Psoriasis is a common inflammatory skin disorder that is characterized by keratinocyte hyperproliferation and abnormal differentiation, resulting in the thickening of the epidermis and stratum corneum. In this study, we investigated in vitro and in vivo pharmacological effects of tussilagonone (TGN), a sesquiterpenoid isolated from Tussilago farfara, on transcription factors relevant for the pathogenesis of psoriasis. TGN inhibited activation of NF-κB and STAT3, leading to the attenuated expression of psoriasis-related inflammatory genes and suppression of keratinocyte hyperproliferation. Mechanistically, we show that the inhibition of NF-κB and STAT3 by TGN is mediated through activation of the cytoprotective transcription factor NRF2. Evaluation of in vivo antipsoriatic effects of topical TGN in the imiquimod-induced psoriasis-like dermatitis mouse model demonstrated amelioration of imiquimod-induced phenotypical changes, lesion severity score, epidermal thickening, and reduction in dermal cellularity. The spleen index also diminished in TGN-treated mice, suggesting anti-inflammatory properties of TGN. Moreover, TGN significantly attenuated the imiquimod-induced mRNA levels of psoriasis-associated inflammatory cytokines and antimicrobial peptides and reduced epidermal hyperproliferation. Taken together, TGN, as a potent NRF2 activator, is a promising therapeutic candidate for the development of antipsoriatic agents derived from medicinal plants.

中文翻译：

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Tussilagonone通过NRF2激活改善小鼠角质形成细胞和咪喹莫特诱导的牛皮癣样病变中的银屑病特征。

牛皮癣是一种常见的炎症性皮肤病，其特征在于角质形成细胞过度增殖和异常分化，导致表皮和角质层增厚。在这项研究中，我们研究了从蚕豆中分离出的倍半萜类植物倍半酮（TGN）对与牛皮癣发病相关的转录因子的体外和体内药理作用。TGN抑制NF-κB和STAT3的激活，导致牛皮癣相关炎症基因的表达减弱，并抑制角质形成细胞过度增殖。从机制上讲，我们显示TGN对NF-κB和STAT3的抑制作用是通过激活细胞保护性转录因子NRF2介导的。在咪喹莫特诱发的牛皮癣样皮炎小鼠模型中对局部TGN的体内抗银屑病作用的评估表明，咪喹莫特诱发的表型变化，病变严重程度评分，表皮增厚和真皮细胞减少均得到改善。经TGN处理的小鼠的脾脏指数也有所降低，表明TGN具有抗炎特性。此外，TGN大大减轻了牛皮癣相关炎性细胞因子和抗菌肽的咪喹莫特诱导的mRNA水平，并减少了表皮过度增殖。两者合计，TGN，作为一种有效的NRF2激活剂，是开发源自药用植物的抗银屑病药物的有希望的治疗候选药物。和减少真皮细胞的流动性。经TGN处理的小鼠的脾脏指数也有所降低，表明TGN具有抗炎特性。此外，TGN大大减轻了牛皮癣相关炎性细胞因子和抗菌肽的咪喹莫特诱导的mRNA水平，并减少了表皮过度增殖。两者合计，TGN，作为一种有效的NRF2激活剂，是开发源自药用植物的抗银屑病药物的有希望的治疗候选药物。和减少真皮细胞的流动性。经TGN处理的小鼠的脾脏指数也有所降低，表明TGN具有抗炎特性。此外，TGN大大减轻了牛皮癣相关炎性细胞因子和抗菌肽的咪喹莫特诱导的mRNA水平，并减少了表皮过度增殖。两者合计，TGN，作为一种有效的NRF2激活剂，是开发源自药用植物的抗银屑病药物的有希望的治疗候选药物。