Paeoniflorin inhibits imiquimod-induced psoriasis in mice by regulating Th17 cell response and cytokine secretion.

Paeoniflorin (PF) is the main active ingredients of radix paeoniae rubra and radix paeoniae alba, which are used widely in Traditional Chinese Medicine. This study aimed to assess the capacity of PF to inhibit imiquimod (IMQ)-induced psoriasis. Mice treated with IMQ were divided into four groups and administered 240mg/kg/day or 120mg/kg/day of PF, 1mg/kg/day of methotrexate (MTX), or normal saline intragastrically. Weight-matched mice treated with vaseline were used as controls. Morphology, structural features, keratinocyte proliferation and differentiation, inflammatory cell infiltration, levels of Th1/Th2/Th17/Treg cytokine mRNA, and phosphorylation of Th17 differentiation-related proteins were assessed. Mouse spleen cells were incubated under Th17 polarizing conditions, then with PF (2, 20, and 200μg/ml) and cell viability, Th17 differentiation, and Th17 cytokines and the orphan nuclear receptor (RORγt) mRNA levels were assessed. PF alleviated IMQ-induced keratinocyte proliferation and inflammatory cell infiltration, and reduced mRNA levels of Th17 cytokines at day 4 and phosphorylation of Th17 differentiation-related proteins. However, 2, 20, or 200μg/ml PF did not affect spleen cell viability, and 2 and 20μg/ml PF reduced IL-17 secretion under Th17 polarizing conditions. Finally, 2 and 20μg/ml PF inhibited mRNA expression of Th17 cytokines and phosphorylation of Stat3 in spleen cells under Th17 polarizing conditions. These results suggest that PF inhibits IMQ-induced psoriasis by regulating Th17 cell response and cytokine secretion via phosphorylation of Stat3.

Zhao J ，Di T ，Wang Y ，Wang Y ，Liu X ，Liang D ，Li P ... -  《-》

Paeoniflorin inhibits skin lesions in imiquimod-induced psoriasis-like mice by downregulating inflammation.

Psoriasis is a common chronic immune-mediated inflammatory disease. It is well known that macrophages, neutrophils and T-helper 1 (Th1)/T-helper 17 (Th17) cells play important roles in skin lesions by provoking inflammation. Paeoniflorin (PF) is the major effective component extracted from the root of Paeonia lactiflora, which has been widely used in China to treat inflammatory and autoimmune diseases, including psoriasis. Although PF shows a clinical therapeutic effect on psoriasis patients, how PF affects infiltrated immune cells in psoriasis skin lesions is still unknown. In this study, using a generated imiquimod (IMQ)-induced psoriasis-like mouse model, we found that PF ameliorates inflammation and skin lesions. Subsequent analyses showed that PF decreases the number of F4/80(+)CD68(+) macrophages and their related cytokine production (TNF-α, IL-1β, IL-6, IL-12 and inducible nitric oxide synthase (iNOS)) in the skin of IMQ-challenged mice. Moreover, PF suppresses the number of CD11b(+)Gr-1(+) neutrophils and the expression of macrophage inflammatory protein-2 (MIP-2; a counterpart of human IL-8, which is responsible for the recruitment of neutrophils in mice). Finally, PF also down-regulates Th1- and Th17-related cytokine expression. Therefore, our new findings reveal that PF alleviates psoriatic skin lesions by inhibiting inflammation, which provides new insights into the immunomodulatory effect of PF in psoriasis treatment.

Sun Y ，Zhang J ，Huo R ，Zhai T ，Li H ，Wu P ，Zhu X ，Zhou Z ，Shen B ，Li N ... -  《-》

Indirubin ameliorates imiquimod-induced psoriasis-like skin lesions in mice by inhibiting inflammatory responses mediated by IL-17A-producing γδ T cells.

Xie XJ ，Di TT ，Wang Y ，Wang MX ，Meng YJ ，Lin Y ，Xu XL ，Li P ，Zhao JX ... -  《-》

Astilbin inhibits Th17 cell differentiation and ameliorates imiquimod-induced psoriasis-like skin lesions in BALB/c mice via Jak3/Stat3 signaling pathway.

The flavonoid astilbin is the major active component extracted from the rhizome of Smilax glabra, which has been widely used in China to treat inflammatory and autoimmune diseases, Psoriasis is a common chronic inflammatory disease in which T helper 17 (Th17) cells play an important role, provoking inflammation. We employed an imiquimod (IMQ)-induced psoriasis-like mouse model to investigate the effect of astilbin in inflammation. Mice were administered 25 to 50mg/kg astilbin. Inflammation of psoriasis-like lesions was assessed by histology, circulating levels of T cells were assessed by flow cytometry and cytokines by bead-based immunoassay. Jak/Stat3 in isolated T cells was assessed by Western blotting and RORγt expression was assessed by RT-PCR. Administration of astilbin ameliorated IMQ-induced keratinocyte proliferation, infiltration of CD3+ cells to psoriatic lesions and ameliorated elevations in circulating CD4+ and CD8+ T cells and inflammatory cytokines (IL-17A, TNF-α, IL-6, IFN-γ and IL-2). In vitro, astilbin inhibited Th17 cell differentiation and IL-17 secretion of isolated T cells, and inhibited Jak/Stat3 signaling in Th17 cells, while up-regulating Stat3 inhibitor SCOSE3 expression in psoriatic lesions. Thus, astilbin likely alleviates psoriasis-like skin lesions by inhibiting Th17 related inflammation. Astilbin represents as an interesting candidate drug for immunoregulation of psoriasis.

Di TT ，Ruan ZT ，Zhao JX ，Wang Y ，Liu X ，Wang Y ，Li P ... -  《-》

Effect of γ-secretase inhibitor on Th17 cell differentiation and function of mouse psoriasis-like skin inflammation.

Ma L ，Xue H ，Qi R ，Wang Y ，Yuan L ... -  《Journal of Translational Medicine》