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韩国红参提取物和人参皂苷Rg3通过抑制MrgprA3/TRPA1介导的途径对氯喹诱导的瘙痒具有止痒作用。

Korean Red Ginseng extract and ginsenoside Rg3 have anti-pruritic effects on chloroquine-induced itch by inhibition of MrgprA3/TRPA1-mediated pathway.

作者信息

Lee Wook-Joo, Kim Young-Sik, Shim Won-Sik

机构信息

College of Pharmacy, Gachon University, Incheon, Republic of Korea.

Gachon Institute of Pharmaceutical Sciences, Incheon, Republic of Korea.

出版信息

J Ginseng Res. 2018 Oct;42(4):470-475. doi: 10.1016/j.jgr.2017.05.004. Epub 2017 May 18.

Abstract

BACKGROUND

It was previously found that Korean Red Ginseng water extract (KRGE) inhibits the histamine-induced itch signaling pathway in peripheral sensory neurons. Thus, in the present study, we investigated whether KRGE inhibited another distinctive itch pathway induced by chloroquine (CQ); a representative histamine-independent pathway mediated by MrgprA3 and TRPA1.

METHODS

Intracellular calcium changes were measured by the calcium imaging technique in the HEK293T cells transfected with both and ("), and in primary culture of mouse dorsal root ganglia (DRGs). Mouse scratching behavior tests were performed to verify proposed antipruritic effects of KRGE and ginsenoside Rg3.

RESULTS

CQ-induced Ca influx was strongly inhibited by KRGE (10 μg/mL) in , and notably ginsenoside Rg3 dose-dependently suppressed CQ-induced Ca influx in . Moreover, both KRGE (10 μg/mL) and Rg3 (100 μM) suppressed CQ-induced Ca influx in primary culture of mouse DRGs, indicating that the inhibitory effect of KRGE was functional in peripheral sensory neurons. tests revealed that not only KRGE (100 mg) suppressed CQ-induced scratching in mice [bouts of scratching: 274.0 ± 51.47 (control) vs. 104.7 ± 17.39 (KRGE)], but also Rg3 (1.5 mg) oral administration significantly reduced CQ-induced scratching as well [bouts of scratching: 216.8 ± 33.73 (control) vs. 115.7 ± 20.94 (Rg3)].

CONCLUSION

The present study verified that KRGE and Rg3 have a strong antipruritic effect against CQ-induced itch. Thus, KRGE is as a promising antipruritic agent that blocks both histamine-dependent and -independent itch at peripheral sensory neuronal levels.

摘要

背景

先前发现韩国红参水提取物(KRGE)可抑制外周感觉神经元中组胺诱导的瘙痒信号通路。因此,在本研究中,我们调查了KRGE是否能抑制由氯喹(CQ)诱导的另一种独特的瘙痒途径;这是一种由MrgprA3和TRPA1介导的典型的非组胺依赖性途径。

方法

通过钙成像技术在同时转染了[具体基因1]和[具体基因2]的HEK293T细胞以及小鼠背根神经节(DRG)的原代培养物中测量细胞内钙变化。进行小鼠搔抓行为测试以验证KRGE和人参皂苷Rg3的抗瘙痒作用。

结果

在[具体细胞类型1]中,KRGE(10μg/mL)强烈抑制CQ诱导的钙内流,值得注意的是,人参皂苷Rg3在[具体细胞类型1]中剂量依赖性地抑制CQ诱导的钙内流。此外,KRGE(10μg/mL)和Rg3(100μM)均抑制小鼠DRG原代培养物中CQ诱导的钙内流,表明KRGE的抑制作用在外周感觉神经元中起作用。[行为测试名称]显示,不仅KRGE(100mg)可抑制小鼠中CQ诱导的搔抓[搔抓次数:274.0±51.47(对照)对104.7±17.39(KRGE)],而且口服Rg3(1.5mg)也能显著减少CQ诱导的搔抓[搔抓次数:216.8±33.73(对照)对115.7±20.94(Rg3)]。

结论

本研究证实KRGE和Rg3对CQ诱导的瘙痒具有强大的抗瘙痒作用。因此,KRGE是一种有前景的抗瘙痒剂,可在外周感觉神经元水平阻断组胺依赖性和非组胺依赖性瘙痒。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3c3b/6187082/7170a148a7b0/gr1.jpg

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