人参皂苷Rg3通过下调MDM2/HIF1α信号通路减轻皮肤疾病。

Ginsenoside Rg3 attenuates skin disorders via down-regulation of MDM2/HIF1α signaling pathway.

作者信息

Han Na-Ra, Ko Seong-Gyu, Moon Phil-Dong, Park Hi-Joon

机构信息

College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul, Republic of Korea.

出版信息

J Ginseng Res. 2021 Sep;45(5):610-616. doi: 10.1016/j.jgr.2021.06.008. Epub 2021 Jun 24.

Abstract

BACKGROUND

Thymic stromal lymphopoietin (TSLP) acts as a master switch for inflammatory responses. Ginsenoside Rg3 (Rg3) which is an active ingredient of Panax ginseng Meyer (Araliaceae) is known to possess various therapeutic effects. However, a modulatory effect of Rg3 on TSLP expression in the inflammatory responses remains poorly understood.

METHODS

We investigated antiinflammatory effects of Rg3 on an in vitro model using HMC-1 cells stimulated by PMA plus calcium ionophore (PMACI), as well as an in vivo model using PMA-induced mouse ear edema. TSLP and vascular endothelial growth factor (VEGF) levels were detected using enzyme-linked immunosorbent assay or real-time PCR analysis. Murine double minute 2 (MDM2) and hypoxia-inducible factor 1α (HIF1α) expression levels were detected using Western blot analysis.

RESULTS

Rg3 treatment restrained the production and mRNA expression levels of TSLP and VEGF in activated HMC-1 cells. Rg3 down-regulated the MDM2 expression level increased by PMACI stimulation. The HIF1α expression level was also reduced by Rg3 in activated HMC-1 cells. In addition, Rg3-administered mice showed the decreased redness and ear thickness in PMA-irritated ear edema. Rg3 inhibited the TSLP and VEGF levels in the serum and ear tissue homogenate. Moreover, the MDM2 and HIF1α expression levels in the ear tissue homogenate were suppressed by Rg3.

CONCLUSION

Taken together, the current study identifies new mechanistic evidence about MDM2/HIF1α pathway in the antiinflammatory effect of Rg3, providing a new effective therapeutic strategy for the treatment of skin inflammatory diseases.

摘要

背景

胸腺基质淋巴细胞生成素(TSLP)是炎症反应的主要开关。人参皂苷Rg3(Rg3)是五加科植物人参的活性成分,已知具有多种治疗作用。然而,Rg3对炎症反应中TSLP表达的调节作用仍知之甚少。

方法

我们研究了Rg3对体外模型(使用佛波酯加钙离子载体(PMACI)刺激的HMC-1细胞)的抗炎作用,以及对体内模型(使用PMA诱导的小鼠耳水肿)的抗炎作用。使用酶联免疫吸附测定或实时PCR分析检测TSLP和血管内皮生长因子(VEGF)水平。使用蛋白质免疫印迹分析检测小鼠双微体2(MDM2)和缺氧诱导因子1α(HIF1α)的表达水平。

结果

Rg3处理抑制了活化的HMC-1细胞中TSLP和VEGF的产生及mRNA表达水平。Rg3下调了由PMACI刺激而增加的MDM2表达水平。在活化的HMC-1细胞中,Rg3也降低了HIF1α的表达水平。此外,给予Rg3的小鼠在PMA诱发的耳水肿中表现出红肿减轻和耳厚度减小。Rg3抑制了血清和耳组织匀浆中TSLP和VEGF的水平。此外,Rg3抑制了耳组织匀浆中MDM2和HIF1α的表达水平。

结论

综上所述,本研究确定了Rg3抗炎作用中关于MDM2/HIF1α途径的新机制证据,为皮肤炎症性疾病的治疗提供了一种新的有效治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e3f/8587510/63d2f255aa80/ga1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索