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Objective:Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system.The medicinal properties of Morinda citrifolia L.have been widely exploited for the treatment of age-associated diseases.This study aims to investigate the in vitro and in vivo effects of noni (M.citrifolia) fruit juice (NFJ) on neuro-immunomodulation in the lymph node lymphocytes of F344 rats.Methods:Lymphocytes isolated from axillary and inguinal lymph nodes of young (3-4 months) and old (18-21 months) rats were treated in vitro with different concentrations (0.0001％,0.01％,and 1％) of NFJ for a period of 24h.In the in vivo study,old (16-17 months) male F344 rats were treated with 5 mL/kg body weight of 5％,10％ and 20％ of NFJ,twice a day,by oral gavage,and lymph node lymphocytes were isolated after 60 d.Concanavalin A (Con A)-induced lymphocyte proliferation,interleukin-2 (IL-2) and interferon-γ (IFN-γ) production and expression of intracellular markers,such as phosphoextracellular signal-regulated kinase (p-ERK1/2),phospho-cAMP response element-binding protein,phospho-protein kinase B (p-Akt),phospho-tyrosine hydroxylase (p-TH),phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α (p-IκB-α) and phospho-nuclear factor-κB (p-NF-κB p65 and p50) were examined in the lymphocytes of lymph nodes.Results:NFJ increased Con A-induced lymphocyte proliferation,IL-2 and IFN-γ production,and p-ERK1 /2 expression both in vitro and in vivo.In in vivo NFJ-treated old rats,lymph node lymphocytes showed increased expression of p-TH and Akt,nitric oxide production and decreased expression of p-NF-κB p65 and p50.Conclusion:These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2,Akt and NF-κB.