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BACKGROUND AND 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. STUDY DESIGN/MATERIALS AND 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.
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.
Full article11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
3.5 Molecular biology incl. SiRNA (Part of: 3 Laboratory methods)