{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T20:52:58Z","timestamp":1789678378165,"version":"4.0.1"},"reference-count":51,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100014219","name":"National Science Fund for Distinguished Young Scholars","doi-asserted-by":"publisher","award":["81825021"],"award-info":[{"award-number":["81825021"]}],"id":[{"id":"10.13039\/501100014219","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81773707, 32161143019"],"award-info":[{"award-number":["81773707, 32161143019"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004739","name":"Youth Innovation Promotion Association","doi-asserted-by":"publisher","award":["2020284"],"award-info":[{"award-number":["2020284"]}],"id":[{"id":"10.13039\/501100004739","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["19431906000"],"award-info":[{"award-number":["19431906000"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004775","name":"Natural Science Foundation of Gansu Province","doi-asserted-by":"publisher","award":["20JR5RA570"],"award-info":[{"award-number":["20JR5RA570"]}],"id":[{"id":"10.13039\/501100004775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>(\u2212)-Naringenin 4\u2032,7-dimethyl ether ((\u2212)-NRG-DM) was isolated for the first time by our lab from Nardostachys jatamansi DC, a traditional medicinal plant frequently used to attenuate pain in Asia. As a natural derivative of analgesic, the current study was designed to test the potential analgesic activity of (\u2212)-NRG-DM and its implicated mechanism. The analgesic activity of (\u2212)-NRG-DM was assessed in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model, in which the mice were intraperitoneally administrated with vehicle or (\u2212)-NRG-DM (30 or 50 mg\/kg) (n = 10 for each group). Our data showed that (\u2212)-NRG-DM can dose dependently (30~50 mg\/kg) relieve the pain behaviors. Notably, (\u2212)-NRG-DM did not affect motor coordination in mice evaluated by the rotarod test, in which the animals were intraperitoneally injected with vehicle or (\u2212)-NRG-DM (100, 200, or 400 mg\/kg) (n = 10 for each group). In acutely isolated mouse dorsal root ganglion neurons, (\u2212)-NRG-DM (1~30 \u03bcM) potently dampened the stimulated firing, reduced the action potential threshold and amplitude. In addition, the neuronal delayed rectifier potassium currents (IK) and voltage-gated sodium currents (INa) were significantly suppressed. Consistently, (\u2212)-NRG-DM dramatically inhibited heterologously expressed Kv2.1 and Nav1.8 channels which represent the major components of the endogenous IK and INa. A pharmacokinetic study revealed the plasma concentration of (\u2212)-NRG-DM is around 7 \u00b5M, which was higher than the effective concentrations for the IK and INa. Taken together, our study showed that (\u2212)-NRG-DM is a potential analgesic candidate with inhibition of multiple neuronal channels (mediating IK and INa).<\/jats:p>","DOI":"10.3390\/molecules27051735","type":"journal-article","created":{"date-parts":[[2022,3,9]],"date-time":"2022-03-09T01:53:54Z","timestamp":1646790834000},"page":"1735","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["(\u2212)-Naringenin 4\u2032,7-dimethyl Ether Isolated from Nardostachys jatamansi Relieves Pain through Inhibition of Multiple Channels"],"prefix":"10.3390","volume":"27","author":[{"given":"Ru-Rong","family":"Gu","sequence":"first","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3414-7583","authenticated-orcid":false,"given":"Xian-Hua","family":"Meng","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhan","sequence":"additional","affiliation":[{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao-Bing","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Chinese Materia Medica, Nanjing University of Chinese Medicine, Nanjing 210023, China"},{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"},{"name":"Zhongshan Institute of Drug Discovery, Institution for Drug Discovery Innovation, Chinese Academy of Sciences, Zhongshan 528400, China"},{"name":"University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Li","family":"Yang","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0677-0316","authenticated-orcid":false,"given":"Yue-Ming","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Neurological and Psychiatric Research and Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/B978-1-4160-4836-7.00070-5","article-title":"Chapter 70\u2014Psychological Aspects of Pain","volume":"24","author":"Okifuji","year":"2009","journal-title":"Curr. 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