Exploring the Mechanism of Action of Canmei Formula Against Colorectal Adenoma Through Multi-Omics Technique

Background: Canmei formula (CMF) is a traditional Chinese medicine compound with definite effect on the prevention and treatment of colorectal adenoma (CRA). CMF can prevent the transformation of intestinal inflammation to cancer. This study explored the mechanism of action of CMF in anti-CRA using multi-omics techniques.Method: The mice were randomly divided into four groups: blank group (Control), high-fat diet (HFD) + AOM/DSS colorectal adenoma model (ADH) groups, Canmei formula treatment group (ADH-CMF) and sulfasalazine treatment group (Sul). Except for the blank group, ADH model was established in the other three groups by intraperitoneal injection with AOM reagent, and then mice were given 2.5% DSS in free drinking water and high-fat diet. The mice in the blank group and ADH groups were intragastrically perfused with normal saline, and the mice in the other two groups were treated with corresponding drugs for 20 weeks. During this period, the changes of physical signs of mice in each group were observed. The differentially expressed genes and proteins in the Control group, ADH group and ADH-CMF group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. After the combined analysis and verification, the key targets were analyzed by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Moreover, the changes of intestinal flora in mice of the three groups were examined.Results: A total of 2,548 differential genes were obtained by transcriptomics analysis, and 45 differential proteins were obtained by proteomics analysis. The results of proteomics data and experimental verification showed that CMF mainly affected the Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase (LHPP) target. GO analysis showed that the targets of CMF were involved in the biological processes such as cellular process, metabolic process and biological regulation. KEGG analysis showed that those genes were involved in oxidative phosphorylation, cell senescence, and metabolic pathways. Studies have shown that LHPP overexpression impeded colorectal cancer cell growth and proliferation in vitro, and was associated with a change in PI3K/AKT activity. The results of 16S DNA high-throughput sequencing showed that CMF could effectively regulate the abundance of Bifidobacterium, Candidatus_Saccharimonas and Erysipelatoclostridium in the intestinal flora at the genus level.Conclusion: CMF regulates LHPP via the PI3K/AKT signaling pathway. CMF affects the abundance of specific intestinal flora and can regulate the disorder of intestinal flora to achieve the role of prevention and treatment of CRA.

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Therapeutic potential of human umbilical cord mesenchymal stem cells on aortic atherosclerotic plaque in a high-fat diet rabbit model

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02490-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yanhong Li ◽

Guiying Shi ◽

Yunlin Han ◽

Haiquan Shang ◽

Huiwu Li ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Treatment Group ◽

Atherosclerotic Plaque ◽

High Fat Diet ◽

Rabbit Model ◽

Intestinal Flora ◽

Human Umbilical Cord ◽

High Fat ◽

Blood Filling

Abstract Background Atherosclerosis (AS) is a complex disease caused in part by dyslipidemia and chronic inflammation. AS is associated with serious cardiovascular disease and remains the leading cause of mortality worldwide. Mesenchymal stem cells (MSCs) have evolved as an attractive therapeutic agent in various diseases including AS. Human umbilical cord MSCs (UCSCs) have been used in cell therapy trials due to their ability to differentiate and proliferate. The present study aimed to investigate the effect of UCSCs treatment on atherosclerotic plaque formation and the progression of lesions in a high-fat diet rabbit model. Methods Rabbits were fed a high-fat diet and then randomly divided into three groups: control, model, and treatment groups. Rabbits in the treatment group were injected with UCSCs (6 × 106 in 500 μL phosphate buffered saline) after 1 month of high-fat diet, once every 2 weeks, for 3 months. The model group was given PBS only. We analyzed serum biomarkers, used ultrasound and histopathology to detect arterial plaques and laser Doppler imaging to measure peripheral blood vessel blood filling, and analyzed the intestinal flora and metabolism. Results Histological analysis showed that the aortic plaque area was significantly reduced in the treatment group. We also found a significant decrease in macrophage accumulation and apoptosis, an increase in expression of scavenger receptors CD36 and SRA1, a decrease in uptake of modified low–density protein (ox-LDL), and a decrease in levels of pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α following UCSCs treatment. We also found that anti-inflammatory cytokines IL-10 and transforming growth factor (TGF)-β expression increased in the aorta atherosclerotic plaque of the treatment group. UCSCs treatment improved the early peripheral blood filling, reduced the serum lipid level, and inhibited inflammation progression by regulating the intestinal flora dysbiosis caused by the high-fat diet. More specifically, levels of the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) were down-regulated in the treatment group. Conclusions UCSCs treatment alleviated atherosclerotic plaque burden by reducing inflammation, regulating the intestinal flora and TMAO levels, and repairing the damaged endothelium.

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Transcriptomic and Proteomic Study on the High-Fat Diet Combined With AOM/DSS-Induced Adenomatous Polyps in Mice

Frontiers in Oncology ◽

10.3389/fonc.2021.736225 ◽

2021 ◽

Vol 11 ◽

Author(s):

Cui Guo ◽

Yimin Xu ◽

Xinyue Han ◽

Xiaoqiang Liu ◽

Runnan Xie ◽

...

Keyword(s):

Mouse Model ◽

Colorectal Adenoma ◽

High Fat Diet ◽

Transcriptome Sequencing ◽

Intestinal Flora ◽

Molecular Targets ◽

Adenomatous Polyps ◽

Rna Seq ◽

High Fat ◽

Intestinal Adenoma

ObjectiveTo screen and identify molecular targets and bacteria genus leading to adenomatous polyps in mouse induced by high-fat diet (HFD) +AOM/DSS using omics technology.MethodsThe molecular targets of colorectal adenoma disease were obtained from the GeneCards and OMIM database. The SPF C57BL mice were randomly divided into blank (Control) and AOM/DSS+HFD colorectal adenoma model (ADH) groups. The ADH model group was intraperitoneally injected with AOM reagent. Then, mice were given with 2.5% DSS (in free drinking water) and high-fat diet to establish the mouse model. During this period, the changes of physical signs of mice in each group were observed. After the end of modeling, HE staining was used to evaluate the histopathological change of mice. The differentially expressed genes and proteins in the Control group and ADH group were detected by RNA-seq transcriptome sequencing and Tandem Mass Tags (TMT) quantitative proteomics. The histological results were analyzed by intersection with the intestinal adenoma molecular targets obtained from the database. Moreover, the changes of intestinal flora in the two groups were examined. The correlation between targets and differential bacteria was analyzed and verified by Parallel Reaction Monitoring (PRM) to comprehensively evaluate the mouse model of adenomatous polyp induced by AOM/DSS+HFD.ResultsThe general condition and histopathological results of mice confirmed that the ADH mouse model was successfully established and tubular adenoma was formed. A total of 604 genes and 42 proteins related to intestinal adenoma were obtained by histological analysis and database intersection analysis. The intestinal microflora of ADH mice was different from that of normal mice, and the constituents and abundance of intestinal flora were similar to those of human intestinal adenoma. GATA4 and LHPP were selected as potential pathological markers of the model mice by correlation analysis of targets and intestinal flora. The results of PRM verification were highly consistent with the results of RNA-Seq transcriptome sequencing and TMT analysis.ConclusionThe pathological results, molecular pathological markers and the changes of intestinal flora suggest that the mouse ADH model is ideal for studying the transformation of inflammatory cancer. The ADH model will be helpful for understanding the occurrence and development of human colorectal cancer at the transcriptomic and proteomic level.

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Ginkgolide B treatment regulated intestinal flora to improve high-fat diet induced atherosclerosis in ApoE−/− mice

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.111100 ◽

2021 ◽

Vol 134 ◽

pp. 111100

Author(s):

Zhiyang Lv ◽

Xin Shan ◽

Qingbo Tu ◽

Jie Wang ◽

Jing Chen ◽

...

Keyword(s):

High Fat Diet ◽

Intestinal Flora ◽

Ginkgolide B ◽

High Fat

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Histologi Lumen Dan Endotelium Arteri Dorsal Penis Tikus Wistar (Rattus Novergicus) Yang Diinduksi Pakan Tinggi Lemak

Metamorfosa Journal of Biological Sciences ◽

10.24843/metamorfosa.2020.v07.i01.p10 ◽

2020 ◽

Vol 7 (1) ◽

pp. 73

Author(s):

I Wayan Rosiana ◽

I Gede Widhiantara

Keyword(s):

Treatment Group ◽

High Fat Diet ◽

Wistar Rats ◽

Wistar Rat ◽

Lumen Diameter ◽

Control Group ◽

High Fat ◽

Arterial Lumen ◽

Male Wistar Rats ◽

The Difference

This study aims to look at the histopathological picture of the dorsal arteries of the penis of the hiperlipidemic wistar rats (Rattus novergicus) induction by high-fat diet that seen in terms of lumen diameter and thickness of the arterial endotelium wall. Hyperlipidemia is a risk factor for ateriosclerosis in the penile arteries causing erectile dysfunction in men. This study is an experimental study with a randomized posttest only control goup design. The sample are 10 individuals adult male wistar rats aged 3-4 months with a range of body weight 150-200 grams. Before treatment, adaptation was carried out for 7 days. After that the sample rats in the treatment group were made hyperlidemic by feeding lard for 50 days. Then surgery is performed for histopathological preparations at the posttest. To determine the differences in endotelium thickness and arterial lumen diameter in the two groups, an independent t-test was used. Thick diameter data of the endotelium and dorsal arteries of the penis of the wistar rat between the lower treatment group and the control group. The difference that occurred was statistically significant (p <0.05). So it can be concluded that the provision of high-fat diet (hyperlipidemia) decreases the lumen diameter and endotelium thickness of dorsal arteries penis. Keywords: Dorsal arteries, high-fat diet, Wistar rats

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Saturated hydrogen improves lipid metabolism disorders and dysbacteriosis induced by a high-fat diet

Experimental Biology and Medicine ◽

10.1177/1535370219898407 ◽

2020 ◽

Vol 245 (6) ◽

pp. 512-521 ◽

Cited By ~ 5

Author(s):

Xiangjie Qiu ◽

Qiaona Ye ◽

Mengxing Sun ◽

Lili Wang ◽

Yurong Tan ◽

...

Keyword(s):

Fatty Acid ◽

High Fat Diet ◽

Metabolic Disorders ◽

Metabolic Diseases ◽

Isocitrate Lyase ◽

Intestinal Flora ◽

Glyoxylic Acid ◽

Density Lipoprotein ◽

High Fat ◽

Acid Cycle

Studies have shown that metabolic diseases, such as obesity, are significantly associated with intestinal flora imbalance. The amplification of opportunistic pathogens induced by the glyoxylic acid cycle contributes to intestinal flora imbalance. Promising, though, is that saturated hydrogen can effectively improve the occurrence and development of metabolic diseases, such as obesity. However, the specific mechanism of how saturated hydrogen operates is still not very clear. In this study, after a high-fat diet, the level of total cholesterol, total glyceride, and low-density lipoprotein in the peripheral blood of mice increased, and that of high-density lipoprotein decreased. Intestinal fatty acid metabolism-related gene Apolipoprotein E (ApoE), fatty acid synthase (FAS), intestinal fatty acid-binding protein (I-FAPB), acetyl-CoA carboxylase 1 (ACC1), peroxisome proliferator-activated receptor γ (PPARγ), and stearoyl-CoA desaturase 1 (SCD1) increased significantly. Bacteroides, Bifidobacteria, and Lactobacillus counts in feces decreased considerably, while Enterobacter cloacae increased. The activity of isocitrate lyase in feces increased markedly. Treatment of mice with saturated hydrogen led to decreased total cholesterol, total glyceride, and low-density lipoprotein and increased high-density lipoprotein in the peripheral blood. FAS and I-FAPB gene expression in the small intestine decreased. Bacteroides, Bifidobacteria, and Lactobacillus in feces increased significantly, whereas Enterobacter cloacae decreased. The activity of isocitrate lyase also diminished remarkably. These results suggest that saturated hydrogen could improve intestinal structural integrity and lipid metabolism disorders by inhibiting the glyoxylic acid cycle of the intestinal flora. Impact statement Past studies have shown that hydrogen can improve metabolic disorders, but its mechanism of action remains unclear. It is well known that metabolic diseases, such as obesity, are significantly associated with changes in the intestinal flora. The glyoxylic acid cycle is an essential metabolic pathway in prokaryotes, lower eukaryotes, and plants and could be the portal for mechanisms related to metabolic disorders. Many opportunistic pathogenic bacteria can recycle fatty acids to synthesize sugars and other pathogenic substances using the glyoxylic acid cycle. So, the glyoxylic acid cycle may be involved in intestinal dysbacteriosis under high-fat diet. This study, therefore, seeks to provide the mechanism of how hydrogen improves metabolic diseases and a new basis for the use of hydrogen in the treatment of metabolic disorders.

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Sorghum resistant starch reduces adiposity in high-fat diet-induced overweight and obese rats via mechanisms involving adipokines and intestinal flora

Food and Agricultural Immunology ◽

10.1080/09540105.2013.876976 ◽

2014 ◽

Vol 26 (1) ◽

pp. 120-130 ◽

Cited By ~ 24

Author(s):

Rui-Ling Shen ◽

Wen-Li Zhang ◽

Ji-Lin Dong ◽

Gui-Xing Ren ◽

Ming Chen

Keyword(s):

Resistant Starch ◽

High Fat Diet ◽

Intestinal Flora ◽

High Fat ◽

Obese Rats

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A Metabolomic Study on the Intervention of Traditional Chinese Medicine Qushi Huayu Decoction on Rat Model of Fatty Liver Induced by High-Fat Diet

BioMed Research International ◽

10.1155/2019/5920485 ◽

2019 ◽

Vol 2019 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Xiao-jun Gou ◽

Shanshan Gao ◽

Liang Chen ◽

Qin Feng ◽

Yi-yang Hu

Keyword(s):

Chinese Medicine ◽

Traditional Chinese Medicine ◽

Fatty Liver ◽

Mechanism Of Action ◽

High Fat Diet ◽

Gas Chromatography Mass Spectrometry ◽

Control Group ◽

High Fat ◽

Pattern Recognition Analysis ◽

And Control

Qushi Huayu Decoction (QHD), an important clinically proved herbal formula, has been reported to be effective in treating fatty liver induced by high-fat diet in rats. However, the mechanism of action has not been clarified at the metabolic level. In this study, a urinary metabolomic method based on gas chromatography-mass spectrometry (GC-MS) coupled with pattern recognition analysis was performed in three groups (control, model, and QHD group), to explore the effect of QHD on fatty liver and its mechanism of action. There was obvious separation between the model group and control group, and the QHD group showed a tendency of recovering to the control group in metabolic profiles. Twelve candidate biomarkers were identified and used to explore the possible mechanism. Then, a pathway analysis was performed using MetaboAnalyst 3.0 to illustrate the pathways of therapeutic action of QHD. QHD reversed the urinary metabolite abnormalities (tryptophan, uridine, and phenylalanine, etc.). Fatty liver might be prevented by QHD through regulating the dysfunctions of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, and tryptophan metabolism. This work demonstrated that metabolomics might be helpful for understanding the mechanism of action of traditional Chinese medicine for future clinical evaluation.

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Sesamin Modulation of Intestinal Microflora in Rats on High-Fat Diet

Current Topics in Nutraceutical Research ◽

10.37290/ctnr2641-452x.19:312-316 ◽

2020 ◽

Vol 19 (3) ◽

pp. 312-316

Author(s):

Pan Liu ◽

Yu Deng ◽

Mengxi Wang ◽

Lingyan Kong ◽

Na Xu ◽

...

Keyword(s):

High Fat Diet ◽

Intestinal Microflora ◽

High Throughput Sequencing ◽

Intestinal Flora ◽

Short Chain Fatty Acids ◽

Sequencing Analysis ◽

Anaerobic Culture ◽

High Fat ◽

E Coli

The present study aimed to investigate the effects of sesamin on intestinal flora in rats on high-fat diet by in vitro animal fecal anaerobic culture system. Results showed that treatment with sesamin increased the abundance of Lactobacillus acidophilus and inhibited the growth of E. coli. High throughput sequencing analysis showed that treatment with sesamin increased the abundance of probiotics such as Lactobacillus and Flavonifractor, and decreased the abundance of harmful bacteria such as Bacteroides, Enterococcus, Clostridium_XlVa, and Parabacteroides. Moreover, treatment with sesamin increased the concentration of total short chain fatty acids (acetic acid and isovaleric acid). In conclusion, sesamin intervention improved the composition and abundance of intestinal microorganisms of high fat diet rats, which would be beneficial to intestinal health.

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