Catalpol inhibits LPS plus IFN-γ-induced inflammatory response in astrocytes primary cultures

A large body of evidence suggests that the inflammatory reaction plays an important role in the pathogenesis of neurodegenerative diseases. Our previous studies described the neuroprotective effects of catalpol in lipopolysaccharide (LPS)-induced inflammatory models, in which catalpol was shown to prevent mesencephalic neuron death and ameliorate cognitive ability animals. To further investigate the protective effect and underlying mechanism of catalpol, astrocytes were pretreated with low (0.1 mM) and high dose (0.5 mM) catalpol for 1 h prior to LPS plus interferon-γ stimulation. Biochemical analyses showed that NO and ROS production and iNOS activity were significantly reduced by catalpol. Data at transcriptional level also demonstrated that catalpol potently attenuated gene expressions involved in inflammation, such as iNOS, COX-2 and TLR4. In addition, our exploration further revealed that the suppressive action of catalpol on inflammation was mediated via inhibiting nuclear factor-κB (NF-κB) activation. Collectively, these results suggest that catalpol can exert inhibitory effects on the inflammatory reaction in astrocytes and that inactivation of NF-κB could be the major determinant for its anti-inflammatory mechanism. Therefore, catalpol may potentially be a highly effective therapeutic agent in treating neurodegenerative diseases associated with inflammation.

► Catalpol recovered the morphology of astrocytes induced by LPS. ► In this model of inflammation, catalpol attenuated NO, ROS production and iNOS activity. ► Catalpol also blunted the transcription of iNOS, COX-2 and TLR4 at mRNA level. ► Further, the underlying protective mechanism of catalpol in this model might be via inhibiting the activation of NF-κB.