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鲱形目鱼类中的H和I这一对天然差向异构体,通过JNK-STAT3轴在THP-1细胞中抑制炎症。

Scrodentoids H and I, a Pair of Natural Epimerides from , Inhibit Inflammation through JNK-STAT3 Axis in THP-1 Cells.

作者信息

Mao Gaohui, Sun Liqin, Xu Jinwen, Li Yiming, Dunzhu Ciren, Zhang Liuqiang, Qian Fei

机构信息

Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

Evid Based Complement Alternat Med. 2020 Jul 27;2020:1842347. doi: 10.1155/2020/1842347. eCollection 2020.

Abstract

BACKGROUND

is an important medicinal plant and used for the treatment of exanthema and fever in Traditional Tibetan Medicine. Scrodentoids H and I (SHI), a pair of epimerides of C-norditerpenoids isolated from , could transfer to each other in room temperature and were firstly reported in our previous work. Here, we first reported the anti-inflammatory effects of SHI on LPS-induced inflammation.

PURPOSE

To evaluate the anti-inflammatory property of SHI, we investigated the effects of SHI on LPS-activated THP-1 cells.

METHODS

THP-1 human macrophages were pretreated with SHI and stimulated with LPS. Proinflammatory cytokines IL-1 and IL-6 were measured by RT-PCR and enzyme-linked immunosorbent assays (ELISA). The mechanism of action involving phosphorylation of ERK, JNK, P38, and STAT3 was measured by western Blot. The NF-B promoter activity was evaluated by Dual-Luciferase Reporter Assay System in TNF- stimulated 293T cells.

RESULTS

SHI dose-dependently reduced the production of proinflammatory cytokines IL-1 and IL-6. The ability of SHI to reduce production of cytokines is associated with phosphorylation depress of JNK and STAT3 rather than p38, ERK, and NF-B promoter.

CONCLUSIONS

Our experimental results indicated that anti-inflammatory effects of SHI exhibit attenuation of LPS-induced inflammation and inhibit activation through JNK/STAT3 pathway in macrophages. These results suggest that SHI might have a potential in treating inflammatory disease.

摘要

背景

是一种重要的药用植物,在传统藏药中用于治疗皮疹和发热。从该植物中分离出的一对C-降二萜类差向异构体Scrodentoids H和I(SHI),在室温下可相互转化,这是我们之前的工作首次报道的。在此,我们首次报道了SHI对脂多糖(LPS)诱导的炎症的抗炎作用。

目的

为了评估SHI的抗炎特性,我们研究了SHI对LPS激活的THP-1细胞的影响。

方法

用SHI预处理THP-1人巨噬细胞,并用LPS刺激。通过逆转录聚合酶链反应(RT-PCR)和酶联免疫吸附测定(ELISA)检测促炎细胞因子白细胞介素-1(IL-1)和白细胞介素-6(IL-6)。通过蛋白质印迹法检测涉及细胞外信号调节激酶(ERK)、应激活化蛋白激酶(JNK)、p38丝裂原活化蛋白激酶(P38)和信号转导子和转录激活子3(STAT3)磷酸化的作用机制。在肿瘤坏死因子-α(TNF-α)刺激的293T细胞中,通过双荧光素酶报告基因检测系统评估核因子-κB(NF-κB)启动子活性。

结果

SHI剂量依赖性地降低促炎细胞因子IL-1和IL-6的产生。SHI降低细胞因子产生的能力与JNK和STAT3的磷酸化抑制有关,而不是与P38、ERK和NF-κB启动子有关。

结论

我们的实验结果表明,SHI的抗炎作用表现为减轻LPS诱导的炎症,并通过巨噬细胞中的JNK/STAT3途径抑制激活。这些结果表明,SHI可能在治疗炎症性疾病方面具有潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6efb/7403932/1d64ea1c729e/ECAM2020-1842347.001.jpg

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