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This study aimed to investigate the in vitro and in vivo immunostimulatory activity of <jats:italic>M.\u00a0citrifolia<\/jats:italic> fruit water extract treated with enzymes (Mc\u2010eWE). In vitro studies revealed that Mc\u2010eWE stimulated the cells by inducing nitric oxide (NO) production and the expression of inflammatory cytokines, such as interleukin (IL)\u20101\u03b2, IL\u20106, IL\u201012, tumor necrosis factor\u2010alpha (TNF\u2010\u03b1), and interferon\u2010gamma (IFN\u2010\u03b3). The immunostimulatory activity was mediated by activation of NF\u2010\u03baB and AP\u20101. Ex vivo studies showed that Mc\u2010eWE stimulated splenocytes isolated from mice by inducing NO production and expression of immunostimulatory cytokines and by downregulating the expression of the immunosuppressive cytokine IL\u201010 without cytotoxicity. In vivo demonstrated that Mc\u2010eWE induced immunostimulation by modulating populations of splenic immune cells, especially by increasing the population of IFN\u2010\u03b3<jats:sup>+<\/jats:sup> NK cells. Mc\u2010eWE enhanced the expression of inflammatory genes and immunostimulatory cytokines and inhibited the expression of IL\u201010 in the mouse splenocytes and sera. Taken together, these results suggest that Mc\u2010eWE plays an immunostimulatory role by activating innate and adaptive immune responses.<\/jats:p>","DOI":"10.1002\/ptr.6256","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T10:01:13Z","timestamp":1547200873000},"page":"676-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["<i>Morinda citrifolia<\/i> noni water extract enhances innate and adaptive immune responses in healthy mice, ex vivo, and in vitro"],"prefix":"10.1002","volume":"33","author":[{"given":"Yo Han","family":"Hong","sequence":"first","affiliation":[{"name":"Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Su","family":"Yi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering Cheongju University  Cheongju Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Yun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7696-1025","authenticated-orcid":false,"given":"Nur","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Gyung","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Integrative Biotechnology and Biomedical Institute for Convergence (BICS) Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sang Hee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biocosmetics Sungkyunkwan University  Suwon Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad Amjad","family":"Hossain","sequence":"additional","affiliation":[{"name":"College of Veterinary Medicine Chonbuk National University  Iksan Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kwang Soo","family":"Baik","sequence":"additional","affiliation":[{"name":"Functional Ingredient Development Team Nutribiotech Co., Ltd.  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