Yangxue Jiedu Fang Ameliorates Psoriasis by Regulating Vascular Regression via Survivin/PI3K/Akt Pathway

Author:

Lv Hongpeng12,Liu Xin13,Chen Weiwen12,Xiao Shiju14,Ji Yunrun1,Han Xuyang13,Li Yafan12,Wang Xiaoxu14,Zhang Guangzhong1ORCID,Li Ping13ORCID

Affiliation:

1. Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing 100010, China

2. Beijing University of Chinese Medicine, Beijing 100029, China

3. Beijing Institute of Traditional Chinese Medicine, Beijing 100010, China

4. Graduate School, Capital Medical University, Beijing 100069, China

Abstract

Background. Psoriasis (PA) is a chronic autoimmune disease of the skin that adversely affects patients’ quality of life. Yangxue Jiedu Fang (YXJD) has been used for decades to treat psoriasis in China. However, its antipsoriatic mechanisms are still poorly understood. In this study, we explored the effects of YXJD on angiogenesis and apoptosis of microvessels in PA, the underlying mechanisms in HUVEC cells transfected by Survivin overexpression plasmid and in a mouse model of imiquimod-induced psoriasis and the relationship between VEGF (vascular endothelial growth factor) and Survivin. Methods. A BALB/c mouse model of imiquimod- (IMQ-) induced PA was established, and the mice were treated with YXJD. Cell viability was assessed by CCK8 assay. Apoptosis was detected by annexin V–FITC/PI double-staining and caspase-3 assays. The PI3K/Akt/β-catenin pathway was analyzed by western blotting, ELISA, and immunochemical analysis. Results. YXJD ameliorated symptoms and psoriasis area and severity index (PASI) scores and also reduced the number of microvessels, as determined by the microvessel density (MVD). The expression of apoptotic protein Survivin in endothelial cells, autophagy-related proteins p62, and angiogenic proteins VEGF was inhibited by YXJD, and the repressed expression of LC3II/I increased by YXJD. The proteins related to the PI3K/Akt pathway and β-catenin expression and the nuclear entry of β-catenin were reduced in IMQ-induced PA mice treated with YXJD. In HUVEC cells transfected by Survivin overexpression plasmid, we observed YXJD regulated the expression of Survivin, LC3II/I, and p62, VEGF, and PI3K/Akt pathway-relative proteins and the nuclear entry of β-catenin. Conclusions. YXJD inhibited the expression of Survivin via PI3K/Akt pathway to adjust apoptosis, autophagy, and angiogenesis of microvessels and thus improve the vascular sustainability in psoriasis. YXJD may represent a new direction of drug research and development for immunomodulatory therapy for psoriasis.

Funder

Beijing Municipal Natural Science Foundation

Publisher

Hindawi Limited

Subject

Immunology,General Medicine,Immunology and Allergy

Reference40 articles.

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4. Effects of Yangxue Jiedu decoction and its separated formula containing serum on ERK/NF-κB pathway of phorbol ester induced in vascular endothelial cells;X. Liu;Journal of Traditional Chinese Medicine,2018

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