Immunomodulatory and radioprotective effects of lignans derived from fresh nutmeg mace (Myristica fragrans) in mammalian splenocytes

Recently, the lignans present in the aqueous extract of fresh nutmeg mace (aril of the fruit of Myristica fragrans) were shown to possess antioxidant properties in cell free systems and protected PUC18 plasmid against radiation-induced DNA damage. The present report describes the immunomodulatory and radiomodifying properties of lignans present in the aqueous extract of fresh nutmeg mace in mammalian splenocytes. These macelignans (ML) inhibited the proliferation of splenocytes in response to polyclonal Tcell mitogen concanavalin A (Con A). This inhibition of proliferation was due to cell cycle arrest in G1 phase and augmentation of apoptosis as shown by increase in pre G1 cells. The increase in activation induced cell death by ML was dose dependent. It was found to inhibit the transcription of IL-2 and IL-4 genes in response to Con A. The production of IL-2, IL-4 and IFN-gamma cytokines was significantly inhibited by ML in Con A-stimulated lymphocytes in a dose dependent manner. ML protected splenocytes against radiation-induced intracellular ROS production in a dose dependent manner. ML was not cytotoxic towards lymphocytes. On the contrary, it significantly inhibited the radiation-induced DNA damage in splenocytes as indicated by decrease in DNA fragmentation. To our knowledge, this is the first report showing the antioxidant, radioprotective and immunomodulatory effects of lignans in mammalian cells. (c) 2008 Elsevier B.V. All rights reserved.