{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T20:18:55Z","timestamp":1788121135295,"version":"build-2803163510"},"reference-count":55,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2022,10,25]],"date-time":"2022-10-25T00:00:00Z","timestamp":1666656000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002383","name":"King Saud University","doi-asserted-by":"publisher","award":["RSP2022R504"],"award-info":[{"award-number":["RSP2022R504"]}],"id":[{"id":"10.13039\/501100002383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The liver is a crucial organ among body organs due to its wide functions, in particular, detoxification and metabolism. Exposure to detrimental chemicals or viral infections may provoke liver dysfunction and ultimately induce liver tissue damage. Finding natural substances for liver disease treatment to overcome the conventional treatments\u2019 side effects has attracted the attention of researchers worldwide. Our current work was conducted to investigate the hepato-therapeutic activities of essential oil (EO) isolated from Tagetes patula flowers. EO was extracted using the hydro-distillation (HD) technique and its chemical composition was identified by GC\/MS. Then, the hepatic treatment potential of extracted EO was evaluated in vivo against CCL4 in rats. HD of T. patula flowers yielded highly chemical constituents of EO along with significant antioxidant potential. A coherent molecular network was fashioned via the Global Natural Products Social Molecular Networking (GNPS) to visualize the essential components and revealed that the sesquiterpene (E)-\u03b2-caryophyllene was the most predominant volatile constituent which accounted for 24.1%. The treatment of CCL4 led to significant induced oxidative stress markers malonaldehyde, total protein, and non-protein sulfhydryl, as well as elevated serum aminotransferase, gamma-glutamyl transferase, alkaline phosphatase, and bilirubin. In addition, it disrupted the level of lipid profile. The post-treatment using T. patula EO succeeded in relieving all toxic effects of CCl4 and recuperating the histopathological signs induced by CCL4. Silymarin was used as a standard hepatoprotective agent. The obtained results demonstrated that the extracted EO exerted high protective activities against the toxicity of CCL4. Moreover, the T. patula flowers EO can be used as a natural remedy to relieve many contemporary liver diseases related to oxidative stress.<\/jats:p>","DOI":"10.3390\/molecules27217242","type":"journal-article","created":{"date-parts":[[2022,10,26]],"date-time":"2022-10-26T02:47:26Z","timestamp":1666752446000},"page":"7242","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Chemical Composition of Tagetes patula Flowers Essential Oil and Hepato-Therapeutic Effect against Carbon Tetrachloride-Induced Toxicity (In-Vivo)"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1598-2273","authenticated-orcid":false,"given":"Hanan Y.","family":"Aati","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7741-7435","authenticated-orcid":false,"given":"Mahmoud","family":"Emam","sequence":"additional","affiliation":[{"name":"Phytochemistry and Plant Systematics Department, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jawaher","family":"Al-Qahtani","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, College of Pharmacy, King Saud University, P.O. Box 22452, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sultan","family":"Aati","sequence":"additional","affiliation":[{"name":"UWA Dental School, University of Western Australia, 17 Monash Avenue, Nedlands, WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulrahman","family":"Aati","sequence":"additional","affiliation":[{"name":"Rokn Al-Madaein Pharmaceutical Warehouse Co., P.O. Box 2990, Riyadh 11495, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juergen","family":"Wanner","sequence":"additional","affiliation":[{"name":"Kurt Kitzing Co., Hinterm Alten Schloss 21, D-86757 Wallerstein, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0131-0030","authenticated-orcid":false,"given":"Mohamed M.","family":"Seif","sequence":"additional","affiliation":[{"name":"Toxicology and Food Contaminants Department, Food Industries and Nutrition Research Institute, National Research Centre, Giza 12622, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S1462399411002110","article-title":"Molecular mechanisms underlying chemical liver injury","volume":"14","author":"Gu","year":"2012","journal-title":"Expert Rev. Mol. Med."},{"key":"ref_2","first-page":"91","article-title":"Oxidative stress biomarkers as indicator of chronic inflammatory joint diseases stage","volume":"6","author":"Ruiz","year":"2010","journal-title":"Reumatol. Clin."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.jep.2008.06.020","article-title":"Hepatoprotective activity of Woodfordia fruticosa Kurz flowers against carbon tetrachloride induced hepatotoxicity","volume":"119","author":"Chandan","year":"2008","journal-title":"J. Ethnopharmacol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Farzaei, M.H., Zobeiri, M., Parvizi, F., El-Senduny, F.F., Marmouzi, I., Coy-Barrera, E., Naseri, R., Nabavi, S.M., Rahimi, R., and Abdollahi, M. (2018). Curcumin in liver diseases: A systematic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients, 10.","DOI":"10.3390\/nu10070855"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1016\/j.foodchem.2010.05.052","article-title":"Protective effect of Pracparatum mungo extract on carbon tetrachloride-induced hepatotoxicity in rats","volume":"123","author":"Kuo","year":"2010","journal-title":"Food Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1080\/01480545.2018.1504960","article-title":"Protective effects of combined Losartan and Nilotinib on carbon tetrachloride (CCl4)-induced liver fibrosis in rats","volume":"43","author":"Karimi","year":"2020","journal-title":"Drug Chem. Toxicol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"6605","DOI":"10.3748\/wjg.v18.i45.6605","article-title":"Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice","volume":"18","author":"Huang","year":"2012","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1007\/s11095-014-1483-3","article-title":"Protective effects of calycosin against CCl 4-induced liver injury with activation of FXR and STAT3 in mice","volume":"32","author":"Chen","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1371\/journal.pone.0210576","article-title":"Metabolic profile and hepatoprotective effect of Aeschynomene elaphroxylon (Guill. & Perr.)","volume":"14","author":"Hashem","year":"2019","journal-title":"PLoS ONE"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1515\/reveh-2020-0048","article-title":"Toxicity of carbon tetrachloride, free radicals and role of antioxidants","volume":"36","author":"Unsal","year":"2020","journal-title":"Rev. Environ. Health"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.cbi.2014.07.017","article-title":"Oleanolic acid co-administration alleviates ethanol-induced hepatic injury via Nrf-2 and ethanol-metabolizing modulating in rats","volume":"221","author":"Liu","year":"2014","journal-title":"Chem.-Biol. Interact."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"62943","DOI":"10.1007\/s11356-021-15142-4","article-title":"Ephedra sinica mitigates hepatic oxidative stress and inflammation via suppressing the TLR4\/MyD88\/NF-\u03baB pathway in fipronil-treated rats","volume":"28","author":"Seif","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.13172\/2052-7845-1-1-518","article-title":"Aromatherapy: Overview, safety and quality issues","volume":"1","author":"Dunning","year":"2013","journal-title":"OA Altern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"9080","DOI":"10.1021\/jf201611b","article-title":"Isolation of nematicidal compounds from Tagetes patula L. yellow flowers: Structure\u2013activity relationship studies against cyst nematode Heterodera zeae infective stage larvae","volume":"59","author":"Faizi","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"8209","DOI":"10.1016\/j.arabjc.2020.09.055","article-title":"Chemical composition and antimicrobial activity of the essential oils of Artemisia absinthium, Artemisia scoparia, and Artemisia sieberi grown in Saudi Arabia","volume":"13","author":"Aati","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1038\/nbt.3597","article-title":"Sharing and community curation of mass spectrometry data with Global Natural Products Social Molecular Networking","volume":"34","author":"Wang","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A software environment for integrated models of biomolecular interaction networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_18","first-page":"217","article-title":"Antioxidant activity of Melissa officinalis leaves","volume":"5","author":"Koksal","year":"2011","journal-title":"J. Med. Plants Res."},{"key":"ref_19","first-page":"105","article-title":"Nitric oxide scavenging by curcuminoids","volume":"49","author":"Rao","year":"1997","journal-title":"J. Pharm. Pharmacol."},{"key":"ref_20","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_21","first-page":"262","article-title":"Evaluation of phytochemical, antimicrobial and toxicity studies of ethanolic stem extract of Phyllanthus amarus Thonn and Schum (Euphorbiacea)","volume":"3","author":"Mamza","year":"2015","journal-title":"Int. J. Sci. Technoledge"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/j.toxrep.2021.01.001","article-title":"Hepatoprotective, antioxidant and, anti-inflammatory potentials of gallic acid in carbon tetrachloride-induced hepatic damage in Wistar rats","volume":"8","author":"Ojeaburu","year":"2021","journal-title":"Toxicol. Rep."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.biortech.2012.12.144","article-title":"Hydrothermal liquefaction of Spirulina and Nannochloropsis salina under subcritical and supercritical water conditions","volume":"131","author":"Toor","year":"2013","journal-title":"Bioresour. Technol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1016\/0003-2697(79)90738-3","article-title":"Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction","volume":"95","author":"Ohkawa","year":"1979","journal-title":"Anal. Biochem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of total, protein-bound, and nonprotein sulfhydryl groups in tissue with Ellman\u2019s reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_26","unstructured":"Lowery, G.H. (1951). A Quantitative Study of The Nocturnal Migration of Birds, University of Kansas."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/ajcp\/28.1.56","article-title":"A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases","volume":"28","author":"Reitman","year":"1957","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0021-9258(18)43072-4","article-title":"A method for the rapid determination of alkaline phosphatase with five cubic millimeters of serum","volume":"164","author":"Otto","year":"1946","journal-title":"J. Biol. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1080\/20014091084227","article-title":"Gamma glutamyl transferase","volume":"38","author":"Whitfield","year":"2001","journal-title":"Crit. Rev. Clin. Lab. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1093\/clinchem\/31.11.1779","article-title":"Candidate reference method for determination of total bilirubin in serum: Development and validation","volume":"31","author":"Doumas","year":"1985","journal-title":"Clin. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"52E","DOI":"10.1016\/j.amjcard.2009.09.020","article-title":"Novel targets that affect high-density lipoprotein metabolism: The next frontier","volume":"104","author":"Davidson","year":"2009","journal-title":"Am. J. Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/0972060X.2018.1454343","article-title":"Chemical composition and biological activity of Mentha longifolia L. essential oil growing in Taif, KSA extracted by hydrodistillation, solvent free microwave and microwave hydrodistillation","volume":"21","author":"Salman","year":"2018","journal-title":"J. Essent. Oil Bear. Plants"},{"key":"ref_33","first-page":"32","article-title":"Chemical composition and antibacterial activity of the essential oil of Tagetes patula L. (Asteraceae) collected from the Venezuela Andes","volume":"34","author":"Rondon","year":"2006","journal-title":"Rev. Latinoam. Qu\u00edm."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Francomano, F., Caruso, A., Barbarossa, A., Fazio, A., La Torre, C., Ceramella, J., Mallamaci, R., Saturnino, C., Iacopetta, D., and Sinicropi, M.S. (2019). \u03b2-Caryophyllene: A sesquiterpene with countless biological properties. Appl. Sci., 9.","DOI":"10.3390\/app9245420"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"755","DOI":"10.17582\/journal.pjz\/2019.51.2.755.761","article-title":"Evaluation of Hepatotoxicity of Carbon Tetrachloride and Pharmacological Intervention by Vitamin E in Balb C Mice","volume":"51","author":"Mughal","year":"2019","journal-title":"Pak. J. Zool."},{"key":"ref_36","first-page":"1","article-title":"In vivo protective effect of Rosmarinus officinalis oil against carbon tetrachloride (CCl4)-induced hepatotoxicity in rats","volume":"9","author":"Elsanhoty","year":"2019","journal-title":"PharmaNutrition"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"243","DOI":"10.3109\/15376516.2016.1159769","article-title":"New mechanism in the modulation of carbon tetrachloride hepatotoxicity in rats using different natural antioxidants","volume":"26","author":"Fadda","year":"2016","journal-title":"Toxicol. Mech. Methods"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/0717-6287-47-49","article-title":"Protective effect of bixin on carbon tetrachloride-induced hepatotoxicity in rats","volume":"47","author":"Moreira","year":"2014","journal-title":"Biol. Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1080\/713611034","article-title":"Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model","volume":"33","author":"Weber","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1152\/ajplegacy.1966.210.1.31","article-title":"Choline-deficiency fatty liver: Relation of plasma phospholipids to liver triglycerides","volume":"210","author":"Lombardi","year":"1966","journal-title":"Am. J. Physiol.-Leg. Content"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12906-020-02906-7","article-title":"Poncirin attenuates CCL4-induced liver injury through inhibition of oxidative stress and inflammatory cytokines in mice","volume":"20","author":"Ullah","year":"2020","journal-title":"BMC Complement. Med. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1016\/j.etap.2014.03.011","article-title":"Ursolic acid protects mouse liver against CCl4-induced oxidative stress and inflammation by the MAPK\/NF-\u03baB pathway","volume":"37","author":"Ma","year":"2014","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Recknagel, R.O., Glende, E.A., and Britton, R.S. (2020). Free radical damage and lipid peroxidation. Hepatotoxicology, CRC Press.","DOI":"10.1201\/9780367812041-9"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/j.etp.2011.06.003","article-title":"Chlorella vulgaris extract ameliorates carbon tetrachloride-induced acute hepatic injury in mice","volume":"65","author":"Li","year":"2013","journal-title":"Exp. Toxicol. Pathol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0278-6915(01)00104-1","article-title":"Protective effect of Platycodi radix on carbon tetrachloride-induced hepatotoxicity","volume":"40","author":"Lee","year":"2002","journal-title":"Food Chem. Toxicol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2020.112718","article-title":"Traditional uses, Phyto-chemistry and pharmacological activities of Tagetes patula L.","volume":"255","author":"Riaz","year":"2020","journal-title":"J. Ethnopharmacol."},{"key":"ref_48","first-page":"16","article-title":"A Review on Pharmacological aspects of Tagetes erecta Linn","volume":"7","author":"Singh","year":"2019","journal-title":"PharmaTutor"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1515\/jbcpp-2012-0026","article-title":"Yoyo Bitters, a polyherbal formulation influenced some biochemical parameters in Wistar rats","volume":"23","author":"Adeyemi","year":"2012","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/S0378-8741(98)00087-7","article-title":"Anti-hepatotoxic effects of root and root callus extracts of Cichorium intybus L.","volume":"63","author":"Zafar","year":"1998","journal-title":"J. Ethnopharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"122","DOI":"10.4103\/1735-5362.253359","article-title":"Metformin attenuates oxidative stress and liver damage after bile duct ligation in rats","volume":"14","author":"Sadeghi","year":"2019","journal-title":"Res. Pharm. Sci."},{"key":"ref_52","first-page":"1","article-title":"4-OI Attenuates Carbon Tetrachloride-Induced Hepatic Injury via Regulating Oxidative Stress and the Inflammatory Response","volume":"12","author":"Li","year":"2021","journal-title":"Front. Pharmacol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.intimp.2017.09.013","article-title":"Docosahexaenoic acid attenuates carbon tetrachloride-induced hepatic fibrosis in rats","volume":"53","author":"He","year":"2017","journal-title":"Int. Immunopharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2478","DOI":"10.2174\/1568026614666141203120833","article-title":"Antioxidant, pro-oxidant and other biological activities of sesquiterpenes","volume":"14","author":"Bartikova","year":"2014","journal-title":"Curr. Top. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1017\/S0007114512001298","article-title":"The antioxidant effect of \u03b2-caryophyllene protects rat liver from carbon tetrachloride-induced fibrosis by inhibiting hepatic stellate cell activation","volume":"109","author":"Calleja","year":"2013","journal-title":"Br. J. Nutr."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7242\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:02:30Z","timestamp":1760144550000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/27\/21\/7242"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,25]]},"references-count":55,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["molecules27217242"],"URL":"https:\/\/doi.org\/10.3390\/molecules27217242","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,25]]}}}