{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:44:51Z","timestamp":1787319891492,"version":"build-2736575974"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Psoriasis, a chronic and autoimmune inflammatory disorder of the skin, has been often underdiagnosed and underestimated despite its prevalence and considerable negative effects on the quality of life. In this study, the anti-inflammatory activity of Ficus carica fruit extract (FFE) was investigated against LPS-stimulated RAW 264.7 cells. The in vitro results showed that FFE reduced the production of nitric oxide (NO) and iNOS expression. Moreover, FFE reduced the level of \u03b2-hexosaminidase released with histamine in allergic reactions. However, the MAPK and NF\u03baB signaling molecules associated with the inflammatory response were not significantly regulated by FFE. In contrast, the phosphorylation of JAK1 and STAT3 in the JAK\u2013STAT signaling pathway was dramatically reduced by FFE treatment. Psoriasis-like skin lesions were induced in BALB\/c mice using imiquimod (IMQ) to test the feasibility of FFE as a treatment for psoriasis. The efficacy of FFE was evaluated based on phenotypic and histological features. FFE was effective in relieving the symptoms of psoriasis-like skin lesions, such as erythema, dryness, scales, and thick epidermis. Notably, STAT3 modulation was also contributable to the in vivo ameliorative activity of FFE. Taken together, FFE with anti-psoriasis activity in vitro and in vivo through the JAK\u2013STAT modulation could be developed as a therapeutic agent against psoriasis.<\/jats:p>","DOI":"10.3390\/life13081671","type":"journal-article","created":{"date-parts":[[2023,8,1]],"date-time":"2023-08-01T09:14:40Z","timestamp":1690881280000},"page":"1671","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["In Vitro and In Vivo Anti-Psoriasis Activity of Ficus carica Fruit Extracts via JAK-STAT Modulation"],"prefix":"10.3390","volume":"13","author":[{"given":"Jeong Hwa","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Medical Science, Soonchunhyang University, 22 Soonchunhyang-ro, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3511-9522","authenticated-orcid":false,"given":"Mi-Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Science, Soonchunhyang University, 22 Soonchunhyang-ro, Asan 31538, Republic of Korea"},{"name":"Department of Medical Biotechnology, Soonchunhyang University, 22 Soonchunhyang-ro, Asan 31538, Republic of Korea"},{"name":"Eshel Biopharm Co., Ltd., Soonchunhyang-ro, Asan 31538, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2022, April 01). Global Report on Psoriasis. World Health Organization, 2016. Available online: https:\/\/apps.who.int\/iris\/handle\/10665\/204417."},{"key":"ref_2","unstructured":"(2022, April 08). Available online: https:\/\/www.nhs.uk\/conditions\/psoriasis\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1111\/j.1365-4362.1996.tb03687.x","article-title":"Skin disease and socioeconomic conditions in rural Africa: Tanzania","volume":"35","author":"Gibbs","year":"1996","journal-title":"Int. J. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1303","DOI":"10.1111\/bjd.12230","article-title":"Is the prevalence of psoriasis increasing? A 30-year follow-up of a population-based cohort","volume":"168","author":"Danielsen","year":"2013","journal-title":"Br. J. Dermatol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Mahmoudi, M. (2010). Challenging Cases in Allergic and Immunologic Diseases of the Skin, Springer Science & Business Media.","DOI":"10.1007\/978-1-60761-296-4"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1038\/cmi.2012.15","article-title":"New insights of T cells in the pathogenesis of psoriasis","volume":"9","author":"Cai","year":"2012","journal-title":"Cell. Mol. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1002\/cbf.3813","article-title":"The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation","volume":"41","author":"Mansoor","year":"2023","journal-title":"Cell Biochem. Funct."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Woo, Y.R., Cho, D.H., and Park, H.J. (2017). Molecular mechanisms and management of a cutaneous inflammatory disorder: Psoriasis. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122684"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Christian, F., Smith, E.L., and Carmody, R.J. (2016). The regulation of NF-\u03baB subunits by phosphorylation. Cells, 5.","DOI":"10.3390\/cells5010012"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"566","DOI":"10.2174\/156800909788486759","article-title":"The biological functions of NF-\u03baB1 (p) and its potential as an anti-cancer target","volume":"9","author":"Wan","year":"2009","journal-title":"Curr. Cancer Drug Targets"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"a000034","DOI":"10.1101\/cshperspect.a000034","article-title":"The NF- B family of transcription factors and its regulation","volume":"1","author":"Oeckinghaus","year":"2009","journal-title":"Cold Spring Harb. Perspect. Biol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1080\/13510002.2019.1658377","article-title":"Salidroside inhibits MAPK, NF-\u03baB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation","volume":"24","author":"Xu","year":"2019","journal-title":"Redox Rep."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1016\/j.bbadis.2009.12.009","article-title":"Pathological roles of MAPK signaling pathways in human diseases","volume":"1802","author":"Kim","year":"2010","journal-title":"Biochim. Biophys. Acta (BBA) Mol. Basis Dis."},{"key":"ref_14","first-page":"569751","article-title":"The Role of p38 MAPK in the aetiopathogenesis of psoriasis and psoriatic arthritis","volume":"2013","author":"Mavropoulos","year":"2013","journal-title":"J. Immunol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"88","DOI":"10.3109\/08977194.2012.660936","article-title":"Biology and significance of the JAK\/STAT signalling pathways","volume":"30","author":"Kiu","year":"2012","journal-title":"Growth Factors"},{"key":"ref_16","first-page":"268","article-title":"Inhibitory effects of Ficus carica and Olea europaea on pro-inflammatory cytokines: A review","volume":"25","author":"Rezagholizadeh","year":"2022","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1487","DOI":"10.3109\/13880209.2014.892515","article-title":"Traditional uses, phytochemistry and pharmacology of Ficus carica: A review","volume":"52","author":"Badgujar","year":"2014","journal-title":"Pharm. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"110237","DOI":"10.1016\/j.cbi.2022.110237","article-title":"Phytochemistry, biological activities, industrial and traditional uses of fig (Ficus carica): A review","volume":"368","author":"Hajam","year":"2022","journal-title":"Chem. Interact."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Abe, T., Koyama, Y., Nishimura, K., Okiura, A., and Takahashi, T. (2022). Efficacy and Safety of Fig (Ficus carica L.) Leaf Tea in Adults with Mild Atopic Dermatitis: A Double-Blind, Randomized, Placebo-Controlled Preliminary Trial. Nutrients, 14.","DOI":"10.3390\/nu14214470"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4558","DOI":"10.1007\/s11356-020-10778-0","article-title":"Synergistic effects of Ficus Carica extract and extra virgin olive oil against oxidative injury, cytokine liberation, and inflammation mediated by 5-Fluorouracil in cardiac and renal tissues of male albino rats","volume":"28","author":"Elghareeb","year":"2021","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"571535","DOI":"10.3389\/fphar.2020.571535","article-title":"A Review of the Pharmacological Properties of Psoralen","volume":"11","author":"Ren","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.ejps.2016.10.025","article-title":"Psoralen loaded liposomal nanocarriers for improved skin penetration and efficacy of topical PUVA in psoriasis","volume":"96","author":"Doppalapudi","year":"2017","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1016\/S0076-6879(99)99017-1","article-title":"Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent","volume":"299","author":"Vl","year":"1999","journal-title":"Methods Enzymol."},{"key":"ref_24","first-page":"3","article-title":"Estimation of total flavonoid content in propolis by two complementary colometric methods","volume":"10","author":"Chang","year":"2002","journal-title":"J. Food Drug Anal."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/0003-2697(76)90527-3","article-title":"A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding","volume":"72","author":"Bradford","year":"1976","journal-title":"Anal. Biochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"6241017","DOI":"10.1155\/2018\/6241017","article-title":"Rutin as a potent antioxidant: Implications for neurodegenerative disorders","volume":"2018","author":"Enogieru","year":"2018","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"11625","DOI":"10.1021\/jf303771s","article-title":"Antioxidant and DNA-protective Activities of chlorogenic acid Isomers","volume":"60","author":"Xu","year":"2012","journal-title":"J. Agric. Food Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6139308","DOI":"10.1155\/2021\/6139308","article-title":"Antioxidant effects of protocatechuic acid and protocatechuic aldehyde: Old Wine in a new bottle","volume":"2021","author":"Zhang","year":"2021","journal-title":"Evid. Based Complement Altern. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.jaad.2008.03.018","article-title":"Safety of dermatologic drugs used in pregnant patients with psoriasis and other inflammatory skin diseases","volume":"59","author":"Lam","year":"2008","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jphs.2018.10.012","article-title":"Schaftoside ameliorates oxygen glucose deprivation-induced inflammation associated with the TLR4\/Myd88\/Drp1-related mitochondrial fission in BV2 microglia cells","volume":"139","author":"Zhou","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.molstruc.2014.01.002","article-title":"Antioxidant potential of orientin: A combined experimental and DFT approach","volume":"1061","author":"Praveena","year":"2014","journal-title":"J. Mol. Struct."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6131","DOI":"10.1002\/ptr.7221","article-title":"Bergapten: A review of its pharmacology, pharmacokinetics, and toxicity","volume":"35","author":"Liang","year":"2021","journal-title":"Phytother. Res."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.biopha.2017.10.073","article-title":"Vitexin inhibits inflammation in murine ovalbumin-induced allergic asthma","volume":"97","author":"Venturini","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_34","first-page":"117217","article-title":"Preventive effects of fraxin on ischemia\/reperfusion-induced acute kidney injury in rats","volume":"242","author":"Tanyeli","year":"2019","journal-title":"Life Sci."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Khalil, H.E., Abdelwahab, M.F., Ibrahim, H.-I.M., AlYahya, K.A., Altaweel, A.A., Alasoom, A.J., Burshed, H.A., Alshawush, M.M., and Waz, S. (2022). Cichoriin, a Biocoumarin, Mitigates Oxidative Stress and Associated Adverse Dysfunctions on High-Fat Diet-Induced Obesity in Rats. Life, 12.","DOI":"10.3390\/life12111731"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Lee, E.H., Shin, J.H., Kim, S.S., and Seo, S.R. (2021). Sinapic acid controls inflammation by suppressing NLRP3 inflammasome activation. Cells, 10.","DOI":"10.3390\/cells10092327"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/01480545.2019.1681445","article-title":"Antioxidant and cytoprotective properties of loganic acid isolated from seeds of Strychnos potatorum L. against heavy metal induced toxicity in PBMC model","volume":"45","author":"Abirami","year":"2019","journal-title":"Drug Chem. Toxicol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1007\/s10753-021-01473-4","article-title":"Anti-inflammatory effects of sweroside on LPS-induced ALI in mice via activating SIRT1","volume":"44","author":"Wang","year":"2021","journal-title":"Inflammation"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"172797","DOI":"10.1016\/j.ejphar.2019.172797","article-title":"Salidroside ameliorates endothelial inflammation and oxidative stress by regulating the AMPK\/NF-\u03baB\/NLRP3 signaling pathway in AGEs-induced HUVECs","volume":"867","author":"Hu","year":"2020","journal-title":"Eur. J. Pharmacol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1159\/000525690","article-title":"Nodakenetin Alleviates Inflammatory Pain Hypersensitivity by Suppressing NF-\u03baB Signal Pathway","volume":"29","author":"Lin","year":"2022","journal-title":"Neuroimmunomodulation"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.lfs.2003.10.042","article-title":"iNOS-mediated nitric oxide production and its regulation","volume":"75","author":"Aktan","year":"2004","journal-title":"Life Sci."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1126\/science.1072682","article-title":"Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases","volume":"298","author":"Johnson","year":"2002","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.cmet.2010.12.008","article-title":"NF-\u03baB, inflammation, and metabolic disease","volume":"13","author":"Baker","year":"2011","journal-title":"Cell Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/s40265-017-0701-9","article-title":"JAK\u2013STAT signaling as a target for inflammatory and autoimmune diseases: Current and future prospects","volume":"77","author":"Banerjee","year":"2017","journal-title":"Drugs"},{"key":"ref_45","first-page":"155","article-title":"Ursolic acid inhibits Th17 cell differentiation via STAT3\/ROR\u03b3t pathway and suppresses Schwann cell-mediated Th17 cell migration by reducing CXCL9\/10 expression","volume":"28","author":"Xu","year":"2022","journal-title":"J. Endotoxin Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.4049\/jimmunol.1302520","article-title":"Does \u03b2-hexosaminidase function only as a degranulation indicator in mast cells? The Primary Role of \u03b2-Hexosaminidase in Mast Cell Granules","volume":"193","author":"Fukuishi","year":"2014","journal-title":"J. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6892","DOI":"10.3748\/wjg.v21.i22.6892","article-title":"Nonalcoholic fatty liver disease, spleen and psoriasis: New aspects of low-grade chronic inflammation","volume":"21","author":"Balato","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.3109\/09546634.2014.880396","article-title":"Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper","volume":"26","author":"Girolomoni","year":"2015","journal-title":"J. Dermatol. Treat."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/S0140-6736(20)32549-6","article-title":"Psoriasis","volume":"397","author":"Griffiths","year":"2021","journal-title":"Lancet"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Xu, Y., Shi, Y., Huang, J., Gu, H., Li, C., Zhang, L., Liu, G., Zhou, W., and Du, Z. (2022). The Essential Oil Derived from Perilla frutescens (L.) Britt. Attenuates Imiquimod\u2013Induced Psoriasis-like Skin Lesions in BALB\/c Mice. Molecules, 27.","DOI":"10.3390\/molecules27092996"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"22707","DOI":"10.1074\/jbc.C111.250407","article-title":"Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of ROR\u03b3t protein","volume":"286","author":"Xu","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_52","first-page":"760405","article-title":"Methanolic extract of Ficus carica Linn. leaves exerts antiangiogenesis effects based on the rat air pouch model of inflammation","volume":"2015","author":"Allahyari","year":"2015","journal-title":"Evidence-Based Complement. Altern. Med."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Pastwi\u0144ska, J., Kara\u015b, K., Sa\u0142kowska, A., Karwaciak, I., Cha\u0142a\u015bkiewicz, K., Wojtczak, B.A., Bachorz, R.A., and Ratajewski, M. (2022). identification of corosolic and oleanolic acids as molecules antagonizing the human ROR\u03b3T nuclear receptor using the calculated fingerprints of the molecular similarity. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031906"}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1671\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:23:25Z","timestamp":1760127805000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/8\/1671"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["life13081671"],"URL":"https:\/\/doi.org\/10.3390\/life13081671","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]}}}