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

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.

P. granatum Peel Polysaccharides Ameliorate Imiquimod-Induced Psoriasis-Like Dermatitis in Mice via Suppression of NF-κB and STAT3 Pathways

“…On the basis of our previous study (Chen et al, 2020), BALB/c mice were subjected to topical treatment with 5% IMQ cream (62.5 mg), which was applied on a shaved area (3 cm × 2.5 cm) on the back for 7 consecutive days. The PASI, measured on the 7th day, is an assessment tool combining (Lu et al, 2021a) skin erythema, scaling, and thickness, which was employed to evaluate the severity grade of psoriasis-like lesions. Transepidermal water loss (TEWL) was measured on the back skin of the psoriasis-like mouse model with VAPOSCANAS-VT100 (Tokyo, Japan).…”

“…Therefore, research and development of innovative effective and safe anti-psoriatic drugs is still an urgent need. Recently, the application of Chinese herbal medicines in psoriasis treatment has been widely reported (Di et al, 2021;Lu et al, 2021b;Lv et al, 2021;Yao et al, 2021).…”

Recent Update on Immunopathogenesis of Psoriasis

“…[ 154 155 ] Disruption of the oxidative stress–inflammation–angiogenesis axis with activation of the attendant MAPK signaling pathway resulting in the release of variety of angiogenic factors promoting the expansion of vascular networks completes the picture of full-blown clinical psoriasis. [ 156 157 ] Angiogenesis in psoriasis displays a closely knit, complex, reciprocal molecular cross-talk between diverse pathological networks including vascular endothelium activation, angiogenesis, inflammation and immunity. [ 157 ]…”

Deciphering the mechanism of PSORI-CM02 in suppressing keratinocyte proliferation through the mTOR/HK2/glycolysis axis

“…Specifically, the physician's global assessment (PGA) score decreased from 3.3 ± 1.0 before treatment to 2.8 ± 1.1 after treatment (n = 619), body surface area (BSA) decreased from 6.6% ± 9.7% before treatment to 6.3% ± 8.5% after treatment (n = 90), psoriasis area and severity index (PASI) decreased from 5.8 ± 3.6 before treatment to 4.4 ± 3.0 after treatment (n = 89) (WANG et al, 2021). Our group has conducted several studies on the pharmacodynamic mechanism of PSORI-CM02 in the treatment of psoriasis, revealing its multi-targeted effects in blocking the pathological interaction between keratinocytes and immune cells, such as reducing inflammatory cell infiltration (Li et al, 2020), promoting Treg differentiation (Chen et al, 2018), down-regulating cytokine production (Wu et al, 2019), and inhibiting angiogenesis (Lu et al, 2021). However, the effects of PSORI-CM02 on keratinocytes remain unclear, apart from its ability to induce autophagy of keratinocytes via suppressing the phosphatidylinositol 3-kinase (PI3K)/Akt/mTOR pathway (Yue et al, 2019).…”