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胃肠安丸对大剂量5-氟尿嘧啶诱导的小鼠肠道黏膜炎的保护作用及潜在机制

Protective effect and potential mechanisms of Wei-Chang-An pill on high-dose 5-fluorouracil-induced intestinal mucositis in mice.

作者信息

Chen Yuling, Zheng Hong, Zhang Jingze, Wang Lei, Jin Zhaoxiang, Gao Wenyuan

机构信息

Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China.

School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China.

出版信息

J Ethnopharmacol. 2016 Aug 22;190:200-11. doi: 10.1016/j.jep.2016.05.057. Epub 2016 May 27.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU).

AIM OF THE STUDY

To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms.

MATERIALS AND METHODS

The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice.

RESULTS

Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances.

CONCLUSIONS

These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy.

摘要

民族药理学相关性

胃肠安丸(WCA丸)是一种传统中药制剂,在消化系统疾病中具有潜在的抗炎优势和显著的胃肠调节作用,这可能使其成为治疗5-氟尿嘧啶(5-FU)诱导的肠道黏膜炎(IM)的有前景的候选药物。

研究目的

分析胃肠安丸甲醇提取物(WCA提取物)的生物活性成分,并研究其对5-FU诱导的IM的影响及潜在机制。

材料与方法

采用超高效液相色谱-四极杆-飞行时间质谱法分析大鼠给予WCA提取物后的血清生物活性成分。在小鼠中,用5-FU诱导IM,并在给药期间测量身体表现。分别通过苏木精和伊红染色、免疫组织化学染色以及细胞因子酶联免疫吸附测定试验,对一半小鼠的组织学、回肠和血浆中炎症细胞因子的表达进行评估。此外,在另一半5-FU诱导的小鼠中进一步检测胃排空(GE)和胃肠转运(GIT)。

结果

鉴定或初步表征了22种化合物。用WCA提取物治疗后,5-FU诱导的IM得到显著改善,表现为体重减轻减少、严重腹泻缓解、GE和GIT受到抑制。进一步评估证实,WCA提取物促进了肠黏膜的恢复,评估了肠上皮细胞增殖活性,维持了紧密连接的完整性,并改善了炎症紊乱。

结论

这些结果表明,WCA提取物通过调节肠道内稳态的多个作用位点,促进了5-FU诱导的IM中肠道功能的恢复。因此,胃肠安丸可能是预防癌症化疗期间IM的有前景的治疗候选药物。

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