首页> 外文期刊>Microbial Pathogenesis >Quercetin a major biomarker of Psidium guajava L. inhibits SepA protease activity of Shigella flexneri in treatment of infectious diarrhoea
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Quercetin a major biomarker of Psidium guajava L. inhibits SepA protease activity of Shigella flexneri in treatment of infectious diarrhoea

机译:槲皮素Psidium Guajava L的主要生物标志物。抑制Sepa蛋白酶的Sepa蛋白酶活性在感染性腹泻的治疗中

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The leaves of the plant Psidium guajava L. (Myrtaceae) has been traditionally used in treatment of various gastrointestinal disorders including diarrhoea and have also been reported for its potent antidiarrhoeal activity on various chemical induced diarrhoea models. The objective of our present study was to evaluate the potency of the leaf extract of the plant Psidium guajava (PGE) along with its major biomarker quercetin against Shigella fiexneri-induced sub chronic model of infectious diarrhoea. PGE at 100, 200 and 400 mg/kg, p.o. and quercetin at 50 mg/kg, p.o. were administered to Shigella flexneri-induced diarrhoeal rats for five days and various behavioural parameters were evaluated on 1st, 3rd and 5th day of treatment. This was followed by assessment of stool water content, density of Shigella flexneri in stools and blood parameters examination. After treatment, colon and small intestine of rats was dissected and subjected to biochemical estimations, cytokine profiling, antioxidant evaluations, ion concentration determination, Na+/K+-ATPase activity and histopathology. Molecular docking studies on crystal structure of Secreted Extracellular Protein A (SepA) from Shigella flexneri with biomarker quercetin was also performed. PGE at 200 mg/kg followed by quercetin depicted maximum antidiarrhoeal potential, which was confirmed through diarrhoea score and % protection, while PGE at 400 mg/kg showed similar effect to PGE 200 mg/kg thus, the later may have ceiling effect. PGE and quercetin also significantly reduced the density of Shigella fiexneri in stools, water content of stools and restored the alterations observed in blood parameters, antioxidant status and pro-inflammatory cytokines (IL-6 and TNF-alpha) expression. These parameters contributed in normalization of electrolyte balance, reactivation of Na+/K+ ATPase activity and repairing of epithelial tissue damage, confirmed through histopathology. Docking simulation studies revealed the role of quercetin in inactivating the protease activity of SepA, a protein secreted by Shigella, which disrupts epithelial barrier integrity during infection and also manages its signal production. Thus, the overall results confirmed the role of quercetin as a major biomarker for the observed antidiarrhoeal potential of P. guajava against Shigella jiexneri induced infectious diarrhoea.
机译:植物Psidium Guajava L.(myrtaceae)的叶子传统上用于治疗各种胃肠疾病,包括腹泻,并且还据报道其在各种化学诱导的腹泻模型上的有效的抗神经性活性。我们目前的研究目的是评估植物Psidium Guajava(PGE)的叶子提取物的效力以及其主要生物标志物槲皮素对抗志贺氏菌诱导的传染性腹泻亚慢性模型。 PGE在100,200和400 mg / kg,p.o.和槲皮素在50 mg / kg,p.o.施用于Shigella Flexeri诱导的腹泻大鼠5天,并在第1天,第3和第5天进行各种行为参数。随后是对粪便水含量的评估,植物柔菌氏菌的密度和粪便和血液参数检查。处理后,对大鼠的结肠和小肠进行解剖并进行生物化学估计,细胞因子分析,抗氧化剂评价,离子浓度测定,Na + / K + -ATP酶活性和组织病理学。还进行了对来自生物标志物槲皮素的Shigella Flexneri的分泌细胞外蛋白A(SEPA)晶体结构的分子对接研究。 PGE以200mg / kg,然后是槲皮素描绘了最大的反症素,通过腹泻评分和%保护证实,而PGE为400 mg / kg显示出类似的效果以PGE 200 mg / kg,因此可能具有天花板效应。 PGE和槲皮素还显着降低了粪菌Fiexneri的粪便密度,粪便含水量,并恢复了血液参数,抗氧化状态和促炎细胞因子(IL-6和TNF-α)表达中观察到的改变。这些参数促进了电解质平衡的标准化,通过组织病理学证实了Na + / K + ATP酶活性和上皮组织损伤的重新激活。对接模拟研究揭示了槲皮素在失活的作用在Sepa的蛋白酶活性中,志贺氏细胞分泌的蛋白质,这在感染期间破坏上皮阻挡完整性,并且还可以管理其信号产生。因此,总体结果证实了槲皮素作为主要生物标志物的作用,用于观察到对富氏氏菌的抗病群岛诱导的感染性腹泻的抗神鹰潜力的主要生物标志物。

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