Z-ligustilide attenuates lipopolysaccharide-induced proinflammatory response via inhibiting NF-KB pathway in primary rat microglia

• Published in: Acta pharmacologica Sinica no. 7; pp. 791 - 797
• Main Author: Jing WANG Jun-rong DU Yu WANG Xi KUANG Cheng-yuan WANG
• Format: Journal Article
• Language: English
• Published: 2010
• Subjects: 化学检测; 反应途径; 小胶质细胞; 肿瘤坏死因子; 脂多糖; 诱导型一氧化氮合酶
• ISSN: 1671-4083; 1745-7254

Aim： To investigate the anti-inflammatory effect of Z-ligustilide （LIG） on lipopolysaccharide （LPS）-activated primary rat microglia. Methods： Microglia were pretreated with LIG I h prior to stimulation with LPS （1 pg/mL）. After 24 h, cell viability was tested with MTT, nitric oxide （NO） production was assayed with Griess reagent, and the content of tumor necrosis factor-α （TNF-α）, interleukin-1β （IL-1β）, and monocyte chemoattractant protein （MCP-1） was measured with ELISA. Protein expression of the nuclear factor-KB （NF-KB） p65 subunit, cyclooxygenase-2 （COX-2）, and inducible nitric oxide synthase （iNOS） was detected with immunocytochemistry I h or 24 h after LPS treatment. Results： LIG showed a concentration-dependent anti-inflammatory effect in LPS-activated microglia, without causing cytotoxicity. Pretreatment with LIG at 2.5, 5, 10, and 20 pmol/L decreased LPS-induced NO production to 75.9%, 54.4%, 43.1%, and 47.6% （P〈0.05 or P〈0.01）, TNF-α content to 86.2%, 68.3%, 40.1%, and 39.9% （P〈0.01, with the exception of 86.2% for 2.5 pmol/L LIG）, LI-1β content to 31.5%, 27.7%, 0.6%, and 0% （P〈0.01）, and MCP-1 content to 84.4%, 50.3%, 45.1%, and 42.2% （P〈0.05 or P〈0.01）, respectively, compared with LPS treatment alone. LIG （10 μmol/L） significantly inhibited LPS-stimulated immunoreactivity of activated NF-KB, COX- 2, and iNOS （P〈0.01 vs LPS group）. Conclusion： LIG exerted a potent anti-inflammatory effect on microglia through inhibition of NF-κB pathway. The data provide direct evidence of the neuroprotective effects of LIG and the potential application of LIG for the treatment of the neuroinflammatory diseases characterized by excessive microglial activation.