title: Gambogic acid exhibits anti-psoriatic efficacy through inhibition of angiogenesis and inflammation.
abstract: BACKGROUND
  Psoriasis is a chronic T cell-mediated inflammatory skin disease. Studies have shown that angiogenesis plays an important role in the pathogenesis of psoriasis. Studies have also indicated that Gambogic acid (GA) inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis therapies.
  
  
  OBJECTIVE
  The aim of this study was to investigate the anti-psoriatic effect of GA and the possible mechanisms.
  
  
  METHODS
  MTT test on HaCaT cells and immunofluorescence on HUVEC cells were processed. An O/W cream of GA was prepared and topically applied to the ears of K14-VEGF transgenic mice and psoriasis-like guinea-pigs, and the tail skin of Balb/C mice independently. Furthermore, hematoxylin-eosin staining of tissues from three models and immunohistochemistry staining of ear samples from K14-VEGF mice were performed.
  
  
  RESULTS
  In vitro, GA inhibited proliferation of HaCaTs and TNF-α-induced activation of NF-κB in HUVECs. In vivo, animals treated with GA showed significant morphological and histological improvements. Immunohistochemical analysis of K14-VEGF transgenic mice revealed that hyperplastic and inflamed vessels were suppressed with GA treatment. The expression of adhesion molecules such as ICAM-1 and E-selectin was significantly decreased. GA inhibited angiogenesis and the expression of VEGFR2 and p-VEGFR2. T lymphocyte infiltration and the expression of IL-17 and IL-22 were also reduced by GA treatment.
  
  
  CONCLUSIONS
  Our results suggest that GA has anti-psoriatic efficacy through inhibition of angiogenesis and inflammation. Therefore, GA is attractive and offers future potential for application in patients with psoriasis.
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Jiaolin
authors.initials: J
authors.lastname: Wen
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Heying
authors.initials: H
authors.lastname: Pei
authors.affiliation: Tianjin Medical University Cancer Institute and Hospital, Tianjin, 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, Chengdu, China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 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, Chengdu, China.
authors.forename: Li
authors.initials: L
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, 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, Chengdu, 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, Chengdu, 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, Chengdu, China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D029760:Garcinia; D006168:Guinea Pigs; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006965:Hyperplasia; D007249:Inflammation / Q000188:drug therapy; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000188:drug therapy; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D010946:Plants, Medicinal; D011565:Psoriasis / Q000188:drug therapy*; D011897:Random Allocation; D012867:Skin / Q000187:drug effects / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D044004:Xanthones / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D016328:NF-kappa B; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D044004:Xanthones; C052659:gambogic acid
keywords: Angiogenesis; CD3; GA; K14-VEGF transgenic mice; Psoriasis; VEGFR2