Phthalide Lactones from Ligusticum chuanxiong Inhibit Lipopolysaccharide-Induced TNF-α Production and TNF-α-Mediated NF-κB Activation

Abstract

The dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae) is a traditional Chinese medicine (TCM) herb for the prevention and treatment of inflammatory and cardiovascular diseases. However, the role of phthalide lactones from Ligusticum chuanxiong in the therapeutic actions is not yet fully understood. In the present study, two phthalide lactones from the herb, Z-ligustilide and senkyunolide A, were identified and characterized as inhibitors of lipopolysaccharide (LPS)-induced TNF-α production in monocytes. The results of gene expression studies showed that the observed TNF-α suppression was related to their inhibitory activity on TNF-α mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-α-mediated nuclear factor-κB (NF-κB) activation in reporter gene assays. Taken together, the results suggest that Z-ligustilide and senkyunolide A may have potential applications in the treatment of inflammation and related diseases based on their inhibitory activity on TNF-α production and TNF-α bioactivity. New insights into the therapeutic basis of the TCM herb, Ligusticum chuanxiong, are presented.

Abbreviations

TCM:traditional Chinese medicine

LPS:lipopolysaccharide

TNF-α:tumor necrosis factor-α

NF-κB:nuclear factor-κB

MAPK:mitogen-activated protein kinase

RT-PCR:reverse transcription polymerase chain reaction

Key words

TNF-α - LPS - monocytes - NF-κB - phthalide lactones - Ligusticum chuanxiong - Umbelliferae

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