Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors
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http://hdl.handle.net/10045/118818
Títol: | Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors |
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Autors: | Alberola-Die, Armando | Encinar, José A. | Cobo, Raúl | Fernández-Ballester, Gregorio | González-Ros, José M. | Ivorra, Isabel | Morales, Andrés |
Grups d'investigació o GITE: | Fisiología de Membranas |
Centre, Departament o Servei: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología |
Paraules clau: | Peimine | Traditional Chinese medicine | Anti-inflammatory compound | Nicotinic receptors | Electrophysiological recordings | Xenopus oocytes | Molecular docking | Dynamics simulations |
Àrees de coneixement: | Fisiología |
Data de publicació: | 19-d’octubre-2021 |
Editor: | MDPI |
Citació bibliogràfica: | Alberola-Die A, Encinar JA, Cobo R, Fernández-Ballester G, González-Ros JM, Ivorra I, Morales A. Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors. International Journal of Molecular Sciences. 2021; 22(20):11287. https://doi.org/10.3390/ijms222011287 |
Resum: | Fritillaria bulbs are used in Traditional Chinese Medicine to treat several illnesses. Peimine (Pm), an anti-inflammatory compound from Fritillaria, is known to inhibit some voltage-dependent ion channels and muscarinic receptors, but its interaction with ligand-gated ion channels remains unexplored. We have studied if Pm affects nicotinic acetylcholine receptors (nAChRs), since they play broad functional roles, both in the nervous system and non-neuronal tissues. Muscle-type nAChRs were incorporated to Xenopus oocytes and the action of Pm on the membrane currents elicited by ACh (IAChs) was assessed. Functional studies were combined with virtual docking and molecular dynamics assays. Co-application of ACh and Pm reversibly blocked IACh, with an IC50 in the low micromolar range. Pm inhibited nAChR by: (i) open-channel blockade, evidenced by the voltage-dependent inhibition of IAch, (ii) enhancement of nAChR desensitization, revealed by both an accelerated IACh decay and a decelerated IACh deactivation, and (iii) resting-nAChR blockade, deduced from the IACh inhibition elicited by Pm when applied before ACh superfusion. In good concordance, virtual docking and molecular dynamics assays demonstrated that Pm binds to different sites at the nAChR, mostly at the transmembrane domain. Thus, Pm from Fritillaria bulbs, considered therapeutic herbs, targets nAChRs with high affinity, which might account for its anti-inflammatory actions. |
Patrocinadors: | This research was funded by grants SAF2017-82977-P (AEI/FEDER, UE), RTI2018-096724-B-C21, RTI2018-097189-B-C21, and PGC2018-093505-B-I00 from MINECO, PROMETEO/2016/006 from Generalitat Valenciana and GRE17-01 from Universidad de Alicante. R.C. held a predoctoral fellowship from Universidad de Alicante (FPUUA36). |
URI: | http://hdl.handle.net/10045/118818 |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms222011287 |
Idioma: | eng |
Tipus: | info:eu-repo/semantics/article |
Drets: | © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
Revisió científica: | si |
Versió de l'editor: | https://doi.org/10.3390/ijms222011287 |
Apareix a la col·lecció: | INV - Fisiología de Membranas - Artículos de Revistas |
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