title: Phytochemicals in Morinda citrifolia fruit selectively modulate age-associated immunity and antioxidant enzyme activities through ERK pathway in splenic lymphocytes of male F344 rats.
abstract: OBJECTIVE
  The mechanisms of immunomodulatory effects of Morinda citrifolia (Noni) were examined through intracellular signaling pathways in the splenocytes and their modulation by phytochemicals using bioinformatics tools.
  
  
  METHODS
  Noni fruit juices without seeds (NSL) and with seeds (NWS) were co-incubated in vitro with splenocytes from young, middle-aged and old F344 male rats and proliferation of lymphocytes, cytokine production, antioxidant enzyme activities and intracellular signaling markers were measured.
  
  
  RESULTS
  NSL decreased lymphoproliferation in early middle-aged rats, and IL-2 and IFN-γ production in old rats. In contrast, NWS enhanced lymphoproliferation in young and old rats, IL-2 and IFN-γ production in middle-aged and old rats. The activities of antioxidant enzymes were augmented by NWS and NSL in old rats. NWS reversed age-related increase in lipid peroxidation in all age-groups, while NSL increased lipid peroxidation in old rats. NSL increased p-ERK in old rats and decreased p-CREB in young and middle-aged rats. In contrast, NWS decreased p-ERK in all age groups and increased p-CREB in old rats. Both NSL and NWS increased p-Akt expression in middle-aged and old rats. Both NSL and NWS suppressed p-NF-κB expression in middle-aged and old rats. Docking studies demonstrated that Noni phytochemicals, damnacanthal, myricetin and ursolic acid, are potent inhibitors of ERK with binding sites in the catalytic and phosphorylation sites of the molecule.
  
  
  CONCLUSIONS
  These results suggest that Noni fruit juices with or without seeds modulate cell-mediated immunity and antioxidant enzyme activities based on the phytochemicals that may differentially influence cell signaling and therefore, age-associated immunity.
authors.affiliation: a Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University , Kattankulathur , Tamil Nadu , India and.
authors.forename: Uday P
authors.initials: UP
authors.lastname: Pratap
authors.affiliation: b Centre of Advanced Study in Crystallography and Biophysics, University of Madras Guindy Campus , Chennai , Tamil Nadu , India.
authors.forename: Krithika
authors.initials: K
authors.lastname: Anand
authors.affiliation: a Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University , Kattankulathur , Tamil Nadu , India and.
authors.forename: Fariya
authors.initials: F
authors.lastname: Yasmine
authors.affiliation: a Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University , Kattankulathur , Tamil Nadu , India and.
authors.forename: Lalgi
authors.initials: L
authors.lastname: Hima
authors.affiliation: a Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University , Kattankulathur , Tamil Nadu , India and.
authors.forename: Hannah P
authors.initials: HP
authors.lastname: Priyanka
authors.affiliation: a Integrative Medicine Laboratory, Department of Biotechnology, School of Bioengineering, SRM University , Kattankulathur , Tamil Nadu , India and.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Thyagarajan
mesh_terms: D000375:Aging / Q000187:drug effects* / Q000276:immunology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005638:Fruit / Q000737:chemistry; D007109:Immunity / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D032066:Morinda / Q000737:chemistry*; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D064209:Phytochemicals / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D013154:Spleen / Q000187:drug effects / Q000201:enzymology / Q000276:immunology
chemical_list: D000975:Antioxidants; D064209:Phytochemicals; D009569:Nitric Oxide
keywords: Catalase; cytokine; glutathione peroxidase; glutathione-S-transferase; lipid peroxidation; noni; superoxide dismutase