关键词: NLRP3 cleaved IL-1β cleaved caspase 1 cynaroside intestinal inflammation methotrexate

Mesh : Animals NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Inflammasomes / metabolism Methotrexate Rats Rats, Sprague-Dawley Male Enteritis / chemically induced drug therapy Anti-Inflammatory Agents / pharmacology therapeutic use Cytokines / metabolism Glucosides / pharmacology therapeutic use Disease Models, Animal

来  源:   DOI:10.3389/fimmu.2024.1405084   PDF(Pubmed)

Abstract:
UNASSIGNED: Cynaroside exhibits various biological properties, including anti-inflammatory, antiviral, antitumor, and cardioprotective effects. However, its involvement in methotrexate (MTX)-induced intestinal inflammation remains inadequately understood. Thus, we investigated the impact of cynaroside on MTX-induced intestinal inflammation and its potential mechanisms.
UNASSIGNED: To assess the protective potential of cynaroside against intestinal inflammation, Sprague-Dawley rats were subjected to a regimen of 7 mg/kg MTX for 3 days, followed by treatment with cynaroside at varying doses (10, 20, or 40 mg/kg). Histopathological evaluations were conducted alongside measurements of inflammatory mediators to elucidate the involvement of the NLRP3 inflammasome in alleviating intestinal inflammation.
UNASSIGNED: Administration of 7 mg/kg MTX resulted in decreased daily food intake, increased weight loss, and elevated disease activity index in rats. Conversely, treatment with cynaroside at 20 or 40 mg/kg ameliorated the reductions in body weight and daily food intake and suppressed the MTX-induced elevation in the disease activity index. Notably, cynaroside administration at 20 or 40 mg/kg attenuated inflammatory cell infiltration, augmented goblet cell numbers and lowered serum levels of tumor necrosis factor-α, interleukin (IL)-1β, and IL-18, as well as the CD68-positive cell rate in the intestines of MTX-induced rats. Furthermore, cynaroside downregulated the expression levels of NLRP3, cleaved caspase 1, and cleaved IL-1β in MTX-induced rats.
UNASSIGNED: Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
摘要:
Cynaroside表现出各种生物学特性,包括消炎药,抗病毒,抗肿瘤,和心脏保护作用。然而,其与甲氨蝶呤(MTX)诱导的肠道炎症的关系尚不清楚.因此,我们研究了西纳苷对MTX诱导的肠道炎症的影响及其潜在机制.
为了评估西纳苷对肠道炎症的保护潜力,Sprague-Dawley大鼠接受7mg/kgMTX的方案3天,然后用不同剂量(10、20或40mg/kg)的西纳苷治疗。组织病理学评估与炎症介质的测量一起进行,以阐明NLRP3炎症小体在减轻肠道炎症中的参与。
服用7mg/kg的MTX导致每日食物摄入量减少,增加体重减轻,大鼠疾病活动指数升高。相反,以20或40mg/kg的西纳苷治疗可改善体重和每日食物摄入量的降低,并抑制MTX引起的疾病活动指数升高。值得注意的是,以20或40mg/kg的剂量施用西纳苷可减轻炎症细胞浸润,杯状细胞数量增加,血清肿瘤坏死因子-α水平降低,白细胞介素(IL)-1β,和IL-18,以及MTX诱导的大鼠肠道中CD68阳性细胞率。此外,在MTX诱导的大鼠中,西纳苷下调NLRP3,caspase1裂解和IL-1β裂解的表达水平。
集体,研究结果表明,在MTX诱导的大鼠中,cymaroside通过抑制NLRP3炎症小体的激活,可以减轻肠道炎症损伤。
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