{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T21:25:17Z","timestamp":1790803517519,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2024,10,16]],"date-time":"2024-10-16T00:00:00Z","timestamp":1729036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NUS","award":["T2EP30121-0012"],"award-info":[{"award-number":["T2EP30121-0012"]}]},{"name":"NUS","award":["BZ2022056"],"award-info":[{"award-number":["BZ2022056"]}]},{"name":"Biomedical and Health Technology Platform, National University of Singapore (Suzhou) Research Institute","award":["T2EP30121-0012"],"award-info":[{"award-number":["T2EP30121-0012"]}]},{"name":"Biomedical and Health Technology Platform, National University of Singapore (Suzhou) Research Institute","award":["BZ2022056"],"award-info":[{"award-number":["BZ2022056"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Foods"],"abstract":"<jats:p>Papaya leaves have been used as food and traditional herbs for the treatment of cancer, diabetes, asthma, and virus infections, but the active principle has not been understood. We hypothesized that the anti-inflammatory activity could be the predominant underlying principle. To test this, we extracted papaya leaf juice with different organic solvents and found that the ethyl acetate (EA) fraction showed the most outstanding anti-inflammatory activity by suppressing the production of nitric oxide (NO, IC50 = 24.94 \u00b1 2.4 \u03bcg\/mL) and the expression of pro-inflammatory enzymes, such as inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX-2), and cytokines including interleukins (IL-1\u03b2 and IL-6), and a tumor necrosis factor (TNF-\u03b1) in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Transcriptomic analysis and Western blot results revealed its anti-inflammatory mechanisms were through the MAPK signaling pathway by inhibiting the phosphorylation of ERK1\/2, JNKs, and p38 and the prevention of the cell surface expression of TLR4. Furthermore, we discovered that the EA fraction could inhibit the replication of alpha-coronavirus (HCoV-229E) and beta-coronavirus (HCoV-OC43 and SARS-CoV-2) and might be able to prevent cytokine storms caused by the coronavirus infection. From HPLC-QTOF-MS data, we found that the predominant phytochemicals that existed in the EA fraction were quercetin and kaempferol glycosides and carpaine. Counter-intuitively, further fractionation resulted in a loss of activity, suggesting that the synergistic effect of different components in the EA fraction contribute to the overall potent activity. Taken together, our results provide preliminary evidence for papaya leaf as a potential anti-inflammatory and anti-coronavirus agent, warranting further study for its use for human health promotion.<\/jats:p>","DOI":"10.3390\/foods13203274","type":"journal-article","created":{"date-parts":[[2024,10,21]],"date-time":"2024-10-21T04:45:35Z","timestamp":1729485935000},"page":"3274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Dual Functionality of Papaya Leaf Extracts: Anti-Coronavirus Activity and Anti-Inflammation Mechanism"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9984-3080","authenticated-orcid":false,"given":"Yujia","family":"Cao","sequence":"first","affiliation":[{"name":"Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kah-Man","family":"Lai","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuo-Chang","family":"Fu","sequence":"additional","affiliation":[{"name":"AgriGADA Biotech Pte Ltd., 8 Eu Tong Sen Street #17\u201382, The Central, Singapore 059818, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Liang","family":"Kuo","sequence":"additional","affiliation":[{"name":"AgriGADA Biotech Pte Ltd., 8 Eu Tong Sen Street #17\u201382, The Central, Singapore 059818, Singapore"},{"name":"Ph.D. Program for Aging, College of Medicine, China Medical University, Taichung 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2278-4497","authenticated-orcid":false,"given":"Yee-Joo","family":"Tan","sequence":"additional","affiliation":[{"name":"Infectious Diseases Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117545, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6497-0864","authenticated-orcid":false,"given":"Liangli (Lucy)","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Food Science, University of Maryland, College Park, MD 20742, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dejian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Food Science and Technology, National University of Singapore, Singapore 117542, Singapore"},{"name":"Biomedical and Health Technology Platform, National University of Singapore (Suzhou) Research Institute, Suzhou 215123, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Antunes Carvalho, F., and Renner, S.S. 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