scholarly journals Integrating Pharmacology and Microbial Network Analysis with Experimental Validation to Reveal the Mechanism of Composite Sophora Colon-Soluble Capsule against Ulcerative Colitis

2020 ◽  
Vol 2020 ◽  
pp. 1-16 ◽  
Author(s):  
Yuxuan Ding ◽  
Mingjun Chen ◽  
Qiying Wang ◽  
Lu Gao ◽  
Yang Feng ◽  
...  

Ulcerative colitis (UC) has multifactorial pathogenesis that acts synergistically, such as immune system dysregulation and expansion of infectious gut microbiota. Therefore, a multicomponent treatment derived from Chinese herbal medicine that interacts with multiple targets synergistically is needed. Composite sophora colon-soluble capsule (CSCC) is a Chinese herbal formula that has shown therapeutic efficacy against UC in randomized clinical trials. However, its bioactive components and potential target genes against UC remain unclear. Here, we used a network pharmacology approach to detect component-target-pathway interactions of CSCC against UC. A total of 29 gene targets, 91 bioactive components, and 20 enriched pathways of CSCC were identified. The IL-17 signaling pathway activated by infectious gastrointestinal microbes and predicted by the network analysis to be a major pathway modulated by CSCC against UC was studied in a dextran sulfate sodium-induced colitis model. CSCC showed remarkable efficacy against UC with respect to the attenuation of colon length, body weight loss, and disease activity index through gut microbiota recovery and intestinal immune homeostasis. The rectal administration of CSCC reduced the numbers of Th17 cells isolated from both mesenteric lymph nodes and lamina propria mononuclear cells and the levels of IL-17A, IL-6, IL-1β, and TNF-α. Additionally, the percentage of Treg cells and the levels of their hallmark cytokines were upregulated. Rectal administration of CSCC led to microbiota regulation with a significant correlation between suppression of Verrucomicrobiaceae and Ruminococcaceae, as well as the elevation of Lactobacillaceae, and CSCC administration via microbiome correlation heatmaps and cooccurrence network analysis at multiple time points. Thus, our study presents an effective herbal formula, CSCC, for UC treatment and explores its components and mechanisms of efficacy through the examination of gut microbiota and hallmark cytokines in the IL-17 pathway.

2021 ◽  
Author(s):  
Jing Yang ◽  
Chao-Tao Tang ◽  
Ruiri Jin ◽  
Bixia Liu ◽  
Peng Wang ◽  
...  

Abstract Huanglian jiedu decoction (HLJDD) is a heat-clearing and detoxifying agent composed of four kinds of Chinese herbal medicine. Previous studies have shown that HLJDD can improve the inflammatory response of ulcerative colitis (UC) and maintain intestinal barrier function. However, its molecular mechanism is not completely clear. In this study, we verified the bioactive components (BCI) and potential targets of HLJDD in the treatment of UC by means of network pharmacology and molecular docking, and constructed the pharmacological network and PPI network. Then the core genes were enriched by GO and KEGG. Finally, the bioactive components were docked with the key targets to verify the binding ability between them. A total of 54 active components related to UC were identified. Ten genes are considered to be very important to PPI network. Functional analysis showed that these target genes were mainly involved in the regulation of cell response to different stimuli, IL-17 signal pathway and TNF signal pathway. The results of molecular docking showed that the active components of HLJDD had good affinity with Hub gene. This study systematically elucidates the "multi-component, multi-target, multi-pathway" mechanism of anti-UC with HLJDD for the first time, suggesting that HLJDD or its active components may be candidate drugs for the treatment of ulcerative colitis.


2014 ◽  
Vol 9 (3) ◽  
pp. 552-562 ◽  
Author(s):  
Jia Xu ◽  
Fengmei Lian ◽  
Linhua Zhao ◽  
Yufeng Zhao ◽  
Xinyan Chen ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-7
Author(s):  
Chunyan Wang ◽  
Xudong Tang ◽  
Li Zhang

Ulcerative colitis (UC) is the most common inflammatory bowel disease worldwide. Current therapies in UC cause limitations, and herb medicine provides an important choice for UC treatment. Huangqin-Tang (HQT) is a well-known classical traditional Chinese herbal formula and has been used in China for thousands of years. A large number of pharmacological studies demonstrated HQT and its ingredients to be effective in treating UC. Though the therapeutic effect has been evaluated, comprehensive up-to-date reviews in this field are not yet available. Here we aim to review our current understanding of HQT and its ingredients in treating UC and how the agents modulate the main pathogenesis of the disease, including the intestinal environment, immune imbalance, inflammatory pathways, and oxidative stress. The summary on this issue may provide better understanding of HQT and its ingredients in treating UC and possibly help in promoting its clinical application.


mBio ◽  
2018 ◽  
Vol 9 (3) ◽  
Author(s):  
Xiaolin Tong ◽  
Jia Xu ◽  
Fengmei Lian ◽  
Xiaotong Yu ◽  
Yufeng Zhao ◽  
...  

ABSTRACT Accumulating evidence implicates gut microbiota as promising targets for the treatment of type 2 diabetes mellitus (T2DM). With a randomized clinical trial, we tested the hypothesis that alteration of gut microbiota may be involved in the alleviation of T2DM with hyperlipidemia by metformin and a specifically designed herbal formula (AMC). Four hundred fifty patients with T2DM and hyperlipidemia were randomly assigned to either the metformin- or AMC-treated group. After 12 weeks of treatment, 100 patients were randomly selected from each group and assessed for clinical improvement. The effects of the two drugs on the intestinal microbiota were evaluated by analyzing the V3 and V4 regions of the 16S rRNA gene by Illumina sequencing and multivariate statistical methods. Both metformin and AMC significantly alleviated hyperglycemia and hyperlipidemia and shifted gut microbiota structure in diabetic patients. They significantly increased a coabundant group represented by Blautia spp., which significantly correlated with the improvements in glucose and lipid homeostasis. However, AMC showed better efficacies in improving homeostasis model assessment of insulin resistance (HOMA-IR) and plasma triglyceride and also exerted a larger effect on gut microbiota. Furthermore, only AMC increased the coabundant group represented by Faecalibacterium spp., which was previously reported to be associated with the alleviation of T2DM in a randomized clinical trial. Metformin and the Chinese herbal formula may ameliorate type 2 diabetes with hyperlipidemia via enriching beneficial bacteria, such as Blautia and Faecalibacterium spp. IMPORTANCE Metabolic diseases such as T2DM and obesity have become a worldwide public health threat. Accumulating evidence indicates that gut microbiota can causatively arouse metabolic diseases, and thus the gut microbiota serves as a promising target for disease control. In this study, we evaluated the role of gut microbiota during improvements in hyperglycemia and hyperlipidemia by two drugs: metformin and a specifically designed Chinese herbal formula (AMC) for diabetic patients with hyperlipidemia. Both drugs significantly ameliorated blood glucose and lipid levels and shifted the gut microbiota. Blautia spp. were identified as being associated with improvements in glucose and lipid homeostasis for both drugs. AMC exerted larger effects on the gut microbiota together with better efficacies in improving HOMA-IR and plasma triglyceride levels, which were associated with the enrichment of Faecalibacterium spp. In brief, these data suggest that gut microbiota might be involved in the alleviation of diabetes with hyperlipidemia by metformin and the AMC herbal formula.


2018 ◽  
Vol 12 (3) ◽  
pp. 161-169 ◽  
Author(s):  
Yongcheng Ni ◽  
Chunlong Mu ◽  
Xiangyu He ◽  
Kaiming Zheng ◽  
Hongmin Guo ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Jindong Zhao ◽  
Yan Li ◽  
Min Sun ◽  
Ling Xin ◽  
Tianming Wang ◽  
...  

Objective. The aim of this study is to investigate the implication of the Chinese herbal formula (CHF) Shenzhu tiaopi Granule (STG) in type 2 diabetes mellitus (T2DM) and discuss the mechanisms by which STG regulates the gut microbiota.Method. Goto-Kakizaki (GK) rats and age-matched Wistar (W) rats were acclimatized for 1 week. The GK rats were randomly divided into 3 groups and orally gavaged with saline (model group, M), acarbose (acarbose group, A), and STG (granule of CHF group, G; the component of this formula includesCodonopsis pilosula,Rhizoma Atractylodis,Pinellia,Poria cocos,Pericarpium Citri Reticulatae,Coptis chinensis Franch,and Pueraria). The W rats were orally gavaged with saline (control group, C). The observation time was 8 weeks. The weight, fasting blood glucose (FBG) level, and blood lipid levels were tested. The 16S rRNA genes in the V3-V4 region were sequenced, and the structure of the gut microbiota was analysed.Results. Compared to C, M displayed significant differences in blood glucose, gut microbiota, etc. (P<0.05; P<0.01). Compared to M, A and G showed a similar reduction in the FBG gain and a shift in the structure of the gut microbiota (P<0.05; P<0.01). Compared with A, G exhibited a significant decrease in weight, FBG level, and total cholesterol (P<0.05). The gut microbiota, Bacteroidetes, the Firmicutes/Bacteroidetes ratio,Allobaculum, and Desulfovibrionaceae were significantly decreased in response to the STG treatment, whileLactobacilluswas significantly enriched (P<0.05; P<0.01). The community composition also differed at the phylum and genus levels based on the linear discriminant analysis effect size and heat map.Conclusion. Our findings suggest that the composition of the gut microbiota was significantly changed in the diabetic GK rats compared with that in the normal W rats. STG treatment can improve glucose and lipid levels and modulate the gut microbiota in T2DM rats.


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