title: Pristimerin, a natural anti-tumor triterpenoid, inhibits LPS-induced TNF-α and IL-8 production through down-regulation of ROS-related classical NF-κB pathway in THP-1 cells.
abstract: Pristimerin, a naturally occurring quinonemethide triterpenoid compound, is known to exert a variety of pharmacological activities. In the present study, we investigated the molecular actions of pristimerin against LPS-induced inflammatory responses in human monocytic THP-1 cells. The results showed that pristimerin inhibited the production of TNF-α and IL-8 in a dose-dependent manner. To explore the possible mechanisms underlying these inhibitions by pristimerin, we examined the intracellular ROS level and the NF-κB protein signaling pathway. Pristimerin clearly scavenged LPS-induced intracellular ROS production. In addition, pristimerin prevented LPS-induced NF-κB activation through the inhibition of phosphorylation of IKKα/β, phosphorylation and degradation of IκBα, as well as phosphorylation and nuclear translocation of NF-κB p65. These findings suggest that pristimerin down-regulates the expression of pro-inflammatory mediators through blocking of NF-κB activation by inhibiting interconnected ROS/IKK/NF-κB signaling pathways.
authors: Department of Pharmacology, College of Medicine, Jiaxing University, Jiaxing 314001, China.
authors: Bin
authors: B
authors: Hui
authors: Department of Pharmacology, College of Medicine, Jiaxing University, Jiaxing 314001, China.
authors: Xin
authors: X
authors: Yao
authors: Department of Pharmacology, College of Medicine, Jiaxing University, Jiaxing 314001, China.
authors: Qinhua
authors: Q
authors: Zhou
authors: Department of Pharmacology, College of Medicine, Jiaxing University, Jiaxing 314001, China.
authors: Ziyan
authors: Z
authors: Wu
authors: Haining Maternal and Child Health Hospital, Haining, Zhejiang 314000, China.
authors: Peng
authors: P
authors: Sheng
authors: Department of Emergency Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200023, China. Electronic address: zhanglp-sh@hotmail.com.
authors: Liping
authors: L
authors: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism*; D053978:Pentacyclic Triterpenes; D010766:Phosphorylation / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D020672:I-kappa B Proteins; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D053978:Pentacyclic Triterpenes; D017382:Reactive Oxygen Species; D051996:Transcription Factor RelA; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; D051550:I-kappa B Kinase; C050414:celastrol
keywords: IKKα/β; IL-8; NF-κB; Pristimerin; ROS; TNF-α