Ghosh, NandiniDas, AmitavaBiswas, NirupamMahajan, Sanskruti P.Madeshiya, Amit K.Khanna, SavitaSen, Chandan K.Roy, Sashwati2022-03-102022-03-102022Ghosh, N., Das, A., Biswas, N., Mahajan, S. P., Madeshiya, A. K., Khanna, S., Sen, C. K., & Roy, S. (2022). Myo-Inositol in Fermented Sugar Matrix Improves Human Macrophage Function. Molecular Nutrition & Food Research, 2100852. https://doi.org/10.1002/mnfr.2021008521613-4125, 1613-4133https://hdl.handle.net/1805/28133Scope Reactive oxygen species production by innate immune cells plays a central role in host defense against invading pathogens at wound-site. A weakened hos-defense results in persistent infection leading to wound chronicity. Fermented Papaya Preparation (FPP), a complex sugar matrix, bolstered respiratory burst activity and improved wound healing outcomes in chronic wound patients. The objective of the current study was to identify underlying molecular factor/s responsible for augmenting macrophage host defense mechanisms following FPP supplementation. Methods and results In depth LC-MS/MS analysis of cells supplemented with FPP led to identification of myo-inositol as a key determinant of FPP activity towards improving macrophage function. Myo-inositol, in quantities that is present in FPP, significantly improved macrophage respiratory burst and phagocytosis via de novo synthesis pathway of ISYNA1. Additionally, myo-inositol transporters, HMIT and SMIT1, played a significant role in such activity. Blocking these pathways using siRNA attenuated FPP-induced improved macrophage host defense activities. FPP supplementation emerges as a novel approach to increase intracellular myo-inositol levels. Such supplementation also modified wound microenvironment in chronic wound patients to augment myo-inositol levels in wound fluid. Conclusion These observations indicate that myo-inositol in FPP influences multiple aspects of macrophage function critical for host defense against invading pathogens.en-USPublisher Policydietary supplementmacrophagemyo-inositolphagocytosisROSArticle