Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists

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	Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists
	Dong, Fa-Wu; Jiang, He-Hai; Yang, Liu; Gong, Ye; Zi, Cheng-Ting; Yang, Dan; Ye, Chen-Jun; Li, Huan; Yang, Jian; Nian, Yin; Zhou, Jun; Hu, Jiang-Miao
	2018
发表期刊	FRONTIERS IN PHARMACOLOGY
ISSN	1663-9812
卷号	9 页码:885
摘要	The roots and rhizomes of Valeriana jatamansi have long been used as folk medicine in Asia and usually named as "Zhizhuxiang" in Chinese for the treatment of abdominal distention and pain. However, its active ingredients and molecular targets for treatment of abdominal pain remain unrevealed. Inhibitors of Ca(v)2.2 N-type voltage-gated calcium channels (VGCCs) are actively sought after for their potential in treating pain, especially chronic pain. As far as we know, the method used for seeking analgesic active ingredient from plant material has rarely been reported. The analgesic potentials of the EtOH extract (0.01 mg/ml) of the roots and rhizomes of V. jatamansi and its EtOAc, n-BuOH and H2O soluble parts (0.01 mg/ml, respectively) were tested herein on Ca(v)2.2, using whole-oocyte recordings in vitro by tow-electrode voltage clamp. The results indicated that the EtOAc-soluble part exhibited the most potent inhibition of Ca(v)2.2 peak current (20 mv). The EtOAc-soluble part was then subjected to silica gel column chromatography (CC) and giving 9 fractions. Phytochemical studies were carried out by repeated CC and extensive spectroscopic analyses after the fraction (0.01 mg/ml) was identified to be active and got seventeen compounds (1-17). All isolates were then sent for further bioactive verification (1 and 3 at concentration of 10 mu M, others at 30 mu M). In addition, the selectivity of the active compounds 1 and 3 were tested on various ion channels including Ca(v)1.2, Ca(v)2.1 and Ca(v)3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. The results indicated that compound 1 and 3 (an abundant compound) inhibited Ca(v)2.2 with an EC50 of 3.3 and 4.8 mu M, respectively, and had weaker or no effect on Ca(v)1.2, Ca(v)2.1 and Ca(v)3.1 VGCCs and Kv1.2, Kv2.1, Kv3.1 and BK potassium channels. Compounds 1 and 3 appear to act as allosteric modulators rather than pore blockers of Ca(v)2.2, which may play crucial role in attenuating nociception. The results of present research indicated that the ethnopharmacological utilization of V. jatamansi for relieving the abdominal distention and pain may mediate through Ca(v)2.2 channel. Our work is the first demonstration of inhibition of Ca(v)2.2 by iridoids, which may provide a fresh source for finding new analgesics.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/64694
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Dong, Fa-Wu,Jiang, He-Hai,Yang, Liu,et al. Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists[J]. FRONTIERS IN PHARMACOLOGY,2018,9:885.
APA	Dong, Fa-Wu.,Jiang, He-Hai.,Yang, Liu.,Gong, Ye.,Zi, Cheng-Ting.,...&Hu, Jiang-Miao.(2018).Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists.FRONTIERS IN PHARMACOLOGY,9,885.
MLA	Dong, Fa-Wu,et al."Valepotriates From the Roots and Rhizomes of Valeriana jatamansi Jones as Novel N-Type Calcium Channel Antagonists".FRONTIERS IN PHARMACOLOGY 9(2018):885.