title: Anti-psoriatic effects of Honokiol through the inhibition of NF-κB and VEGFR-2 in animal model of K14-VEGF transgenic mouse.
abstract: Honokiol (HK), a biphenolic neolignan isolated from Magnolia officinalis, has been reported to possess anti-inflammatory and anti-angiogenic activaties. In this study, our aim was to investigate anti-psoriatic activities of HK and the involved mechanisms. In vitro, the effects of HK on the regulation of Th1/Th2 and TNF-α-induced NF-κB (p65) activation were analyzed by respective FCS and immunofluorescence. Additionally, the K14-VEGF transgenic model was used for the in vivo study. ELISA and Q-PCR were performed to evaluate serum levels of Th1/Th2 cytokines and their corresponding mRNA expressions. Effects on VEGFR-2 and p65 activation, as well as other angiogenic and inflammatory parameters were studied by immunostainings. Importantly, we found that HK significantly decreased the ratio of Th1/Th2-expression CD4(+) T cells and inhibited TNF-α-induced activation of NF-κB. The morphology and histological features of psoriasis were effectively improved by HK treatment. The expression of TNF-α and IFN-γ, and their corresponding mRNA levels were down-regulated and the expression of nuclear p65, VEGFR-2, as well as related phosphorylated proteins (p-VEGFR-2, p-ERK1/2, p-AKT and p-p38) were also suppressed. Overall, these results in our study suggested that HK exhibits anti-psoriatic effects through the inhibition of NF-κB and VEGFR-2.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Wen
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, China.
authors.forename: Xianhuo
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Heying
authors.initials: H
authors.lastname: Pei
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: Department of Chemical & Pharmaceutical Engineering, College of Materials and Chemistry and Chemical Engineering, Chengdu University of Technology, No.1, East Third Road, Erxianqiao, Chengdu, Sichuan, China.
authors.forename: Neng
authors.initials: N
authors.lastname: Qiu
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Shucai
authors.initials: S
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Wenwen
authors.initials: W
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Cheng
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors; D000818:Animals; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D015496:CD4-Positive T-Lymphocytes; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D017705:Lignans / Q000302:isolation & purification / Q000494:pharmacology* / Q000627:therapeutic use*; D031566:Magnolia; D008822:Mice, Transgenic; D058990:Molecular Targeted Therapy; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D008517:Phytotherapy; D011565:Psoriasis / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D058408:Th1-Th2 Balance / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D020533:Angiogenesis Inhibitors; D000893:Anti-Inflammatory Agents; D001713:Biphenyl Compounds; D017705:Lignans; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols
keywords: Honokiol; K14-VEGF; NF-κB; Psoriasis; VEGFR-2