title: Effect of sesamin against cytokine production from influenza type A H1N1-induced peripheral blood mononuclear cells: computational and experimental studies.
abstract: In 2009, swine flu (H1N1) had spread significantly to levels that threatened pandemic influenza. There have been many treatments that have arisen for patients since the WHO first reported the disease. Although some progress in controlling influenza has taken place during the last few years, the disease is not yet under control. The development of new and less expensive anti-influenza drugs is still needed. Here, we show that sesamin from the seeds of the Thai medicinal plant Sesamum indicum has anti-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) induced by 2009 influenza virus type A H1N1. In this study, the combinatorial screening method combined with the computational approach was applied to investigate the new molecular binding structures of sesamin against the 2009 influenza virus type A H1N1 (p09N1) crystallized structure. Experimental methods were applied to propose the mechanisms of sesamin against cytokine production from H1N1-induced human PBMC model. The molecular dynamics simulation of sesamin binding with the p09N1 crystallized structure showed new molecular binding structures at ARG118, ILE222, ARG224, and TYR406, and it has been proposed that sesamin could potentially be used to produce anti-H1N1 compounds. Furthermore, the mechanisms of sesamin against cytokine production from influenza type A H1N1-induced PBMCs by ELISA and signaling transduction showed that sesamin exhibits the ability to inhibit proinflammatory cytokines, IL-1β and TNF-α, and to enhance the activity of the immune cell cytokine IL-2 via downregulating the phosphorylated JNK, p38, and ERK1/2 MAPK signaling pathways. This information might very well be useful in the prevention and treatment of immune-induced inflammatory disorders.
authors.affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. iamkanda54@gmail.com.
authors.forename: Kanda
authors.initials: K
authors.lastname: Fanhchaksai
authors.affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. tkanchanok@gmail.com.|Computational Simulation and Molecular Modeling Laboratory (CSML), Department of Chemistry, Faculty of Science, Chiang Mai University, Chiang Mai, 50200, Thailand. tkanchanok@gmail.com.
authors.forename: Kanchanok
authors.initials: K
authors.lastname: Kodchakorn
authors.affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. peraphan.pothacharoen@gmail.com.
authors.forename: Peraphan
authors.initials: P
authors.lastname: Pothacharoen
authors.affiliation: Thailand Excellence Center for Tissue Engineering and Stem Cells, Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand. prachya.kongtawelert@gmail.com.
authors.forename: Prachya
authors.initials: P
authors.lastname: Kongtawelert
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D004149:Dioxoles / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D053118:Influenza A Virus, H1N1 Subtype / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics; D007251:Influenza, Human / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D053583:Interleukin-1beta / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000737:chemistry / Q000187:drug effects; D017705:Lignans / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009976:Orthomyxoviridae Infections; D015398:Signal Transduction / Q000187:drug effects; D013552:Swine; D013553:Swine Diseases / Q000453:epidemiology / Q000821:virology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D004149:Dioxoles; D053583:Interleukin-1beta; D007376:Interleukin-2; D017705:Lignans; D014409:Tumor Necrosis Factor-alpha; C054125:sesamin
keywords: Influenza A neuraminidase; Influenza type A H1N1 virus; Molecular dynamics simulation; Peripheral blood mononuclear cells; Sesamin