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

Hongpeng Lv,Xiaoxu Wang,Xuyang Han,Ping Li,Guangzhong Zhang,Yafan Li,Shiju Xiao,Weiwen Chen,Xin Liu,Yunrun Ji,Cristina R Reschke

doi:10.1155/2021/4678087

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.

Highlights

Psoriasis (PA) is a chronic, autoimmune skin disease that is recognized as a major global health problem by the World Health Organization, and it affects 2-4% of the population [1]
The psoriasis area and severity index (PASI) scores of the Yangxue Jiedu Fang (YXJD) group and cyclosporin-A group were significantly lower than the score of the model group, demonstrating YXJD had a therapeutic effect on PASI scores in the PA mouse model, and its effect was equal to cyclosporin-A, which has a curative effect
In HUVEC cells transfected by Survivin overexpression plasmid (Survivin OE), we observed that the cell viability increased compared with the HUVEC cells transfected by normal control plasmid (NC), and when different concentrations of YXJD (0, 1, and 4 mg/mL) intervened into Survivin OE, we found YXJD could inhabit the cell viability (Figure 7(a))

Summary

Introduction

Psoriasis (PA) is a chronic, autoimmune skin disease that is recognized as a major global health problem by the World Health Organization, and it affects 2-4% of the population [1]. 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. 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. YXJD inhibited the expression of Survivin via PI3K/Akt pathway to adjust apoptosis, autophagy, and angiogenesis of microvessels and improve the vascular sustainability in psoriasis. YXJD may represent a new direction of drug research and development for immunomodulatory therapy for psoriasis

Methods

Results

Conclusion