A novel isoquinoline alkaloid HJ-69 isolated from Zanthoxylum bungeanum attenuates inflammatory pain by inhibiting voltage-gated sodium and potassium channels
文献类型：期刊论文
| 作者 | Wang, Long3,4; Hao, Haishuang2; Meng, Xianhua1; Zhang, Wenbo2; Zhang, Yin4; Chai, Tian1; Wang, Xingrong1; Gao, Zhaobing2,4 ; Zheng, Yueming4; Yang, Junli1
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| 刊名 | JOURNAL OF ETHNOPHARMACOLOGY
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| 出版日期 | 2024-08-10 |
| 卷号 | 330页码:12 |
| 关键词 | HJ-69 Zanthoxylum bungeanum Isoquinoline alkaloid Nav Kv Inflammatory pain |
| ISSN号 | 0378-8741 |
| DOI | 10.1016/j.jep.2024.118218 |
| 通讯作者 | Gao, Zhaobing(zbgao@simm.ac.cn) ; Zheng, Yueming(zhengyueming@simm.ac.cn) ; Yang, Junli(yangjl@licp.cas.cn) |
| 英文摘要 | Ethnopharmacology relevance Zanthoxylum bungeanum Maxim. (Z. bungeanum), a member of the Rutaceae family, has a rich history of traditional use in Asia for treating arthritis and toothache conditions. As characteristic chemical components, numerous kinds of alkaloids have been extracted from plants and their diverse biological activities have been reported. However, research on the isoquinoline alkaloid, a specific type of alkaloids, in Z. bungeanum was scarce. Aim of the study The study aimed to isolate a novel isoquinoline alkaloid from Z. bungeanum and explore its pharmacological activity in vitro and analgesic activity in vivo. Materials and methods Isoquinoline alkaloid isolation and identification from Z. bungeanum were conducted using chromatographic and spectroscopic methods. The whole-cell patch-clamp technique was applied to assess its impact on neuronal excitability, and endogenous voltage-gated potassium (Kv) and sodium (Nav) currents in acutely isolated mouse small-diameter dorsal root ganglion (DRG) neurons. Its inhibitory impacts on channels were further validated with HEK293 cells stably expressing Nav1.7 and Nav1.8, and Chinese hamster ovary (CHO) cells transiently expressing Kv2.1. The formalin inflammatory pain model was utilized to evaluate the potential analgesic activity in vivo. Results A novel isoquinoline alkaloid named HJ-69 (N-13-(3-methoxyprop-1-yl)rutaecarpine) was isolated and identified from Z. bungeanum for the first time. HJ-69 significantly suppressed the firing frequency and amplitudes of action potentials in DRG neurons. Consistently, it state-dependently inhibited endogenous Nav currents of DRG neurons, with half maximal inhibitory concentration (IC50) values of 13.06 +/- 2.06 mu M and 30.19 +/- 2.07 mu M for the inactivated and resting states, respectively. HJ-69 significantly suppressed potassium currents in DRG neurons, which notably inhibited the delayed rectifier potassium (I-K) currents (IC50 = 6.95 +/- 1.29 mu M) and slightly affected the transient outward potassium (I-A) currents (IC50 = 523.50 +/- 39.16 mu M). Furtherly, HJ-69 exhibited similar potencies on heterologously expressed Nav1.7, Nav1.8, and Kv2.1 channels, which correspondingly represent the main components in neurons. Notably, intraperitoneal administration of 30 mg/kg and 100 mg/kg HJ-69 significantly alleviated pain behaviors in the mouse inflammatory pain model induced by formalin. Conclusion The study concluded that HJ-69 is a novel and active isoquinoline alkaloid, and the inhibition of Nav and Kv channels contributes to its analgesic activity. HJ-69 may be a promising prototype for future analgesic drug discovery based on the isoquinoline alkaloid. |
| WOS关键词 | FORMALIN TEST ; K+ CHANNEL ; KV2.1 ; MECHANISM ; CURRENTS ; NITIDUM |
| 资助项目 | National Science Fund for Distinguished Young Scholars[81825021] ; Youth Innovation Promotion Association of the Chinese Academy of Sciences[2020284] ; National Science and Technology Innovation 2030 Major Program[2021ZD0200900] ; Science and Technology Major Program of Gansu Province[23ZDNA002] ; Major Program of the Lanzhou Institute of Chemical Physics, CAS[ZYFZFX-6] |
| WOS研究方向 | Plant Sciences ; Pharmacology & Pharmacy ; Integrative & Complementary Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001325511900001 |
| 出版者 | ELSEVIER IRELAND LTD |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313681]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gao, Zhaobing; Zheng, Yueming; Yang, Junli |
| 作者单位 | 1.Chinese Acad Sci, Lanzhou Inst Chem Phys, Lanzhou 730000, Peoples R China 2.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China 3.Fudan Univ, Human Phenome Inst, Pharmacophen Lab, Shanghai 201203, Peoples R China 4.Chinese Acad Sci, Ctr Neurol & Psychiat Res & Drug Discovery, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wang, Long,Hao, Haishuang,Meng, Xianhua,et al. A novel isoquinoline alkaloid HJ-69 isolated from Zanthoxylum bungeanum attenuates inflammatory pain by inhibiting voltage-gated sodium and potassium channels[J]. JOURNAL OF ETHNOPHARMACOLOGY,2024,330:12. |
| APA | Wang, Long.,Hao, Haishuang.,Meng, Xianhua.,Zhang, Wenbo.,Zhang, Yin.,...&Yang, Junli.(2024).A novel isoquinoline alkaloid HJ-69 isolated from Zanthoxylum bungeanum attenuates inflammatory pain by inhibiting voltage-gated sodium and potassium channels.JOURNAL OF ETHNOPHARMACOLOGY,330,12. |
| MLA | Wang, Long,et al."A novel isoquinoline alkaloid HJ-69 isolated from Zanthoxylum bungeanum attenuates inflammatory pain by inhibiting voltage-gated sodium and potassium channels".JOURNAL OF ETHNOPHARMACOLOGY 330(2024):12. |
入库方式： OAI收割
来源：上海药物研究所
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