Taxifolin attenuates IMQ-induced murine psoriasis-like dermatitis by regulating T helper cell responses via Notch1 and JAK2/STAT3 signal pathways.

Psoriasis is a T cells mediated chronic skin inflammation in which helper T (Th) cells play in critical roles in its pathogenesis. Taxifolin (TXL) has been discovered to exert various pharmacological activities. In this study, we wished to observe whether TXL had potential activities on psoriasis, and how it works. We found that TXL can inhibit LPS-induced abnormal proliferation in Hacat cell line, ant also significantly alleviate the IMQ-induced psoriasis in BALB/c mice, comparing with the control group. Although TXL has no significant effects on the ratio of total T cells in skin draining lymph nodes (SDLN), it decreases the ratio of pro-inflammatory Th1 and Th17 cells, both in skin lesions and SDLN. Our results also disclosed that TXL may regulate Th cells differentiation by inhibiting the transcript factors, including T-bet, GATA-3 and RORγt. Further data show that TXL can inhibit Notch1 and Jak2/Stat3 signal pathways. In summary, TXL may be able to treat psoriasis by regulating Th cells differentiation via inhibiting Notch1 and Jak2/Stat3 pathways.

Yuan X ，Li N ，Zhang M ，Lu C ，Du Z ，Zhu W ，Wu D ... -  《-》

Rosmarinic acid protects mice from imiquimod induced psoriasis-like skin lesions by inhibiting the IL-23/Th17 axis via regulating Jak2/Stat3 signaling pathway.

IL-23/Th17 (IL-17) axis plays a critical role in psoriasis. Rosmarinic acid (RA) was proved the inhibitory effect of T cell infiltration in the skin. However, whether and how RA has beneficial effects on psoriasis did not really know yet. So lipopolysaccharide (LPS)-induced abnormal proliferation Hacat cell line and Imiquimod (IMQ)-induced psoriasis-like mouse dermatitis were used to assess the pharmacological effects and mechanisms of RA by Psoriasis Area Severity Index (PASI) score, histopathology, flow cytometry, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting. The results showed that RA inhibited LPS-induced aberrant expression of Hacat cell line, and significantly alleviated IMQ-induced skin inflammation. Although RA had no obviously effect on the ratio of epidermal Langerhans cell (LC) and LC migration from the skin to the skin draining lymph nodes, RA inhibited the expression of IL-23 in skin lesions, as well as reduced the differentiation of Th17 cells and producing of IL-17A by down regulating the transcriptor factor RORγt and JAK2/Stat3 signal pathway, comparing to IMQ treated group. The findings suggest that RA inhibits psoriasis-like skin inflammation in vivo and in vitro by reducing the expression of IL-23, inhibiting Th17 dominated inflammation and down regulating the Jak2/Stat3 signal pathway.

Zhang M ，Li N ，Cai R ，Gu J ，Xie F ，Wei H ，Lu C ，Wu D ... -  《-》

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 ... -  《-》

Tetrastigma hemsleyanum polysaccharides alleviate imiquimod-induced psoriasis-like skin lesions in mice by modulating the JAK/STAT3 signaling pathway.

The pathogenesis of psoriasis involves the interaction between keratinocytes and immune cells, leading to immune imbalance. While most current clinical treatment regimens offer rapid symptom relief, they often come with significant side effects. Tetrastigma hemsleyanum polysaccharides (THP), which are naturally nontoxic, possess remarkable immunomodulatory and anti-inflammatory properties. In this study, we utilized an imiquimod (IMQ)-induced psoriasis mouse model and a LPS/IL-6-stimulated HaCaT model. The potential and mechanism of action of THP in psoriasis treatment were assessed through methods including Psoriasis Area Severity Index (PASI) scoring, histopathology, flow cytometry, immunoblotting, and reverse transcription-polymerase chain reaction (RT-PCR). Percutaneous administration of THP significantly alleviated symptoms and manifestations in IMQ-induced psoriatic mice, including improvements in psoriatic skin appearance (erythema, folds, scales), histopathological changes, decreased PASI scores, and spleen index. Additionally, THP suppressed abnormal proliferation of Th17 cells and excessive proliferation and inflammation of keratinocytes. Furthermore, THP exhibited the ability to regulate the JAK/STAT3 signaling pathway. Findings from in vivo and in vitro studies suggest that THP can inhibit abnormal cell proliferation and excessive inflammation in lesional skin, balance Th17 immune cells, and disrupt the interaction between keratinocytes and Th17 cells. This mechanism of action may involve the modulation of the JAK/STAT3 signaling pathway, offering potential implications for psoriasis treatment.

Lv Y ，Yang L ，Mao Z ，Zhou M ，Zhu B ，Chen Y ，Ding Z ，Zhou F ，Ye Y ... -  《-》