title: Diosgenin down-regulates NF-κB p65/p50 and p38MAPK pathways and attenuates acute lung injury induced by lipopolysaccharide in mice.
abstract: Diosgenin (Dio), a major active component of steroidal sapogenin of the traditional Chinese herb Dioscorea zingiberensis C.H.Wright, shows various activities including anti-inflammatory, anti-thrombotic activities, anti-cancer properties etc. In the present study, we found that diosgenin significantly suppressed the phosphorylation of lung NF-κB p50/p65 and MAPK/p38 in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, when given orally at doses of 0.1, 1.0 and 10mg/kg 1h prior to LPS challenge (30 mg/kg, intravenous injection). Moreover, diosgenin attenuated the lung histopathological changes such as pulmonary edema, coagulation and infiltration of inflammatory cells. In addition, diosgenin significantly decreased the lung wet to dry weight (W/D) ratio and nitrite/nitrate content at three doses, and also markedly inhibited LPS-induced body temperature decrease and nitrite/nitrate elevation in plasma. Besides, diosgenin could significantly suppress activation of NF-κB p65/p50, p38 and expression of inducible nitric oxide synthase (iNOS) in LPS-induced THP-1 cells. Our findings indicate the potential application of diosgenin for ALI treatment.
authors.affiliation: Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, PR China.
authors.forename: Mengyu
authors.initials: M
authors.lastname: Gao
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.forename: Haixiang
authors.initials: H
authors.lastname: Yu
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.forename: Junping
authors.initials: J
authors.lastname: Kou
authors.forename: Boyang
authors.initials: B
authors.lastname: Yu
mesh_terms: D055371:Acute Lung Injury; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D027742:Dioscorea / Q000276:immunology; D004144:Diosgenin / Q000008:administration & dosage*; D004195:Disease Models, Animal; D015536:Down-Regulation; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000473:pathology; D008297:Male; D008516:Medicine, Chinese Traditional; D051379:Mice; D008813:Mice, Inbred ICR; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D048051:p38 Mitogen-Activated Protein Kinases; D004144:Diosgenin