Anti-Angiogenic Efficacy of PSORI-CM02 and the Associated Mechanism in Psoriasis In Vitro and In Vivo.

Yue Lu,Li Li,Jianan Wei,Yuqi Yang,Chuanjian Lu,Junhong Zhang,Haiming Chen,Xiaojuan Tang,Jingjing Wu,Hongyu Zhang,Ling Han,Changju Ma

doi:10.3389/fimmu.2021.649591

Yue Lu, Li Li + Show 10 more

Open Access

https://doi.org/10.3389/fimmu.2021.649591

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Abstract

Psoriasis is a chronic proliferative autoimmune dermatologic disease characterised by abnormal angiogenesis. Thus, regulating angiogenesis in the skin is an important treatment strategy for psoriasis. PSORI-CM02, an empirical Chinese medicine formula optimised from Yin Xie Ling, was created by the Chinese medicine specialist, Guo-Wei Xuan. Clinical studies have shown that PSORI-CM02 is safe and effective for the treatment of psoriasis. However, its anti-psoriatic mechanisms remain to be further explored. In this study, we investigated the effects of PSORI-CM02 on angiogenesis in the skin and the underlying mechanisms in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a murine model of imiquimod (IMQ)-induced psoriasis. In vitro, PSORI-CM02 significantly inhibited the proliferation and migration of IL-17A-stimulated HUVECs in a dose-dependent manner. Further, it markedly regulated the antioxidative/oxidative status and inflammation; suppressed the expression of VEGF, VEGFR1, VEGFR2, ANG1, and HIF-1α; and reduced the phosphorylation of MAPK signalling pathway components in IL-17A-stimulated HUVECs. In vivo studies showed that PSORI-CM02 markedly reduced angiogenesis in the skin of mice with IMQ-induced psoriasis, while significantly rebalancing antioxidant/oxidant levels; inhibiting the production of IL-6, TNF-α, IL-17A, and IL-17F; and repressing the synthesis of angiogenic mediators. In addition, PSORI-CM02 markedly reduced the activation of the MAPK signalling pathway in psoriatic skin tissue. Taken together, our results demonstrated that PSORI-CM02 inhibited psoriatic angiogenesis by reducing the oxidative status and inflammation, suppressing the expression of angiogenesis-related molecules, and inhibiting the activation of the MAPK signalling pathway in vitro and in vivo.

Highlights

Psoriasis is a chronic autoimmune skin disorder that affects approximately 125 million people worldwide [1]
We investigated the effects of PSORI-CM02 on angiogenesis in IL-17A-stimulated human umbilical vein endothelial cells (HUVECs) and a mouse model of IMQinduced psoriasis
The migration of IL-17A-stimulated HUVECs was significantly inhibited after PSORI-CM02 treatment (Figures 1B, C), indicating that HUVEC migration was promoted by IL-17A treatment, but markedly inhibited by PSORI-CM02 treatment

Summary

Introduction

Psoriasis is a chronic autoimmune skin disorder that affects approximately 125 million people worldwide [1]. Keratinocyte overproliferation, multiple immune cell infiltration, and hypervascular hyperplasia are the characteristic pathological manifestations of psoriasis [2]. The development of psoriasis is related to various factors, including innate and adaptive immune responses, genetic factors, environmental factors, and metabolic disorders [3]. Topical agents, including corticosteroids, vitamin D analogues, calcineurin inhibitors, and keratolytics, remain the cornerstone of treatment for patients with mild psoriasis [4]. Biologics that inhibit tumour necrosis factor (TNF)-a, p40IL-12/ 23, interleukin (IL)-17, or p19IL-23 are an option for the first-line treatment of moderate to severe plaque psoriasis [5]. As angiogenesis is a key pathological feature in the development of psoriasis, antibodies and other types of molecules that exert anti-angiogenic effects are currently being evaluated and represent promising approaches to treatment [7]

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