Zuojin Pill ameliorates inflammation in indomethacin-induced gastric injury via inhibition of MAPK pathway,Journal of Ethnopharmacology

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Zuojin Pill ameliorates inflammation in indomethacin-induced gastric injury via inhibition of MAPK pathway
Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2021-04-06 , DOI: 10.1016/j.jep.2021.114103
Ying Wei ₁ , Ruilin Wang ₂ , Sichen Ren ₁ , Xia Liu ₃ , Manyi Jing ₃ , Ruisheng Li ₄ , Yuling Tong ₁ , Jianxia Wen ₁ , Tao Yang ₁ , Jian Wang ₅ , Yanling Zhao ₁

Affiliation

Ethnopharmacological relevance

Zuojin Pill (ZJP) has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. But its effect on non-steroidal anti-inflammatory drugs (NSAIDs) induced gastric injury (GI) is still uncharted.

Aim of the study

This study aims to investigate the therapeutic effect and molecular mechanism of ZJP on indomethacin (IDO) induced gastric injury.

Materials and methods

GI was induced in rat by oral administration of 5 mg/kg IDO. Then the rats were treated with ZJP (1.26, 2.52, 5.04 g/kg, ig). The changes of food intake, body weight, gastric pH and general state observation were carried out to determine the improvement of ZJP in IDO-induced GI: HE staining and AB-PAS staining was analyzed to characterize the thickness of gastric mucosa and micro mucosal injury; in order to elucidate the effect of ZJP on IDO-induced inflammatory injury, the inflammatory infiltration of gastric tissue was observed by MPO immunohistochemical method, and the contents of TNF-α, IL-6 and IL-10 were measured. Furthermore, the regulatory mechanism of ZJP in treating IDO-induced GI was predicted with the help of network pharmacology, and the expression levels of key proteins ERK, p-ERK, P38, p-P38, JNK, p-JNK were determined to elucidate the molecular mechanism of ZJP.

Results

Current data strongly demonstrated that ZJP alleviated food intake reduction, weight loss and gastric injury caused by IDO and made gastric pH and mucosal thickness return to normal. In addition, ZJP could reduce the level of MPO to alleviate the inflammatory infiltration of gastric tissue. Simultaneously, ZJP could down regulate the expression of TNF-α and IL-6 and up regulate the expression of IL-10 to reduce the damage caused by inflammatory, and create a healing environment. Furthermore, ZJP could significantly inhibit the phosphorylation of ERK, p38 and JNK, which leaded to the increase of inflammatory factors and the damage of gastric mucosa.

Conclusion

ZJP improved local inflammation by inhibiting MAPK signaling pathway, and had a good therapeutic effect on IDO-induced GI. This study has reference significance for the study of ZJP in the prevention and treatment of NSAID induced gastric injury. In addition, ZJP may be a new treatment option for the prevention and treatment of NSAID induced gastric disease.

中文翻译：

左金丸通过抑制MAPK通路改善吲哚美辛胃损伤炎症

民族药理学相关性

左金丸（ZJP）自古以来就是我国治疗胃肠疾病的经典方剂。但其对非甾体抗炎药（NSAID）引起的胃损伤（GI）的作用仍不清楚。

研究目的

本研究旨在探讨ZJP对吲哚美辛（IDO）所致胃损伤的治疗作用及分子机制。

材料和方法

通过口服5mg/kg IDO诱导大鼠GI。然后用ZJP（1.26、2.52、5.04 g/kg，ig）治疗大鼠。通过食物摄入量、体重、胃pH值的变化和一般状态观察来确定ZJP对IDO诱导的GI的改善作用：分析HE染色和AB-PAS染色来表征胃粘膜厚度和微粘膜损伤;为了阐明ZJP对IDO所致炎症损伤的影响,采用MPO免疫组化法观察胃组织炎症浸润情况,并测定TNF-α、IL-6、IL-10的含量。此外，利用网络药理学预测ZJP治疗IDO诱导GI的调节机制，并测定关键蛋白ERK、p-ERK、P38、p-P38、JNK、p-JNK的表达水平以阐明ZJP治疗IDO诱导GI的调节机制。 ZJP的分子机制。

结果

目前的数据有力地表明，ZJP缓解了IDO引起的食物摄入减少、体重减轻和胃损伤，并使胃pH和粘膜厚度恢复正常。此外，ZJP还可降低MPO水平，减轻胃组织炎症浸润。同时，ZJP可以下调TNF-α和IL-6的表达，上调IL-10的表达，以减轻炎症造成的损伤，创造愈合环境。此外，ZJP还可显着抑制ERK、p38和JNK的磷酸化，从而导致炎症因子增加和胃粘膜损伤。