Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Int J Mol Sci
2021 Oct 19;2220:. doi: 10.3390/ijms222011287.
Show Gene links
Show Anatomy links
Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors.
Alberola-Die A
,
Encinar JA
,
Cobo R
,
Fernández-Ballester G
,
González-Ros JM
,
Ivorra I
,
Morales A
.
???displayArticle.abstract???
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.
SAF2017-82977-P Ministry of Economy, Industry and Competitiveness, RTI2018-096724-B-C21 Ministry of Economy, Industry and Competitiveness, RTI2018-097189-B-C21 Ministry of Economy, Industry and Competitiveness, PGC2018-093505-B-I00 Ministry of Economy, Industry and Competitiveness, PROMETEO/2016/006 Generalitat Valenciana, GRE17-01 University of Alicante, FPUUA36 University of Alicante
Alberola-Die,
Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine.
2016, Pubmed,
Xenbase
Alberola-Die,
Muscle-Type Nicotinic Receptor Blockade by Diethylamine, the Hydrophilic Moiety of Lidocaine.
2016,
Pubmed
,
Xenbase
Alberola-Die,
Multiple inhibitory actions of lidocaine on Torpedo nicotinic acetylcholine receptors transplanted to Xenopus oocytes.
2011,
Pubmed
,
Xenbase
Alberola-Die,
Muscle-Type Nicotinic Receptor Modulation by 2,6-Dimethylaniline, a Molecule Resembling the Hydrophobic Moiety of Lidocaine.
2016,
Pubmed
,
Xenbase
Alberola-Die,
Lidocaine effects on acetylcholine-elicited currents from mouse superior cervical ganglion neurons.
2013,
Pubmed
Albuquerque,
Mammalian nicotinic acetylcholine receptors: from structure to function.
2009,
Pubmed
Cetin,
The Structure, Function, and Physiology of the Fetal and Adult Acetylcholine Receptor in Muscle.
2020,
Pubmed
Chai,
Circumvention of multi-drug resistance of cancer cells by Chinese herbal medicines.
2010,
Pubmed
Changeux,
Nicotinic receptors, allosteric proteins and medicine.
2008,
Pubmed
Chen,
Mechanistic studies of the transport of peimine in the Caco-2 cell model.
2016,
Pubmed
Chen,
Comparative pharmacokinetic studies of peimine and peiminine in rat plasma by LC-MS-MS after oral administration of Fritillaria thunbergii Miq. and Fritillaria thunbergii Miq. - Glycyrrhiza uralensis Fisch. couple extract.
2011,
Pubmed
Cobo,
Mechanisms Underlying the Strong Inhibition of Muscle-Type Nicotinic Receptors by Tetracaine.
2018,
Pubmed
,
Xenbase
Cobo,
Mechanisms of Blockade of the Muscle-Type Nicotinic Receptor by Benzocaine, a Permanently Uncharged Local Anesthetic.
2020,
Pubmed
,
Xenbase
Encinar,
In silico approach for the discovery of new PPARγ modulators among plant-derived polyphenols.
2015,
Pubmed
Encinar,
Potential Drugs Targeting Early Innate Immune Evasion of SARS-Coronavirus 2 via 2'-O-Methylation of Viral RNA.
2020,
Pubmed
Godin,
A silent agonist of α7 nicotinic acetylcholine receptors modulates inflammation ex vivo and attenuates EAE.
2020,
Pubmed
Gonzalez-Ros,
Lipid environment of acetylcholine receptor from Torpedo californica.
1982,
Pubmed
Gotti,
Neuronal nicotinic receptors: from structure to pathology.
2004,
Pubmed
Heidmann,
Rapid kinetics of agonist binding and permeability response analyzed in parallel on acetylcholine receptor rich membranes from Torpedo marmorata.
1983,
Pubmed
Huang,
The Natural Compound Cinnamaldehyde is a Novel Activator of Calcium-Activated Chloride Channel.
2018,
Pubmed
Hurst,
Nicotinic acetylcholine receptors: from basic science to therapeutics.
2013,
Pubmed
Ivorra,
Protein orientation affects the efficiency of functional protein transplantation into the xenopus oocyte membrane.
2002,
Pubmed
,
Xenbase
Iwashina,
Flavonoid function and activity to plants and other organisms.
2003,
Pubmed
KATZ,
A study of the desensitization produced by acetylcholine at the motor end-plate.
1957,
Pubmed
Kan,
Peimine inhibits hERG potassium channels through the channel inactivation states.
2017,
Pubmed
Krieger,
Fast empirical pKa prediction by Ewald summation.
2006,
Pubmed
Kusano,
Cholinergic and catecholaminergic receptors in the Xenopus oocyte membrane.
1982,
Pubmed
,
Xenbase
Morales,
Incorporation of reconstituted acetylcholine receptors from Torpedo into the Xenopus oocyte membrane.
1995,
Pubmed
,
Xenbase
Namkung,
Inhibition of Ca2+-activated Cl- channels by gallotannins as a possible molecular basis for health benefits of red wine and green tea.
2010,
Pubmed
Nielsen,
Flavonoids as positive allosteric modulators of α7 nicotinic receptors.
2019,
Pubmed
,
Xenbase
Nury,
One-microsecond molecular dynamics simulation of channel gating in a nicotinic receptor homologue.
2010,
Pubmed
Oh,
Angiotensin converting enzyme (ACE) inhibitory alkaloids from Fritillaria ussuriensis.
2003,
Pubmed
Olivera-Bravo,
The acetylcholinesterase inhibitor BW284c51 is a potent blocker of Torpedo nicotinic AchRs incorporated into the Xenopus oocyte membrane.
2005,
Pubmed
,
Xenbase
Olivera-Bravo,
Diverse inhibitory actions of quaternary ammonium cholinesterase inhibitors on Torpedo nicotinic ACh receptors transplanted to Xenopus oocytes.
2007,
Pubmed
,
Xenbase
Pettersen,
UCSF Chimera--a visualization system for exploratory research and analysis.
2004,
Pubmed
Popot,
Interaction of the acetylcholine (nicotinic) receptor protein from Torpedo marmorata electric organ with monolayers of pure lipids.
1978,
Pubmed
Rahman,
Structure of the Native Muscle-type Nicotinic Receptor and Inhibition by Snake Venom Toxins.
2020,
Pubmed
Sine,
End-plate acetylcholine receptor: structure, mechanism, pharmacology, and disease.
2012,
Pubmed
Tan,
Peimine inhibits the growth and motility of prostate cancer cells and induces apoptosis by disruption of intracellular calcium homeostasis through Ca2+ /CaMKII/JNK pathway.
2020,
Pubmed
Unwin,
Refined structure of the nicotinic acetylcholine receptor at 4A resolution.
2005,
Pubmed
Unwin,
Gating movement of acetylcholine receptor caught by plunge-freezing.
2012,
Pubmed
Unwin,
Protein-lipid architecture of a cholinergic postsynaptic membrane.
2020,
Pubmed
Verdura,
Resveratrol targets PD-L1 glycosylation and dimerization to enhance antitumor T-cell immunity.
2020,
Pubmed
Voss,
3V: cavity, channel and cleft volume calculator and extractor.
2010,
Pubmed
Wang,
Antitussive, expectorant and anti-inflammatory alkaloids from Bulbus Fritillariae Cirrhosae.
2011,
Pubmed
Wang,
Simultaneous Determination and Pharmacokinetics of Peimine and Peiminine in Beagle Dog Plasma by UPLC-MS/MS after the Oral Administration of Fritillariae ussuriensis Maxim and Fritillariae thunbergii Miq Powder.
2018,
Pubmed
Xu,
Peimine, a main active ingredient of Fritillaria, exhibits anti-inflammatory and pain suppression properties at the cellular level.
2016,
Pubmed
Yang,
Recent scientific studies of a traditional chinese medicine, tea, on prevention of chronic diseases.
2014,
Pubmed
Yin,
Pharmacological Effects of Verticine: Current Status.
2019,
Pubmed
Zhou,
The effects of five alkaloids from Bulbus Fritillariae on the concentration of cAMP in HEK cells transfected with muscarinic M(2) receptor plasmid.
2006,
Pubmed
