Abstract
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.
Similar content being viewed by others
Article PDF
References
Ho LJ, Lai JH . Chinese herbs as immunomodulators and potential disease-modifying antirheumatic drugs in autoimmune disorders. Curr Drug Metab 2004; 5: 181–92.
Xie QM, Tang HF, Chen JQ, Bian RL . Pharmacological actions of tetrandrine in inflammatory pulmonary diseases. Acta Pharmacol Sin 2002; 23: 1107–13.
Lai JH . Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases. Acta Pharmacol Sin 2002; 23: 1093–101.
Rao MR . Effects of tetrandrine on cardiac and vascular remodeling. Acta Pharmacol Sin 2002; 23: 1075–85.
Shi X, Mao Y, Saffiotti U, Wang L, Rojanasakul Y, Leonard SS, et al. Antioxidant activity of tetrandrine and its inhibition of quartz-induced lipid peroxidation. J Toxicol Environ Health 1995; 46: 233–48.
Chen F, Sun S, Kuhn DC, Lu Y, Gaydos LJ, Shi X, et al. Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages. Biochem Biophys Res Commun 1997; 231: 99–102.
Ho LJ, Chang DM, Lee TC, Chang ML, Lai JH . Plant alkaloid tetrandrine downregulates protein kinase C-dependent signaling pathway in T cells. Eur J Pharmacol 1999; 367: 389–98.
Ferrante A, Seow WK, Rowan-Kelly B, Thong YH . Tetrandrine, a plant alkaloid, inhibits the production of tumour necrosis factor-alpha (cachectin) by human monocytes. Clin Exp Immunol 1990; 80: 232–5.
Wang B, Yang L, Yan HL, Wang M, Xiao JG . Effect of tetrandrine on calcium-dependent tumour necrosis factor-alpha production in glia-neurone mixed cultures. Basic Clin Pharmacol Toxicol 2005; 97: 244–8.
Gremo F, Sogos V, Ennas MG, Meloni A, Persichini T, Colasanti M, et al. Features and functions of human microglia cells. Adv Exp Med Biol 1997; 429: 79–97.
Ryu JK, Shin WH, Kim J, Joe EH, Lee YB, Cho KG, et al. Trisialoganglioside GT1b induces in vivo degeneration of nigral dopaminergic neurons: role of microglia. Glia 2002; 38: 15–23.
Iadecola C, Zhang F, Xu S, Casey R, Ross ME . Inducible nitric oxide synthase gene expression in brain following cerebral ischemia. J Cereb Blood Flow Metab 1995; 15: 378–84.
Paresce DM, Chung H, Maxfield FR . Slow degradation of aggregates of the Alzheimer's disease amyloid beta-protein by micro-glial cells. J Biol Chem 1997; 272: 29390–7.
Bal-Price A, Brown GC . Nitric-oxide-induced necrosis and apoptosis in PC12 cells mediated by mitochondria. J Neurochem 2000; 75: 1455–64.
Combs CK, Karlo JC, Kao SC, Landreth GE . Beta-amyloid stimulation of microglia and monocytes results in TNF-alpha-dependent expression of inducible nitric oxide synthase and neuronal apoptosis. J Neurosci 2001; 21: 1179–88.
Xiao BG, Diab A, Zhu J, van der Meide P, Link H . Astrocytes induce hyporesponses of myelin basic protein-reactive T and B cell function. J Neuroimmunol 1998; 89: 113–21.
Griess P . Bemerkungen zu der abhandlung der H. H. Weselsky und Benedikt “Ueber einige azoverbindungen”. Chem Ber 1879; 12: 426–8.
McDonald DR, Brunden KR, Landreth GE . Amyloid fibrils activate tyrosine kinase-dependent signaling and superoxide production in microglia. J Neurosci 1997; 17: 2284–94.
Takeuchi H, Jin S, Wang J, Zhang G, Kawanokuchi J, Kuno R, et al. Tumor necrosis factor-alpha induces neurotoxicity via glutamate release from hemichannels of activated microglia in an autocrine manner. J Biol Chem 2006; 281: 21362–8.
Le W, Rowe D, Xie W, Ortiz I, He Y, Appel SH . Microglial activation and dopaminergic cell injury: an in vitro model relevant to Parkinson's disease. J Neurosci 2001; 21: 8447–55.
Brown GC, Bal-Price A . Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol 2003; 27: 325–55.
Liu B, Jiang JW, Wilson BC, Du L, Yang SN, Wang J Y, et al. Systemic infusion of naloxone reduces degeneration of rat substantia nigral dopaminergic neurons induced by intranigral injection of lipopolysaccharide. J Pharmacol Exp Ther 2000; 295: 125–32.
Liu B, Du L, Hong JS . Naloxone protects rat dopaminergic neurons against inflammatory damage through inhibition of microglia activation and superoxide generation. J Pharmacol Exp Ther 2000; 293: 607–17.
Kowalski J, Labuzek K, Herman ZS . Flupentixol and trifluperidol reduce secretion of tumor necrosis factor-α and nitric oxide by rat microglial cells. Neurochem Int 2003; 1289: 1–6.
Li R, Huang YG, Fang D, Le WD . (-)-Epigallocatechin gallate inhibits lipopolysaccharide-induced microglial activation and protects against inflammation-mediated dopaminergic neuronal injury. J Neurosci Res 2004; 78: 723–31.
Kondo Y, Takano F, Hojo H . Inhibitory effect of bisbenzyliso-quinoline alkaloids on nitric oxide production in activated macrophages. Biochem Pharmacol 1993; 46: 1887–92.
Lai JH, Ho LJ, Kwan CY, Chang DM, Lee TC . Plant alkaloid tetrandrine and its analog block CD28-costimulated activities of human peripheral blood T cells: potential immunosuppressants in transplantation immunology. Transplantation 1999; 68: 1383–92.
Castranova V . Generation of oxygen radicals and mechanisms of injury prevention. Environ Health Perspect 1994; Suppl 10: 65–8.
Bal-Price A, Matthias A, Brown GC . Stimulation of the NADPH oxidase in activated rat microglia removes nitric oxide but induces peroxynitrite production. J Neurochem 2002; 80: 73–80.
Riobo NA, Clementi E, Melani M, Boveris A, Cadenas E, Moncada S, et al. Nitric oxide inhibits mitochondrial NADH: ubiquinone reductase activity through peroxynitrite formation. Biochem J 2001; 359: 139–45.
Seow WK, Ferrante A, Li SY, Thong YH . Antiphagocytic and antioxidant properties of plant alkaloid tetrandrine. Int Arch Allergy Appl Immunol 1988; 85: 404–9.
Grau GE, Lou J . TNF in vascular pathology: the importance of platelet-endothelial interactions. Res Immunol 1993; 144: 355–63.
Satoh J, Kastrukoff LF, Kim SU . Cytokine-induced expression of intercellular adhesion molecule-1 (ICAM-1) in cultured human oligodendrocytes and astrocytes. J Neuropathol Exp Neurol 1991; 50: 215–26.
McManus CM, Brosnan CF, Berman JW . Cytokine induction of MIP-1α and MIP-1β in human fetal microglia. J Immunol 1998; 160: 1449–55.
Hayashi M, Luo Y, Laning J, Strieter RM, Dorf ME . Production and function of monocyte chemoattractant protein-1 and other β-chemokines in murine glial cells. J Neuroimmunol 1995; 60: 143–50.
Hurwitz AA, Lyman WD, Berman JW . Tumor necrosis factor α and transforming growth factor? upregulate astrocyte expression of monocyte chemoattractant protein-1. J Neuroimmunol 1995; 57: 193–8.
Louis JC, Magal E, Takayama S, Varon S . CNTF protection of oligodendrocytes against natural and tumor necrosis factor-induced death. Science 1993; 259: 689–92.
Klein MA, Moller JC, Jones LL, Bluethmann H, Kreutzberg GW, Raivich G . Impaired neuroglial activation in interleukin-6-deficient mice. Glia 1997; 19: 227–33.
Ho LJ, Juan TY, Chao P, Wu WL, Chang DM, Chang SY, et al. Plant alkaloid tetrandrine downregulates IkappaBalpha kinases-IkappaBalpha-NF-kappaB signaling pathway in human peripheral blood T cell. Br J Pharmacol 2004; 143: 919–27.
Chen F, Sun S, Kuhn DC, Lu Y, Gaydos LJ, Shi X, et al. Tetrandrine inhibits signal-induced NF-kappa B activation in rat alveolar macrophages. Biochem Biophys Res Commun 1997; 231: 99–102.
Author information
Authors and Affiliations
Corresponding author
Additional information
Project 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).
Rights and permissions
About this article
Cite this article
Xue, Y., Wang, Y., Feng, Dc. et al. Tetrandrine suppresses lipopolysaccharide-induced microglial activation by inhibiting NF-κB pathway. Acta Pharmacol Sin 29, 245–251 (2008). https://doi.org/10.1111/j.1745-7254.2008.00734.x
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1111/j.1745-7254.2008.00734.x