Rottlerin as a therapeutic approach in psoriasis: Evidence from in vitro and in vivo studies.
Rottlerin as a therapeutic approach in psoriasis: Evidence from in vitro and in vivo studies.
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Rottlerin 作为牛皮癣的治疗方法：来自体外和体内研究的证据。
DOI：
10.1371/journal.pone.0190051
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Man XY
中科院分区：
文献类型：
--
作者：
Min M;Yan BX;Wang P;Landeck L;Chen JQ;Li W;Cai SQ;Zheng M;Man XY
Rottlerin是一种天然多酚化合物，最初被指示为PKCδ抑制剂。然而，最近发现它可以靶向许多分子并对各种细胞类型具有生物学效应，并被认为是肿瘤和细胞增殖性疾病的可能药剂。银屑病是一种病因不明的慢性炎症性皮肤疾病，其特征在于异常的细胞增殖、血管生成和炎症。因此，本文研究了rottlerin对正常人表皮角质形成细胞（NHEKs）和咪喹莫特（IMQ）诱导的银屑病样（IPI）病变的调节作用。体外实验结果表明，rottlerin通过抑制NHEKs细胞增殖和NFκB的表达而抑制NHEKs细胞的增殖。它还可以在自噬依赖性途径中诱导细胞凋亡。我们发现rottlerin抑制人微血管内皮细胞在基质胶上的管形成。Rottlerin还降低角质形成细胞的细胞衰老和细胞内ROS的产生，这表明其具有抗氧化作用。我们还发现，rottlerin影响角质形成细胞增殖生物标志物的表达。在12-O-十四烷酰基佛波醇13-乙酸酯（TPA）诱导的角质形成细胞中，罗特勒素显着抑制诱导的促炎细胞因子在角质形成细胞中的表达。动物实验提供了相应的证据，基于此证据，在体外，通过使用IPI模型，我们发现rottlerin可以减轻BALB/c小鼠银屑病样通过抑制角质形成细胞增殖，炎症细胞浸润，血管增生。总之，我们的研究结果表明，rottlerin可能被证明是有用的治疗药物对银屑病的发展。但其深层机制仍需进一步研究。
Rottlerin is a natural polyphenolic compound that was initially indicated as a PKCδ inhibitor. However, it was recently revealed that it may target a number of molecules and have biological effects on various cell types and is considered as a possible agent for tumor and cell proliferative diseases. Psoriasis is a chronic inflammatory cutaneous disorder with undefined etiology and is characterized by abnormal cellular proliferation, angiogenesis, and inflammation. Therefore, this paper investigates the regulatory effects of rottlerin on normal human epidermal keratinocytes (NHEKs) and imiquimod (IMQ)-induced psoriasiform (IPI) lesions. In vitro results showed that rottlerin inhibited cell proliferation in NHEKs through growth arrest and NFκB inhibition. It may also induce apoptosis in an autophagy-dependent pathway. We found that rottlerin inhibited human microvascular endothelial cells tube formation on matrigel. Rottlerin also decreased the cell senescence of keratinocytes and intracellular ROS generation, which indicated its antioxidant effect. We also showed that rottlerin affects the expression of keratinocyte proliferation biomarkers. In 12-O-tetradecanoylphorbol13-acetate (TPA)–induced keratinocytes, rottlerin significantly inhibited the expression of the induced pro-inflammatory cytokines in keratinocytes. An animal experiment provided the corresponding evidence based on this evidence in vitro, by using IPI model, we found that rottlerin could relieve the psoriasiform of BALB/c mice by inhibiting keratinocyte proliferation, inflammatory cell infiltration, and vascular proliferation. In conclusion, our results suggest that rottlerin may prove useful in the development of therapeutic agents against psoriasis. However, the deep mechanism still requires further study.
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影响因子：
8.6
作者：
Kim, Byung Eui;Leung, Donald Y. M.;Howell, Michael D.
通讯作者：
Howell, Michael D.
影响因子：
3.5
作者：
Joyce, Cailin E.;Zhou, Xiang;Bowcock, Anne M.
通讯作者：
Bowcock, Anne M.
DOI：
10.1038/jid.2011.24
发表时间：
2011-06
期刊：
The Journal of investigative dermatology
影响因子：
--
作者：
Kim BE;Howell MD;Guttman-Yassky E;Gilleaudeau PM;Cardinale IR;Boguniewicz M;Krueger JG;Leung DY
通讯作者：
Leung DY
影响因子：
6.5
作者：
Lehmann, B
通讯作者：
Lehmann, B
DOI：
10.1006/bbrc.1994.1199
发表时间：
1994-02-28
影响因子：
3.1
作者：
GSCHWENDT, M;MULLER, HJ;MARKS, F
通讯作者：
MARKS, F