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通过细胞膜固定色谱法从苦参中筛选出的氧化苦参碱可缓解非组胺依赖性瘙痒。

Oxymatrine screened from Sophora flavescens by cell membrane immobilized chromatography relieves histamine-independent itch.

作者信息

Zhang Zhe, Pan Jianhao, Zhu Tao, Malewicz Nathalie, Ye Kaihe, Rong Jianhui, Luo Yong, Situ Yongli, Verkhratsky Alexei, Wang Yong, Zhao Jianhao, Tang Dan, Nie Hong

机构信息

Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research, College of Pharmacy, Jinan University, Guangzhou, China.

Department of Anesthesiology, Yale University School of Medicine, New Haven, CT, USA.

出版信息

J Pharm Pharmacol. 2021 Dec 7;73(12):1617-1629. doi: 10.1093/jpp/rgab145.

Abstract

OBJECTIVES

This study aimed to discover the active compounds of Sophora flavescens Ait. (SF), the anti-itch effects and underlying mechanisms of oxymatrine (OMT), one of the bioactive compounds from SF.

METHODS

Dorsal root ganglion cell membrane immobilized chromatography was used to screen potential anti-pruritic active compounds from SF. The scratching behaviour was analysed to systematically study the anti-pruritic effects of OMT in chloroquine- (CQ), peptide Ser-Leu-Ile-Gly-Arg-Leu- (SLIGRL), histamine- (HIS) and allyl-isothiocyanate-(AITC)-induced itch mice models. Real-time quantitative PCR, in-vivo study and molecular docking were employed to explore the underlying mechanisms.

KEY FINDINGS

All in all, 21 compounds of SF were identified and 5 potential bioactive compounds were discovered. OMT significantly reduced scratching bouts in two HIS-independent itch models induced by CQ and SLIGRL but was not effective in the HIS-induced itch model. OMT reduced scratching bouts in a dose-dependent manner and decreased the messenger RNA (mRNA) expression of transient receptor potential ankyrin 1 (TRPA1) channel in two HIS-independent itch models; in addition, OMT reduced the wipes and scratching bouts induced by AITC.

CONCLUSIONS

This study discovered five potential anti-pruritic compounds including OMT in the SF extract, and OMT has strong anti-pruritic effects in HIS-independent itch via TRPA1 channel.

摘要

目的

本研究旨在发现苦参的活性成分,以及苦参生物活性成分之一氧化苦参碱(OMT)的止痒作用及潜在机制。

方法

采用背根神经节细胞膜固定色谱法筛选苦参中潜在的止痒活性成分。通过分析搔抓行为,系统研究氧化苦参碱在氯喹(CQ)、肽Ser-Leu-Ile-Gly-Arg-Leu-(SLIGRL)、组胺(HIS)和异硫氰酸烯丙酯(AITC)诱导的瘙痒小鼠模型中的止痒作用。采用实时定量PCR、体内研究和分子对接技术探讨其潜在机制。

主要发现

总共鉴定出21种苦参化合物,发现了5种潜在的生物活性化合物。氧化苦参碱在CQ和SLIGRL诱导的两种非组胺依赖性瘙痒模型中显著减少搔抓次数,但在组胺诱导的瘙痒模型中无效。氧化苦参碱在两种非组胺依赖性瘙痒模型中以剂量依赖性方式减少搔抓次数,并降低瞬时受体电位锚蛋白1(TRPA1)通道的信使核糖核酸(mRNA)表达;此外,氧化苦参碱减少了AITC诱导的擦拭和搔抓次数。

结论

本研究在苦参提取物中发现了包括氧化苦参碱在内的五种潜在止痒化合物,氧化苦参碱通过TRPA1通道在非组胺依赖性瘙痒中具有较强的止痒作用。

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