title: Phthalide Lactones from Ligusticum chuanxiong inhibit lipopolysaccharide-induced TNF-alpha production and TNF-alpha-mediated NF-kappaB 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-alpha production in monocytes. The results of gene expression studies showed that the observed TNF-alpha suppression was related to their inhibitory activity on TNF-alpha mRNA transcription. Furthermore, the two phthalides exhibited significant suppressive effects on TNF-alpha-mediated nuclear factor-kappaB (NF-kappaB) 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-alpha production and TNF-alpha bioactivity. New insights into the therapeutic basis of the TCM herb, Ligusticum chuanxiong, are presented.
authors.affiliation: Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, P. R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Ning
authors.forename: Song
authors.initials: S
authors.lastname: Shan
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.forename: Tuo
authors.initials: T
authors.lastname: Deng
authors.forename: Xian-Ping
authors.initials: XP
authors.lastname: Lu
authors.forename: Yi-Yu
authors.initials: YY
authors.lastname: Cheng
mesh_terms: D001572:Benzofurans / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D030004:Ligusticum; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000096:biosynthesis / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D020133:Reverse Transcriptase Polymerase Chain Reaction; D027343:Rhizome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000187:drug effects*
chemical_list: D001572:Benzofurans; D007783:Lactones; D008070:Lipopolysaccharides; D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C082022:phthalide