Pure Total Flavonoids From Citrus Protect Against Nonsteroidal Anti-inflammatory Drug-Induced Small Intestine Injury by Promoting Autophagy in vivo and in vitro.
Pure Total Flavonoids From Citrus Protect Against Nonsteroidal Anti-inflammatory Drug-Induced Small Intestine Injury by Promoting Autophagy in vivo and in vitro.
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通过促进体内和体外自噬，来自柑橘的纯总类黄酮可以预防非甾体类抗炎药诱导的小肠损伤。
DOI：
10.3389/fphar.2021.622744
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发表时间：
2021
影响因子：
5.6
通讯作者：
Zhang S
中科院分区：
文献类型：
--
作者：
Chen S;Jiang J;Chao G;Hong X;Cao H;Zhang S
小肠损伤是非甾体抗炎药（NSAID）的一种不良反应，迫切需要解决其安全应用。尽管柑橘类黄酮（PTFC）已被用于治疗消化系统疾病，但其对小肠损伤的影响及其潜在的作用机制仍不清楚。本研究旨在研究自噬在体内和体外NSAID（双氯芬酸）诱导的肠损伤机制中的潜在作用，并证明PTFC对NSAID诱导的小肠疾病的保护作用。qRT-PCR、Western blotting和免疫组化结果显示，与对照组相比，NSAID诱导的小肠损伤大鼠和diclazac-treated IEC-6细胞中自噬相关5（Atg 5）、轻链3（LC 3）-II和紧密连接（TJ）蛋白ZO-1、claudin-1和occludin的表达水平降低。在PTFC组中，Atg 5和LC 3-II表达，TJ蛋白表达以及LC 3-II/LC 3-I比值增加。此外，PTFC促进自噬在体内和体外的机制进行了评估，通过蛋白质印迹。与对照组相比，模型组p-PI 3 K和p-Akt表达水平升高，PTFC组p-PI 3 K和p-Akt表达水平降低。用PI 3 K抑制剂处理后，IEC-6细胞的自噬上调，并且PTFC处理后的上调显著更多，表明PTFC通过PI 3 K/Akt信号通路促进自噬。总之，PTFC通过促进自噬保护肠屏障完整性，这表明其作为NSAID诱导的小肠损伤的治疗候选物的潜力。
Small intestine injury is an adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) that urgently needs to be addressed for their safe application. Although pure total flavonoids from citrus (PTFC) have been marketed for the treatment of digestive diseases, their effects on small intestine injury and the underlying mechanism of action remain unknown. This study aimed to investigate the potential role of autophagy in the mechanism of NSAID (diclofenac)-induced intestinal injury in vivo and in vitro and to demonstrate the protective effects of PTFC against NSAID-induced small intestine disease. The results of qRT-PCR, western blotting, and immunohistochemistry showed that the expression levels of autophagy-related 5 (Atg5), light chain 3 (LC3)-II, and tight junction (TJ) proteins ZO-1, claudin-1, and occludin were decreased in rats with NSAID-induced small intestine injury and diclofenac-treated IEC-6 cells compared with the control groups. In the PTFC group, Atg5 and LC3-II expression, TJ protein expression, and the LC3-II/LC3-I ratio increased. Furthermore, the mechanism by which PTFC promotes autophagy in vivo and in vitro was evaluated by western blotting. Expression levels of p-PI3K and p-Akt increased in the intestine disease-induced rat model group compared with the control, but decreased in the PTFC group. Autophagy of IEC-6 cells was upregulated after treatment with a PI3K inhibitor, and the upregulation was significantly more after PTFC treatment, suggesting PTFC promoted autophagy through the PI3K/Akt signaling pathway. In conclusion, PTFC protected intestinal barrier integrity by promoting autophagy, which demonstrates its potential as a therapeutic candidate for NSAID-induced small intestine injury.
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影响因子：
5.6
作者：
Heydarpour F;Sajadimajd S;Mirzarazi E;Haratipour P;Joshi T;Farzaei MH;Khan H;Echeverría J
通讯作者：
Echeverría J
影响因子：
7
作者：
Guirro, Maria;Gual-Grau, Andreu;Mayneris-Perxachs, Jordi
通讯作者：
Mayneris-Perxachs, Jordi
影响因子：
7.9
作者：
Jiang Jianping;Yan Li;Efferth, Thomas
通讯作者：
Efferth, Thomas
影响因子：
7.5
作者：
Li, Zhiling;Gao, Ming;Yang, Mingshi
通讯作者：
Yang, Mingshi
影响因子：
30.8
作者：
Ravikumar, B;Vacher, C;Rubinsztein, DC
通讯作者：
Rubinsztein, DC