{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:16:04Z","timestamp":1761365764841,"version":"build-2065373602"},"reference-count":109,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T00:00:00Z","timestamp":1761004800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Jiangsu key laboratory on innovation for Marine Medicine and Modern Chinese Medicine","award":["BM2024008"],"award-info":[{"award-number":["BM2024008"]}]},{"name":"The Lianyungang Postdoctoral Research Funding Program","award":["LYG20230010"],"award-info":[{"award-number":["LYG20230010"]}]},{"name":"The Foundation from Jiangsu Province","award":["JSSCBS20211307"],"award-info":[{"award-number":["JSSCBS20211307"]}]},{"name":"The Scientific Research Foundation of Jiangsu Ocean University","award":["KQ20047"],"award-info":[{"award-number":["KQ20047"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The bleeding sap of Luffa cylindrica (L.) Roem has been used for the treatment of tuberculosis since the record of Supplements to Compendium of Materia Medica. The active components and possible mechanism of it are yet ambiguous. Hence, this study is focused on investigating the possible mechanism underpinning this effect on the perspective of the antioxidant ingredients from the bleeding sap. Through organic solvents extraction, HPLC fractionation, DPPH trials evaluation, and UHPLC-Orbitrap tandem MS identification, a total of 37 compounds were identified from the bleeding sap with the strongest antioxidant ability. Network pharmacology, bioinformatics, and molecular docking as well as literature review revealed 13 compounds, including linoleic acid, abietic acid, and tretinoin, that might exert their anti-tuberculosis function via actions with PPAR\u03b3 or MAPK pathway. These findings offer guidance for the potential applications of Luffa cylindrica (L.) Roem as a functional food.<\/jats:p>","DOI":"10.3390\/ijms262010231","type":"journal-article","created":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T13:42:03Z","timestamp":1761054123000},"page":"10231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The UHPLC-Orbitrap MS\/MS and Network Pharmacology Strategies Reveal the Active Antioxidants of Bleeding Sap from Sponge Gourd in Treating Tuberculosis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7470-130X","authenticated-orcid":false,"given":"Di","family":"Zhang","sequence":"first","affiliation":[{"name":"Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang 222005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Jiang","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang 222005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yujiang","family":"Dai","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang 222005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0393-4223","authenticated-orcid":false,"given":"Xinxin","family":"Si","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang 222005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2268-5496","authenticated-orcid":false,"given":"Huifang","family":"Li","sequence":"additional","affiliation":[{"name":"Jiangsu Institute of Marine Resources Development, Jiangsu Ocean University, Lianyungang 222005, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3276-7439","authenticated-orcid":false,"given":"Komal","family":"Anjum","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacy, Ocean University of China, Qingdao 266000, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,21]]},"reference":[{"key":"ref_1","first-page":"355","article-title":"Research progress on pharmacological action of different parts of Luffa cylindrica (L.) roem","volume":"42","author":"Li","year":"2021","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_2","first-page":"156","article-title":"Antidiabetic and antihyperlipidemic activity of Luffa acutangula fruit extracts in streptozotocin induced NIDDM rats","volume":"4","author":"Pimple","year":"2011","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"ref_3","unstructured":"Hou, R.-Y. (2020). Supplements to the Compendium of Materia Medica, China Medical Science and Technology Press. Original Work Published 1765."},{"key":"ref_4","first-page":"822","article-title":"Hepatoprotective activity of Luffa acutangula against CCl4 and rifampicin induced liver toxicity in rats: A biochemical and histopathological evaluation","volume":"48","author":"Jadhav","year":"2010","journal-title":"Indian J. Exp. Biol."},{"key":"ref_5","first-page":"5227","article-title":"In vivo and ex vivo evaluation of Luffa acutangula fruit extract and its fractions for hepatoprotective activity in wistar rats","volume":"8","author":"Mishra","year":"2017","journal-title":"Int. J. Pharm. Sci. Res."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Zhang, L., Wang, P.-P., Shi, M.-X., Fang, Z.-Z., Ji, J.-F., Liao, X.-J., Hu, X.-S., and Chen, F. (2020). The modulation of Luffa cylindrica (L.) roem supplementation on gene expression and amino acid profiles in liver for alleviating hepatic steatosis via gut microbiota in high-fat diet-fed mice: Insight from hepatic transcriptome analysis. J. Nutr. Biochem., 80.","DOI":"10.1016\/j.jnutbio.2020.108365"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"103941","DOI":"10.1016\/j.jff.2020.103941","article-title":"Lucyoside B, a triterpenoid saponin from Luffa cylindrica, inhibits the production of inflammatory mediators via both nuclear factor-\u03baB and activator protein-1 pathways in activated macrophages","volume":"69","author":"Han","year":"2020","journal-title":"J. Funct. Foods"},{"key":"ref_8","first-page":"519","article-title":"Anti-inflammatory activity of ethanolic extract of Luffa acutangular","volume":"6","author":"Palash","year":"2017","journal-title":"World J. Pharm. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/j.bionut.2012.03.002","article-title":"Luffa acutangula and Lippia nodiflora leaf extract induces growth inhibitory effect through induction of apoptosis on human lung cancer cell line","volume":"2","author":"Vanajothia","year":"2012","journal-title":"Biomed. Prev. Nutr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"111877","DOI":"10.1016\/j.jep.2019.111877","article-title":"Cytotoxic effect of aqueous ethanolic extract of Luffa cylindrica leaves on cancer stem cells CD44\/24 in breast cancer patients with various molecular sub-typesusing tissue samples in vitro","volume":"238","author":"Ashour","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"315","DOI":"10.33786\/JCPR.2011.v01i04.005","article-title":"Protective role of Luffa cylindrica linn. against erythromycin estolate induced hepatotoxicity","volume":"1","author":"Shete","year":"2011","journal-title":"J. Curr. Pharma Res."},{"key":"ref_12","first-page":"143","article-title":"Hepatoprotective activity of Luffa cylindrica (L.) M. J. Roem. leaf extract in paracetamol intoxicated rats","volume":"5","author":"Sharma","year":"2014","journal-title":"Indian J. Nat. Prod. Resour."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"59","DOI":"10.5530\/pj.2011.23.9","article-title":"Comparative study of in vitro antioxidant, antibacterial and cytotoxic activity of two Bangladeshi medicinal plants-Luffa cylindrica L. and Luffa acutangular","volume":"3","author":"Bulbul","year":"2011","journal-title":"Pharmacogn. J."},{"key":"ref_14","first-page":"1264","article-title":"Effects of Retinervus luffae fructus on serum lipid level in experimental hyperlipidemia rats","volume":"20","author":"Li","year":"2004","journal-title":"Chin. J. Pathophysiol."},{"key":"ref_15","first-page":"1156","article-title":"Effects of Retinervus luffae fructus on mRNA expression of low-density lipoprotein receptor in hyperlipidemia mice","volume":"25","author":"Li","year":"2009","journal-title":"Chin. J. Pathophysiol."},{"key":"ref_16","first-page":"4","article-title":"Effect of aerobic exercise combined with Retinervus Luffae fructus on AQP2 mRNA expression in kidney of diabetic rat model","volume":"53","author":"Fang","year":"2013","journal-title":"Shandong Med. J."},{"key":"ref_17","first-page":"1020","article-title":"Effects of Luffae on cardiac function in chronic heart failure rats","volume":"22","author":"Pu","year":"2011","journal-title":"Lishizhen Med. Mater. Med. Res."},{"key":"ref_18","first-page":"2588","article-title":"Effect of Luffae on myocardial calmodulin mRNA expression in chronic heart failure rats","volume":"33","author":"Fang","year":"2013","journal-title":"Chin. J. Gerontol."},{"key":"ref_19","first-page":"293","article-title":"Preliminary studies of Luffa-extract on allergy and acute inflammation","volume":"32","author":"Kou","year":"2001","journal-title":"J. China Pharm. Univ."},{"key":"ref_20","first-page":"1","article-title":"Study on the mechanism of extracts in vine of Luffa on the treatment of allergic rhinitis","volume":"18","author":"Chen","year":"2015","journal-title":"J. Guangxi Univ. Chin. Med."},{"key":"ref_21","first-page":"149","article-title":"Study on the antioxidant activity and its stability of bleeding sap from Luffa cylindrica roem","volume":"34","author":"Wang","year":"2009","journal-title":"Food Sci. Technol."},{"key":"ref_22","first-page":"84","article-title":"Preliminary study on antioxidants in bleeding sap from Luffa cylindrica roem","volume":"30","author":"Wang","year":"2009","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_23","first-page":"609","article-title":"Purification and characterization of two luffaculins, ribosome-inactivating proteins from seeds of Luffa acutangular","volume":"18","author":"Lin","year":"2002","journal-title":"Chin. J. Biochem. Mol. Biol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"372","DOI":"10.3724\/SP.J.1009.2008.00372","article-title":"Anti-HIV-1 activities of luffaculin 1","volume":"6","author":"Long","year":"2008","journal-title":"Chin. J. Nat. Med."},{"key":"ref_25","first-page":"349","article-title":"Differentiation-inducing effect of luffaculin-2 on B16 melanoma cells","volume":"39","author":"Xie","year":"2005","journal-title":"J. Fujian Med. Univ."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4186","DOI":"10.1021\/jf0604790","article-title":"Antioxidant constituents in the fruits of Luffa cylindrica (L.) roem","volume":"54","author":"Du","year":"2006","journal-title":"J. Agric. Food. Chem."},{"key":"ref_27","first-page":"148","article-title":"Optimization of ethanol extraction process of total flavonoids from pumpkin leaves","volume":"28","author":"Du","year":"2007","journal-title":"Sci. Technol. Food Ind."},{"key":"ref_28","first-page":"36","article-title":"Determination of the content of polysaccharide in Retinervus luffac fructus produced in Henan province with phenol-sulfuric acid","volume":"25","author":"Yu","year":"2008","journal-title":"J. Xinxiang Med. Coll."},{"key":"ref_29","first-page":"86","article-title":"Extraction and contents analysis of oleanolic acid from stem Luffa and leaf Luffa","volume":"25","author":"Zhou","year":"2014","journal-title":"J. Guangxi Univ. Sci. Technol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.13189\/ujps.2016.040101","article-title":"Nutritional analysis of selected cucurbitaceae species","volume":"4","author":"Ogunbanjo","year":"2016","journal-title":"Univ. J. Plant Sci."},{"key":"ref_31","first-page":"166","article-title":"Overview of research on the medicinal value of Loofah","volume":"20","author":"Song","year":"2004","journal-title":"Chin. Agric. Sci. Bull."},{"key":"ref_32","first-page":"1173","article-title":"Application of combined detection of Mycobacterium tuberculosis-specific IFN-\u03b3 and IL-2 in the differential diagnosis of pulmonary tuberculosis and bacterial pneumonia","volume":"23","author":"Xu","year":"2024","journal-title":"Chin. J. Infect. Control"},{"key":"ref_33","first-page":"102","article-title":"Traditional and medicinal uses of Luffa cylindrica: A review","volume":"1","author":"Azeez","year":"2013","journal-title":"J. Med. Plants Stud."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4288","DOI":"10.1039\/c3ay40367j","article-title":"Application of free radical diphenylpicrylhydrazyl (DPPH) to estimate the antioxidant capacity of food samples","volume":"5","author":"Pyrzynska","year":"2013","journal-title":"Anal. Methods"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/s41592-021-01116-4","article-title":"Ultra-high-performance liquid chromatography high-resolution mass spectrometry variants for metabolomics research","volume":"18","author":"Alseekh","year":"2021","journal-title":"Nat. Methods"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"110","DOI":"10.3724\/SP.J.1009.2013.00110","article-title":"Traditional Chinese medicine network pharmacology: Theory, methodology and application","volume":"11","author":"Li","year":"2013","journal-title":"Chin. J. Nat. Med."},{"key":"ref_37","first-page":"1","article-title":"TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches","volume":"19","author":"Wang","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Jiao, X.-Y., Jin, X., Ma, Y.-Y., Yang, Y., Li, J.-J., Liang, L.-Y., Liu, R., and Li, Z. (2021). A comprehensive application: Molecular docking and network pharmacology for the prediction of bioactive constituents and elucidation of mechanisms of action in component-based Chinese medicine. Comput. Biol. Chem., 90.","DOI":"10.1016\/j.compbiolchem.2020.107402"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Liang, H., Ruan, H., Ouyang, Q., and Lai, L.-H. (2016). Herb-target interaction network analysis helps to disclose molecular mechanism of traditional Chinese medicine. Sci. Rep., 6.","DOI":"10.1038\/srep36767"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1002\/(SICI)1096-9888(199602)31:2<184::AID-JMS283>3.0.CO;2-2","article-title":"Identification of fatty acids by electrospray mass spectrometry and tandem mass spectrometry","volume":"31","author":"Kerwin","year":"1996","journal-title":"J. Mass Spectrom."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.chroma.2016.01.038","article-title":"Profiling of 3-hydroxy fatty acids as environmental markers of endotoxin using liquid chromatography coupled to tandem mass spectrometry","volume":"1434","author":"Uhlig","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"12223","DOI":"10.1021\/acs.analchem.7b03020","article-title":"Twin derivatization strategy for high-coverage quantification of free fatty acids by liquid chromatography\u2013tandem mass spectrometry","volume":"89","author":"Jiang","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1016\/j.microc.2018.03.018","article-title":"Liquid chromatography-tandem mass spectrometric analysis of acetyl tributyl citrate for migration testing of food contact materials","volume":"139","author":"Kim","year":"2018","journal-title":"Microchem. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9216","DOI":"10.1016\/j.arabjc.2020.11.006","article-title":"Phytochmical and biological characterization of Tephrosia nubica Boiss. growing in Saudi Arabia","volume":"13","author":"Abdelaziz","year":"2020","journal-title":"Arab. J. Chem."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1016\/j.foodchem.2012.12.052","article-title":"Fatty acid profiling of the seed oils of some varieties of field peas (Pisum sativum) by RP-LC\/ESI-MS\/MS: Towards the development of an oilseed pea","volume":"139","author":"Patel","year":"2013","journal-title":"Food Chem."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1007\/s11745-998-0280-0","article-title":"Analysis of novel hydroperoxides and other metabolites of oleic, linoleic, and linolenic acids by liquid chromatography-mass spectrometry with ion trap MSn","volume":"33","author":"Oliw","year":"1998","journal-title":"Lipids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"10270","DOI":"10.1021\/acs.analchem.7b01870","article-title":"Identification and quantitation of C=C location isomers of unsaturated fatty acids by epoxidation reaction and tandem mass spectrometry","volume":"89","author":"Zhao","year":"2017","journal-title":"Anal. Chem."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Zhao, X., He, Y.-Z., Chen, J.-G., Zhang, J.-Y., Chen, L., Wang, B.-C., Wu, C.-Y., and Yuan, Y.-Z. (2021). Identification and direct determination of fatty acids profile in oleic acid by HPLC-CAD and MS-IT-TOF. J. Pharm. Biomed. Anal., 204.","DOI":"10.1016\/j.jpba.2021.114238"},{"key":"ref_49","first-page":"e2024045","article-title":"Bioactive compounds and antioxidant activity in Greek-style yoghurt infused with shield aralia leaves","volume":"23","author":"Pertami","year":"2024","journal-title":"Nat. Life Sci. Commun."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.sajb.2022.02.004","article-title":"GC-MS and UHPLC-HRMS based metabolite profiling of Bruguiera gymnorhiza reveals key bioactive compounds","volume":"149","author":"Dahibhate","year":"2022","journal-title":"S. Afr. J. Bot."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1002\/rcm.467","article-title":"Study of mass spectrometric fragmentations of tributyl phosphate via collision-induced dissociation","volume":"15","author":"Lesage","year":"2001","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.chroma.2016.02.058","article-title":"Simultaneous determination of 16 organophosphorus flame retardants and plasticizers in fish by liquid chromatography-tandem mass spectrometry","volume":"1441","author":"Eljarrat","year":"2016","journal-title":"J. Chromatogr. A"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1002\/rcm.2937","article-title":"Liquid chromatography\/tandem mass spectrometry determination of organophosphorus flame retardants and plasticizers in drinking and surface waters","volume":"21","author":"Bacaloni","year":"2007","journal-title":"Rapid Commun. Mass Spectrom."},{"key":"ref_54","first-page":"6654611","article-title":"Identification of 24 unknown substances (NIAS\/IAS) from food contact polycarbonate by LC-Orbitrap Tribrid HRMS-DDMS3: Safety assessment","volume":"2021","author":"Dualde","year":"2021","journal-title":"Int. J. Anal. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1093\/jaoac\/94.2.428","article-title":"A new approach to the analysis of nicarbazin and ionophores in eggs by HPLC\/MS\/MS","volume":"94","author":"Dmitrovic","year":"2011","journal-title":"J. AOAC Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2750","DOI":"10.1002\/jssc.201901204","article-title":"Simultaneous separation and determination of 20 potential adulterant antigout and antiosteoporosis pharmaceutical compounds in herbal food products using LC with electrospray ionization MS\/MS and LC with quadrupole-time-of-flight MS","volume":"43","author":"Kim","year":"2020","journal-title":"J. Sep. Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1021\/ac00265a004","article-title":"Analysis of anionic surfactants by mass spectrometry\/mass spectrometry with fast atom bombardment","volume":"56","author":"Lyon","year":"1984","journal-title":"Anal. Chem."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1021\/ac00207a006","article-title":"Ion chromatography\/mass spectrometry for the determination of organic ammonium and sulfate compounds","volume":"62","author":"Conboy","year":"1990","journal-title":"Anal. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"134025","DOI":"10.1016\/j.jhazmat.2024.134025","article-title":"Innovative non-targeted screening approach using high-resolution mass spectrometry for the screening of organic chemicals and identification of specific tracers of soil and dust exposure in children","volume":"469","author":"Ogunbiyi","year":"2024","journal-title":"J. Hazard. Mater."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"12385","DOI":"10.1021\/acs.est.6b03762","article-title":"Highly selective screening of estrogenic compounds in consumer-electronics plastics by liquid chromatography in parallel combined with nano fractionation-bioactivity detection and mass spectrometry","volume":"50","author":"Jonker","year":"2016","journal-title":"Environ. Sci. Technol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1093\/chrsci\/49.4.337","article-title":"Simultaneous determination of nine types of phthalate residues in commercial milk products using HPLC-ESI-MS-MS","volume":"49","author":"Li","year":"2011","journal-title":"J. Chromatogr. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1255\/ejms.1096","article-title":"Structural characterisation of degradation products formed upon di-n-butyl phthalate radiolysis by high-performance liquid chromatography electrospray tandem mass spectrometry","volume":"16","author":"Tintaru","year":"2010","journal-title":"Eur. J. Mass Spectrom."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"107834","DOI":"10.1016\/j.envint.2023.107834","article-title":"Target analysis and suspect screening of UV filters, parabens and other chemicals used in personal care products in human cord blood: Prenatal exposure by mother-fetus transfer","volume":"173","year":"2023","journal-title":"Environ. Int."},{"key":"ref_64","first-page":"75","article-title":"Determination of abietic acid compounds in poultry by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry coupled with dispersive solid phase extraction","volume":"39","author":"Lin","year":"2023","journal-title":"Food Mach."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"6599","DOI":"10.1007\/s00216-016-9772-9","article-title":"Analysis of diterpenic compounds by GC-MS\/MS: Contribution to the identification of main conifer resins","volume":"408","author":"Azemard","year":"2016","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Patyra, A., Dudek, M.K., and Kiss, A.K. (2022). LC-DAD-ESI-MS\/MS and NMR analysis of conifer wood specialized metabolites. Cells, 11.","DOI":"10.3390\/cells11203332"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1002\/etc.322","article-title":"Determination and occurrence of retinoic acids and their 4-oxo metabolites in Liaodong Bay, China, and its adjacent rivers","volume":"29","author":"Wu","year":"2010","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1702","DOI":"10.1021\/ac702030f","article-title":"Quantitative profiling of endogenous retinoic acid in vivo and in vitro by tandem mass spectrometry","volume":"80","author":"Kane","year":"2008","journal-title":"Anal. Chem."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/S1044-0305(01)00226-4","article-title":"Determination of flavone, flavonol, and flavanone aglycones by negative ion liquid chromatography electrospray ion trap mass spectrometry","volume":"12","author":"Fabre","year":"2001","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1247","DOI":"10.1016\/S1044-0305(03)00534-8","article-title":"Identification of diethylene glycol monobutyl ether as a source of contamination in an ion trap mass spectrometer","volume":"14","author":"Gibson","year":"2003","journal-title":"J. Am. Soc. Mass Spectrom."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.aca.2008.04.040","article-title":"Confirmatory analysis of trenbolone using accurate mass measurement with LC\/TOF-MS","volume":"618","author":"Blokland","year":"2008","journal-title":"Anal. Chim. Acta"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.steroids.2008.10.004","article-title":"Doping control analysis of trenbolone and related compounds using liquid chromatography\u2013tandem mass spectrometry","volume":"74","author":"Thevis","year":"2009","journal-title":"Steroids"},{"key":"ref_73","first-page":"881","article-title":"Xinglou Chengqi Decoction improves neurological function in experimental stroke mice as evidenced by gut microbiota analysis and network pharmacology","volume":"19","author":"Gao","year":"2021","journal-title":"Chin. J. Nat. Med."},{"key":"ref_74","unstructured":"World Health Organization (2023). Global Tuberculosis Report 2023 [R\/OL], WHO."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Alashavi, H., Daher, M., Chorgoliani, D., Saflo, M., Zeidan, M., Huseyinibrahim, F., Ismail, E., Yousef, A.R.H., Ayat, K., and Elobayd, E. (2021). Descriptive epidemiology of the tuberculosis service delivery project beneficiaries in northwest Syria: 2019\u20132020. Front. Public Health, 9.","DOI":"10.3389\/fpubh.2021.672114"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1016\/j.ijantimicag.2017.01.042","article-title":"Role of second-line injectable antituberculosis drugs in the treatment of MDR\/XDR tuberculosis","volume":"50","author":"Quenard","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_77","first-page":"186","article-title":"Study on preparing juice of towel gourd into solid powder by spray drying and it\u2019s bactriostasis","volume":"2012","author":"Yang","year":"2012","journal-title":"Nor. Horticul."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101","DOI":"10.12677\/HJFNS.2015.44014","article-title":"Chemical composition of bleeding sap of sponge gourd and in vitro antioxidant activity","volume":"4","author":"Wang","year":"2015","journal-title":"Hans J. Food Nutr. Sci."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1038\/aps.2017.208","article-title":"Astragaloside IV ameliorates neuroinflammation-induced depressive-like behaviors in mice via the PPAR\u03b3\/NF-\u03baB\/NLRP3 inflammasome axis","volume":"39","author":"Song","year":"2018","journal-title":"Acta Pharmacol. Sin."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1002\/JLB.3RU1018-378RR","article-title":"M2b macrophage polarization and its roles in diseases","volume":"106","author":"Wang","year":"2019","journal-title":"J. Leukoc. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1111\/j.1749-6632.2002.tb04258.x","article-title":"PPARs: Transcription factors controlling lipid and lipoprotein metabolism","volume":"967","author":"Bocher","year":"2002","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"154338","DOI":"10.1016\/j.metabol.2020.154338","article-title":"The role of peroxisome proliferator-activated receptors (PPAR) in immune responses","volume":"114","author":"Christofides","year":"2021","journal-title":"Metabolism"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1016\/S0014-5793(03)00859-7","article-title":"Abietic acid activates peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) in RAW264.7 macrophages and 3T3-L1 adipocytes to regulate gene expression involved in inflammation and lipid metabolism","volume":"550","author":"Takahashi","year":"2003","journal-title":"FEBS Lett."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"383829","DOI":"10.1155\/2012\/383829","article-title":"PPAR\u03b3 expression and function in mycobacterial infection: Roles in lipid metabolism, immunity, and bacterial killing","volume":"2012","author":"Almeida","year":"2012","journal-title":"PPAR Res."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Arnett, E., Weaver, A.M., Woodyard, K.C., Montoya, M.J., Li, M., Hoang, K.V., Hayhurst, A., Azad, A.K., and Schlesinger, L.S. (2018). PPAR\u03b3 is critical for Mycobacterium tuberculosis induction of Mcl-1 and limitation of human macrophage apoptosis. PLOS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007100"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Ye, Y.-T., Liu, J., Guo, Y., Gao, Y.-J., Rao, J.-Y., Su, R.-G., Zhang, L., Huang, Z.-K., Luo, Q., and Li, J.-M. (2022). PPAR\u03b3 ameliorates Mycobacterium tuberculosis H37Ra-induced foamy macrophage formation via the ABCG1-dependent cholesterol efflux pathway in THP-1 macrophages. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.829870"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"eaay8085","DOI":"10.1126\/science.aay8085","article-title":"Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense","volume":"370","author":"Bosch","year":"2020","journal-title":"Science"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"102567","DOI":"10.1016\/j.tube.2024.102567","article-title":"Tuberculosis and T cells: Impact of T cell diversity in tuberculosis infection","volume":"149","author":"Vats","year":"2024","journal-title":"Tuberculosis"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1023\/A:1023309928879","article-title":"Role of mitogen-activated protein kinase pathways in the production of tumor necrosis factor-alpha, interleukin-10, and monocyte chemotactic protein-1 by Mycobacterium tuberculosis H37Rv-infected human monocytes","volume":"23","author":"Song","year":"2003","journal-title":"J. Clin. Immunol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.molimm.2020.11.020","article-title":"Mycobacterium tuberculosis EsxL induces TNF-\u03b1 secretion through activation of TLR2 dependent MAPK and NF-\u03baB pathways","volume":"130","author":"Pattanaik","year":"2021","journal-title":"Mol. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"115368","DOI":"10.1016\/j.jep.2022.115368","article-title":"The licorice flavonoid isoliquiritigenin attenuates Mycobacterium tuberculosis-induced inflammation through Notch1\/NF-\u03baB and MAPK signaling pathways","volume":"294","author":"Sun","year":"2022","journal-title":"J. Ethnopharmacol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1093\/infdis\/jiad460","article-title":"Adjunct therapy with all-trans-retinoic acid improves therapeutic efficacy through immunomodulation while treating tuberculosis with antibiotics in mice","volume":"229","author":"Singh","year":"2024","journal-title":"J. Infect. Dis."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1002\/jcp.26575","article-title":"Abietic acid attenuates RANKL induced osteoclastogenesis and inflammation associated osteolysis by inhibiting the NF-KB and MAPK signaling","volume":"234","author":"Thummuri","year":"2018","journal-title":"J. Cell. Physiol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.4314\/tjpr.v22i8.7","article-title":"Abietic acid ameliorates pancreatic injury in acute pancreatitis by modulating MAPK pathway","volume":"22","author":"Ye","year":"2023","journal-title":"Trop. J. Pharm. Res."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"114396","DOI":"10.1016\/j.ecoenv.2022.114396","article-title":"Dibutyl phthalate affects insulin synthesis and secretion by regulating the mitochondrial apoptotic pathway and oxidative stress in rat insulinoma cells","volume":"249","author":"Yang","year":"2023","journal-title":"Ecotoxicol. Environ. Saf."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"938","DOI":"10.1177\/0960327119843583","article-title":"Dibutyl phthalate-induced activation of ROS and ERK1\/2 causes hepatic and renal damage in Kunming mice","volume":"38","author":"Cheng","year":"2019","journal-title":"Hum. Exp. Toxicol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.etap.2018.08.007","article-title":"Phthalates promote prostate cancer cell proliferation through activation of ERK5 and p38","volume":"63","author":"Zhu","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"116933","DOI":"10.1016\/j.taap.2024.116933","article-title":"Di-n-butyl phthalate induces toxicity in male fetal mouse testicular development by regulating the MAPK signaling pathway","volume":"486","author":"Wan","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_99","unstructured":"(2025, August 12). GeneCards. Available online: https:\/\/www.genecards.org\/."},{"key":"ref_100","unstructured":"(2025, August 12). The GEO Database, Available online: https:\/\/www.ncbi.nlm.nih.gov\/geo\/."},{"key":"ref_101","unstructured":"(2025, August 12). Venny 2.1.0. Available online: https:\/\/bioinfogp.cnb.csic.es\/tools\/venny\/\/."},{"key":"ref_102","unstructured":"(2025, August 12). The Protein Data Bank. Available online: https:\/\/www.rcsb.org\/."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Wang, D., Li, X.-B., Li, Y.-F., Wang, R.-L., Wang, C.-X., and Li, Y.-W. (2024). New molecular mechanisms of quercetin in improving recurrent spontaneous abortion based on in-depth network pharmacology and molecular docking. Front. Chem., 12.","DOI":"10.3389\/fchem.2024.1407667"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Shah, A.B., Baiseitova, A., Amzeyeva, U., Shang, X., and Jenis, J. (2025). \u03b1-Glucosidase Inhibition-Guided Network Pharmacology and Molecular Docking Reveal the Antidiabetic Potential of Cichorium intybus as a Functional Food. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26199497"},{"key":"ref_105","unstructured":"(2025, August 12). PubChem, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/."},{"key":"ref_106","unstructured":"(2025, August 12). SwissTargetPrediction. Available online: http:\/\/www.swisstargetprediction.ch\/."},{"key":"ref_107","unstructured":"(2025, August 12). The OMIM. Available online: https:\/\/www.omim.org\/."},{"key":"ref_108","unstructured":"(2025, August 12). DISGENET. Available online: https:\/\/disgenet.com\/."},{"key":"ref_109","unstructured":"(2025, August 12). The STRING database. Available online: https:\/\/string-db.org\/."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,25]],"date-time":"2025-10-25T04:11:28Z","timestamp":1761365488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,21]]},"references-count":109,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010231"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010231","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2025,10,21]]}}}