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芍药苷治疗通过抑制肠腔内细菌积聚和生物膜形成来延长感染者的寿命。

Treatment with paeoniflorin increases lifespan of infected by inhibiting bacterial accumulation in intestinal lumen and biofilm formation.

作者信息

Wang Yuxing, Zhang Le, Yuan Xiaoan, Wang Dayong

机构信息

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

出版信息

Front Pharmacol. 2023 Mar 27;14:1114219. doi: 10.3389/fphar.2023.1114219. eCollection 2023.

Abstract

Paeoniflorin is one of the important components in plants. In this study, we used as a model host and as a bacterial pathogen to investigate the possible role of paeoniflorin treatment against infection in the host and the underlying mechanisms. Posttreatment with 1.25-10 mg/L paeoniflorin could significantly increase the lifespan of infected nematodes. After the infection, the colony-forming unit (CFU) and accumulation in intestinal lumen were also obviously reduced by 1.25-10 mg/L paeoniflorin treatment. The beneficial effects of paeoniflorin treatment in increasing lifespan in infected nematodes and in reducing accumulation in intestinal lumen could be inhibited by RNAi of , , and . In addition, paeoniflorin treatment suppressed the inhibition in expressions of , , and caused by infection in nematodes, suggesting that paeoniflorin could increase lifespan of infected nematode by activating PMK-1, EGL-1, and BAR-1. Moreover, although treatment with 1.25-10 mg/L paeoniflorin did not show obvious anti- activity, the biofilm formation and expressions of related virulence genes (, , , , , , and ) were significantly inhibited by paeoniflorin treatment. Treatment with 1.25-10 mg/L paeoniflorin could further decrease the levels of related virulence factors of pyocyanin, elastase, and rhamnolipid. In addition, 2.5-10 mg/L paeoniflorin treatment could inhibit the swimming, swarming, and twitching motility of , and treatment with 2.5-10 mg/L paeoniflorin reduced the cyclic-di-GMP (c-di-GMP) level. Therefore, paeoniflorin treatment has the potential to extend lifespan of infected hosts by reducing bacterial accumulation in intestinal lumen and inhibiting bacterial biofilm formation.

摘要

芍药苷是植物中的重要成分之一。在本研究中,我们以[具体生物A]作为模式宿主,以[具体生物B]作为细菌病原体,来研究芍药苷处理对宿主感染[具体生物B]的可能作用及其潜在机制。用1.25 - 10毫克/升芍药苷进行后处理可显著延长感染线虫的寿命。感染后,1.25 - 10毫克/升芍药苷处理也明显降低了肠道腔中[具体生物B]的菌落形成单位(CFU)和[某种物质]的积累。芍药苷处理在延长感染线虫寿命以及减少肠道腔中[某种物质]积累方面的有益作用可被[基因1]、[基因2]和[基因3]的RNA干扰所抑制。此外,芍药苷处理抑制了线虫感染[具体生物B]所导致的[基因4]、[基因5]和[基因6]表达的抑制,这表明芍药苷可通过激活PMK - 1、EGL - 1和BAR - 1来延长感染线虫的寿命。此外,尽管用1.25 - 10毫克/升芍药苷处理未显示出明显的抗[具体生物B]活性,但芍药苷处理显著抑制了[具体生物B]的生物膜形成及相关毒力基因([基因7]、[基因8]、[基因9]、[基因10]、[基因11]、[基因12]和[基因13])的表达。用1.25 - 10毫克/升芍药苷处理可进一步降低绿脓菌素、弹性蛋白酶和鼠李糖脂等相关毒力因子的水平。此外,2.5 - 10毫克/升芍药苷处理可抑制[具体生物B]的游动、群体运动和颤动运动,并且2.5 - 10毫克/升芍药苷处理降低了环二鸟苷酸(c - di - GMP)水平。因此,芍药苷处理有可能通过减少肠道腔中的细菌积累和抑制细菌生物膜形成来延长感染宿主的寿命。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e8e8/10083309/cc4b3c583504/fphar-14-1114219-g001.jpg

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