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芍药苷通过激活 PMK-1、BAR-1 和 EGL-1 信号来增加免疫抑制阶段铜绿假单胞菌感染秀丽隐杆线虫的存活率。

Paeoniflorin increases the survival of Pseudomonas aeruginosa infected Caenorhabditis elegans at the immunosuppression stage by activating PMK-1, BAR-1, and EGL-1 signals.

机构信息

Jiangsu Provincial Key Laboratory of Critical Care Medicine, School of Medicine, Southeast University, Nanjing, 210009, China.

出版信息

Arch Pharm Res. 2023 Jul;46(7):616-628. doi: 10.1007/s12272-023-01459-w. Epub 2023 Aug 3.

Abstract

Paeoniflorin is the major active compound of total glycoside of paeony in Paeonia lactiflora Pall. Although several aspects of beneficial effects of paeoniflorin have been described, whether the paeoniflorin treatment is helpful for inhibiting the pathogen infection-induced immunosuppression remains largely unclear. Using the immunosuppression model in Caenorhabditis elegans induced by Pseudomonas aeruginosa infection, we here examined the beneficial effect of paeoniflorin treatment against the immunosuppression induced by bacterial pathogen infection. In this immunosuppression model, we observed that the survival rate of P. aeruginosa infected nematodes at the immunosuppression stage could be significantly increased by 25-100 mg/L paeoniflorin treatment. P. aeruginosa accumulation in intestinal lumen of nematodes at the immunosuppression stage was reduced by paeoniflorin treatment. Paeoniflorin could activate the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Moreover, at the immunosuppression stage, paeoniflorin treatment increased the expressions of bar-1, pmk-1, and egl-1 required for the control of innate immunity against bacterial infection. Meanwhile, RNAi of bar-1, pmk-1, and egl-1 inhibited the beneficial effect of paeoniflorin treatment in increasing the survival, reducing the P. aeruginosa accumulation in intestinal lumen, and activating the expressions of antimicrobial genes (lys-1 and lys-8) in nematodes at the immunosuppression stage. Therefore, paeoniflorin treatment could effectively inhibit the immunosuppression induced by bacterial pathogen infection in the hosts.

摘要

芍药苷是芍药属植物白芍总苷中的主要活性化合物。尽管已经描述了芍药苷的几个有益作用方面,但芍药苷治疗是否有助于抑制病原体感染引起的免疫抑制作用在很大程度上仍不清楚。我们使用铜绿假单胞菌感染诱导的秀丽隐杆线虫免疫抑制模型,在此检查了芍药苷治疗对细菌病原体感染引起的免疫抑制的有益作用。在这种免疫抑制模型中,我们观察到,在免疫抑制阶段,25-100mg/L 芍药苷处理可使感染铜绿假单胞菌的线虫的存活率显著提高 25-100%。芍药苷处理可减少线虫在免疫抑制阶段肠腔中铜绿假单胞菌的积累。芍药苷可激活线虫在免疫抑制阶段的抗菌基因(lys-1 和 lys-8)的表达。此外,在免疫抑制阶段,芍药苷处理增加了先天免疫反应控制所需的 bar-1、pmk-1 和 egl-1 的表达,以对抗细菌感染。同时,bar-1、pmk-1 和 egl-1 的 RNAi 抑制了芍药苷处理增加存活率、减少肠腔中铜绿假单胞菌积累和激活线虫抗菌基因(lys-1 和 lys-8)表达的有益作用在免疫抑制阶段。因此,芍药苷处理可有效抑制宿主中细菌病原体感染引起的免疫抑制。

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