PSORI-CM02 formula alleviates imiquimod-induced psoriasis via affecting macrophage infiltration and polarization.

Psoriasis is a refractory skin disease characterized by macrophage cell infiltrated in the dermal layer. Macrophages can simultaneously polarize into two distinct functional subtypes, M1 and M2, and this process is affected by the microenvironment, cytokines and JAK/STAT pathways. Formula PSORI-CM02 is a novel Chinese medicine used to alleviate psoriasis symptoms and regulate T cell differentiation and epithelial cell proliferation. However, the effects of PSORI-CM02 in imiquimod (IMQ)-induced psoriasis and macrophage infiltration and polarization in the dermis remain unknown. Imiquimod induced psoriasis mice model and M1/M2 polarization model on mice peritoneal macrophages cell line RAW264.7 in vitro were used to observe the therapeutic effect of PSORI-CM02 on skin and its molecular mechanisms. PSORI-CM02 can significantly improve skin lesions and reduce macrophage infiltration in mice induced by imiquimod. After treatment with PSORI-CM02 formula, M1 macrophage mediators were significantly reduced, while M2 mediators were significantly increased in mice. Similarly in vitro, M1 macrophage proliferation was suppressed and M2 macrophage proliferation was elevated by PSORI-CM02 in the presence of LPS and IL-4, respectively. The elevated expression of TNF-α, iNOS, and IL-1β induced by LPS was reduced, while the expression of Arg-1, Fizz-1, Ym-1, and IL-10 induced by IL-4 was elevated in PSORI-CM02-treated cells. Finally, we found that the effects of PSORI-CM02 in macrophage polarization were associated with regulation of STAT1 and STAT6 expression, which were activated by LPS and IL-4, respectively. Our novel findings reveal that PSORI-CM02 may possess therapeutic action in psoriasis treatment by regulating the infiltration and polarization of macrophages in the dermal layer.

Li L ，Zhang HY ，Zhong XQ ，Lu Y ，Wei J ，Li L ，Chen H ，Lu C ，Han L ... -  《-》

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

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.

Lu Y ，Yang Y ，Zhang J ，Zhang H ，Ma C ，Tang X ，Wu J ，Li L ，Wei J ，Chen H ，Lu C ，Han L ... -  《Frontiers in Immunology》

PSORI-CM02 alleviates IMQ-induced mouse dermatitis via differentially regulating pro- and anti-inflammatory cytokines targeting of Th2 specific transcript factor GATA3.

The IL-17-producing CD4+ T cell and γδT cells play critical roles in the pathogenesis of psoriasis (PS). PSORI-CM02 is a representative herbal formula for the treatment for PS in South China. It was confirmed to improve PS without obvious side effects in the clinic. Here we sought to clarify whether and how PSORI-CM02 regulates T cell differentiation and functions in IMQ-induced psoriasis-like BALB/c mouse model. Mice pre-treated 3 days with PSORI-CM02 significantly alleviated skin inflammation, as reduced in PASI score and classic psoriatic characteristics in pathological sections. CD3 and CD4 positive T cells were also fewer in the skin lesions of PSORI-CM02 groups, comparing to control group. PSORI-CM02 also decreased pro-inflammatory IFNγ mRNA and IL-17 A mRNA, while increased IL-4 mRNA in mouse skin lesions. In skin draining lymph nodes (DLN), PSORI-CM02 reduced the ratio of γδT cells and inhibited their function of producing IL-17 A. Nevertheless PSORI-CM02 had no effects on the ratio of total TCRβ+T cells and CD4 + T cells. But it regulated CD4 + T helper cells differentiation, and resulted in the decreasing percentage of IFNγ producing Th1 cells and IL-17 A producing Th17 cells, while increasing the ratio of IL-4 producing Th2 cells in DLN. Further data showed that PSORI-CM02 promote expression of Th2 specific transcript factor GATA3, but had no effects on T-bet and RORγ. Thus, we tentatively interpret that PSORI-CM02 impairs IMQ-induced psoriasis by promoting Th2 cell response targeting of GATA3.

Wu DH ，Zhang MM ，Li N ，Li X ，Cai QW ，Yu WL ，Liu LP ，Zhu W ，Lu CJ ... -  《-》

PSORI-CM02 Formula Increases CD4+ Foxp3+ Regulatory T Cell Frequency and Ameliorates Imiquimod-Induced Psoriasis in Mice.

Chen H ，Liu H ，Lu C ，Wang M ，Li X ，Zhao H ，Yan Y ，Yu W ，Han L ，Dai Z ... -  《Frontiers in Immunology》

PSORI-CM02 ameliorates psoriasis in vivo and in vitro by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Psoriasis is an inflammatory skin disease that affects an estimated 3% of the world's population. PSORI-CM02 is an empirically developed Chinese medicine formula optimised from Yin Xie Ling, summarised by national medical master Guo-Wei Xuan, that has been used for decades to treat psoriasis in the Guangdong Provincial Hospital of Chinese Medicine. However, its anti-psoriatic mechanisms are still poorly understood. In this study, we explored the effects of PSORI-CM02 on autophagy and the underlying mechanisms in TNF-α-stimulated HaCaT cells and in a mouse model of imiquimod-induced psoriasis. Cell viability was assessed by MTT assay. Apoptosis was detected by annexin V-FITC/PI double-staining and caspase-3 assays. Autophagy was detected by electron microscopy, RT-PCR and western blotting. The PI3K/Akt/mTOR pathway was analysed by western blotting and immunochemical analysis. PSORI-CM02 induced autophagy and thus inhibited the proliferation of HaCaT cells via suppression of the PI3K/Akt/mTOR pathway. In mice with IMQ-induced psoriasis, PSORI-CM02 relieved psoriasis symptoms, induced autophagy and inhibited the phosphorylation of the PI3K/AKT/mTOR pathway in the skin. These results suggest that PSORI-CM02 treats psoriasis by inducing autophagy via inhibition of the PI3K/Akt/mTOR pathway.

Yue L ，Ailin W ，Jinwei Z ，Leng L ，Jianan W ，Li L ，Haiming C ，Ling H ，Chuanjian L ... -  《-》