title: Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB and ERK signaling pathways in BV2 cells.
abstract: OBJECTIVE
  Tetrandrine (TET) is a bisbenzylisoquinoline alkaloid extracted from Stephania tetrandra Moore. Recent studies have suggested that TET can reduce the inflammatory response in microglia, but the mechanisms remain unclear. The aim of this study is to investigate whether TET can inhibit lipopolysaccharide (LPS)-induced microglial activation and clarify its possible mechanisms.
  
  
  METHODS
  Cell viability assays and cell apoptosis assays were used to determine the working concentrations of TET. Then, BV2 cells were seeded and pretreated with TET for 2 h. LPS was then added and incubated for an additional 24 hours. qRT-PCR and ELISA were used to measure the mRNA or protein levels of IL1β and TNFα. Western blotting was utilized to quantify the expression of CD11b and cell signaling proteins.
  
  
  RESULTS
  TET at optimal concentrations (0.1 µM, 0.5 µM or 1 µM) did not affect the cell viability. After TET pretreatment, the levels of IL1β and TNFα (both in transcription and translation) were significantly inhibited in a dose-dependent manner. Further studies indicated that phospho-p65, phospho-IKK, and phospho-ERK 1/2 expression were also suppressed by TET.
  
  
  CONCLUSIONS
  Our results indicate that TET can effectively suppress microglial activation and inhibit the production of IL1β and TNFα by regulating the NF-kB and ERK signaling pathways. Together with our previous studies, we suggest that TET would be a promising candidate to effectively suppress overactivated microglia and alleviate neurodegeneration in glaucoma.
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China; Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Yalong
authors.initials: Y
authors.lastname: Dang
authors.affiliation: Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Wentao
authors.initials: W
authors.lastname: Wu
authors.affiliation: Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Yanran
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou City, Henan Province, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Clinical Stem Cell Research Center, Peking University Third Hospital, Beijing, People's Republic of China; Department of Ophthalmology, Peking University Third Hospital, Beijing, People's Republic of China.
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D044182:Benzylisoquinolines / Q000494:pharmacology*; D039481:CD11b Antigen / Q000235:genetics / Q000378:metabolism; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015870:Gene Expression; D053583:Interleukin-1beta / Q000096:biosynthesis; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D044182:Benzylisoquinolines; D039481:CD11b Antigen; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine; D048049:Extracellular Signal-Regulated MAP Kinases