Peimine，一种来自中草药提取物的抗炎化合物，调节肌肉型烟碱受体,International Journal of Molecular Sciences

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Peimine，一种来自中草药提取物的抗炎化合物，调节肌肉型烟碱受体
International Journal of Molecular Sciences ( IF 4.9 ) Pub Date : 2021-10-19 , DOI: 10.3390/ijms222011287
Armando Alberola-Die ₁ , José Antonio Encinar ₂ , Raúl Cobo ₁ , Gregorio Fernández-Ballester ₂ , José Manuel González-Ros ₂ , Isabel Ivorra ₁ , Andrés Morales ₁

Affiliation

贝母球茎在中医中用于治疗多种疾病。Peimine (Pm) 是一种来自贝母的抗炎化合物，已知可抑制一些电压依赖性离子通道和毒蕈碱受体，但其与配体门控离子通道的相互作用仍未得到探索。我们研究了 Pm 是否影响烟碱型乙酰胆碱受体 (nAChR)，因为它们在神经系统和非神经元组织中都发挥着广泛的功能作用。将肌肉型 nAChR 并入非洲爪蟾卵母细胞，并评估Pm 对 ACh ( I _ACh s)引起的膜电流的作用。功能研究与虚拟对接和分子动力学分析相结合。ACh和Pm的共同应用可逆地被阻断I _ACh，IC ₅₀在低微摩尔范围内。Pm 通过以下方式抑制 nAChR：（i）开放通道阻断，由I _Ach的电压依赖性抑制证明，（ii）nAChR 脱敏的增强，由加速的I _ACh衰减和减速的I _ACh失活揭示，以及（iii） ) 静息-nAChR 阻断，由 Pm 在 ACh 灌注前应用时引起的I _ACh抑制推断。一致的是，虚拟对接和分子动力学分析表明 Pm 与 nAChR 的不同位点结合，主要在跨膜域。因此，来自贝母的Pm 球茎被认为是治疗性草药，以高亲和力靶向 nAChR，这可能是其抗炎作用的原因。

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Peimine, an Anti-Inflammatory Compound from Chinese Herbal Extracts, Modulates Muscle-Type Nicotinic Receptors

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 (I_AChs) was assessed. Functional studies were combined with virtual docking and molecular dynamics assays. Co-application of ACh and Pm reversibly blocked I_ACh, with an IC₅₀ in the low micromolar range. Pm inhibited nAChR by: (i) open-channel blockade, evidenced by the voltage-dependent inhibition of I_Ach, (ii) enhancement of nAChR desensitization, revealed by both an accelerated I_ACh decay and a decelerated I_ACh deactivation, and (iii) resting-nAChR blockade, deduced from the I_ACh 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.

更新日期：2021-10-19

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