{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:58:00Z","timestamp":1762181880267,"version":"build-2065373602"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Van Lang University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objective:\u00a0Eclipta prostrata (L.) L. is a traditional medicinal herb utilized throughout Asia that is widely used for hepatoprotective activity, wound healing, and blood cooling\/bleeding disorders. This work aimed to identify bioactive constituents from E. prostrata collected in Vietnam, and clarify their anti-inflammatory capacity of the extract and active fraction. Method: Extraction and isolation of compounds from the extract of E. prostrata were performed. The extract, fractions, and isolated compounds were evaluated for inflammatory cytokines in LPS-stimulated RAW264.7 cells. Isolates showed inflammatory potential by in silico approaches. Results: Thirteen compounds, comprising a first isolated compound (diosmin), flavonoids, and phenolic derivatives, were separated and identified. The protein\u2013protein interaction (PPI) network demonstrated TNF, IL6, AKT1, NFKB1, EGFR, and PTGS2 as central targets, highlighting their significance in inflammatory signaling. Gene Ontology and KEGG pathway enrichment underscored substantial participation in TNF and IL-17 cytokine signaling pathways. Molecular docking demonstrated robust interactions between several flavonoids and core targets, indicating their function as essential regulators. Experimental validation in LPS-stimulated RAW264.7 macrophages revealed that wedelolactone, luteolin, apigenin, and quercetin significantly inhibited TNF-\u03b1 and IL-6 production. Conclusions: The results proposed that E. prostrata demonstrates its anti-inflammatory efficacy via a multi-target, poly-pharmacological strategy that encompasses central cytokine pathways and upstream receptor-mediated signaling. Our findings offer new mechanistic evidence that supports the ethnomedicinal application of E. prostrata and indicates its potential as a valuable natural resource for treating anti-inflammatory diseases.<\/jats:p>","DOI":"10.3390\/ph18111653","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T13:47:58Z","timestamp":1762177678000},"page":"1653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification and Integrative Discovery of Anti-Inflammatory Compounds Isolated from Eclipta prostrata (L.) L. by Network Pharmacology, Molecular Docking, and In Vitro Evaluation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7984-641X","authenticated-orcid":false,"given":"Cao","family":"Van Anh","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Education, Vietnam Military Medical University, Hanoi 100000, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1060-6116","authenticated-orcid":false,"given":"Nguyen Ngoc","family":"Linh","sequence":"additional","affiliation":[{"name":"Institute of Medicine and Pharmacy, Thanh Do University, Hoai Duc, Hanoi, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2792-5842","authenticated-orcid":false,"given":"Phuochien","family":"Phan","sequence":"additional","affiliation":[{"name":"Institute of Applied Science and Technology, Van Lang School of Technology, Van Lang University, Ho Chi Minh City, Vietnam"},{"name":"Faculty of Applied Technology, Van Lang School of Technology, Van Lang University, Ho Chi Minh City, Vietnam"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"112109","DOI":"10.1016\/j.jep.2019.112109","article-title":"A review on traditional uses, phytochemistry and pharmacology of Eclipta prostrata (L.) L.","volume":"245","author":"Feng","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1248\/bpb.b20-00994","article-title":"PTP1B inhibitory and anti-inflammatory properties of constituents from Eclipta prostrata L.","volume":"44","author":"Le","year":"2021","journal-title":"Biol. Pharm. Bull."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4016","DOI":"10.1016\/j.fct.2012.08.007","article-title":"Eclipta prostrata L. phytochemicals: Isolation, structure elucidation, and their antitumor activity","volume":"50","author":"Liu","year":"2012","journal-title":"Food Chem. Toxicol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Yang, J., Kim, J.S., Kwon, Y.S., Seong, E.S., and Kim, M.J. (2023). Antioxidant and antiproliferative activities of Eclipta prostrata (L.) L. extract and isolated compounds. Molecules, 28.","DOI":"10.3390\/molecules28217354"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/ptr.2252","article-title":"HIV-1 protease and HIV-1 integrase inhibitory substances from Eclipta prostrata","volume":"21","author":"Tewtrakul","year":"2007","journal-title":"Phytother. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"115764","DOI":"10.1016\/j.biopha.2023.115764","article-title":"Biochemical aspects of the inflammatory process: A narrative review","volume":"168","author":"Soares","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Soliman, A.M., and Barreda, D.R. (2023). Acute inflammation in tissue healing. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24010641"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"7204","DOI":"10.18632\/oncotarget.23208","article-title":"Inflammatory responses and inflammation-associated diseases in organs","volume":"9","author":"Chen","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/intimm\/dxaa078","article-title":"IL-6 in inflammation, autoimmunity and cancer","volume":"33","author":"Hirano","year":"2021","journal-title":"Int. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"365","DOI":"10.3389\/fcell.2020.00365","article-title":"The balance of TNF mediated pathways regulates inflammatory cell death signaling in healthy and diseased tissues","volume":"8","author":"Webster","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4157","DOI":"10.7150\/ijbs.86492","article-title":"The PTGS2\/COX2-PGE2 signaling cascade in inflammation: Pro or anti? A case study with type 1 diabetes mellitus","volume":"19","author":"Lorenzo","year":"2023","journal-title":"Int. J. Biol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"14552","DOI":"10.1073\/pnas.0904073106","article-title":"Akt1 is critical for acute inflammation and histamine-mediated vascular leakage","volume":"106","author":"Cirino","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1111\/febs.13627","article-title":"NFKB1: A suppressor of inflammation, ageing and cancer","volume":"283","author":"Cartwright","year":"2016","journal-title":"FEBS J."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"18180","DOI":"10.1039\/C7RA12568B","article-title":"Deconvoluting the dual hypoglycemic effect of wedelolactone isolated from Wedelia calendulacea: Investigation via experimental validation and molecular docking","volume":"8","author":"Kumar","year":"2018","journal-title":"RSC Adv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s12858-018-0095-7","article-title":"Isolation of quercetin and mandelic acid from Aesculus indica fruit and their biological activities","volume":"19","author":"Zahoor","year":"2018","journal-title":"BMC Biochem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e05412","DOI":"10.1016\/j.heliyon.2020.e05412","article-title":"Botanicals from the leaves of Acacia sieberiana had better cytotoxic effects than isolated phytochemicals towards MDR cancer cells lines","volume":"6","author":"Ngaffo","year":"2020","journal-title":"Heliyon"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Kim, J.H., and Jin, C.H. (2020). Inhibitory activity of flavonoids, chrysoeriol and luteolin-7-O-glucopyranoside, on soluble epoxide hydrolase from Capsicum chinense. Biomolecules, 10.","DOI":"10.3390\/biom10020180"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1007\/s10600-021-03308-y","article-title":"Chemical constituents of Eclipta prostrata","volume":"57","author":"Xiong","year":"2021","journal-title":"Chem. Nat. Compd."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"119","DOI":"10.20307\/nps.2018.24.2.119","article-title":"Antioxidant compounds isolated from the roots of Phlomis umbrosa Turcz","volume":"24","author":"Nguyen","year":"2018","journal-title":"Nat. Prod. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1002\/ptr.3383","article-title":"Antiinflammatory constituents from Eclipta prostrata using RAW264.7 macrophage cells","volume":"25","author":"Tewtrakul","year":"2011","journal-title":"Phytother. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"104243","DOI":"10.1016\/j.compbiomed.2021.104243","article-title":"Construction and analysis of protein-protein interaction network of non-alcoholic fatty liver disease","volume":"131","author":"Amanatidou","year":"2021","journal-title":"Comput. Biol. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e162","DOI":"10.1055\/s-0042-1751315","article-title":"Structural Characterization of Chemical Compounds Based on Their Fragmentation Rules in Sophorae fructus by UPLC-QTOF-MS\/MS","volume":"04","author":"He","year":"2022","journal-title":"Pharm. Front."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1453529","DOI":"10.3389\/fcimb.2024.1453529","article-title":"Combining network pharmacology, machine learning, molecular docking and molecular dynamic to explore the mechanism of Chufeng Qingpi decoction in treating schistosomiasis","volume":"14","author":"Liu","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_24","first-page":"5484","article-title":"LPS-induced proinflammatory cytokine expression in human airway epithelial cells and macrophages via NF-\u03baB, STAT3 or AP-1 activation","volume":"17","author":"Liu","year":"2018","journal-title":"Mol. Med. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Baek, S.-H., Park, T., Kang, M.-G., and Park, D. (2020). Anti-inflammatory activity and ROS regulation effect of sinapaldehyde in LPS-stimulated RAW 264.7 macrophages. Molecules, 25.","DOI":"10.3390\/molecules25184089"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/s42004-019-0205-5","article-title":"An investigation of structural stability in protein-ligand complexes reveals the balance between order and disorder","volume":"2","author":"Majewski","year":"2019","journal-title":"Commun. Chem."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"20974","DOI":"10.1038\/s41598-020-77750-3","article-title":"Identification of potential TNF-\u03b1 inhibitors: From in silico to in vitro studies","volume":"10","author":"Zia","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e15112","DOI":"10.1111\/febs.15112","article-title":"A natural AKT inhibitor swertiamarin targets AKT-PH domain, inhibits downstream signaling, and alleviates inflammation","volume":"287","author":"Zhang","year":"2020","journal-title":"FEBS J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"114917","DOI":"10.1016\/j.biopha.2023.114917","article-title":"Betanin improves motor function and alleviates experimental Parkinsonism via downregulation of TLR4\/MyD88\/NF-\u03baB pathway: Molecular docking and biological investigations","volume":"164","author":"ElSayed","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"106313","DOI":"10.1016\/j.fbio.2025.106313","article-title":"Identification of SRC, AKT1 and MAPK3 as therapeutic targets of apigenin and luteolin in colorectal and colon carcinoma through network pharmacology","volume":"67","author":"Hon","year":"2025","journal-title":"Food Biosci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Ahmad, V., Khan, M.I., Jamal, Q.M., Alzahrani, F.A., and Albiheyri, R. (2024). Computational molecular docking and simulation-based assessment of anti-inflammatory properties of Nyctanthes arbor-tristis Linn phytochemicals. Pharmaceuticals, 17.","DOI":"10.3390\/ph17010018"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.foodchem.2015.05.037","article-title":"Simultaneous extraction, identification and quantification of phenolic compounds in Eclipta prostrata using microwave-assisted extraction combined with HPLC\u2013DAD\u2013ESI\u2013MS\/MS","volume":"188","author":"Fang","year":"2015","journal-title":"Food Chem."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Phan, T.K., Wang, S.-L., Nguyen, Q.V., Phan, T.Q., Nguyen, T.T., Tran, T.T., Nguyen, A.D., Nguyen, V.B., and Doan, M.D. (2023). Assessment of the chemical profile and potential medical effects of a flavonoid-rich extract of Eclipta prostrata L. collected in the central highlands of Vietnam. Pharmaceuticals, 16.","DOI":"10.3390\/ph16101476"},{"key":"ref_34","first-page":"568","article-title":"Antioxidant activity, phenolic compound content and phytochemical constituents of Eclipta prostrata (Linn.) Linn","volume":"41","author":"Chansakaow","year":"2014","journal-title":"Chiang Mai J. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"103621","DOI":"10.1016\/j.fbio.2024.103621","article-title":"Comparison of the regulatory effects of flavonoids and saponins from Eclipta prostrate on insulin resistance in HepG2 cells","volume":"59","author":"Yang","year":"2024","journal-title":"Food Biosci."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/path.2287","article-title":"TNF-mediated inflammatory disease","volume":"214","author":"Bradley","year":"2008","journal-title":"J. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.it.2011.10.004","article-title":"TNF superfamily in inflammatory disease: Translating basic insights","volume":"33","author":"Croft","year":"2012","journal-title":"Trends Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"100544","DOI":"10.1016\/j.jaim.2022.100544","article-title":"Anti-inflammatory effect of wedelolactone on DSS induced colitis in rats: IL-6\/STAT3 signaling pathway","volume":"14","author":"Prakash","year":"2023","journal-title":"J. Ayurveda Integr. Med."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9966750","DOI":"10.1155\/2022\/9966750","article-title":"Flavonols and flavones as potential anti-inflammatory, antioxidant, and antibacterial compounds","volume":"2022","author":"Chagas","year":"2022","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Al-Khayri, J.M., Sahana, G.R., Nagella, P., Joseph, B.V., Alessa, F.M., and Al-Mssallem, M.Q. (2022). Flavonoids as potential anti-inflammatory molecules: A review. Molecules, 27.","DOI":"10.3390\/molecules27092901"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.intimp.2011.03.012","article-title":"Anti-inflammatory activity of structurally related flavonoids, apigenin, luteolin and fisetin","volume":"11","author":"Nakamura","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113359","DOI":"10.1016\/j.intimp.2024.113359","article-title":"Wedelolactone alleviates inflammation and cartilage degeneration by suppressing the NF-\u03baB signaling pathway in osteoarthritis","volume":"143","author":"Sun","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"109088","DOI":"10.1016\/j.biopha.2019.109088","article-title":"Wedelolactone alleviates doxorubicin-induced inflammation and oxidative stress damage of podocytes by I\u03baK\/I\u03baB\/NF-\u03baB pathway","volume":"117","author":"Zhu","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"301","DOI":"10.5603\/FHC.a2022.0025","article-title":"Wedelolactone ameliorates synovial inflammation and cardiac complications in a murine model of collagen-induced arthritis by inhibiting NF-\u03baB\/NLRP3 inflammasome activation","volume":"60","author":"Cao","year":"2022","journal-title":"Folia Histochem. Cytobiol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/s40538-022-00340-0","article-title":"Pharmacophore study, molecular docking and molecular dynamic simulation of virgin coconut oil derivatives as anti-inflammatory agent against COX-2","volume":"9","author":"Jack","year":"2022","journal-title":"Chem. Biol. Technol. Agric."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1653\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:05:30Z","timestamp":1762178730000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/18\/11\/1653"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":45,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2025,11]]}},"alternative-id":["ph18111653"],"URL":"https:\/\/doi.org\/10.3390\/ph18111653","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}