title: Cucurbitacin E inhibits TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via suppression of PI3K/Akt/NF-κB pathways.
abstract: Increasing studies indicated that Cucurbitacin E (CuE), a compound isolated from Cucurbitaceae, has been shown anti-inflammatory effect. However, the effect of CuE on rheumatoid arthritis (RA) inflammatory response and its potential molecular mechanism are still unknown. In this study, we demonstrated that CuE significantly suppressed TNF-α-induced inflammatory cytokines production interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-8 (IL-8) mRNA and protein expression in human synoviocyte MH7A cells. Furthermore, we found that CuE also inhibited TNF-α-induced phosphorylation of NF-κBp65, IKKα/β, and IκBα in a dose-and time-dependent manner as well as NF-κBp65 nuclear translocation. Finally, we showed that CuE blocked the upstream targets of NF-κB pathway RIP1/PI3K/Akt. Interestingly, PI3K inhibitor LY294002 completely blocked the TNF-α-induced activation of p85, Akt and the whole cascade of the NF-κB signaling components and suppressed inflammatory cytokines production in mRNA and protein levels similarly as CuE. Our studies provided the first evidence that CuE inhibited TNF-α-induced inflammatory cytokine production in human synoviocyte MH7A cells via modulation of PI3K/Akt/NF-κB pathway. These findings indicated that CuE is a potential candidate for RA therapy.
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shandong University of Traditional Chinese Medicine, Ji'nan 250355, China; Department of orthopedics, Rizhao Hospital of Traditional Chinese Medicine, Rizhao 276800, China.
authors.forename: Qingyun
authors.initials: Q
authors.lastname: Jia
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Cheng
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yue
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Yipping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Laboratory for Reproductive Health, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of orthopedics, Shenzhen Bao'an People's Hospital, Shenzhen 518100, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Pan
authors.affiliation: Shandong University of Traditional Chinese Medicine, Ji'nan 250355, China. Electronic address: xzw6001@163.com.
authors.forename: Zhanwang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Translational Medicine R&D Center, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China; Shenzhen Bioactive Materials Engineering Lab for Medicine, Shenzhen 518100, China. Electronic address: peng.zhang@siat.ac.cn.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D051058:Oncogene Protein v-akt / Q000187:drug effects / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000166:cytology* / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D016207:Cytokines; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014315:Triterpenes; D014409:Tumor Necrosis Factor-alpha; C102326:cucurbitacin E
keywords: Cucurbitacin E; Inflammation; MH7A; NF-κB; PI3K/Akt; Rheumatoid arthritis