{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:56:41Z","timestamp":1785927401914,"version":"3.56.0"},"reference-count":51,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2017R1A6A1A03015642"],"award-info":[{"award-number":["2017R1A6A1A03015642"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Plants"],"abstract":"<jats:p>Many species in the genus Guettarda are known to exert anti-inflammatory effects and are used as traditional medicinal plants to treat various inflammatory symptoms. However, no studies on the inflammatory activities of Guettarda crispiflora Vahl have been reported. The aim of the study was to investigate in vitro and in vivo the anti-inflammatory effects of a methanol extract of Guettarda crispiflora Vahl (Gc-ME). To determine the anti-inflammatory activity of Gc-ME, lipopolysaccharide (LPS)-, poly(I:C)-, or Pam3CSK4-treated RAW264.7 cells, HCl\/EtOH- and LPS-treated mice were employed for in vitro and in vivo tests. LPS-induced nitric oxide production in RAW264.7 cells was determined by Griess assays and cytokine gene expression in LPS-activated RAW264.7 cells, confirmed by RT- and real-time PCR. Transcriptional activation was evaluated by luciferase reporter gene assay. Target protein validation was assessed by Western blot analysis and cellular thermal shift assays (CETSA) with LPS-treated RAW264.7 and gene-transfected HEK293 cells. Using both a HCl\/EtOH-induced gastritis model and an LPS-induced lung injury model, inflammatory states were checked by scoring or evaluating gastric lesions, lung edema, and lung histology. Phytochemical fingerprinting of Gc-ME was observed by using liquid chromatography\u2013mass spectrometry. Nitric oxide production induced by LPS and Pam3CSK4 in RAW264.7 cells was revealed to be reduced by Gc-ME. The LPS-induced upregulation of iNOS, COX-2, IL-6, and IL-1\u03b2 was also suppressed by Gc-ME treatment. Gc-ME downregulated the promotor activities of AP-1 and NF-\u03baB triggered by MyD88- and TRIF induction. Upstream signaling proteins for NF-\u03baB activation, namely, p-p50, p-p65, p-I\u03baB\u03b1, and p-Src were all downregulated by Ch-EE. Moreover, Src was revealed to be directly targeted by Gc-ME. This extract, orally treated strongly, attenuated the inflammatory symptoms in HCl\/EtOH-treated stomachs and LPS-treated lungs. Therefore, these results strongly imply that Guettarda crispiflora can be developed as a promising anti-inflammatory remedy with Src-suppressive properties.<\/jats:p>","DOI":"10.3390\/plants11243560","type":"journal-article","created":{"date-parts":[[2022,12,19]],"date-time":"2022-12-19T07:27:30Z","timestamp":1671434850000},"page":"3560","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Guettarda crispiflora Vahl Methanol Extract Ameliorates Acute Lung Injury and Gastritis by Suppressing Src Phosphorylation"],"prefix":"10.3390","volume":"11","author":[{"given":"Dahae","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3117-3698","authenticated-orcid":false,"given":"Ji Won","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0857-5944","authenticated-orcid":false,"given":"Chae Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Hyun","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyeong","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung A","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wooram","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Kyoung","family":"Noh","sequence":"additional","affiliation":[{"name":"Instituto de BioEconomia, Quito 170135, Ecuador"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong-Keun","family":"Yi","sequence":"additional","affiliation":[{"name":"International Biological Material Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon 34141, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minkyung","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4730-9801","authenticated-orcid":false,"given":"Han Gyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Research Institute of Biomolecule Control, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Republic of Korea"},{"name":"Research Institute of Biomolecule Control, Sungkyunkwan University, Suwon 16419, Republic of Korea"},{"name":"Biomedical Institute for Convergence at SKKU, Sungkyunkwan University, Suwon 16419, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.jgr.2016.08.004","article-title":"Role of ginsenosides, the main active components of Panax ginseng, in inflammatory responses and diseases","volume":"41","author":"Kim","year":"2017","journal-title":"J. Ginseng Res."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Liu, Y., Huang, L., Kim, M.Y., and Cho, J.Y. (2022). The Role of Thymoquinone in Inflammatory Response in Chronic Diseases. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810246"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.canlet.2021.09.011","article-title":"Neutrophils: Driving inflammation during the development of hepatocellular carcinoma","volume":"522","author":"Chen","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1016\/j.canlet.2020.10.038","article-title":"sORF-Encoded MicroPeptides: New players in inflammation, metabolism, and precision medicine","volume":"500","author":"Chen","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"10689","DOI":"10.1074\/jbc.274.16.10689","article-title":"Toll-like Receptor-4 Mediates Lipopolysaccharide-induced Signal Transduction","volume":"274","author":"Chow","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/j.addr.2007.11.005","article-title":"TLR3: Interferon induction by double-stranded RNA including poly(I:C)","volume":"60","year":"2008","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"114219","DOI":"10.1016\/j.bcp.2020.114219","article-title":"Isoprenylcysteine carboxyl methyltransferase inhibitors exerts anti-inflammatory activity","volume":"182","author":"Yang","year":"2020","journal-title":"Biochem. Pharmacol."},{"key":"ref_9","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_10","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.canlet.2021.04.014","article-title":"PLD1 promotes tumor invasion by regulation of MMP-13 expression via NF-kappaB signaling in bladder cancer","volume":"511","author":"Nagumo","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/j.canlet.2020.10.047","article-title":"lncRNA LINC01057 promotes mesenchymal differentiation by activating NF-kappaB signaling in glioblastoma","volume":"498","author":"Tang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/j.canlet.2020.02.033","article-title":"Dysbindin promotes pancreatic ductal adenocarcinoma metastasis by activating NF-\u03baB\/MDM2 via miR-342-3p","volume":"477","author":"Zhu","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"154338","DOI":"10.1016\/j.phymed.2022.154338","article-title":"Callerya atropurpurea suppresses inflammation in vitro and ameliorates gastric injury as well as septic shock in vivo via TLR4\/MyD88-dependent cascade","volume":"105","author":"You","year":"2022","journal-title":"Phytomedicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1089\/jamp.2009.0775","article-title":"Acute Lung Injury: Epidemiology, Pathogenesis, and Treatment","volume":"23","author":"Johnson","year":"2010","journal-title":"J. Aerosol Med. Pulm. Drug Deliv."},{"key":"ref_15","first-page":"1783","article-title":"Methanol extract of Guettarda speciosa Linn. inhibits the production of inflammatory mediators through the inactivation of Syk and JNK in macrophages","volume":"41","author":"Le","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kim, K.H., Lee, J.Y., Ahn, S., Won, R., Kim, S.-J., Jeong, S.-I., Lee, J.J., Kim, J.-I., Choi, J.-Y., and Joo, M. (2020). The methanol extract of Guettarda speciosa Linn. Ameliorates acute lung injury in mice. BMC Complement. Med. Ther., 20.","DOI":"10.1186\/s12906-020-2828-6"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Tan, M.A., Lagamayo, M.W.D., Alejandro, G.J.D., and An, S.S.A. (2019). Anti-Amyloidogenic and Cyclooxygenase Inhibitory Activity of Guettarda speciosa. Molecules, 24.","DOI":"10.3390\/molecules24224112"},{"key":"ref_18","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_19","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_20","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.jep.2019.01.024","article-title":"Suppression of Src and Syk in the NF-kappaB signaling pathway by Olea europaea methanol extract is leading to its anti-inflammatory effects","volume":"235","author":"Song","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jep.2018.11.013","article-title":"Mycetia cauliflora methanol extract exerts anti-inflammatory activity by directly targeting PDK1 in the NF-kappaB pathway","volume":"231","author":"Jeong","year":"2019","journal-title":"J. Ethnopharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.biopha.2017.12.081","article-title":"Alpha, 2\u2019-dihydroxy-4,4\u2019-dimethoxydihydrochalcone inhibits cell proliferation, invasion, and migration in gastric cancer in part via autophagy","volume":"98","author":"Wan","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.cbi.2012.05.005","article-title":"Reactive oxygen species-mediated mitochondrial pathway is involved in Baohuoside I-induced apoptosis in human non-small cell lung cancer","volume":"199","author":"Song","year":"2012","journal-title":"Chem. -Biol. Interact."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/0192-0561(94)90016-7","article-title":"Immunopharmacology and toxicology of the plant flavonoid baohuoside-1 in mice","volume":"16","author":"Li","year":"1994","journal-title":"Int. J. Immunopharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1248\/cpb.49.154","article-title":"Analgesic Components of Saposhnikovia Root (Saposhnikovia divaricata)","volume":"49","author":"Okuyama","year":"2001","journal-title":"Chem. Pharm. Bull."},{"key":"ref_26","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. Pharmacal Res."},{"key":"ref_27","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_28","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_29","doi-asserted-by":"crossref","first-page":"767366","DOI":"10.3389\/fimmu.2021.767366","article-title":"Syk-MyD88 Axis Is a Critical Determinant of Inflammatory-Response in Activated Macrophages","volume":"12","author":"Yi","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/j.biocel.2008.08.011","article-title":"Distinct role of spleen tyrosine kinase in the early phosphorylation of inhibitor of kappaB alpha via activation of the phosphoinositide-3-kinase and Akt pathways","volume":"41","author":"Lee","year":"2009","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.canlet.2021.09.024","article-title":"Fas signaling in adipocytes promotes low-grade inflammation and lung metastasis of colorectal cancer through interaction with Bmx","volume":"522","author":"Yang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1016\/j.canlet.2020.10.029","article-title":"Macrophages in pancreatic cancer: An immunometabolic perspective","volume":"498","author":"Yang","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_33","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":"2018","journal-title":"Oncotarget"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.canlet.2021.01.003","article-title":"COX-2 promotes mammary adipose tissue inflammation, local estrogen biosynthesis, and carcinogenesis in high-sugar\/fat diet treated mice","volume":"502","author":"Goncalves","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Rahmawati, L., Park, S.H., Kim, D.S., Lee, H.P., Aziz, N., Lee, C.Y., Kim, S.A., Jang, S.G., Kim, D.S., and Cho, J.Y. (2021). Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway. Molecules, 27.","DOI":"10.3390\/molecules27010194"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.canlet.2020.01.019","article-title":"Mitochondrial oxidative stress by Lon-PYCR1 maintains an immunosuppressive tumor microenvironment that promotes cancer progression and metastasis","volume":"474","author":"Kuo","year":"2020","journal-title":"Cancer Lett."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1021\/np50064a002","article-title":"Plant metabolites. Structure and in vitro antiviral activity of quinovic acid glycosides from Uncaria tomentosa and Guettarda platypoda","volume":"52","author":"Aquino","year":"1989","journal-title":"J. Nat. Prod."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1055\/s-2006-957449","article-title":"Phytochemical and pharmacological studies of Guettarda acreana","volume":"64","author":"Capasso","year":"1998","journal-title":"Planta Med."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kim, S.A., Lee, C.Y., Mitra, A., Kim, H., Woo, B.Y., Hong, Y.D., Noh, J.K., Yi, D.K., Kim, H.G., and Cho, J.Y. (2021). Anti-Inflammatory Effects of Huberia peruviana Cogn. Methanol Extract by Inhibiting Src Activity in the NF-kappaB Pathway. Plants, 10.","DOI":"10.3390\/plants10112335"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1111\/j.1474-8673.2005.00332.x","article-title":"The effects of apigenin-7-O-beta-D-glucuronopyranoside on reflux oesophagitis and gastritis in rats","volume":"25","author":"Min","year":"2005","journal-title":"Auton. Autacoid Pharmacol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kim, S.A., Oh, J., Choi, S.R., Lee, C.H., Lee, B.H., Lee, M.N., Hossain, M.A., Kim, J.H., Lee, S., and Cho, J.Y. (2021). Anti-Gastritis and Anti-Lung Injury Effects of Pine Tree Ethanol Extract Targeting Both NF-kappaB and AP-1 Pathways. Molecules, 26.","DOI":"10.3390\/molecules26206275"},{"key":"ref_42","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_43","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.semarthrit.2008.08.001","article-title":"Nonsteroidal anti-inflammatory drugs: Adverse effects and their prevention","volume":"39","author":"Vonkeman","year":"2010","journal-title":"Semin. Arthritis Rheum."},{"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."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"215803","DOI":"10.1016\/j.canlet.2022.215803","article-title":"The EEF1AKMT3\/MAP2K7\/TP53 axis suppresses tumor invasiveness and metastasis in gastric cancer","volume":"544","author":"Hong","year":"2022","journal-title":"Cancer Lett."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.canlet.2021.07.035","article-title":"SGLT2 promotes pancreatic cancer progression by activating the Hippo signaling pathway via the hnRNPK-YAP1 axis","volume":"519","author":"Ren","year":"2021","journal-title":"Cancer Lett."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Yang, W.S., Kim, H.G., Kim, E., Han, S.Y., Aziz, N., Yi, Y.S., Kim, S., Lee, Y., Yoo, B.C., and Han, J.W. (2020). Isoprenylcysteine Carboxyl Methyltransferase and Its Substrate Ras Are Critical Players Regulating TLR-Mediated Inflammatory Responses. Cells, 9.","DOI":"10.3390\/cells9051216"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"690","DOI":"10.1016\/j.jgr.2022.04.003","article-title":"Korean Red Ginseng water extract inhibits cadmium-induced lung injury via suppressing MAPK\/ERK1\/2\/AP-1 pathway","volume":"46","author":"Mitra","year":"2022","journal-title":"J. Ginseng Res."},{"key":"ref_50","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_51","doi-asserted-by":"crossref","unstructured":"Song, C., Kim, M.Y., and Cho, J.Y. (2021). Olea europaea Suppresses Inflammation by Targeting TAK1-Mediated MAP Kinase Activation. Molecules, 26.","DOI":"10.3390\/molecules26061540"}],"container-title":["Plants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/24\/3560\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:42:53Z","timestamp":1760146973000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2223-7747\/11\/24\/3560"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,16]]},"references-count":51,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["plants11243560"],"URL":"https:\/\/doi.org\/10.3390\/plants11243560","relation":{},"ISSN":["2223-7747"],"issn-type":[{"value":"2223-7747","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,16]]}}}