{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:12:35Z","timestamp":1788433955841,"version":"build-2803163510"},"reference-count":87,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005076","name":"Agricultural Research Development Agency","doi-asserted-by":"publisher","award":["CRP6105022430"],"award-info":[{"award-number":["CRP6105022430"]}],"id":[{"id":"10.13039\/501100005076","id-type":"DOI","asserted-by":"publisher"}]},{"award":["CRP6105022430"],"award-info":[{"award-number":["CRP6105022430"]}],"id":[{"id":"https:\/\/ror.org\/01shbv660","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Thunbergia laurifolia has long been used in traditional medicine for detoxification; however, the biological basis of its detoxifying effects remains poorly understood. This study investigated the detoxifying effects of a phenolic-rich aqueous extract of T. laurifolia using integrated in vitro and in vivo approaches. Caffeic acid (CA) and rosmarinic acid (RA) were used as marker compounds for extract standardization. The aqueous extract was evaluated for antioxidant, acetylcholinesterase, and apoptosis-modulating activities in vitro, followed by evaluation in a chlorpyrifos-induced oxidative stress model in vivo. The extract exhibited antioxidant activity and maintained acetylcholinesterase (AChE) activity. In LX-2 hepatic stellate cells, the extract induced predominantly early apoptosis, whereas CA and RA induced predominantly late apoptosis. In chlorpyrifos-exposed rats, the extract restored AChE activity, reduced lipid peroxidation, and enhanced endogenous antioxidant defenses, as evidenced by decreased malondialdehyde (MDA) levels and increased glutathione (GSH) levels and superoxide dismutase (SOD) activity. Collectively, these findings suggest that attenuation of oxidative stress may represent one of the mechanisms underlying the detoxifying effects traditionally attributed to T. laurifolia.<\/jats:p>","DOI":"10.3390\/ijms27177876","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"7876","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Detoxifying Effects of a Phenolic-Rich Thunbergia laurifolia Water Extract Against Chlorpyrifos-Induced Oxidative Stress: Evidence from an Integrated In Vitro and In Vivo Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-5114","authenticated-orcid":false,"given":"Phraepakaporn","family":"Kunnaja","sequence":"first","affiliation":[{"name":"Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4793-6269","authenticated-orcid":false,"given":"Supaporn","family":"Intatham","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1516-0106","authenticated-orcid":false,"given":"Parirat","family":"Khonsung","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-6583-1669","authenticated-orcid":false,"given":"Kanjana","family":"Jaijoy","sequence":"additional","affiliation":[{"name":"McCormick Faculty of Nursing, Payap University, Chiang Mai 50000, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5974-7278","authenticated-orcid":false,"given":"Thunyatorn","family":"Yimsoo","sequence":"additional","affiliation":[{"name":"Laboratory Animal Center, Office of Advanced Science and Technology, Thammasat University, Pathum Thani 12120, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3068-0081","authenticated-orcid":false,"given":"Piyanuch","family":"Rojsanga","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9620-4590","authenticated-orcid":false,"given":"Seewaboon","family":"Sireeratawong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"},{"name":"Clinical Research Center for Food and Herbal Product Trials and Development (CR-FAH), Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.5530\/pj.2011.24.1","article-title":"Phytochemistry and Pharmacological Properties of Thunbergia laurifolia: A Review","volume":"3","author":"Chan","year":"2011","journal-title":"Pharmacogn. J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"19","DOI":"10.2306\/scienceasia1513-1874.2013.39.019","article-title":"Thunbergia laurifolia Leaf Extract Mitigates Cadmium Toxicity in Rats","volume":"39","author":"Ruangyuttikarn","year":"2013","journal-title":"ScienceAsia"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Junsi, M., Takahashi Yupanqui, C., Usawakesmanee, W., Slusarenko, A., and Siripongvutikorn, S. (2020). Thunbergia laurifolia Leaf Extract Increased Levels of Antioxidant Enzymes and Protected Human Cell-Lines In Vitro Against Cadmium. Antioxidants, 9.","DOI":"10.3390\/antiox9010047"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Vongthip, W., Sillapachaiyaporn, C., Kim, K.-W., Sukprasansap, M., and Tencomnao, T. (2021). Thunbergia laurifolia Leaf Extract Inhibits Glutamate-Induced Neurotoxicity and Cell Death through Mitophagy Signaling. Antioxidants, 10.","DOI":"10.3390\/antiox10111678"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/j.sajb.2024.09.059","article-title":"Anti-Inflammatory, Antioxidant, and Anti-Apoptotic Properties of Thunbergia laurifolia Lindl. Aqueous Leaf Extract on LPS-Stimulated RAW 264.7 Macrophages","volume":"174","author":"Senghoi","year":"2024","journal-title":"S. Afr. J. Bot."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22086","DOI":"10.1039\/D5RA02501J","article-title":"Polyphenol-Enriched Extraction from Thunbergia laurifolia Using Natural Deep Eutectic Solvents for Enhanced Antioxidant and Anti-Inflammatory Activities","volume":"15","author":"Srimawong","year":"2025","journal-title":"RSC Adv."},{"key":"ref_7","first-page":"53","article-title":"Anti-Diabetic Effect of Thunbergia laurifolia Linn. Aqueous Extract","volume":"35","author":"Aritajat","year":"2004","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_8","first-page":"S98","article-title":"Effect of Thunbergia laurifolia Lindl. Extract on Anti-Inflammatory, Analgesic and Antipyretic Activity","volume":"100","author":"Nanna","year":"2017","journal-title":"J. Med. Assoc. Thail."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1007\/s00436-012-2846-5","article-title":"Anti-Inflammatory, Antioxidant and Hepatoprotective Effects of Thunbergia laurifolia Linn. on Experimental Opisthorchiasis","volume":"111","author":"Wonkchalee","year":"2012","journal-title":"Parasitol. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1016\/j.jep.2005.06.036","article-title":"Hepatoprotective Activity of Thunbergia laurifolia Linn Extract in Rats Treated with Ethanol: In Vitro and In Vivo Studies","volume":"102","author":"Pramyothin","year":"2005","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","first-page":"238","article-title":"Mutagenicity of Pueraria mirifica Airy Shaw & Suvatabandhu and Antimutagenicity of Thunbergia laurifolia Linn","volume":"36","author":"Saenphet","year":"2005","journal-title":"Southeast Asian J. Trop. Med. Public Health"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"93","DOI":"10.59796\/jcst.V15N2.2025.93","article-title":"Pharmacological Effects of Thunbergia laurifolia Lindl. Extract on Gastric Ulceration in Rats","volume":"15","author":"Chularojanamontri","year":"2025","journal-title":"J. Curr. Sci. Technol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e09234","DOI":"10.1016\/j.heliyon.2022.e09234","article-title":"Thunbergia laurifolia Aqueous Leaf Extract Ameliorates Paraquat-Induced Kidney Injury by Regulating NADPH Oxidase in Rats","volume":"8","author":"Palipoch","year":"2022","journal-title":"Heliyon"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Intatham, S., Taychaworaditsakul, W., Kunnaja, P., Wongnoppavich, A., Jaijoy, K., Chansakaow, S., Rojsanga, P., and Sireeratawong, S. (2025). Anti-Hangover and Hepatoprotective Effects of the Leaf Extract of Thunbergia laurifolia in Sprague\u2013Dawley Rats. Pharmaceuticals, 18.","DOI":"10.3390\/ph18050685"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1136\/gut.2004.042127","article-title":"Human Hepatic Stellate Cell Lines, LX-1 and LX-2: New Tools for Analysis of Hepatic Fibrosis","volume":"54","author":"Xu","year":"2005","journal-title":"Gut"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jcmgh.2023.05.010","article-title":"In Vitro and In Vivo Models to Study Liver Fibrosis: Mechanisms and Limitations","volume":"16","author":"Lee","year":"2023","journal-title":"Cell. Mol. Gastroenterol. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/10408440802272158","article-title":"Review of the Toxicology of Chlorpyrifos with an Emphasis on Human Exposure and Neurodevelopment","volume":"38","author":"Eaton","year":"2008","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1023\/A:1022579416322","article-title":"Immunotoxicity of Organophosphorous Pesticides","volume":"12","author":"Galloway","year":"2003","journal-title":"Ecotoxicology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1177\/0960327110388959","article-title":"Toxic Influence of Organophosphate, Carbamate, and Organochlorine Pesticides on Cellular Metabolism of Lipids, Proteins, and Carbohydrates: A Systematic Review","volume":"30","author":"Abdollahi","year":"2011","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Kunnaja, P., Chansakaow, S., Taychaworaditsakul, W., Intatham, S., Jaijoy, K., Wittayapraparat, A., Yusuk, P., Suksathan, R., and Sireeratawong, S. (2026). Hepatoprotective Effects and Antioxidant Properties of a Herbal Detoxifying Formula Against Chlorpyrifos-Induced Toxicity in Sprague\u2013Dawley Rats. Biology, 15.","DOI":"10.3390\/biology15010017"},{"key":"ref_21","unstructured":"Suwanvecho, C., Sithisarn, P., Timum, S., Archeepsudjarit, N., and Rojsanga, P. (2019, January 22). Stability Evaluations on Thunbergia laurifolia Lindl. Leaf Extract through HPLC, TLC and Free Radical Scavenging Activity Analysis. Proceedings of the 1st Pharmaceutical Sciences Asia Conference (PSA 2019), Bangkok, Thailand."},{"key":"ref_22","first-page":"117","article-title":"Antioxidant-Guided Isolation of Rosmarinic Acid, a Major Constituent from Thunbergia laurifolia, and Its Use as a Bioactive Marker for Standardization","volume":"41","author":"Suwanchaikasem","year":"2014","journal-title":"Chiang Mai J. Sci."},{"key":"ref_23","first-page":"615","article-title":"In Vitro Biological Activities of Thunbergia laurifolia Stem and Leaf with Reference to Rosmarinic Acid","volume":"42","author":"Hongsing","year":"2020","journal-title":"Songklanakarin J. Sci. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kicel, A., Owczarek, A., Kapusta, P., Kolodziejczyk-Czepas, J., and Olszewska, M.A. (2020). Contribution of Individual Polyphenols to Antioxidant Activity of Cotoneaster bullatus and Cotoneaster zabelii Leaves\u2014Structural Relationships, Synergy Effects and Application for Quality Control. Antioxidants, 9.","DOI":"10.3390\/antiox9010069"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1016\/S0891-5849(98)00315-3","article-title":"Antioxidant Activity Applying an Improved ABTS Radical Cation Decolorization Assay","volume":"26","author":"Re","year":"1999","journal-title":"Free Radic. Biol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/S0023-6438(95)80008-5","article-title":"Use of a Free Radical Method to Evaluate Antioxidant Activity","volume":"28","author":"Cuvelier","year":"1995","journal-title":"LWT\u2014Food Sci. Technol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1006\/abio.1996.0292","article-title":"The Ferric Reducing Ability of Plasma (FRAP) as a Measure of \u201cAntioxidant Power\u201d: The FRAP Assay","volume":"239","author":"Benzie","year":"1996","journal-title":"Anal. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.aca.2013.07.027","article-title":"Superoxide Generated by Pyrogallol Reduces Highly Water-Soluble Tetrazolium Salt to Produce a Soluble Formazan: A Simple Assay for Measuring Superoxide Anion Radical Scavenging Activities of Biological and Abiological Samples","volume":"793","author":"Xu","year":"2013","journal-title":"Anal. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s43014-025-00326-z","article-title":"How to Assess Antioxidant Activity? Advances, Limitations, and Applications of In Vitro, In Vivo, and Ex Vivo Approaches","volume":"7","author":"Shahidi","year":"2025","journal-title":"Food Prod. Process. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1021\/acs.jafc.5b04739","article-title":"Antioxidant Activity\/Capacity Measurement. 1. Classification, Physicochemical Principles, Mechanisms, and Electron Transfer (ET)-Based Assays","volume":"64","author":"Apak","year":"2016","journal-title":"J. Agric. Food Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4290","DOI":"10.1021\/jf0502698","article-title":"Standardized Methods for the Determination of Antioxidant Capacity and Phenolics in Foods and Dietary Supplements","volume":"53","author":"Prior","year":"2005","journal-title":"J. Agric. Food Chem."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Kotha, R.R., Tareq, F.S., Yildiz, E., and Luthria, D.L. (2022). Oxidative Stress and Antioxidants\u2014A Critical Review on In Vitro Antioxidant Assays. Antioxidants, 11.","DOI":"10.3390\/antiox11122388"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3203","DOI":"10.1039\/C3AY41807C","article-title":"Caffeic Acid: A Review of Its Potential Use in Medications and Cosmetics","volume":"6","author":"Magnani","year":"2014","journal-title":"Anal. Methods"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Nadeem, M., Imran, M., Gondal, T.A., Imran, A., Shahbaz, M., Amir, R.M., Sajid, M.W., Qaisrani, T.B., Atif, M., and Hussain, G. (2019). Therapeutic Potential of Rosmarinic Acid: A Comprehensive Review. Appl. Sci., 9.","DOI":"10.3390\/app9153139"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"100726","DOI":"10.1016\/j.phyplu.2024.100726","article-title":"Unlocking the Potential of Rosmarinic Acid: A Review on Extraction, Isolation, Quantification, Pharmacokinetics and Pharmacology","volume":"5","author":"Harindranath","year":"2025","journal-title":"Phytomed. Plus"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Guan, H., Luo, W., Bao, B., Cao, Y., Cheng, F., Yu, S., Fan, Q., Zhang, L., Wu, Q., and Shan, M. (2022). A Comprehensive Review of Rosmarinic Acid: From Phytochemistry to Pharmacology and Its New Insight. Molecules, 27.","DOI":"10.3390\/molecules27103292"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Esp\u00edndola, K.M.M., Ferreira, R.G., Narvaez, L.E.M., Rosario, A.C.R.S., da Silva, A.H.M., Silva, A.G.B., Vieira, A.P.O., and Monteiro, M.C. (2019). Chemical and Pharmacological Aspects of Caffeic Acid and Its Activity in Hepatocarcinoma. Front. Oncol., 9.","DOI":"10.3389\/fonc.2019.00541"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e24575","DOI":"10.1590\/s2175-97902025e24575","article-title":"Rosmarinic Acid: Insights into Analytical, Pharmacological & Pharmaceutical Aspects","volume":"61","author":"Kumar","year":"2025","journal-title":"Braz. J. Pharm. Sci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8359","DOI":"10.29219\/fnr.v66.8359","article-title":"Rosmarinic Acid Exerts Anti-Inflammatory Effect and Relieves Oxidative Stress via Nrf2 Activation in Carbon Tetrachloride-Induced Liver Damage","volume":"66","author":"Lu","year":"2022","journal-title":"Food Nutr. Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.cca.2005.10.008","article-title":"Current Issues in Organophosphate Toxicology","volume":"366","author":"Costa","year":"2006","journal-title":"Clin. Chim. Acta"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.emc.2014.09.010","article-title":"Organophosphate and Carbamate Poisoning","volume":"33","author":"King","year":"2015","journal-title":"Emerg. Med. Clin. N. Am."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"315","DOI":"10.2174\/1570159X11311030006","article-title":"Acetylcholinesterase Inhibitors: Pharmacology and Toxicology","volume":"11","year":"2013","journal-title":"Curr. Neuropharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/bjc.1972.33","article-title":"Apoptosis: A Basic Biological Phenomenon with Wide-Ranging Implications in Tissue Kinetics","volume":"26","author":"Kerr","year":"1972","journal-title":"Br. J. Cancer"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A Review of Programmed Cell Death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.cell.2023.11.044","article-title":"Cell Death","volume":"187","author":"Newton","year":"2024","journal-title":"Cell"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1038\/s41418-017-0012-4","article-title":"Molecular Mechanisms of Cell Death: Recommendations of the Nomenclature Committee on Cell Death 2018","volume":"25","author":"Galluzzi","year":"2018","journal-title":"Cell Death Differ."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1002\/hep.20051","article-title":"Apoptosis: The Nexus of Liver Injury and Fibrosis","volume":"39","author":"Canbay","year":"2004","journal-title":"Hepatology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/s41420-023-01749-8","article-title":"Programmed Cell Death in Hepatic Fibrosis: Current and Perspectives","volume":"9","author":"Lu","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1152\/physrev.00013.2007","article-title":"Hepatic Stellate Cells: Protean, Multifunctional, and Enigmatic Cells of the Liver","volume":"88","author":"Friedman","year":"2008","journal-title":"Physiol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1038\/s41575-020-00372-7","article-title":"Molecular and Cellular Mechanisms of Liver Fibrosis and Its Regression","volume":"18","author":"Kisseleva","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1016\/j.molmed.2023.08.001","article-title":"ROS\/RNS as Molecular Signatures of Chronic Liver Diseases","volume":"29","author":"Che","year":"2023","journal-title":"Trends Mol. Med."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Taychaworaditsakul, W., Sawong, S., Intatham, S., Chansakaow, S., Kunnaja, P., Chewonarin, T., Jaijoy, K., Wittayapraparat, A., Yusuk, P., and Sireeratawong, S. (2024). The Ameliorative Effect of Litsea martabanica (Kurz) Hook. f. Leaf Water Extract on Chlorpyrifos-Induced Toxicity in Rats and Its Antioxidant Potentials. Foods, 13.","DOI":"10.20944\/preprints202404.1950.v1"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Zhao, Y.-Q., Deng, X.-W., Xu, G.-Q., Lin, J., Lu, H.-Z., and Chen, J. (2023). Mechanical Homeostasis Imbalance in Hepatic Stellate Cells Activation and Hepatic Fibrosis. Front. Mol. Biosci., 10.","DOI":"10.3389\/fmolb.2023.1183808"},{"key":"ref_54","first-page":"6321","article-title":"Reactive Oxygen Species (ROS)-Mediated Oxidative Stress in Chronic Liver Diseases and Its Mitigation by Medicinal Plants","volume":"15","author":"Sharma","year":"2023","journal-title":"Am. J. Transl. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"15","DOI":"10.21608\/mjfmct.2009.53266","article-title":"Potential Ameliorative Role of Silymarin Against Methyl Parathion-Induced Oxidative Stress and Hepato-Renal Toxicity in Albino Rats","volume":"17","author":"Mohamed","year":"2009","journal-title":"Mansoura J. Forens. Med. Clin. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/toxsci\/kfx266","article-title":"Organophosphorus Compounds at 80: Some Old and New Issues","volume":"162","author":"Costa","year":"2018","journal-title":"Toxicol. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.scitotenv.2016.09.009","article-title":"Exposure to Pesticides and the Associated Human Health Effects","volume":"575","author":"Kim","year":"2017","journal-title":"Sci. Total Environ."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Aboubakr, M., Elshafae, S.M., Abdelhiee, E.Y., Fadl, S.E., Soliman, A., Abdelkader, A., Abdel-Daim, M.M., Bayoumi, K.A., Baty, R.S., and Elgendy, E. (2021). Antioxidant and Anti-Inflammatory Potential of Thymoquinone and Lycopene Mitigate the Chlorpyrifos-Induced Toxic Neuropathy. Pharmaceuticals, 14.","DOI":"10.3390\/ph14090940"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.etap.2012.12.009","article-title":"Sub-Chronic Exposure to Chlorpyrifos Induces Hematological, Metabolic Disorders and Oxidative Stress in Rat: Attenuation by Glutathione","volume":"35","author":"Elsharkawy","year":"2013","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"121281","DOI":"10.1016\/j.lfs.2022.121281","article-title":"Rosmarinic Acid Mitigates Chlorpyrifos-Induced Oxidative Stress, Inflammation, and Kidney Injury in Rats by Modulating SIRT1 and Nrf2\/HO-1 Signaling","volume":"313","author":"Abduh","year":"2023","journal-title":"Life Sci."},{"key":"ref_61","unstructured":"Butadej, D., Duangchanchot, M., Inpunkaew, R., and Kengkoom, K. (2011, January 1\u20134). Chemical Parameters in Healthy Sprague\u2013Dawley and Wistar Rats from National Laboratory Animal Center, Mahidol University. Proceedings of the 49th Kasetsart University Annual Conference: Science, Bangkok, Thailand."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/0891-5849(95)91457-3","article-title":"The Definition and Measurement of Antioxidants in Biological Systems","volume":"18","author":"Halliwell","year":"1995","journal-title":"Free Radic. Biol. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.redox.2015.01.002","article-title":"Oxidative Stress: A Concept in Redox Biology and Medicine","volume":"4","author":"Sies","year":"2015","journal-title":"Redox Biol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"219","DOI":"10.5507\/bp.2011.036","article-title":"Cholinesterases, a Target of Pharmacology and Toxicology","volume":"155","author":"Pohanka","year":"2011","journal-title":"Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"145","DOI":"10.4103\/0253-7613.33434","article-title":"Chlorpyrifos-Induced Oxidative Stress and Tissue Damage in the Liver, Kidney, Brain and Fetus in Pregnant Rats: The Protective Role of the Butanolic Extract of Paronychia argentea L.","volume":"39","author":"Zama","year":"2007","journal-title":"Indian J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0140-6736(07)61202-1","article-title":"Management of Acute Organophosphorus Pesticide Poisoning","volume":"371","author":"Eddleston","year":"2008","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e7429","DOI":"10.7717\/peerj.7429","article-title":"Age-Associated Changes of Cytochrome P450 and Related Phase-2 Gene\/Proteins in Livers of Rats","volume":"7","author":"Xu","year":"2019","journal-title":"PeerJ"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1292\/jvms.09-0397","article-title":"Changes in the Gene Expression and Enzyme Activity of Hepatic Cytochrome P450 in Juvenile Sprague\u2013Dawley Rats","volume":"72","author":"Asaoka","year":"2010","journal-title":"J. Vet. Med. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1080\/109374099281205","article-title":"Organophosphorus Pesticides: Do They All Have the Same Mechanism of Toxicity?","volume":"2","author":"Pope","year":"1999","journal-title":"J. Toxicol. Environ. Health B Crit. Rev."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Kunnaja, P., Chansakaow, S., Wittayapraparat, A., Yusuk, P., and Sireeratawong, S. (2021). In Vitro Antioxidant Activity of Litsea martabanica Root Extract and Its Hepatoprotective Effect on Chlorpyrifos-Induced Toxicity in Rats. Molecules, 26.","DOI":"10.3390\/molecules26071906"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.pestbp.2006.11.002","article-title":"In Vivo Chlorpyrifos Induced Oxidative Stress: Attenuation by Antioxidant Vitamins","volume":"88","author":"Verma","year":"2007","journal-title":"Pestic. Biochem. Physiol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"98","DOI":"10.2174\/1567202612666150109113638","article-title":"The Cellular Protective Effects of Rosmarinic Acid: From Bench to Bedside","volume":"12","author":"Nabavi","year":"2015","journal-title":"Curr. Neurovasc. Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1016\/j.jfda.2016.05.003","article-title":"Inhibitory Mechanism against Oxidative Stress of Caffeic Acid","volume":"24","author":"Khan","year":"2016","journal-title":"J. Food Drug Anal."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Pavl\u00edkov\u00e1, N. (2023). Caffeic Acid and Diseases\u2014Mechanisms of Action. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010588"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A Simple Practice Guide for Dose Conversion between Animals and Human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_76","unstructured":"Department of Medical Sciences, Ministry of Public Health (2017). Thai Herbal Pharmacopoeia."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.fjps.2016.03.001","article-title":"Antioxidant, Cytotoxic and Antimicrobial Activities of Green Synthesized Silver Nanoparticles from Crude Extract of Bergenia ciliata","volume":"2","author":"Phull","year":"2016","journal-title":"Future J. Pharm. Sci."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"165457","DOI":"10.1155\/2015\/165457","article-title":"Antioxidant and Anti-Inflammatory Activity Determination of One Hundred Kinds of Pure Chemical Compounds Using Offline and Online Screening HPLC Assay","volume":"2015","author":"Lee","year":"2015","journal-title":"Evid. Based Complement. Alternat. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/antiox2010001","article-title":"High Correlation of 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) Radical Scavenging, Ferric Reducing Activity Potential and Total Phenolics Content Indicates Redundancy in Use of All Three Assays to Screen for Antioxidant Activity of Extracts of Plants from the Malaysian Rainforest","volume":"2","author":"Clarke","year":"2013","journal-title":"Antioxidants"},{"key":"ref_80","first-page":"153","article-title":"Radical Scavenging and Antioxidant Activities of Essential Oil Components\u2014An Experimental and Computational Investigation","volume":"10","author":"Sharopov","year":"2015","journal-title":"Nat. Prod. Commun."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.foodchem.2014.11.009","article-title":"A Universally Calibrated Microplate Ferric Reducing Antioxidant Power (FRAP) Assay for Foods and Applications to Manuka Honey","volume":"174","author":"Henderson","year":"2015","journal-title":"Food Chem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/21553769.2014.1002943","article-title":"Phytochemical Analysis, Antioxidant and Antilipid Peroxidation Effects of a Medicinal Plant, Adhatoda vasica","volume":"8","author":"Bajpai","year":"2015","journal-title":"Front. Life Sci."},{"key":"ref_83","doi-asserted-by":"crossref","unstructured":"Jing, L., Ma, H., Fan, P., Gao, R., and Jia, Z. (2015). Antioxidant Potential, Total Phenolic and Total Flavonoid Contents of Rhododendron anthopogonoides and Its Protective Effect on Hypoxia-Induced Injury in PC12 Cells. BMC Complement. Altern. Med., 15.","DOI":"10.1186\/s12906-015-0820-3"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1093\/jnci\/82.13.1107","article-title":"New Colorimetric Cytotoxicity Assay for Anticancer-Drug Screening","volume":"82","author":"Skehan","year":"1990","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1038\/nprot.2006.179","article-title":"Sulforhodamine B Colorimetric Assay for Cytotoxicity Screening","volume":"1","author":"Vichai","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/978-1-60327-017-5_2","article-title":"Flow Cytometry-Based Apoptosis Detection","volume":"559","author":"Wlodkowic","year":"2009","journal-title":"Methods Mol. Biol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7876\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:14:35Z","timestamp":1788430475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/17\/7876"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":87,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["ijms27177876"],"URL":"https:\/\/doi.org\/10.3390\/ijms27177876","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}