{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T18:56:13Z","timestamp":1789498573149,"version":"build-2803163510"},"reference-count":120,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2024,7,20]],"date-time":"2024-07-20T00:00:00Z","timestamp":1721433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Piano di Sviluppo Rurale (PSR) Abruzzo","award":["DPD018\/DPD018\/571of25\/10\/2018"],"award-info":[{"award-number":["DPD018\/DPD018\/571of25\/10\/2018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Coffee is one of the most widely consumed beverages in the world due to its unique aroma and psychostimulant effects, mainly due to the presence of caffeine. In recent years, experimental evidence has shown that the moderate consumption of coffee (3\/4 cups per day) is safe and beneficial to human health, revealing protective effects against numerous chronic metabolic diseases such as diabetes, cardiovascular, neurodegenerative, and hepatic diseases. This review focuses on two of coffee\u2019s main bioactive compounds, i.e., caffeine and chlorogenic acids, and their effects on the progression of chronic liver diseases, demonstrating that regular coffee consumption correlates with a lower risk of the development and progression of non-alcoholic steatohepatitis, viral hepatitis, liver cirrhosis, and hepatocellular carcinoma. In particular, this review analyzes caffeine and chlorogenic acid from a pharmacological point of view and explores the molecular mechanism through which these compounds are responsible for the protective role of coffee. Both bioactive compounds, therefore, have antifibrotic effects on hepatic stellate cells and hepatocytes, induce a decrease in connective tissue growth factor, stimulate increased apoptosis with anti-cancer effects, and promote a major inhibition of focal adhesion kinase, actin, and protocollagen synthesis. In conclusion, coffee shows many beneficial effects, and experimental data in favor of coffee consumption in patients with liver diseases are encouraging, but further prospective studies are needed to demonstrate its preventive and therapeutic role in chronic liver diseases.<\/jats:p>","DOI":"10.3390\/foods13142280","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T08:24:59Z","timestamp":1721636699000},"page":"2280","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Protective Effect of Caffeine and Chlorogenic Acids of Coffee in Liver Disease"],"prefix":"10.3390","volume":"13","author":[{"given":"Daniela","family":"Di Pietrantonio","sequence":"first","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Pace Palitti","sequence":"additional","affiliation":[{"name":"Internal Medicine and Hepatology Unit, Azienda Sanitaria Locale, Via R. Paolini 47, 65125 Pescara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2987-5738","authenticated-orcid":false,"given":"Angelo","family":"Cichelli","sequence":"additional","affiliation":[{"name":"Department of Innovative Technologies in Medicine and Dentistry, \u201cG. d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Tacconelli","sequence":"additional","affiliation":[{"name":"Department of Neuroscience, Imaging and Clinical Science, \u201cG. d\u2019Annunzio\u201d University, Via dei Vestini 31, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"key":"ref_1","unstructured":"Bozzola, M., Charles, S., Ferretti, T., Rosser, N., von der Goltz, P., and Manson, H. (2021). The Coffee Guide, International Trade Centre. [4th ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.1055\/s-0043-115007","article-title":"The Impact of Coffee on Health","volume":"83","author":"Nieber","year":"2017","journal-title":"Planta Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"j5024","DOI":"10.1136\/bmj.j5024","article-title":"Coffee consumption and health: Umbrella review of meta-analyses of multiple health outcomes","volume":"22","author":"Poole","year":"2017","journal-title":"BMJ"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Westfall, S., and Pasinetti, G.M. (2019). The Gut Microbiota Links Dietary Polyphenols with Management of Psychiatric Mood Disorders. Front. Neurosci., 13.","DOI":"10.3389\/fnins.2019.01196"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/biof.1785","article-title":"Interactions between dietary polyphenols and aging gut microbiota: A review","volume":"48","author":"Davinelli","year":"2022","journal-title":"Biofactors"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Shan, L., Wang, F., Zhai, D., Meng, X., Liu, J., and Lv, X. (2022). Caffeine in liver diseases: Pharmacology and toxicology. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1030173"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1161\/CIRCULATIONAHA.113.005925","article-title":"Long-term coffee consumption and risk of cardiovascular disease: A systematic review and a dose-response meta-analysis of prospective cohort studies","volume":"129","author":"Ding","year":"2014","journal-title":"Circulation"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/j.tcm.2021.08.004","article-title":"Coffee and tea on cardiovascular disease (CVD) prevention","volume":"32","author":"Chieng","year":"2022","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1093\/ajcn\/nqy297","article-title":"Long-term coffee consumption, caffeine metabolism genetics, and risk of cardiovascular disease: A prospective analysis of up to 347,077 individuals and 8368 cases","volume":"109","author":"Zhou","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1718","DOI":"10.1039\/C4FO00290C","article-title":"Variations in caffeine and chlorogenic acid contents of coffees: What are we drinking?","volume":"5","author":"Ludwig","year":"2014","journal-title":"Food Funct."},{"key":"ref_11","first-page":"69","article-title":"Determination of Caffeine Content in Arabica and Robusta Green Coffee of Indian Origin","volume":"4","author":"Caracostea","year":"2021","journal-title":"Eur. J. Nat. Sci. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","article-title":"Global burden of liver disease: 2023 update","volume":"79","author":"Devarbhavi","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1111\/imj.14709","article-title":"Non-alcoholic fatty liver disease: A review of epidemiology, risk factors, diagnosis and management","volume":"50","author":"Huang","year":"2020","journal-title":"Intern. Med. J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"388","DOI":"10.1038\/s41575-023-00759-2","article-title":"Global epidemiology of cirrhosis\u2014Aetiology, trends and predictions","volume":"20","author":"Huang","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41572-020-00240-3","article-title":"Hepatocellular carcinoma","volume":"7","author":"Llovet","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.clnu.2022.01.016","article-title":"Elevated coffee consumption is associated with a lower risk of elevated liver fibrosis biomarkers in patients treated for chronic hepatitis B (ANRS CO22 Hepather cohort)","volume":"41","author":"Fontaine","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1136\/jech.2009.104125","article-title":"Moderate coffee consumption reduces the risk of hepatocellular carcinoma in hepatitis B chronic carriers: A case-control study","volume":"65","author":"Leung","year":"2011","journal-title":"J. Epidemiol. Community Health"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1053\/j.gastro.2011.02.061","article-title":"Coffee consumption is associated with response to peginterferon and ribavirin therapy in patients with chronic hepatitis C","volume":"140","author":"Freedman","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2919","DOI":"10.1038\/s41591-023-02603-1","article-title":"Resmetirom for nonalcoholic fatty liver disease: A randomized, double-blind, placebo-controlled phase 3 trial","volume":"29","author":"Harrison","year":"2023","journal-title":"Nat. Med."},{"key":"ref_20","unstructured":"(2024, June 21). FDA Approves First Treatment for Patients with Liver Scarring Due to Fatty Liver Disease, Available online: https:\/\/www.fda.gov\/news-events\/press-announcements\/fda-approves-first-treatment-patients-liver-scarring-due-fatty-liver-disease."},{"key":"ref_21","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_22","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.jceh.2016.02.003","article-title":"Coffee and Liver Disease","volume":"6","author":"Wadhawan","year":"2016","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/BF00146266","article-title":"Unexpected effects of coffee consumption on liver enzymes","volume":"9","author":"Casiglia","year":"1993","journal-title":"Eur. J. Epidemiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2552","DOI":"10.1016\/j.clnu.2018.11.030","article-title":"A systematic review and a dose-response meta-analysis of coffee dose and nonalcoholic fatty liver disease","volume":"38","author":"Chen","year":"2019","journal-title":"Clin. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Sewter, R., Heaney, S., and Patterson, A. (2021). Coffee Consumption and the Progression of NAFLD: A Systematic Review. Nutrients, 13.","DOI":"10.3390\/nu13072381"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (EASL), European Association for the Study of Diabetes (EASD), and European Association for the Study of Obesity (EASO) (2024). EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD). J. Hepatol., 5, 1\u201351.","DOI":"10.1159\/000539371"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"100254","DOI":"10.1016\/j.aohep.2020.08.071","article-title":"The effect of coffee consumption on the non-alcoholic fatty liver disease and liver fibrosis: A meta-analysis of 11 epidemiological studies","volume":"20","author":"Hayat","year":"2021","journal-title":"Ann. Hepatol."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, J.H., Park, J., and Ahn, S.B. (2023). Different Associations of Coffee Consumption with the Risk of Incident Metabolic Dysfunction-Associated Steatotic Liver Disease and Advanced Liver Fibrosis. Nutrients, 16.","DOI":"10.3390\/nu16010140"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2032","DOI":"10.1016\/j.cgh.2021.09.042","article-title":"Coffee Consumption Is Associated with Lower Liver Stiffness: A Nationally Representative Study","volume":"20","author":"Niezen","year":"2022","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1090","DOI":"10.1016\/j.jhep.2012.07.014","article-title":"Regular coffee but not espresso drinking is protective against fibrosis in a cohort mainly composed of morbidly obese European women with NAFLD undergoing bariatric surgery","volume":"57","author":"Anty","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3200","DOI":"10.1007\/s10620-010-1143-3","article-title":"Protective role of coffee in non-alcoholic fatty liver disease (NAFLD)","volume":"55","author":"Catalano","year":"2010","journal-title":"Dig. Dis. Sci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1016\/S1665-2681(19)30931-7","article-title":"High coffee intake is associated with lower grade nonalcoholic fatty liver disease: The role of peripheral antioxidant activity","volume":"11","author":"Uribe","year":"2012","journal-title":"Ann. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1111\/j.1365-2036.2011.04916.x","article-title":"Caffeine is protective in patients with non-alcoholic fatty liver disease","volume":"35","author":"Birerdinc","year":"2012","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e8","DOI":"10.1097\/MEG.0000000000000776","article-title":"Coffee consumption and risk of nonalcoholic fatty liver disease: A systematic review and meta-analysis","volume":"29","author":"Wijarnpreecha","year":"2017","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1016\/j.trsl.2014.10.008","article-title":"Coffee consumption and nonalcoholic fatty liver onset: A prospective study in the general population","volume":"165","author":"Salomone","year":"2015","journal-title":"Transl. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"5597","DOI":"10.1021\/jf904062c","article-title":"Coffee and caffeine ameliorate hyperglycemia, fatty liver, and inflammatory adipocytokine expression in spontaneously diabetic KK-Ay mice","volume":"58","author":"Yamauchi","year":"2010","journal-title":"J. Agric. Food Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e15","DOI":"10.1017\/jns.2019.10","article-title":"Coffee prevents fatty liver disease induced by a high-fat diet by modulating pathways of the gut-liver axis","volume":"8","author":"Vitaglione","year":"2019","journal-title":"J. Nutr. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Vargas-Pozada, E.E., Ramos-Tovar, E., Rodriguez-Callejas, J.D., Cardoso-Lezama, I., Galindo-G\u00f3mez, S., Talam\u00e1s-Lara, D., V\u00e1squez-Garz\u00f3n, V.R., Arellanes-Robledo, J., Tsutsumi, V., and Villa-Trevi\u00f1o, S. (2022). Caffeine Inhibits NLRP3 Inflammasome Activation by Downregulating TLR4\/MAPK\/NF-\u03baB Signaling Pathway in an Experimental NASH Model. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23179954"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1097\/MEG.0b013e3283644e26","article-title":"Caffeine prevents experimental liver fibrosis by blocking the expression of TGF-beta","volume":"26","author":"Arauz","year":"2014","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Ebadi, M., Ip, S., Bhanji, R.A., and Montano-Loza, A.J. (2021). Effect of Coffee Consumption on Non-Alcoholic Fatty Liver Disease Incidence, Prevalence and Risk of Significant Liver Fibrosis: Systematic Review with Meta-Analysis of Observational Studies. Nutrients, 13.","DOI":"10.3390\/nu13093042"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1136\/gutjnl-2019-318843","article-title":"Albumin in decompensated cirrhosis: New concepts and perspectives","volume":"69","author":"Bernardi","year":"2020","journal-title":"Gut"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Jagdish, R.K., Roy, A., Kumar, K., Premkumar, M., Sharma, M., Rao, P.N., Reddy, D.N., and Kulkarni, A.V. (2023). Pathophysiology and management of liver cirrhosis: From portal hypertension to acute-on-chronic liver failure. Front. Med., 10.","DOI":"10.3389\/fmed.2023.1060073"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2018). EASL Clinical Practice Guidelines for the management of patients with decompensated cirrhosis. J. Hepatol., 69, 406\u2013460.","DOI":"10.1016\/j.jhep.2018.08.009"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1016\/j.dld.2021.06.023","article-title":"Distinctive features of hepatocellular carcinoma in non-alcoholic fatty liver disease","volume":"54","author":"Valenti","year":"2022","journal-title":"Dig. Liver Dis."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1111\/jch.12431","article-title":"Influence of food patterns on endothelial biomarkers: A systematic review","volume":"16","author":"Elorriaga","year":"2014","journal-title":"J. Clin. Hypertens."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"964","DOI":"10.1080\/01635581.2014.932398","article-title":"Coffee intake is associated with lower levels of oxidative DNA damage and decreasing body iron storage in healthy women","volume":"66","author":"Hori","year":"2014","journal-title":"Nutr. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1590\/0102-6720201600040015","article-title":"Serum leptin levens and hepatocellular carcinoma: Review article","volume":"29","author":"Andrighetto","year":"2016","journal-title":"Arq. Bras. Cir. Dig."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Brimson, J.M., Prasanth, M.I., Malar, D.S., Thitilertdecha, P., Kabra, A., Tencomnao, T., and Prasansuklab, A. (2021). Plant Polyphenols for Aging Health: Implication from Their Autophagy Modulating Properties in Age-Associated Diseases. Pharmaceuticals, 14.","DOI":"10.3390\/ph14100982"},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Dei Cas, M., and Ghidoni, R. (2018). Cancer Prevention and Therapy with Polyphenols: Sphingolipid-Mediated Mechanisms. Nutrients, 10.","DOI":"10.3390\/nu10070940"},{"key":"ref_50","first-page":"194","article-title":"Coffee Intake and Cancer Risk: Exploring the Relationship","volume":"5","year":"2024","journal-title":"J. Exp. Basic Med. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s11302-023-09968-5","article-title":"Coffee, adenosine, and the liver","volume":"20","author":"Dranoff","year":"2024","journal-title":"Purinergic Signal."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e013739","DOI":"10.1136\/bmjopen-2016-013739","article-title":"Coffee, including caffeinated and decaffeinated coffee, and the risk of hepatocellular carcinoma: A systematic review and dose-response meta-analysis","volume":"7","author":"Kennedy","year":"2017","journal-title":"BMJ Open"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3945\/ajcn.115.116095","article-title":"The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: Data from the European Prospective Investigation into Cancer and Nutrition","volume":"102","author":"Aleksandrova","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_54","first-page":"88","article-title":"Regular coffee intake improves liver enzyme levels and liver histology in patients with chronic alcohol consumption, non-alcoholic fatty liver and non-alcoholic steatohepatitis: Report of 259 cases","volume":"1","author":"Degertekin","year":"2020","journal-title":"Hepatol. Forum"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cgh.2013.04.039","article-title":"Coffee reduces risk for hepatocellular carcinoma: An updated meta-analysis","volume":"11","author":"Bravi","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3727\/105221617X15046391179559","article-title":"Coffee Consumption and Prevention of Cirrhosis: In Support of the Caffeine Hypothesis","volume":"18","author":"Dranoff","year":"2018","journal-title":"Gene Expr."},{"key":"ref_57","unstructured":"IARC Working Group on the Evaluation of Carcinogenic Risks to Humans (2018). Drinking Coffee, Mate, and Very Hot Beverages, International Agency for Research on Cancer."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/BF00613933","article-title":"The absolute bioavailability of caffeine in man","volume":"24","author":"Blanchard","year":"1983","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"de Paula, J., and Farah, A. (2019). Caffeine Consumption through Coffee: Content in the Beverage, Metabolism, Health Benefits and Risks. Beverages, 5.","DOI":"10.3390\/beverages5020037"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1097\/00008571-200208000-00008","article-title":"The interindividual differences in the 3-demthylation of caffeine alias CYP1A2 is determined by both genetic and environmental factors","volume":"12","author":"Rasmussen","year":"2002","journal-title":"Pharmacogenetics"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.nutres.2020.05.005","article-title":"Caffeine effects on systemic metabolism, oxidative-inflammatory pathways, and exercise performance","volume":"80","author":"Barcelos","year":"2020","journal-title":"Nutr. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1124\/pr.117.014407","article-title":"Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption","volume":"70","author":"Nehlig","year":"2018","journal-title":"Pharmacol. Rev."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1007\/s11064-018-2492-0","article-title":"Impact of Coffee and Cacao Purine Metabolites on Neuroplasticity and Neurodegenerative Disease","volume":"44","author":"Camandola","year":"2019","journal-title":"Neurochem. Res."},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Olechno, E., Pu\u015bcion-Jakubik, A., Zujko, M.E., and Socha, K. (2021). Influence of various factors on caffeine content in coffee brews. Foods, 10.","DOI":"10.3390\/foods10061208"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/978-3-642-13443-2_3","article-title":"Pharmacokinetics and metabolism of natural methylxanthines in animal and man","volume":"200","author":"Arnaud","year":"2011","journal-title":"Handb. Exp. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Leviton, A. (2018). Biases inherent in studies of coffee consumption in early pregnancy and the risks of subsequent events. Nutrients, 10.","DOI":"10.20944\/preprints201807.0467.v1"},{"key":"ref_67","unstructured":"European Food Safety Authority (2021). EFSA Explains Risk Assessment, European Food Safety Authority."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/0896-6273(91)90070-G","article-title":"The brain ryanodine receptor: A caffeine-sensitive calcium release channel","volume":"7","author":"McPherson","year":"1991","journal-title":"Neuron"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1123\/ijsnem.19.2.150","article-title":"Effect of caffeine on quadriceps muscle pain during acute cycling exercise in low versus high caffeine consumers","volume":"19","author":"Gliottoni","year":"2009","journal-title":"Int. J. Sports Nutr. Exerc. Metab."},{"key":"ref_70","unstructured":"Gupta, B.S., and Gupta, U. (1999). Caffeine and the modulation of brain function. Caffeine and Behavior: Current Views and Research Trends, CRC Press."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/0165-0173(92)90012-B","article-title":"Caffeine and the central nervous system: Mechanisms of action, biochemical, metabolic and psychostimulant effects","volume":"17","author":"Nehlig","year":"1992","journal-title":"Brain Res. Rev."},{"key":"ref_72","first-page":"100138","article-title":"Pharmacology of caffeine and its effects on the human body","volume":"10","author":"Vundrala","year":"2024","journal-title":"Eur. J. Med. Chem. Rep."},{"key":"ref_73","first-page":"318","article-title":"Caffeine, the most frequently consumed psychostimulant: A narrative review article","volume":"88","author":"Gahr","year":"2020","journal-title":"Fortschr. Neurol. Psychiatr."},{"key":"ref_74","unstructured":"Caballero, B., Finglas, P.M., and Toldra, F. (2003). Encyclopedia of Food Sciences and Nutrition, Academic Press."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1016\/0165-6147(79)90046-4","article-title":"Are methylxanthine effects due to antagonism of endogenous adenosine?","volume":"1","author":"Fredholm","year":"1980","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1038\/sj.bjp.0706812","article-title":"Adenosine A(2A) receptors play a role in the pathogenesis of hepatic cirrhosis","volume":"148","author":"Chan","year":"2006","journal-title":"Br. J. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.jhep.2008.03.029","article-title":"Pharmacological application of caffeine inhibits TGF-beta-stimulated connective tissue growth factor expression in hepatocytes via PPAR and SMAD2\/3-dependent pathways","volume":"49","author":"Gressner","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1177\/0394632017694898","article-title":"Caffeine intake decreases oxidative stress and inflammatory biomarkers in experimental liver diseases induced by thioacetamide: Biochemical and histological study","volume":"30","author":"Amer","year":"2017","journal-title":"Int. J. Immunopathol. Pharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.biochi.2015.04.019","article-title":"Involvement of cAMP-PKA pathway in adenosine A1 and A2A receptor-mediated regulation of acetaldehyde-induced activation of HSCs","volume":"115","author":"Yang","year":"2015","journal-title":"Biochimie"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.fct.2018.10.005","article-title":"Coffee, caffeine, chlorogenic acid, and the purinergic system","volume":"123","author":"Stefanello","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"22608","DOI":"10.5070\/D3205022608","article-title":"A review of phosphodiesterase-inhibition and the potential role for phosphodiesterase 4-inhibitors in clinical dermatology","volume":"20","author":"Moustafa","year":"2014","journal-title":"Dermatol. Online J."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/0006-2952(72)90397-8","article-title":"Tissue distribution of caffeine and its metabolites in the mouse","volume":"21","author":"Burg","year":"1972","journal-title":"Biochem. Pharmacol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/S0165-1838(00)00110-7","article-title":"Alkylxanthines as research tools","volume":"81","author":"Daly","year":"2000","journal-title":"J. Auton. Nerv. Syst."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"S11","DOI":"10.1097\/00005344-198914003-00003","article-title":"Phosphodiesterase inhibition and positive inotropic effects","volume":"14","author":"Schmitz","year":"1989","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1016\/0006-2952(90)90607-M","article-title":"Activities of caffeine, theophylline, and enprofylline analogs as tracheal relaxants","volume":"39","author":"Brackett","year":"1990","journal-title":"Biochem. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1016\/0024-3205(86)90241-9","article-title":"Effects of enprofylline and theophylline may show the role of adenosine","volume":"38","author":"Persson","year":"1986","journal-title":"Life Sci."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s40272-020-00404-4","article-title":"Caffeine for the Treatment of Apnea in the Neonatal Intensive Care Unit: A Systematic Overview of Meta-Analyses","volume":"22","author":"Alhersh","year":"2020","journal-title":"Paediatr. Drugs"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1054\/ceca.2000.0175","article-title":"Multiple effects of caffeine on Ca2+ release and influx in human B lymphocytes","volume":"29","author":"Sei","year":"2001","journal-title":"Cell Calcium"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"7156","DOI":"10.1021\/acs.jmedchem.1c00261","article-title":"The Medicinal Chemistry of Caffeine","volume":"64","author":"Faudone","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/0006-2952(93)90589-O","article-title":"Stimulation of calcium release by caffeine analogs in pheochromocytoma cells","volume":"46","author":"Daly","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/s41467-022-28240-9","article-title":"Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance","volume":"13","author":"Lebeau","year":"2022","journal-title":"Nat. Commun."},{"key":"ref_92","first-page":"89","article-title":"Interaction of caffeine with benzodiazepines: Behavioral effects in mice","volume":"255","author":"Bertolissi","year":"1982","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1111\/j.1600-0773.1992.tb00473.x","article-title":"Caffeine moderately antagonizes the effects of triazolam and zopiclone on the psychomotor performance of healthy subjects","volume":"70","author":"Mattila","year":"1992","journal-title":"Pharmacol. Toxicol."},{"key":"ref_94","first-page":"1","article-title":"Drugs which induce anxiety: Caffeine","volume":"25","author":"Hughes","year":"1996","journal-title":"N. Z. J. Psychol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/0006-8993(87)90593-2","article-title":"Caffeine-diazepam interaction and local cerebral glucose utilization in the conscious rat","volume":"419","author":"Nehlig","year":"1987","journal-title":"Brain Res."},{"key":"ref_96","first-page":"42","article-title":"Interaction between methylxanthines and the benzodiazepine receptor","volume":"265","author":"Weir","year":"1983","journal-title":"Arch. Int. Pharmacodyn. Ther."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/S0009-8981(00)00201-1","article-title":"Antioxidant ability of caffeine and its metabolites based on the study of oxygen radical absorbing capacity and inhibition of LDL peroxidation","volume":"295","author":"Lee","year":"2000","journal-title":"Clin. Chim. Acta"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.cyto.2004.12.013","article-title":"Caffeine inhibits cytokine expression in lymphocytes","volume":"30","author":"Rittera","year":"2005","journal-title":"Cytokine"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00217-016-2643-y","article-title":"Chlorogenic acids, caffeine content and antioxidant properties of green coffee extracts: Influence of green coffee bean preparation","volume":"242","author":"Sentkowska","year":"2016","journal-title":"Eur. Food Res. Technol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Farah, A., and de Paula, J. (2019). Consumption of Chlorogenic Acids through Coffee and Health Implications. Beverages, 5.","DOI":"10.3390\/beverages5010011"},{"key":"ref_101","doi-asserted-by":"crossref","unstructured":"Nguyen, V., Taine, E.G., Meng, D., Cui, T., and Tan, W. (2024). Chlorogenic Acid: A Systematic Review on the Biological Functions, Mechanistic Actions, and Therapeutic Potentials. Nutrients, 16.","DOI":"10.3390\/nu16070924"},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Rojas-Gonz\u00e1lez, A., Figueroa-Hern\u00e1ndez, C.Y., Gonz\u00e1lez-Rios, O., Su\u00e1rez-Quiroz, M.L., Gonz\u00e1lez-Amaro, R.M., Hern\u00e1ndez-Estrada, Z.J., and Rayas-Duarte, P. (2022). Coffee Chlorogenic Acids Incorporation for Bioactivity Enhancement of Foods: A Review. Molecules, 27.","DOI":"10.3390\/molecules27113400"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"216","DOI":"10.2174\/1570159X17666191021111809","article-title":"Pharmacologic Overview of Chlorogenic Acid and its Metabolites in Chronic Pain and Inflammation","volume":"18","author":"Bagdas","year":"2020","journal-title":"Curr. Neuropharmacol."},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Hada, Y., Uchida, H.A., Otaka, N., Onishi, Y., Okamoto, S., Nishiwaki, M., Takemoto, R., Takeuchi, H., and Wada, J. (2020). The Protective Effect of Chlorogenic Acid on Vascular Senescence via the Nrf2\/HO-1 Pathway. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124527"},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Liu, Y., Feng, Y., Li, Y., Hu, Y., Zhang, Q., Huang, Y., Shi, K., Ran, C., Hou, J., and Zhou, G. (2020). Chlorogenic Acid Decreases Malignant Characteristics of Hepatocellular Carcinoma Cells by Inhibiting DNMT1 Expression. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00867"},{"key":"ref_106","doi-asserted-by":"crossref","unstructured":"Yang, F., Luo, L., Zhu, Z.D., Zhou, X., Wang, Y., Xue, J., Zhang, J., Cai, X., Chen, Z.L., and Ma, Q. (2017). Chlorogenic acid inhibits liver fibrosis by blocking the miR-21-regulated TGF-\u03b21\/Smad7 signaling pathway in vitro and in vivo. Front. Pharmacol., 8.","DOI":"10.3389\/fphar.2017.00929"},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/j.clnu.2016.03.002","article-title":"Chlorogenic acid protects against liver fibrosis in vivo and in vitro through inhibition of oxidative stress","volume":"35","author":"Shi","year":"2016","journal-title":"Clin. Nutr."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.tox.2012.10.025","article-title":"Chlorogenic acid reduces liver inflammation and fibrosis through inhibition of toll-like receptor 4 signaling pathway","volume":"303","author":"Shi","year":"2013","journal-title":"Toxicology"},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1111\/bcpt.13122","article-title":"Protective effect of isochlorogenic acid B on liver fibrosis in non-alcoholic steatohepatitis of mice","volume":"124","author":"Liu","year":"2019","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1080\/17425255.2021.1839412","article-title":"Coffee in cancer chemoprevention: An updated review","volume":"17","author":"Ismail","year":"2021","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Refolo, M.G., Lippolis, C., Carella, N., Cavallini, A., Messa, C., and D\u2019Alessandro, R. (2018). Chlorogenic acid improves the regorafenib effects in human hepatocellular carcinoma cells. Int. J. Mol. Sci., 19.","DOI":"10.3390\/ijms19051518"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/13880209.2020.1818791","article-title":"5-Caffeoylquinic acid ameliorates oxidative stress-mediated cell death via Nrf2 activation in hepatocytes","volume":"58","author":"Chen","year":"2020","journal-title":"Pharm. Biol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1080\/10826068.2020.1786699","article-title":"The chemistry of chlorogenic acid from green coffee and its role in attenuation of obesity and diabetes","volume":"50","author":"Pimpley","year":"2020","journal-title":"Prep. Biochem. Biotechnol."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/hr.2011.195","article-title":"Antihypertensive effects and mechanisms of chlorogenic acids","volume":"35","author":"Zhao","year":"2012","journal-title":"Hypertens. Res."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1007\/s13402-014-0216-2","article-title":"Chlorogenic acid inhibits hypoxia-induced angiogenesis via down-regulation of the HIF-1\u03b1\/AKT pathway","volume":"38","author":"Park","year":"2015","journal-title":"Cell. Oncol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Kennedy, O.J., Fallowfield, J.A., Poole, R., Hayes, P.C., Parkes, J., and Roderick, P.J. (2021). All coffee types decrease the risk of adverse clinical outcomes in chronic liver disease: A UK Biobank study. BMC Public Health, 21.","DOI":"10.1186\/s12889-021-10991-7"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1007\/s40429-014-0024-9","article-title":"Caffeine Use Disorder: A Review of the Evidence and Future Implications","volume":"1","author":"Addicott","year":"2014","journal-title":"Curr. Addict. Rep."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"101294","DOI":"10.1016\/j.tranon.2021.101294","article-title":"Chlorogenic acid: Potential source of natural drugs for the therapeutics of fibrosis and cancer","volume":"15","author":"Nwafor","year":"2022","journal-title":"Transl. Oncol."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1017\/S0007114514001652","article-title":"Chlorogenic acid and caffeine in combination inhibit fat accumulation by regulating hepatic lipid metabolism-related enzymes in mice","volume":"112","author":"Zheng","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Dutra, N.S., da Silva D\u2019\u00c1vila, C.M., da Silva, T.C., de Oliveira Mendes, T., Livinalli, I.C., Bertoncelli, A.C.Z., Saccol, F.K., and Cadon\u00e1, F.C. (2024). 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