title: Tetrandrine suppresses amyloid-β-induced inflammatory cytokines by inhibiting NF-κB pathway in murine BV2 microglial cells.
abstract: Microglial cells play an important role in mediating neuroinflammation in Alzheimer's disease (AD) by production of a series of proinflammatory mediators and clearance of Aβ peptides and senile plaques. Tetrandrine, a bisbenzylisoquinoline alkaloid isolated from the Chinese herb Radix Stephania tetrandra, has been demonstrated to decrease the expression of proinflammatory mediators by inhibition of NF-κB activation. Here we investigated whether tetrandrine may affect the phagocytosis of microglia and the expression of cytokines and NF-κB in murine BV2 microglial cells. We found that fibrillar Amyloid-β (fAβ) induced phagocytosis of microglia and dramatically increased the levels of interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) as well as the expression of phospho NF-κB p65 in microglia cultures. The treatment with tetrandrine resulted in downregulation of phospho NF-κB p65 expression and strikingly reduced the production of IL-1β and TNF-α. However, tetrandrine did not affect fAβ induced phagocytosis of microglia. In conclusion, tetrandrine can decrease microglial detriment of neurotoxicity while maintaining microglial benefit of neuroprotection. Tetrandrine may be an efficacious and promising remedy in the treatment of AD.
authors.affiliation: Department of Geriatrics Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
authors.forename: Fu Qian
authors.initials: FQ
authors.lastname: He
authors.forename: Bo Yun
authors.initials: BY
authors.lastname: Qiu
authors.forename: Tian Ke
authors.initials: TK
authors.lastname: Li
authors.forename: Qin
authors.initials: Q
authors.lastname: Xie
authors.forename: De Jun
authors.initials: DJ
authors.lastname: Cui
authors.forename: Xiao Li
authors.initials: XL
authors.lastname: Huang
authors.forename: Hua Tian
authors.initials: HT
authors.lastname: Gan
mesh_terms: D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D044182:Benzylisoquinolines / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D044182:Benzylisoquinolines; D053583:Interleukin-1beta; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C009438:tetrandrine