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白杨素载药 PLGA 通过调控 TLR/NF-κB/NLRP3 轴减轻 OVA 诱导的变应性哮喘。

Chrysin-loaded PLGA attenuates OVA-induced allergic asthma by modulating TLR/NF-κB/NLRP3 axis.

机构信息

Cancer Biology & Inflammatory Disorder, Indian Institute of Chemical Biology (CSIR-IICB), Kolkata, West Bengal, India.

Department of Food & Nutrition, University of Kalyani, Kalyani, West Bengal, India.

出版信息

Nanomedicine. 2020 Nov;30:102292. doi: 10.1016/j.nano.2020.102292. Epub 2020 Aug 25.

Abstract

Asthma, one of the significant public health problems, is triggered by certain inflammatory processes in the airways that are not addressed propitiously by current therapies. Though pieces of evidence on allergic asthma mitigation by the anti-inflammatory bioflavonoid chrysin (CHR) are accumulating, poor bioavailability, and low solubility curtail drug development. To overcome these shortcomings, CHR loaded nanoparticle (CHR-NP) was formulated, and its salutary effect in preclinical murine allergic asthma model via the peroral route was evaluated. The spherical nanosized particles showed slow, sustained release in vitro. Moreover, CHR-NP dramatically reduced the serum IgE, ovalbumin (OVA)-induced lung histological alteration, as well as Th2 (T-helper 2) cytokines in the bronchoalveolar lavage fluid (BALF). It also suppressed the elevated serum pro-inflammatory cytokines and their upstream TLR/NF-κB/NLRP3 pathway activation in lung superior to CHR and almost identical to dexamethasone (DEX). Thus this study suggests the potentiality of CHR-NP in ameliorating allergic asthma progression.

摘要

哮喘是重大公共卫生问题之一,由气道内某些炎症过程引发,目前的治疗方法对此无法有效应对。尽管越来越多的证据表明抗炎生物类黄酮白杨素(CHR)可缓解过敏性哮喘,但较差的生物利用度和低溶解度限制了药物研发。为克服这些缺点,我们制备了 CHR 负载的纳米颗粒(CHR-NP),并通过口服途径在临床前小鼠过敏性哮喘模型中评估了其有益作用。结果显示,球形纳米颗粒具有缓慢、持续的体外释放特性。此外,CHR-NP 可显著降低血清 IgE、卵清蛋白(OVA)诱导的肺部组织学改变以及支气管肺泡灌洗液(BALF)中的 Th2(辅助性 T 细胞 2)细胞因子。它还能抑制血清中促炎细胞因子的升高,并在上游 TLR/NF-κB/NLRP3 通路的激活方面优于 CHR,与地塞米松(DEX)几乎相同。因此,本研究提示 CHR-NP 具有改善过敏性哮喘进展的潜力。

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