College of Biology Pharmacy and Food Engineering, Shangluo University, Shangluo, China.
Shaanxi Qinling Industrial Technology Research Institute of Special Biological Resources Co. Ltd., Shangluo, China.
Front Immunol. 2024 May 21;15:1405084. doi: 10.3389/fimmu.2024.1405084. eCollection 2024.
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.
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.
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.
Collectively, our findings indicated that cymaroside alleviates intestinal inflammatory injury by inhibiting the activation of NLRP3 inflammasome in MTX-induced rats.
山柰酚苷具有多种生物学特性，包括抗炎、抗病毒、抗肿瘤和心脏保护作用。然而，其在甲氨蝶呤（MTX）诱导的肠道炎症中的作用仍知之甚少。因此，我们研究了山柰酚苷对 MTX 诱导的肠道炎症的影响及其潜在机制。
为了评估山柰酚苷对肠道炎症的保护潜力，将 Sprague-Dawley 大鼠用 7mg/kg MTX 处理 3 天，然后用不同剂量（10、20 或 40mg/kg）的山柰酚苷进行治疗。进行组织病理学评估和炎症介质测量，以阐明 NLRP3 炎性体在缓解肠道炎症中的作用。
给予 7mg/kg MTX 导致大鼠每日食物摄入量减少、体重减轻和疾病活动指数升高。相反，用 20 或 40mg/kg 的山柰酚苷治疗可改善体重和每日食物摄入量的减少，并抑制 MTX 诱导的疾病活动指数升高。值得注意的是，用 20 或 40mg/kg 的山柰酚苷治疗可减轻炎性细胞浸润、增加杯状细胞数量、降低 MTX 诱导大鼠血清肿瘤坏死因子-α、白细胞介素（IL）-1β 和 IL-18 水平以及肠道中 CD68 阳性细胞率。此外，山柰酚苷下调 MTX 诱导大鼠中 NLRP3、切割的半胱天冬酶 1 和切割的 IL-1β 的表达水平。
总的来说，我们的研究结果表明，山柰酚苷通过抑制 MTX 诱导大鼠中 NLRP3 炎性体的激活来减轻肠道炎症性损伤。
