title: Anti-neuroinflammatory effects of grossamide from hemp seed via suppression of TLR-4-mediated NF-κB signaling pathways in lipopolysaccharide-stimulated BV2 microglia cells.
abstract: Grossamide, a representative lignanamide in hemp seed, has been reported to possess potential anti-inflammatory effects. However, the potential anti-neuroinflammatory effects and underlying mechanisms of action of grossamide are still unclear. Therefore, the present study investigated the possible effects and underlying mechanisms of grossamide against lipopolysaccharide (LPS)-induced inflammatory response in BV2 microglia cells. BV2 microglia cells were pre-treated with various concentrations of grossamide before being stimulated with LPS to induce inflammation. The levels of pro-inflammatory cytokines were determined using the enzyme-linked immunoassay (ELISA) and mRNA expression levels were measured by real-time PCR. The translocation of nuclear factor-kappa B (NF-κB) and contribution of TLR4-mediated NF-κB activation on inflammatory effects were evaluated by immunostaining and Western blot analysis. This study demonstrated that grossamide significantly inhibited the secretion of pro-inflammatory mediators such as interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α), and decreased the level of LPS-mediated IL-6 and TNF-α mRNA. In addition, it significantly reduced the phosphorylation levels of NF-κB subunit p65 in a concentration-dependent manner and suppressed translocation of NF-κB p65 into the nucleus. Furthermore, grossamide markedly attenuated the LPS-induced expression of Toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Taken together, these data suggest that grossamide could be a potential therapeutic candidate for inhibiting neuroinflammation in neurodegenerative diseases.
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Yan
authors.affiliation: School of Pharmacy and Medical Sciences, Sansom Institute for Health Research, University of South Australia, Adelaide, SA, 5000, Australia.
authors.forename: Larisa
authors.initials: L
authors.lastname: Bobrovskaya
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Mei
authors.initials: M
authors.lastname: Ji
authors.affiliation: Department of Biochemistry & Molecular Biology, School of Medicine, Shandong University, Jinan, 250100, People's Republic of China.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China.
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
authors.affiliation: Department of Natural Product Chemistry, Key Lab of Chemical Biology of Ministry of Education, School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, People's Republic of China. fanpeihong@sdu.edu.cn.
authors.forename: Peihong
authors.initials: P
authors.lastname: Fan
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002188:Cannabis / Q000737:chemistry*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000009:adverse effects*; D051379:Mice; D017628:Microglia / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D010936:Plant Extracts / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D004365:Drugs, Chinese Herbal; D008070:Lipopolysaccharides; D010936:Plant Extracts
keywords: Anti-neuroinflammatory; BV2 microglia cells; Grossamide; Hemp seed; Lignanamide; NF-κB