201\/9781420040463"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1021\/cr60113a001","article-title":"The Chemistry of Coumarins","volume":"36","author":"Sethna","year":"1945","journal-title":"Chem. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1021\/ja01570a049","article-title":"Chemical Composition of Lemon Oil. I. Isolation of a Series of Substituted Coumarins","volume":"79","author":"Stanley","year":"1957","journal-title":"J. Am. Chem. Soc."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Phucharoenrak, P., Muangnoi, C., and Trachootham, D. (2023). Metabolomic Analysis of Phytochemical Compounds from Ethanolic Extract of Lime (Citrus aurantifolia) Peel and Its Anti-Cancer Effects against Human Hepatocellular Carcinoma Cells. Molecules, 28.","DOI":"10.3390\/molecules28072965"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.jfda.2016.11.008","article-title":"Chemistry and health effects of furanocoumarins in grapefruit","volume":"25","author":"Hung","year":"2017","journal-title":"J. Food Drug Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1016\/j.bmcl.2012.01.081","article-title":"Biotransformations of 6\u2032,7\u2032-dihydroxybergamottin and 6\u2032,7\u2032-epoxybergamottin by the citrus-pathogenic fungi diminish cytochrome P450 3A4 inhibitory activity","volume":"22","author":"Myung","year":"2012","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"ref_17","unstructured":"CaymanChemical (2023, October 31). Product Information: Bergaptol. Available online: https:\/\/www.caymanchem.com\/product\/38742."},{"key":"ref_18","unstructured":"ChemSpider (2023, August 11). Bergaptol. Available online: http:\/\/www.chemspider.com\/Chemical-Structure.4444066.html."},{"key":"ref_19","unstructured":"SelleckChemical (2023, October 31). Bergaptol: Technical Data. Available online: https:\/\/www.selleckchem.com\/datasheet\/bergaptol-S944200-DataSheet.html."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"152","DOI":"10.3390\/encyclopedia1010016","article-title":"Bergamot Oil: Botany, Production, Pharmacology","volume":"1","author":"Valussi","year":"2021","journal-title":"Encyclopedia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.jchromb.2017.06.020","article-title":"Simultaneous assessment of absorption characteristics of coumarins from Angelicae Pubescentis Radix: In vitro transport across Caco-2 cell and in vivo pharmacokinetics in rats after oral administration","volume":"1060","author":"Yang","year":"2017","journal-title":"J. Chromatogr. B"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1021\/acs.jafc.7b00317","article-title":"Furocoumarin Kinetics in Plasma and Urine of Healthy Adults Following Consumption of Grapefruit (Citrus paradisi Macf.) and Grapefruit Juice","volume":"65","author":"Melough","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/s00253-007-1314-0","article-title":"Aspergillus niger metabolism of citrus furanocoumarin inhibitors of human cytochrome P450 3A4","volume":"78","author":"Myung","year":"2008","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3224","DOI":"10.1016\/j.fct.2011.09.005","article-title":"Major furocoumarins in grapefruit juice I: Levels and urinary metabolite(s)","volume":"49","author":"Messer","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2018","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cell.2010.02.029","article-title":"Nonresolving inflammation","volume":"140","author":"Nathan","year":"2010","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.coi.2014.03.007","article-title":"Inflammation, ageing and chronic disease","volume":"29","author":"Pawelec","year":"2014","journal-title":"Curr. Opin. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1021\/tx900163h","article-title":"Notopterygium forbesii Boiss Extract and Its Active Constituent Phenethyl Ferulate Attenuate Pro-Inflammatory Responses to Lipopolysaccharide in RAW 264.7 Macrophages. A \u201cProtective\u201d Role for Oxidative Stress?","volume":"22","author":"Tang","year":"2009","journal-title":"Chem. Res. Toxicol."},{"key":"ref_29","unstructured":"Mandal, S.C., Nayak, A.K., and Dhara, A.K. (2022). Herbal Biomolecules in Healthcare Applications, Academic Press."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1002\/ptr.5490","article-title":"Anti-inflammatory Activity of Constituents Isolated from Aerial Part of Angelica acutiloba Kitagawa","volume":"29","author":"Uto","year":"2015","journal-title":"Phytother. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4915","DOI":"10.1039\/C9FO00255C","article-title":"Bergaptol from blossoms of Citrus aurantium L. var. amara Engl inhibits LPS-induced inflammatory responses and ox-LDL-induced lipid deposition","volume":"11","author":"Shen","year":"2020","journal-title":"Food Funct."},{"key":"ref_32","unstructured":"Bruno, M.A., Mosher, T.J., and Gold, G.E. (2009). Arthritis in Color, W.B. Saunders."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.2174\/1381612033453749","article-title":"Anti-inflammatory actions of the heme oxygenase-1 pathway","volume":"9","author":"Alcaraz","year":"2003","journal-title":"Curr. Pharm. Des."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Lee, Y., and Hyun, C.-G. (2022). Anti-Inflammatory Effects of Psoralen Derivatives on RAW264.7 Cells via Regulation of the NF-\u03baB and MAPK Signaling Pathways. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23105813"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"6199","DOI":"10.2147\/JIR.S383853","article-title":"Bergaptol Alleviates LPS-Induced Neuroinflammation, Neurological Damage and Cognitive Impairment via Regulating the JAK2\/STAT3\/p65 Pathway","volume":"15","author":"Wu","year":"2022","journal-title":"J. Inflamm. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"3684","DOI":"10.1016\/j.bmc.2007.03.047","article-title":"Radical scavenging and cytochrome P450 3A4 inhibitory activity of bergaptol and geranylcoumarin from grapefruit","volume":"15","author":"Girennavar","year":"2007","journal-title":"Bioorganic Med. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Milanovi\u0107, \u017d., Antonijevi\u0107, M., Jovanovi\u0107, J.\u0110., Avdovi\u0107, E., Milenkovi\u0107, D., and Markovi\u0107, Z. (2021). Influence of Nonpolar Medium on Antioxidant Capacity of Bergaptol and Xanthotoxol\u2014Kinetic DFT Study. Chem. Proc., 3.","DOI":"10.3390\/ecsoc-24-08100"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"7119","DOI":"10.1021\/acsomega.1c00120","article-title":"Antioxidant Behavior Affected by Polarity in the Olive Oil: Experimental and Molecular Simulation Investigations","volume":"6","author":"Tang","year":"2021","journal-title":"ACS Omega"},{"key":"ref_40","first-page":"71","article-title":"Comparative Antiradical Activity and Molecular Docking Study of Bergaptol and Xanthotoxol","volume":"13","year":"2020","journal-title":"J. Serb. Soc. Comput."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"I6","DOI":"10.1002\/clc.4960161304","article-title":"Oxidized LDL and antioxidants","volume":"16","author":"Jialal","year":"1993","journal-title":"Clin. Cardiol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"153","DOI":"10.5530\/pres.14.2.22","article-title":"In-vitro Antioxidant and Anti-inflammatory Potential of Ficus infectoria Fruits","volume":"14","author":"Shreya","year":"2022","journal-title":"harmacognosy Res."},{"key":"ref_43","first-page":"1753","article-title":"Chemical constituents and antioxidant activity of Citrus paradisi (star-ruby red grapefruit) and Citrus sinensis (blood sweet orange) Egyptian cultivars","volume":"16","author":"Mohamed","year":"2004","journal-title":"Asian J. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Baron, G., Altomare, A., Mol, M., Garcia, J.L., Correa, C., Raucci, A., Mancinelli, L., Mazzotta, S., Fumagalli, L., and Trunfio, G. (2021). Analytical Profile and Antioxidant and Anti-Inflammatory Activities of the Enriched Polyphenol Fractions Isolated from Bergamot Fruit and Leave. Antioxidants, 10.","DOI":"10.3390\/antiox10020141"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"689094","DOI":"10.3389\/fnut.2021.689094","article-title":"Effects of Cold-Pressing and Hydrodistillation on the Active Non-volatile Components in Lemon Essential Oil and the Effects of the Resulting Oils on Aging-Related Oxidative Stress in Mice","volume":"8","author":"Li","year":"2021","journal-title":"Front. Nutr."},{"key":"ref_46","unstructured":"World Cancer Research Fund International (2023, September 05). Worldwide Cancer Data. Available online: https:\/\/www.wcrf.org\/cancer-trends\/worldwide-cancer-data\/#:~:text=Find%20information%20about%20world%20cancer,and%208.8%20million%20in%20women."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Hashem, S., Ali, T.A., Akhtar, S., Nisar, S., Sageena, G., Ali, S., Al-Mannai, S., Therachiyil, L., Mir, R., and Elfaki, I. (2022). Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents. Biomed. Pharmacother., 150.","DOI":"10.1016\/j.biopha.2022.113054"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.jff.2015.11.018","article-title":"Coumarins from the roots of Angelica dahurica with antioxidant and antiproliferative activities","volume":"20","author":"Bai","year":"2016","journal-title":"J. Funct. Foods"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"489","DOI":"10.3329\/bjp.v11i2.24644","article-title":"Antitumor and apoptotic effects of bergaptol are mediated via mitochondrial death pathway and cell cycle arrest in human breast carcinoma cells","volume":"11","author":"Ge","year":"2016","journal-title":"Bangladesh J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1080\/14786419.2017.1399386","article-title":"Phytochemical constituents from dietary plant Citrus hystrix","volume":"32","author":"Sadasivam","year":"2018","journal-title":"Nat. Prod. Res."},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Connolly, P., Garcia-Carpio, I., and Villunger, A. (2020). Cell-Cycle Cross Talk with Caspases and Their Substrates. Cold Spring Harb. Perspect. Biol., 12.","DOI":"10.1101\/cshperspect.a036475"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2300061","DOI":"10.1002\/mnfr.202300061","article-title":"Ethanol Extract of Citrus grandis \u2018Tomentosa\u2019 Exerts Anticancer Effects by Targeting Skp2\/p27 Pathway in Non-Small Cell Lung Cancer","volume":"67","author":"Huang","year":"2023","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.semcancer.2020.01.013","article-title":"The Skp2 Pathway: A Critical Target for Cancer Therapy","volume":"67","author":"Cai","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Tolomeo, M., and Cascio, A. (2021). The Multifaced Role of STAT3 in Cancer and Its Implication for Anticancer Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22020603"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41568-022-00537-3","article-title":"STAT proteins in cancer: Orchestration of metabolism","volume":"23","author":"Li","year":"2023","journal-title":"Nat. Rev. Cancer"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1151862","DOI":"10.3389\/fonc.2023.1151862","article-title":"Editorial: The role of STAT3 signaling pathway in tumor progression","volume":"13","author":"Chang","year":"2023","journal-title":"Front. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Muniyandi, K., George, B., Parimelazhagan, T., and Abrahamse, H. (2020). Role of Photoactive Phytocompounds in Photodynamic Therapy of Cancer. Molecules, 25.","DOI":"10.3390\/molecules25184102"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1200\/JCO.2011.37.6418","article-title":"Development of therapeutic combinations targeting major cancer signaling pathways","volume":"31","author":"Yap","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"38022","DOI":"10.18632\/oncotarget.16723","article-title":"Combination therapy in combating cancer","volume":"8","author":"Homayouni","year":"2017","journal-title":"Oncotarget"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1369","DOI":"10.1038\/sj.bjp.0703433","article-title":"Effect of furanocoumarin derivatives in grapefruit juice on the uptake of vinblastine by Caco-2 cells and on the activity of cytochrome P450 3A4","volume":"130","author":"Ohnishi","year":"2000","journal-title":"Br. J. Pharmacol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1186\/s12935-022-02624-9","article-title":"Anticancer potential of alkaloids: A key emphasis to colchicine, vinblastine, vincristine, vindesine, vinorelbine, and vincamine","volume":"22","author":"Dhyani","year":"2022","journal-title":"Cancer Cell Int."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Dewanjee, S., Dua, T.K., Bhattacharjee, N., Das, A., Gangopadhyay, M., Khanra, R., Joardar, S., Riaz, M., Feo, V.D., and Zia-Ul-Haq, M. (2017). Natural Products as Alternative Choices for P-Glycoprotein (P-gp) Inhibition. Molecules, 22.","DOI":"10.3390\/molecules22060871"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1002\/mc.2940130302","article-title":"Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: Implications for drug delivery and activity in cancer chemotherapy","volume":"13","author":"Wacher","year":"1995","journal-title":"Mol. Carcinog."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"317","DOI":"10.2174\/1386207326666230622163202","article-title":"Study of Active Phytochemicals and Mechanisms of Cnidii Fructus in Treating Osteoporosis Based on HPLC-Q-TOF-MS\/MS and Network Pharmacology","volume":"27","author":"Xu","year":"2023","journal-title":"Comb. Chem. High. Throughput Screen."},{"key":"ref_65","first-page":"3676","article-title":"Vitamin K2 stimulates MC3T3-E1 osteoblast differentiation and mineralization through autophagy induction","volume":"19","author":"Li","year":"2019","journal-title":"Mol. Med. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ejphar.2007.10.013","article-title":"Enhancement of bone morphogenetic protein-2 expression and bone formation by coumarin derivatives via p38 and ERK-dependent pathway in osteoblasts","volume":"579","author":"Tang","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"114969","DOI":"10.1016\/j.jep.2022.114969","article-title":"System pharmacology analysis to decipher the effect and mechanism of active ingredients combination from herb couple on rheumatoid arthritis in rats","volume":"288","author":"Wu","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.vph.2018.08.002","article-title":"Foam cell formation: A new target for fighting atherosclerosis and cardiovascular disease","volume":"112","author":"Maguire","year":"2019","journal-title":"Vasc. Pharmacol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"113178","DOI":"10.1016\/j.jep.2020.113178","article-title":"Optimization of extraction flavonoids from Exocarpium Citri Grandis and evaluation its hypoglycemic and hypolipidemic activities","volume":"262","author":"Kong","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.13005\/bpj\/2044","article-title":"Preclinical Antihyperlipidemic Effect of Herbalism against Lipid Elevating Agents: A Review","volume":"13","author":"Ansari","year":"2020","journal-title":"Biomed. Pharmacol. J."},{"key":"ref_71","first-page":"555799","article-title":"Evaluation of Hypolipidemic and TNF-\u03b1 Lowering Effect of Ficus Religiosa in Dyslipidemic Wistar Rats","volume":"10","author":"Rathi","year":"2019","journal-title":"Curre Res. Diabetes Obes. J."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Pan, Y., Tan, J., Long, X., Yi, R., Zhao, X., and Park, K.-Y. (2022). Anti-obesity effect of fermented lemon peel on high-fat diet-induced obese mice by modulating the inflammatory response. J. Food Biochem., 46.","DOI":"10.1111\/jfbc.14200"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1006\/scdb.1998.0273","article-title":"The role of TNF alpha in adipocyte metabolism","volume":"10","author":"Sethi","year":"1999","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"72","DOI":"10.4315\/0362-028X-60.1.72","article-title":"Isolation and identification of antimicrobial furocoumarins from parsley","volume":"60","author":"Manderfeld","year":"1997","journal-title":"J. Food Prot."},{"key":"ref_75","unstructured":"Girennavar, B. (2007). Grapefruit-Drug Interaction: Isolation, Synthesis, and Biological Activities of Furocoumarins and Their Variation Due to Pre-and Post\u2013Harvest Factors. [PhD Dissertation, Texas A&M University]."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/1475-2859-1-5","article-title":"Bacterial autoinduction: Looking outside the cell for new metabolic engineering targets","volume":"1","author":"DeLisa","year":"2002","journal-title":"Microb. Cell Fact."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1093\/emboj\/cdg085","article-title":"Vibrio harveyi quorum sensing: A coincidence detector for two autoinducers controls gene expression","volume":"22","author":"Mok","year":"2003","journal-title":"Embo J."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Anbazhagan, D., Mansor, M., Yan, G.O., Md Yusof, M.Y., Hassan, H., and Sekaran, S.D. (2012). Detection of quorum sensing signal molecules and identification of an autoinducer synthase gene among biofilm-forming clinical isolates of Acinetobacter spp.. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0036696"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.jcma.2017.07.012","article-title":"Bacterial biofilm and associated infections","volume":"81","author":"Jamal","year":"2018","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.ijfoodmicro.2008.03.028","article-title":"Grapefruit juice and its furocoumarins inhibits autoinducer signaling and biofilm formation in bacteria","volume":"125","author":"Girennavar","year":"2008","journal-title":"Int. J. Food Microbiol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"3103","DOI":"10.2174\/092986705774933425","article-title":"Quorum Sensing Inhibition: Targeting Chemical Communication in Gram-negative Bacteria","volume":"12","author":"Persson","year":"2005","journal-title":"Curr. Med. Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"e10248","DOI":"10.15252\/emmm.201810248","article-title":"Inflammasomes in neuroinflammatory and neurodegenerative diseases","volume":"11","author":"Voet","year":"2019","journal-title":"EMBO Mol. Med."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Tyrtyshnaia, A., Bondar, A., Konovalova, S., Sultanov, R., and Manzhulo, I. (2020). N-Docosahexanoylethanolamine Reduces Microglial Activation and Improves Hippocampal Plasticity in a Murine Model of Neuroinflammation. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21249703"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12974-021-02204-0","article-title":"Inhibition of microglia overactivation restores neuronal survival in a mouse model of CDKL5 deficiency disorder","volume":"18","author":"Galvani","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"827263","DOI":"10.3389\/fnagi.2022.827263","article-title":"Neuroinflammation: A Possible Link Between Chronic Vascular Disorders and Neurodegenerative Diseases","volume":"14","author":"Moyse","year":"2022","journal-title":"Front. Aging Neurosci."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kuo, P.-C., Liao, Y.-R., Hung, H.-Y., Chuang, C.-W., Hwang, T.-L., Huang, S.-C., Shiao, Y.-J., Kuo, D.-H., and Wu, T.-S. (2017). Anti-inflammatory and Neuroprotective Constituents from the Peels of Citrus grandis. Molecules, 22.","DOI":"10.3390\/molecules22060967"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1002\/mnfr.201100011","article-title":"Update of the toxicological assessment of furanocoumarins in foodstuffs (Update of the SKLM statement of 23\/24 September 2004)\u2014Opinion of the Senate Commission on Food Safety (SKLM) of the German Research Foundation (DFG)","volume":"55","author":"Guth","year":"2011","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1093\/jn\/nxaa062","article-title":"Intake of Furocoumarins and Risk of Skin Cancer in 2 Prospective US Cohort Studies","volume":"150","author":"Sun","year":"2020","journal-title":"J. Nutr."},{"key":"ref_89","unstructured":"(2018). Dietary Assessment: A Resource Guide to Method Selection and Application in Low Resource Settings, Food and Agriculture Organization of the United Nations."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1016\/j.fct.2011.11.023","article-title":"Major furocoumarins in grapefruit juice II: Phototoxicity, photogenotoxicity, and inhibitory potency vs. cytochrome P450 3A4 activity","volume":"50","author":"Messer","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1230","DOI":"10.1007\/s00044-020-02564-x","article-title":"Bergaptol, a mechanism-based inactivator of CYP2C9","volume":"29","author":"Jiang","year":"2020","journal-title":"Med. Chem. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"12","DOI":"10.3389\/fgene.2013.00012","article-title":"Pharmacogenomics of Cytochrome P450 3A4: Recent Progress Toward the \u201cMissing Heritability\u201d Problem","volume":"4","author":"Klein","year":"2013","journal-title":"Front. Genet."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1046\/j.1365-2125.1998.00721.x","article-title":"Cytochrome P4502C9: An enzyme of major importance in human drug metabolism","volume":"45","author":"Miners","year":"1998","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"C417","DOI":"10.1111\/j.1750-3841.2007.00483.x","article-title":"Potent Inhibition of Human Cytochrome P450 3A4, 2D6, and 2C9 Isoenzymes by Grapefruit Juice and Its Furocoumarins","volume":"72","author":"Girennavar","year":"2007","journal-title":"J. Food Sci."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1517\/17425255.2011.553189","article-title":"The effect of grapefruit juice on drug disposition","volume":"7","author":"Hanley","year":"2011","journal-title":"Expert. Opin. Drug Metab. Toxicol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"3865","DOI":"10.1016\/j.bmc.2006.01.046","article-title":"Synthesis of 8-geranyloxypsoralen analogues and their evaluation as inhibitors of CYP3A4","volume":"14","author":"Row","year":"2006","journal-title":"Bioorg. Med. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Deodhar, M., Al Rihani, S.B., Arwood, M.J., Darakjian, L., Dow, P., Turgeon, J., and Michaud, V. (2020). Mechanisms of CYP450 Inhibition: Understanding Drug-Drug Interactions Due to Mechanism-Based Inhibition in Clinical Practice. Pharmaceutics, 12.","DOI":"10.3390\/pharmaceutics12090846"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"378","DOI":"10.18433\/J3W01D","article-title":"Psoralen and Bergapten: In Silico Metabolism and Toxicophoric Analysis of Drugs Used to Treat Vitiligo","volume":"12","author":"Kawano","year":"2009","journal-title":"J. Pharm. Pharm. Sci."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/3\/713\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T13:54:37Z","timestamp":1760104477000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/29\/3\/713"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,2,4]]},"references-count":98,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2024,2]]}},"alternative-id":["molecules29030713"],"URL":"https:\/\/doi.org\/10.3390\/molecules29030713","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,2,4]]}}}