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Efficacy of Compound Herbal Medicine Tong-Xie-Yao-Fang for Acute Radiation Enteritis and Its Potential Mechanisms: Evidence from Transcriptome Analysis.

ABSTRACT: Acute radiation enteritis (ARE) is a common complication with radiotherapy for pelvic and abdominal malignancy. This research is designed to investigate the efficacy of Tong-Xie-Yao-Fang (TXYF) on ARE and to explore the underlying mechanisms by microarray analysis. The ARE rat model was established by a single abdominal irradiation with a gamma-ray dose of 10 Gy. Next, the ARE rats were treated with distilled water, TXYF, and glutamine by gavage for 7 consecutive days according to the scheduled groups. For each group, the jejunal tissue was taken at 6 h after gastric lavage. The morphology of intestinal tissue was observed by hematoxylin and eosin (H&E) stain under a light microscope. The height of the villus and the thickness of the whole layer of the TXYF-treated groups were significantly ameliorative than that of the model control group. The transcriptome analysis was produced using the Agilent SurePrint G3 Rat GE V2.0 microarray. A total of 90 differentially expressed genes (DEGs), including 48 upregulated genes and 42 downregulated genes, were identified by microarray and bioinformatics analysis. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) were conducted to explore the possible mechanisms of DEGs taking part in the TXYF-mediated therapeutic process for ARE. In conclusion, we reveal that TXYF has a protective effect on the intestinal tissue of rats with ARE and summarize several DEGs, suggesting the possible mechanisms of TXYF-mediated efficacy for ARE.

SUBMITTER: Yang C

PROVIDER: S-EPMC7725573 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Efficacy of Compound Herbal Medicine Tong-Xie-Yao-Fang for Acute Radiation Enteritis and Its Potential Mechanisms: Evidence from Transcriptome Analysis.

Yang Cheng C Yang Jiayue J Xia Min M Wei Jianhong J Jiao Yang Y Zhan Qiang Q

BioMed research international 20201201

Acute radiation enteritis (ARE) is a common complication with radiotherapy for pelvic and abdominal malignancy. This research is designed to investigate the efficacy of Tong-Xie-Yao-Fang (TXYF) on ARE and to explore the underlying mechanisms by microarray analysis. The ARE rat model was established by a single abdominal irradiation with a gamma-ray dose of 10 Gy. Next, the ARE rats were treated with distilled water, TXYF, and glutamine by gavage for 7 consecutive days according to the scheduled ...[more]

PMID: 33344641

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Project description:BackgroundIrritable bowel syndrome (IBS) is one kind of common functional bowel disease with obscure pathogenesis, and exploration about whole transcriptome profiling in IBS-D is still negligible. Conventional medications have limited effects, which makes focus shifted to traditional Chinese medicine (TCM). Tong-Xie-Yao-Fang, as a classic herbal formula in TCM, is pretty effective and safe for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), but the underlying therapeutic mechanism remains unknown. We aim to verify the efficacy and safety of TXYF granule (the formula particles mixed together) in IBS-D and elucidate the gene-level mechanism of IBS-D and therapeutic targets of TXYF granule based on whole transcriptome analysis.Methods/designThis is a randomized, double-blind, and placebo-controlled clinical trial consisting of 2 weeks of run-in period, 12 weeks of treatment period, and 8 weeks of follow-up period. We will enroll 120 participants with IBS-D, who will be randomly assigned to the TXYF granule group and the placebo group, and recruit additional 10 healthy individuals as controls for mechanistic outcome. The two groups respectively take TXYF granule or placebo orally for treatment. The primary outcome is the response rate of IBS-Symptom Severity Score (IBS-SSS). The secondary outcomes include adequate relief (AR), IBS-Quality of Life Questionnaire (IBS-QOL), and long-term efficacy. Mechanistic outcome is the whole transcriptome profiling of the intestinal mucosae from IBS participants before and after the treatment and healthy individuals.DiscussionThis trial will prove the effectiveness and safety of TXYF granule with high-quality evidence and provide a penetrating and comprehensive perspective on the molecular mechanism of IBS-D by whole transcriptome analysis, which makes us pinpoint specific biomarkers of IBS-D and therapeutic targets of TXYF.Trial registrationChinese Clinical Trial Registry ChiCTR-IOR-1900021785 . Registered on 9 March 2019.

Project description:BackgroundPsoriasis is a chronic autoimmune disease. At present, it is very difficult to treat; however, clinical trials have shown that the traditional Chinese medicine (TCM) treatment of psoriasis has certain advantages. The Chinese herbal medicine Jia Wei Jing Xie Yin (JWJXY) has its origins in Jing Xie Yin, a medicine created by the TCM doctor Wu Jun. Previous studies have shown that JWJXY has good clinical efficacy for patients with blood-heat type psoriasis, but its mechanism is unknown.MethodsThis paper aimed to further study the therapeutic effect and mechanism of JWJXY on an imiquimod (IMQ)-induced, psoriasis-like mouse model (0.4 mL, i.g., 6 days). The histopathological skin changes were observed by hematoxylin and eosin (HE) staining, the infiltration of cluster of differentiation 11B (CD11b) and cluster of differentiation 4 (CD4) cells was observed by immunohistochemistry, lymphocyte subsets were detected by flow cytometry, T helper (Th)17 cell expression was perceived by flow cytometry, and Th17 cell-related gene expression was detected by real-time quantitative polymerase chain reaction (qPCR).ResultsJWJXY significantly reduced the skin thickness of the IMQ-induced model mouse. Compared with that in the vehicle group, the skin tissue of the mice in the JWJXY group showed significantly reduced infiltration of CD11b+ and CD4+ T cells. Flow cytometry results showed that JWJXY decreased the proportion of B220 and Th17 cells in the spleen tissue of the mice. There was no significant effect on the proportion of Th1 or regulatory T cells (Treg) cells. Compared with that in the vehicle group, the skin tissue of the mice in the JWJXY group showed significantly decreased expression of interleukin-17A (IL-17A), IL-17F, retinoic acid receptor-related orphan receptor gamma t (RORγt), IL-1β, interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α) messenger RNA (mRNA).ConclusionsThe study confirmed the therapeutic effect of JWJXY on psoriasis. Its mechanism of action might be to inhibit the Th17 cell response but not the Th1 and Treg response.

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.

Dataset Information

Efficacy of Compound Herbal Medicine Tong-Xie-Yao-Fang for Acute Radiation Enteritis and Its Potential Mechanisms: Evidence from Transcriptome Analysis.

Publications

Efficacy of Compound Herbal Medicine Tong-Xie-Yao-Fang for Acute Radiation Enteritis and Its Potential Mechanisms: Evidence from Transcriptome Analysis.

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