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植物醇的抗腹泻活性及其通过体内和计算机模拟模型的可能作用机制。

Anti-diarrheal activities of phytol along with its possible mechanism of action through in-vivo and in-silico models.

机构信息

Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City-700000, Vietnam.

Department of Pharmacy, Faculty of Biological Sciences, Jahangirnagar University, Savar (Dhaka)-1342, Bangladesh.

出版信息

Cell Mol Biol (Noisy-le-grand). 2020 Jun 25;66(4):243-249.

Abstract

Phytol (PHY), a chlorophyll-derived diterpenoid, exhibits numerous pharmacological properties, including antioxidant, antimicrobial, and anticancer activities. This study evaluates the anti-diarrheal effect of phytol (PHY) along with its possible mechanism of action through in-vivo and in-silico models. The effect of PHY was investigated on castor oil-induced diarrhea in Swiss mice by using prazosin, propranolol, loperamide, and nifedipine as standards with or without PHY. PHY at 50 mg/kg (p.o.) and all other standards exhibit significant (p < 0.05) anti-diarrheal effect in mice. The effect was prominent in the loperamide and propranolol groups. PHY co-treated with prazosin and propranolol was found to increase in latent periods along with a significant reduction in diarrheal section during the observation period than other individual or combined groups. Furthermore, molecular docking studies also suggested that PHY showed better interactions with the α- and β-adrenergic receptors, especially with α-ADR1a and β-ADR1. In the former case, PHY showed interaction with hydroxyl group of Ser192 at a distance of 2.91Å, while in the latter it showed hydrogen bond interactions with Thr170 and Lys297 with a distance of 2.65 and 2.72Å, respectively. PHY exerted significant anti-diarrheal effect in Swiss mice, possibly through blocking α- and β-adrenergic receptors.

摘要

植物醇(PHY)是一种叶绿素衍生的二萜,具有多种药理作用,包括抗氧化、抗菌和抗癌活性。本研究通过体内和体外模型评估了植物醇(PHY)的抗腹泻作用及其可能的作用机制。用普萘洛尔、心得安、洛哌丁胺和硝苯地平作为标准,用或不用 PHY 研究 PHY 对蓖麻油诱导的瑞士小鼠腹泻的影响。PHY 在 50mg/kg(po)时,所有其他标准均对小鼠表现出显著的(p < 0.05)抗腹泻作用。洛哌丁胺和心得安组的效果更为显著。与普萘洛尔和心得安联合治疗的 PHY 被发现潜伏期延长,在观察期内腹泻段显著减少,比其他单独或联合组都要好。此外,分子对接研究还表明,PHY 与 α-和 β-肾上腺素能受体表现出更好的相互作用,特别是与 α-ADR1a 和 β-ADR1。在前一种情况下,PHY 与 Ser192 的羟基相互作用,距离为 2.91Å,而在后一种情况下,它与 Thr170 和 Lys297 表现出氢键相互作用,距离分别为 2.65 和 2.72Å。PHY 对瑞士小鼠表现出显著的抗腹泻作用,可能是通过阻断 α-和 β-肾上腺素能受体。

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