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刺玫果改善二硝基氯苯诱导的小鼠特应性皮炎,并调节肿瘤坏死因子-α/干扰素-γ诱导的HaCaT细胞皮肤炎症反应。

Rosa davurica Pall. improves DNCB-induced atopic dermatitis in mice and regulated TNF-Alpa/IFN-gamma-induced skin inflammatory responses in HaCaT cells.

作者信息

Hwang Du Hyeon, Koh Phil-Ok, Kang Changkeun, Kim Euikyung

机构信息

Department of Pharmacology and Toxicology, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea; Institute of Animal Medicine, Gyeongsang National University, Jinju 52828, Korea.

Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, Jinju 52828, Korea.

出版信息

Phytomedicine. 2021 Oct;91:153708. doi: 10.1016/j.phymed.2021.153708. Epub 2021 Aug 14.

Abstract

PURPOSE

Rosa davurica Pall., is mainly distributed in Korea, Japan, northeastern China, southeastern Siberia, and eastern Asia. It has been extensively used to treat various kinds of diseases by reason of the significant antioxidant, antiviral and anti-inflammatory activities. However, the pharmacological mechanism of Rosa davurica Pall. in atopic dermatitis (AD) is still ill defined and poorly understood. This study was to examine the anti-inflammatory effects and its mechanism on AD of Rosa davurica Pall. leaves (RDL).

METHODS

To evaluate the therapeutic potential of RDL against AD, we have investigated the effects of RDL on the inflammatory reactions and the productions of inflammatory chemokines and cytokines that were induced by tumor necrosis factor-α (TNF-α)/interferon-γ (IFN-γ) in HaCaT cells. Futhermore, we examined the effects of RDL on the signaling pathways of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB). For the in-vivo studies, RDL extract was topically applied to the dinitrochlorobenzene (DNCB)-induced AD mice, then its therapeutic effect was evaluated physiologically and morphologically.

RESULTS

After the stimulation of HaCaT cells with TNF-α/IFN-γ, RDL considerably reduced the release of inflammatory mediators such as nitric oxide (NO), PEG and other cytokines. RDL also reduced the phosphorylations of MAPK and NF-κB in TNF-α/IFN-γ-stimulated HaCaT cells. In vivo topical application of RDL to DNCB-induced AD mice significantly reduced the dorsal skin and ear thickness, clinical dermatitis severity, and mast cells. Treatment with RDL also markedly decreased the levels of serum IgE, IL-6 and the number of WBCs in the blood.

CONCLUSION

Our studies indicate that RDL inhibits the AD-like skin lesions by modulating skin inflammation. Consequently, these results suggest that RDL may be served as a possible alternative therapeutic treatment for skin disorder such as AD.

摘要

目的

刺玫果主要分布于韩国、日本、中国东北、西伯利亚东南部和东亚地区。因其具有显著的抗氧化、抗病毒和抗炎活性,已被广泛用于治疗各种疾病。然而,刺玫果治疗特应性皮炎(AD)的药理机制仍不明确且了解甚少。本研究旨在探讨刺玫果叶(RDL)对AD的抗炎作用及其机制。

方法

为评估RDL对AD的治疗潜力,我们研究了RDL对肿瘤坏死因子-α(TNF-α)/干扰素-γ(IFN-γ)诱导的HaCaT细胞炎症反应以及炎症趋化因子和细胞因子产生的影响。此外,我们还检测了RDL对丝裂原活化蛋白激酶(MAPK)和核因子-κB(NF-κB)信号通路的影响。在体内研究中,将RDL提取物局部应用于二硝基氯苯(DNCB)诱导的AD小鼠,然后从生理和形态学方面评估其治疗效果。

结果

用TNF-α/IFN-γ刺激HaCaT细胞后,RDL显著降低了一氧化氮(NO)、PEG和其他细胞因子等炎症介质的释放。RDL还降低了TNF-α/IFN-γ刺激的HaCaT细胞中MAPK和NF-κB的磷酸化水平。在体内,将RDL局部应用于DNCB诱导的AD小鼠,可显著降低背部皮肤和耳部厚度、临床皮炎严重程度以及肥大细胞数量。RDL治疗还显著降低了血清IgE、IL-6水平以及血液中白细胞数量。

结论

我们的研究表明,RDL通过调节皮肤炎症来抑制AD样皮肤损伤。因此,这些结果表明RDL可能是治疗AD等皮肤疾病的一种潜在替代疗法。

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