Acta Pharmacologica Sinica 2008 February; 29 (2): 245-251; doi: 10.1111/j.1745-7254.2008.00734.x

Acta Pharmacologica Sinica 2008 February; 29 (2): 245-251; doi: 10.1111/j.1745-7254.2008.00734.x

Original Article

Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB pathway¹

Yang XUE², Ying WANG², De-chun FENG³, Bao-guo XIAO⁴, Ling-yun XU^2,3,5

²Shanghai Institute of Immunology, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; ³Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; ⁴Institute of Neurology, Huashan Hospital, Institute of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai 200040, China

Aim: Microglial activation has been implicated in many neurological diseases. In this study, we examined the effects of tetrandrine (TET), a major pharmacologically-active compound of Chinese herb Stephania tetrandra S Moore on microglial activation.

Methods: The microglia pretreated with or without TET were activated by lipopolysaccharide (LPS) in vitro. Nitric oxide (NO) release, superoxide anion (O₂^_) generation, as well as TNF-α and interleukin-6 (IL-6) production by microglia were measured afterwards. Electrophoretic mobility shift assay was performed to determine whether NF-κB activity in microglia was affected by TET treatment.

Results: We found that TET inhibited the LPS-induced activation of microglia by decreasing the production of NO and O₂^_, consequently affecting the release of TNF-α and IL-6 in LPS-induced microglial activation. Such suppressive effect was accompanied by inhibiting transcription factor NF-κB activation.

Conclusion: Our results suggest that TET might modulate LPS-induced microglial activation by inhibiting the NF-κB-mediated release of inflammatory factors.

Keywords: tetrandrine; microglia; nitric oxide; superoxide anion; cytokine; NF-κB

¹Project supported by grants from the Shanghai Rising-Star Program (No 04QMX1423), Science and Technology Commission of Shanghai Municipality (No 04DZ14902), Shanghai Leading Academic Discipline Project (No T0206), and the Knowledge Innovation Program of the Chinese Academy of Sciences (No J0171-1905).

⁵ Correspondence to Dr Ling-yun XU.
Phn/Fax 86-21-6385-2733.
E-mail lyxu@sibs.ac.cn
Received 2007-06-10 Accepted 2007-09-03

[ Full text ]