莪术制剂的抗炎作用可改善 5-氟尿嘧啶诱导的小鼠肠道黏膜炎。

Anti-inflammatory effects of Radix Aucklandiae herbal preparation ameliorate intestinal mucositis induced by 5-fluorouracil in mice.

机构信息

School of Nursing, National Taipei University of Nursing and Health Sciences, Taipei, 112, Taiwan; Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; Graduate Institute of Acupuncture Science, China Medical University, Taichung, 404, Taiwan.

Institute of Traditional Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan; Department of Radiation Oncology, Far Eastern Memorial Hospital, Taipei, 220, Taiwan; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, 112, Taiwan.

出版信息

J Ethnopharmacol. 2021 May 10;271:113912. doi: 10.1016/j.jep.2021.113912. Epub 2021 Feb 7.

DOI:10.1016/j.jep.2021.113912

PMID:33567307

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

5-Fluorouracil (5-FU) is a chemotherapy agent that is widely used in clinical oncologic practice. However, intestinal mucositis is the most frequently occurring side effect of cancer therapy with 5-FU. Based on a literature survey, Radix Aucklandiae herbal preparation potentially ameliorates intestinal mucositis in 5-FU-treated mice.

AIM OF THE STUDY

The aim of this study was to investigate the inflammation and gastrointestinal regulation of intestinal mucositis induced by 5-FU, including the intestinal morphology, as well as the reduction in food intake, body weight loss, and diarrhea.

MATERIALS AND METHODS

Intestinal mucositis was induced in mice by 5-FU (30 mg/kg, i.p., for 5 consecutive days). The dose-dependent Radix Aucklandiae herbal preparation (0.3, 1, and 3 g/kg/day, p.o.), loperamide (3 mg/kg/day, p.o.) or celecoxib (40 mg/kg/day, p.o.) was concurrently administered until the 7th day. Physical status observation, diarrhea assessment, serum proinflammatory cytokine levels, intestinal villus height and crypt depth, and total goblet cells from tissues were assessed.

RESULTS

The dosage regimen of 5-FU administration caused severe intestinal mucositis in mice, including damage to the intestinal morphology, accompanied by a reduction in food intake, body weight loss, and diarrhea. The high-dose Radix Aucklandiae herbal preparation significantly relieves 5-FU-induced intestinal mucositis by enhancing proliferative activity in epithelial crypts; improving anepithymia, body weight loss, and diarrhea; and displaying protective effects on goblet cells in intestinal mucosal epithelia. Activation of NF-κB in the intestinal mucositis model was also suppressed by the Radix Aucklandiae herbal preparation, suggesting that it is a potent inhibitor of NF-κB and proinflammatory cytokines, such as IL-1β, IL-6, TNF-α, and COX-2.

CONCLUSIONS

Our data support the conclusion that the Radix Aucklandiae herbal preparation could effectively ameliorate 5-FU-induced gastrointestinal toxicity and be applied clinically for the prevention of intestinal mucositis during chemotherapy.

摘要

民族药理学相关性

5-氟尿嘧啶（5-FU）是一种广泛应用于临床肿瘤学实践的化疗药物。然而，5-FU 治疗的癌症患者最常见的副作用是肠道粘膜炎。基于文献综述，白芍草药制剂可能改善 5-FU 治疗的小鼠肠道粘膜炎。

研究目的

本研究旨在探讨 5-FU 诱导的肠道粘膜炎的炎症和胃肠调节，包括肠道形态，以及减少食物摄入、体重减轻和腹泻。

材料和方法

用 5-FU（腹腔注射，30mg/kg，连续 5 天）诱导小鼠肠道粘膜炎。同时给予剂量依赖性白芍草药制剂（0.3、1 和 3g/kg/天，口服）、洛哌丁胺（3mg/kg/天，口服）或塞来昔布（40mg/kg/天，口服）直至第 7 天。观察生理状态，评估腹泻，检测血清促炎细胞因子水平，评估肠道绒毛高度和隐窝深度，以及组织总杯状细胞。

结果

5-FU 给药方案导致小鼠严重的肠道粘膜炎，包括肠道形态损伤，伴有食物摄入减少、体重减轻和腹泻。白芍高剂量制剂通过增强上皮隐窝的增殖活性，显著缓解 5-FU 诱导的肠道粘膜炎；改善上皮缺失、体重减轻和腹泻；并对肠道黏膜上皮中的杯状细胞具有保护作用。肠道粘膜炎模型中 NF-κB 的激活也被白芍制剂抑制，表明其是 NF-κB 和促炎细胞因子（如 IL-1β、IL-6、TNF-α和 COX-2）的有效抑制剂。