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Effects of Thymoquinone on radiation enteritis in mice.

ABSTRACT: Radiation enteritis is an old but emerging question induced by the application of radiation. However, no effective drugs for radiation enteritis in clinic. In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. After exposure to irradiation, TQ-treated improved the irradiated mice survival rate, ameliorated intestinal injury and increased the numbers of intestinal crypts. Furthermore, Lgr5⁺ ISCs and their daughter cells, including Vil1⁺ enterocytes, Ki67⁺ cells and lysozyme⁺ Paneth cells, were all significantly increased with TQ treatment. In addition, P53, γH2AX, caspase8, caspase9 and caspase3 expression were all reduced by TQ. Our data showed that TQ modulated DNA damages and decreased the apoptosis in the small intestine. TQ might be used for radiation enteritis treatment.

SUBMITTER: Hou Q

PROVIDER: S-EPMC6181979 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Effects of Thymoquinone on radiation enteritis in mice.

Hou Qinlian Q Liu Linlin L Dong Yinping Y Wu Jing J Du Liqing L Dong Hui H Li Deguan D

Scientific reports 20181011 1

Radiation enteritis is an old but emerging question induced by the application of radiation. However, no effective drugs for radiation enteritis in clinic. In this study, we found that thymoquinone (TQ) could mitigate intestinal damages induced by irradiation. After exposure to irradiation, TQ-treated improved the irradiated mice survival rate, ameliorated intestinal injury and increased the numbers of intestinal crypts. Furthermore, Lgr5<sup>+</sup> ISCs and their daughter cells, including Vil1 ...[more]

PMID: 30310156

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Project description:BackgroundClinical studies have shown that Compound Kushen Injection (CKI) can alleviate the inflammatory symptoms of radiation enteritis. However, the mechanism of action remains unclear. The aim of this study was to explore the possible targets and mechanisms of CKI in the treatment of radiation enteritis.MethodsNetwork pharmacology was used to predict the potential targets of CKI for the treatment of radiation enteritis, and GO and KEGG enrichment analyses were subsequently performed. SD rats were randomly divided into one of the following groups: control, model, CB1 agonist, CKI and CKI + CB1 antagonist. Except for the control group, the remaining groups were irradiated the abdomen with 6 MV medical high-energy x-ray linear accelerator to establish the model of radiation enteritis. After one week of treatment, the expression of inflammatory factors, SOD and GSH-Px activities, MDA, ROS and NO contents; NF-κB signaling activation and the expression of NOX4, CB1, p38 MAPK, p-p38 MAPK in the ileal tissues of rats were examined to assess the therapeutic effect and possible mechanism of CKI on radiation enteritis, respectively.ResultsAccording to network pharmacology, CB1 might be a target of CKI. GO and KEGG enrichment analyses revealed that CKI was significantly enriched in analgesic, endocannabinoid and inflammatory pathways. In the rat model, Compared with that in the radiotherapy group, the extent of ileal injury was significantly improved in the CKI group compared to the control group. In addition, the infiltration of CD68 and CD16b was significantly reduced, and the expression of MCP1, TNF-α, IL-1β and IL-10 was significantly decreased. In addition, the activities of SOD and GSH-Px were increased, and the activities of MDA, ROS and NO were decreased. The CKI group also showed inhibition of NF-κB signaling and a significant decrease in the expression of NOX4, CB1 and p-p38 MAPK/p38 MAPK. The use of a CB1 agonist could also alleviate radiation enteritis, whereas the addition of a CB1 antagonist could interfere with the ameliorative effect of CKI on radiation enteritis.ConclusionsCKI might exert an anti-radiation enteritis effect by targeting the cannabinoid receptor 1.

Project description:ObjectivesTo perform a meta-analysis and network analysis identification to evaluate the efficacy, safety, and potential mechanisms of modified Baitouweng decoction (mBTWD) in the treatment of radiation enteritis.MethodsWe searched PubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang Databases, SionMed, and Chinese Scientific Journals Database to collect the randomized controlled trials (RCTs) of mBTWD treating radiation enteritis. Rev.Man 5.3 and Stata 14.0 software are employed for meta-analysis. The GRADE online tool is used to evaluate the quality of evidence. Network analysis and molecular docking approach are applied to predict the potential targets and ingredients of representative drugs in mBTWD for the treatment of radiation enteritis.ResultsSeventeen studies are eventually included, covering a total of 1611 patients: (1) The clinical efficacy is significantly higher in mBTWD groups than in control groups (RR = 1.24, 95% CI (1.17, 1.32), P < 0.00001). (2) mBTWD has certain advantages in improving TCM syndromes (MD = -3.41, P < 0.00001). (3) mBTWD has a certain positive effect on the improvement of intestinal signs and symptoms (RR = 1.23, P=0.0001; OR = 3.51, P < 0.00001). (4) Indexes including CRP, KPS, and OB, are better in mBTWD groups than in control groups (P < 0.00001, P=0.002, P=0.03), but the credibility is downgraded for a small sample size. Adverse events and recurrence rates require further confirmation with larger sample sizes. (5) Univariate meta-regression for clinical efficacy shows none of the coefficients are significantly associated with the estimated risk ratio. The clinical efficacy overestimates about 4.9% from publication bias. The quality of the included studies is low according to GRADE evidence. (6) Quercetin, isorhamnetin, and beta-sitosterol are the main ingredients from representative drugs in mBTWD and its key targets are MYC, TP53, and MAPK14/MAPK1.ConclusionsmBTWD may be effective in the treatment of radiation enteritis, but its long-term benefits, safety, and molecular mechanisms remain unclear due to the poor quality of the evidence. Larger sample sizes, high-quality studies, and basic research are essential in the future.

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Effects of Thymoquinone on radiation enteritis in mice.

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Effects of Thymoquinone on radiation enteritis in mice.

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