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颠茄拉亭 A,颠茄属植物颠茄中的一种孕烷类化合物,通过 PI3K-Akt-mTOR 信号通路诱导 HaCaT 自噬。

Daturataturin A, a withanolide in Datura metel L., induces HaCaT autophagy through the PI3K-Akt-mTOR signaling pathway.

机构信息

College of Pharmacy, Heilongjiang University of Chinese Medicine, Harbin, China.

College of Traditional Chinese Medicine, Guangdong Pharmaceutical University, Guangzhou, China.

出版信息

Phytother Res. 2021 Mar;35(3):1546-1558. doi: 10.1002/ptr.6921. Epub 2021 Feb 9.

Abstract

Daturataturin A (DTA), a withanolide compound in Datura metel L., exhibits excellent anti-inflammatory and anti-proliferative activities. Here, we report the study of DTA-induced proliferation and inflammation in human immortalized keratinocytes (HaCaTs) and the associated molecular mechanisms. HaCaTs are a model of the epidermal proliferative state of cells. The pharmacodynamics and mechanism of DTA were studied by western blot, immunofluorescence, apoptosis and proliferation detection, and real-time quantitative polymerase chain reaction. We confirmed that DTA induced HaCaT autophagy, which, in turn, induced HaCaT senescence and, ultimately, led to cell cycle arrest. DTA also negatively regulated inflammation through the activation of autophagy. This may be one of the mechanisms underlying the action of Datura metel L. preparation used for the treatment of psoriasis.

摘要

颠茄拉汀 A(DTA)是颠茄属植物颠茄中的一种乌头烷型生物碱,具有优异的抗炎和抗增殖活性。在这里,我们报告了 DTA 诱导人永生化角质形成细胞(HaCaTs)增殖和炎症的研究及其相关的分子机制。HaCaTs 是表皮细胞增殖状态的模型。通过 Western blot、免疫荧光、凋亡和增殖检测以及实时定量聚合酶链反应研究了 DTA 的药效学和机制。我们证实 DTA 诱导 HaCaT 自噬,进而诱导 HaCaT 衰老,最终导致细胞周期停滞。DTA 还通过自噬的激活负调控炎症。这可能是颠茄属植物制剂用于治疗银屑病的作用机制之一。

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