{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T23:23:32Z","timestamp":1778628212101,"version":"3.51.4"},"reference-count":45,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T00:00:00Z","timestamp":1656547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of Biological Resources (NIBR)","award":["NIBR202231205"],"award-info":[{"award-number":["NIBR202231205"]}]},{"DOI":"10.13039\/501100005880","name":"the Ministry of Environment (MOE) of the Republic of Korea","doi-asserted-by":"publisher","award":["NIBR202231205"],"award-info":[{"award-number":["NIBR202231205"]}],"id":[{"id":"10.13039\/501100005880","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Inflammation is an immune response that protects against harmful stimuli. However, severe inflammation can cause many diseases, such as diabetes, cancer, and arthritis. In this study, we examined the anti-inflammatory efficacy and mechanism of Potentilla paradoxa Nutt. ethanol extract (Pp-EE) as a new strategy for controlling the inflammatory response. Cellular activities and the molecular target of Pp-EE were identified in RAW264.7 cells and HEK293T cells. The effect of Pp-EE was analyzed using the Griess assay, the luciferase assay, reverse transcription-polymerase chain reaction, and Western blotting. To evaluate the in vivo effects, an HCl\/EtOH-induced gastritis mouse model was used. NO production and pro-inflammatory gene (iNOS, COX-2, and TNF-\u03b1) mRNA levels were decreased by Pp-EE in a concentration-dependent manner without showing cytotoxicity. The activation of the transcription factor, particularly NF-\u03baB, was effectively suppressed by Pp-EE. It was also found that Pp-EE directly inhibits the activation of Src in lipopolysaccharide (LPS)-treated RAW264.7 cells and in Src-overexpressed HEK293 cells by Western blotting analysis and cellular thermal shift assay. Experiments in the gastritis mouse model indicated that Pp-EE suppresses HCl\/EtOH-induced gastric lesions, the expression levels of COX-2, IL-6, and TNF-\u03b1, and the phosphorylation of p65, p50, and Src. Taken together, these results suggest that Pp-EE can be applied as an anti-inflammatory remedy with a Src\/NF-\u03baB inhibitory property.<\/jats:p>","DOI":"10.3390\/plants11131750","type":"journal-article","created":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T01:40:36Z","timestamp":1656639636000},"page":"1750","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Potentilla paradoxa Nutt. Ethanol Extract Exhibits Anti-Inflammatory Effects by Suppression of the Src\/NF-\u03baB Signaling Pathway"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-3698","authenticated-orcid":false,"given":"Ji Won","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ki Woong","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Yeon","family":"Kim","sequence":"additional","affiliation":[{"name":"School of Systems Biomedical Science, Soongsil University, Seoul 06978, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8141-9927","authenticated-orcid":false,"given":"Jae Youl","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Korea"},{"name":"Research Institute of Biomolecule Control and Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon 16419, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jgr.2020.09.004","article-title":"Adaptogenic effects of Panax ginseng on modulation of immune functions","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.1016\/j.bbamcr.2014.05.014","article-title":"Cytokines and chemokines: At the crossroads of cell signalling andinflammatory disease","volume":"1834","author":"Turner","year":"2014","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1111\/j.1365-2249.2006.03261.x","article-title":"Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1\u03b2 generation","volume":"147","author":"Nielsen","year":"2007","journal-title":"Clin. Exp. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/j.jgr.2020.02.004","article-title":"Pharmacological potential of ginseng and its major component ginsenosides","volume":"45","author":"Ratan","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1822","DOI":"10.1038\/s41591-019-0675-0","article-title":"Chronic inflammation in the etiology of disease across the life span","volume":"25","author":"Furman","year":"2019","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jgr.2020.07.002","article-title":"Functional roles and mechanisms of ginsenosides from Panax ginseng in atherosclerosis","volume":"45","author":"Xue","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.cels.2016.09.009","article-title":"Defective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humans","volume":"3","author":"Furman","year":"2016","journal-title":"Cell Syst."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10369","DOI":"10.1038\/ncomms10369","article-title":"Pre-vaccination inflammation and B-cell signalling predict age-related hyporesponse to hepatitis B vaccination","volume":"7","author":"Fourati","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1093\/infdis\/jix257","article-title":"Serum C-reactive protein and congestive heart failure as significant predictors of herpes Zoster vaccine response in elderly nursing home residents","volume":"216","author":"Verschoor","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1002\/ajhb.21128","article-title":"Positive antibody response to vaccination in adolescence predicts lower C-reactive protein concentration in young adulthood in the philippines","volume":"23","author":"McDade","year":"2011","journal-title":"Am. J. Hum. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"461","DOI":"10.3389\/fimmu.2014.00461","article-title":"Toll-like receptor signaling pathways","volume":"5","author":"Kawasaki","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6270","DOI":"10.1038\/sj.onc.1204769","article-title":"Adaptor proteins","volume":"20","author":"Flynn","year":"2001","journal-title":"Oncogene"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1016\/j.jgr.2021.03.009","article-title":"Korean Red Ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice","volume":"45","author":"Kim","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"168","DOI":"10.1017\/S0007114509991747","article-title":"Epicatechin induces NF-\u03baB, activator protein-1 (AP-1) and nuclear transcription factor erythroid 2p45-related factor-2 (Nrf2) via phosphatidylinositol-3-kinase\/protein kinase B (PI3K\/AKT) and extracellular regulated kinase (ERK) signalling in HepG2 cells","volume":"103","author":"Haegeman","year":"2010","journal-title":"Br. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Khalaf, H., Jass, J., and Olsson, P.-E. (2010). Differential cytokine regulation by NF-\u03baB and AP-1 in Jurkat T-cells. BMC Immunol., 11.","DOI":"10.1186\/1471-2172-11-26"},{"key":"ref_17","first-page":"1","article-title":"The role of Src kinase in macrophage-mediated inflammatory responses","volume":"2012","author":"Byeon","year":"2012","journal-title":"Mediat. Inflamm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jgr.2020.12.003","article-title":"Enhancement of skin barrier and hydration-related molecules by protopanaxatriol in human keratinocytes","volume":"45","author":"Lee","year":"2021","journal-title":"J. Ginseng Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1016\/j.bcp.2010.01.025","article-title":"Lipoteichoic acid enhances IL-6 production in human synovial fibroblasts via TLR2 receptor, PKC\u03b4 and c-Src dependent pathways","volume":"79","author":"Tang","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"18806","DOI":"10.1074\/jbc.M112.340935","article-title":"Eps8 protein facilitates phagocytosis by increasing TLR4-MyD88 protein interaction in lipopolysaccharide-stimulated macrophages","volume":"287","author":"Chen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"416","DOI":"10.3389\/fphys.2013.00416","article-title":"Src as the link between inflammation and cancer","volume":"4","author":"Liu","year":"2014","journal-title":"Front. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6799","DOI":"10.1074\/jbc.M109434200","article-title":"TNF-related activation-induced cytokine (TRANCE) induces angiogenesis through the activation of Src and phospholipase C (PLC) in human endothelial cells","volume":"277","author":"Kim","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_23","first-page":"523","article-title":"The influence of aqueous extracts of selected Potentilla species on normal human colon cells","volume":"70","author":"Tomczyk","year":"2013","journal-title":"Acta Pol. Pharm."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.jep.2014.06.029","article-title":"A cross-cultural analysis of Jammu, Kashmir and Ladakh (India) medicinal plant use","volume":"155","author":"Gairola","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Lee, H.P., Kim, D.S., Park, S.H., Shin, C.Y., Woo, J.J., Kim, J.W., An, R.-B., Lee, C., and Cho, J.Y. (2022). Antioxidant capacity of Potentilla paradoxa Nutt. and its beneficial effects related to anti-aging in HaCaT and B16F10 cells. Plants, 11.","DOI":"10.3390\/plants11070873"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"76","DOI":"10.5010\/JPB.2017.44.1.076","article-title":"In vitro anti-inflammatory activity of extracts from Potentilla supina in murine macrophage RAW 264.7 cells","volume":"44","author":"Nam","year":"2017","journal-title":"J. Plant Biotechnol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Kim, H., Shin, K.K., Kim, H.G., Jo, M., Kim, J.K., Lee, J.S., Choung, E.S., Li, W.Y., Lee, S.W., and Kim, K.-H. (2020). Src\/NF-\u03baB-targeted anti-inflammatory effects of Potentilla glabra var. Mandshurica (Maxim.) Hand.-Mazz. ethanol extract. Biomolecules, 10.","DOI":"10.3390\/biom10040648"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1007\/s10787-007-0013-x","article-title":"Role of nitric oxide in inflammatory diseases","volume":"15","author":"Sharma","year":"2007","journal-title":"Inflammopharmacology"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1021\/np000620d","article-title":"COX-2 inhibitory effects of naturally occurring and modified fatty acids","volume":"64","author":"Ringbom","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/BF02976695","article-title":"Inhibition of COX-2 activity and proinflammatory cytokines (TNF-\u03b1 and IL-1\u03b2) production by water-soluble sub-fractionated parts from bee (Apis mellifera) venom","volume":"26","author":"Nam","year":"2003","journal-title":"Arch. Pharm. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1097\/AIA.0b013e318034194e","article-title":"Cytokines, inflammation, and pain","volume":"45","author":"Zhang","year":"2007","journal-title":"Int. Anesthesiol. Clin."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1128\/MCB.18.1.78","article-title":"Activation of p38 mitogen-activated protein kinase by sodium salicylate leads to inhibition of tumor necrosis factor-induced I\u03baB\u03b1 phosphorylation and degradation","volume":"18","author":"Schwenger","year":"1998","journal-title":"Mol. Cell. Biol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4396","DOI":"10.1167\/iovs.12-9724","article-title":"Anti-inflammatory effects of alpha linolenic acid on human Corneal epithelial cells","volume":"53","author":"Erdinest","year":"2012","journal-title":"Invest. Opthalmol. Vis. Sci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1111\/j.1747-0285.2012.01418.x","article-title":"Anti-inflammatory property of n-hexadecanoic acid: Structural evidence and kinetic assessment","volume":"80","author":"Aparna","year":"2012","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Kong, F., Lee, B., and Wei, K. (2019). 5-Hydroxymethylfurfural mitigates lipopolysaccharide-stimulated inflammation via suppression of MAPK, NF-\u03baB and mTOR activation in RAW 264.7 Cells. Molecules, 24.","DOI":"10.3390\/molecules24020275"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25","DOI":"10.2174\/1874847301004010025","article-title":"Isolation and identification of \u03b3-sitosterol by GC-MS from the leaves of Girardinia heterophylla (Decne)","volume":"4","author":"Tripathi","year":"2013","journal-title":"Open Bioact. Comp. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"258","DOI":"10.3389\/fimmu.2021.790258","article-title":"Cleavage-mediated regulation of Myd88 signaling by inflammasome-activated caspase-1","volume":"12","author":"Avbelj","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"You, L., Kim, M.Y., and Cho, J.Y. (2021). Protective effect of Potentilla glabra in UVB-induced photoaging process. Molecules, 26.","DOI":"10.3390\/molecules26175408"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"276","DOI":"10.3390\/s30800276","article-title":"Measurement of nitric oxide production in biological systems by using Griess reaction assay","volume":"3","author":"Sun","year":"2003","journal-title":"Sensors"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Lee, C.Y., Kim, H.G., Park, S.H., Jang, S.G., Park, K.J., Kim, D.S., Kim, J.H., and Cho, J.Y. (2020). Anti-inflammatory functions of alverine via targeting Src in the NF-\u03baB pathway. Biomolecules, 10.","DOI":"10.3390\/biom10040611"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.jgr.2022.02.004","article-title":"Korean Red Ginseng saponin fraction exerts anti-inflammatory effects by targeting the NF-kappaB and AP-1 pathways","volume":"46","author":"Lee","year":"2022","journal-title":"J. Ginseng Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/0003-2697(81)90281-5","article-title":"\u201cWestern Blotting\u201d: Electrophoretic transfer of proteins from sodium dodecyl sulfate-polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A","volume":"112","author":"Burnette","year":"1981","journal-title":"Anal. Biochem."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.jgr.2018.11.001","article-title":"Identification of a novel triterpene saponin from Panax ginseng seeds, pseudoginsenoside RT8, and its antiinflammatory activity","volume":"44","author":"Rho","year":"2020","journal-title":"J. Ginseng Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1016\/j.jgr.2019.11.001","article-title":"Gastroprotective effects of the nonsaponin fraction of Korean Red Ginseng through cyclooxygenase-1 upregulation","volume":"44","author":"Lee","year":"2020","journal-title":"J. Ginseng Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"113887","DOI":"10.1016\/j.jep.2021.113887","article-title":"Syk\/NF-kappaB-targeted anti-inflammatory activity of Melicope accedens (Blume) T.G. Hartley methanol extract","volume":"271","author":"Kim","year":"2021","journal-title":"J. Ethnopharmacol."}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/13\/1750\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:41:29Z","timestamp":1760139689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/13\/1750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,30]]},"references-count":45,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["plants11131750"],"URL":"https:\/\/doi.org\/10.3390\/plants11131750","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,30]]}}}