Ginsenoside Rk3 Ameliorates Obesity-Induced Colitis by Regulating of Intestinal Flora and the TLR4/NF-κB Signaling Pathway in C57BL/6 Mice

2021 ◽  
Vol 69 (10) ◽  
pp. 3082-3093
Author(s):  
Hongwei Chen ◽  
Haixia Yang ◽  
Jianjun Deng ◽  
Daidi Fan
2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yingchun Zhao ◽  
Xinglong Liu ◽  
Yinan Zheng ◽  
Wencong Liu ◽  
Chuanbo Ding

AbstractAronia melanocarpa is a natural medicinal plant that has a variety of biological activities, its fruit is often used for food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa fruit. This research evaluated the delay and protection of AMP obtained from Aronia melanocarpa fruit on aging mice by d-Galactose (D-Gal) induction and explored the effect of supplementing AMP on the metabolism of the intestinal flora of aging mice. The aging model was established by intraperitoneal injection of D-Gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks. AMP (100 and 200 mg/kg) was given daily by oral gavage after 6 weeks of D-Gal-induced. The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice determined by the eight-arm maze test. H&E staining showed that AMP significantly reversed brain tissue pathological damage and structural disorders. AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating the AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating the PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family. Importantly, 16S rDNA analysis indicated the AMP treatment significantly retarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammation and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.


2019 ◽  
Vol 111 ◽  
pp. 1429-1437 ◽  
Author(s):  
Zhen-Mei Song ◽  
Fang Liu ◽  
Yan-Ming Chen ◽  
Yi-Jing Liu ◽  
Xiao-Di Wang ◽  
...  

2020 ◽  
Author(s):  
Yingying Liu ◽  
Xinkui Liu ◽  
Wei Zhou ◽  
Jingyuan Zhang ◽  
Siyu Guo ◽  
...  

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease that imposes a huge economic burden on global public health. And the gut-liver axis theory supports the therapeutic role of intestinal flora in the development and progression of NAFLD. To this end, we designed bioinformatics study on the relationship between intestinal flora disorder and NAFLD, so as to explore the molecular mechanism of intestinal flora interfering with NAFLD. Methods Differentially expressed genes for NAFLD were obtained from GEO database. And the disease genes for NAFLD and intestinal flora disorder were obtained from the disease databases. Using string 11.0 database to establish protein-protein interaction network relationship and cytoscape 3.7.2 software visualization. Cytoscape plug-in MCODE and cytoHubba were used to screen the potential genes of intestinal flora disorder and NAFLD, so as to obtain potential targets for intestinal flora to interfere in the occurrence and process of NAFLD. Enrichment analysis of potential targets was carried out using R 4.0.2 software. Results The results showed that PTGS2, SPINK1 and C5AR1 may be the key genes for intestinal flora to interfere with NAFLD. CCL2, IL6, IL1B and FOS may be key genes for the development and progression of NAFLD. The gene function is mainly reflected in basic biological processes, including the regulation of metabolic process, epithelial development and immune influence. The pathway is mainly related to signal transduction, immune regulation and physiological metabolism. The TNF signaling pathway, AGE-RAGE signaling pathway in the diabetic activity, and NF-Kappa B signaling pathways are important pathways for intestinal flora to interfere with NAFLD. Conclusion According to the analysis results, there is a certain correlation between intestinal flora disorder and NAFLD. It is speculated that the mechanism by which intestinal flora may interfere with the occurrence and development of NAFLD is mainly related to inflammatory response and insulin resistance. Nevertheless, further research is needed to explore the specific molecular mechanisms.


2021 ◽  
Author(s):  
Jian Long ◽  
Xue-Ke Liu ◽  
Zeng-Ping Kang ◽  
Meng-Xue Wang ◽  
Hai-Mei Zhao ◽  
...  

Abstract Background: Aberrant M1/M2 macrophage polarization and intestinal flora disruption are involved in the pathological processes associated with ulcerative colitis (UC). Ginsenoside Rg1 has good immunomodulatory and anti-inflammatory effects and is effective in treating UC of humans and animals. However, it is unclear how ginsenoside Rg1 regulate the homeostasis of M1/M2 macrophage polarization and intestinal flora.Methods: BALB/c mice were randomly divided into 4 groups: Control, DSS, DSS+Rg1, DSS+Y27632 groups. In this study, experiment colitis was induced in BALB/c mice using sodium dextran sulfate (DSS). Mice of DSS+Rg1, DSS+Y27632 groups were treated respectively with ginsenoside Rg1 and Rock inhibitor Y27632 for 14 consecutive days. On day 21, all mice were sacrificed. Histopathological analysis of the colon tissues was performed by Hematoxylin Eosin sinning. Cytokines (IL-6, IL-33, CCL-2, TNF-α, IL-4 and IL-10) were detected by Elisa. Flow cytometry was used to analyse macrophage activation and M1/M2 macrophage polarisation. Western blotting were applied to detect the levels of Macrophage polarization-associated protein (Arg-1, MIF-1, PIM-1, TLR2) and Nogo-B/RhoA signaling molecules (Rock1, RhoA and Nogo-B). The fecal microbial populations were analyzed using 16S gene sequencing. Results: After ginsenoside Rg1 and Y27632 treatment, the changes of body weight, colon length, colonic weight index and colonic mucosal injury of colitis mice were effectively improved, accompanied by less ulcer formation and inflammatory cell infiltration, lower levels of pro-inflammatory cytokines (IL-6, IL-33, CCL-2, TNF-α) and higher anti-inflammatory cytokines (IL-4 and IL-10). Importantly, the percentage of CD11b+F4/80+, CD11b+F4/80+Tim-1+, CD11b+F4/80+TLR4+, and CD11b+F4/80+iNOS+ cells and the expression levels of MIF-1 and PIM-1 proteins were down-regulated significantly after ginsenoside Rg1 and Y27632 treatment, and CD11b+F4/80+CD206+ and CD11b+F4/80+CD163+ cells and Arg-1 up-regulated significantly. Intestinal flora composition were effectively improved after administration of ginsenoside Rg1. The Nogo-B/RchoA signaling pathway were obviously inhibited after ginsenoside Rg1 and Y27632 treatment, and the levels of Rock1, RhoA and Nogo-B proteins were significantly reduced. Conclusions: Ginsenoside Rg1 has the protective effect on UC by inhibiting macrophage activation, restoring the balance of M1/M2 macrophage polarization, and improving intestinal flora composition, associated with inhibition of the Nogo-B/RhoA signaling pathway.


2020 ◽  
pp. 1-7
Author(s):  
Hongquan Pi ◽  
Libing Huang ◽  
Huifang Liu ◽  
Shulan Liang ◽  
Juanjuan Mei

2020 ◽  
Author(s):  
Xiaoya Li ◽  
Chenyang Zhang ◽  
Huaying Hui ◽  
Xinxin Peng ◽  
Nenqun Xiao ◽  
...  

Abstract Background: Ge-gen-qin-lian Decoction (GD) has been extensively used for the treatment of diarrhea with intestinal dampness heat syndrome(IDHS) with a satisfying therapeutic effect. However, the active ingredients and mechanism of GD against diarrhea with IDHS have not been fully elucidated. The occurrence of diarrhea is closely related to the intestinal flora, and the compound of Traditional Chinese Medicine(TCM) can exert its curative effect by regulating the intestinal flora, and exploring the relationship between the two is conducive to the clarification of pharmacology. Results: Animal experiments indicted that the OTU number and Alpha diversity index in the intestinal mucosa flora of the treatment group(cttm) recovered and higher than that of the control group(ctcm). PCoA results showed that there were differences in the community structure between the Con and GD. At the species level, the abundance of Lactobacillus crispatus and Muribaculum intestinal in the model group(ctmm) decreased, and the Neisseria mucosa increased (p<0.05). After being treated with GD, Muribaculum intestinal increased, and Lactobacillus curlyus and Neisseria mucosa decreased (p<0.05). Combined with network pharmacology analysis, we screened out 146 active ingredients in GD corresponding to 252 component targets, and 328 disease targets in diarrhea to obtain 31 drug-disease common targets. The key targets involved TNF, IL-6, EFGR etc. KEGG pathway enrichment resulted in HIF-1 signaling pathway, VEGFA signaling pathway, Adipocytokine signaling pathway and so on (p<0.05). Conclusions: GD could restore the diversity and abundance of intestinal mucosa in diarrheal mice with IDHS, promote the abundance of Muribaculum intestinal, inhibit the abundance of Neisseria mucosa. Through the characteristic of multiple targets and multiple channels, the active ingredients of GD intervened from oxidative stress and inflammatory response to adjust the balance of intestinal mucosa flora, thereby playing the role of treating diarrhea.


2021 ◽  
Author(s):  
Yingchun Zhao ◽  
Xinglong Liu ◽  
Yinan Zheng ◽  
Wencong Liu ◽  
Chuanbo Ding

Abstract Aronia melanocarpa, as a natural medicinal plant, has been widely proved to have a variety of biological activities used as a novel food and medicine. Aronia melanocarpa polysaccharide (AMP) is the main component of the Aronia melanocarpa. The purpose of this research is to evaluate the delay and protection of AMP on aging mice by D-galactose (D-gal) induced, and to explore the effect of supplementing AMP on the metabolism of the intestinal flora of aging organisms.The aging model was established by intraperitoneal injection of D-gal (200 mg/kg to 1000 mg/kg) once per 3 days for 12 weeks, and administer AMP (100 and 200 mg/kg) were given daily by oral gavage after 6 weeks of D-Gal-induced.The results showed that AMP treatment significantly improved the spatial learning and memory impairment of aging mice through the eight-arm maze test, and H&E staining provedthat AMP significantly reversed brain tissue pathological damage and structural disorders.AMP alleviated inflammation and oxidative stress injury in aging brain tissue by regulating AMPK/SIRT1/NF-κB and Nrf2/HO-1 signaling pathways. Particularly, AMP reduced brain cell apoptosis and neurological deficits by activating PI3K/AKT/mTOR signaling pathway and its downstream apoptotic protein family.Importantly, 16S rDNA analysis indicated the AMP treatment significantly redarded the aging process by improving the composition of intestinal flora and abundance of beneficial bacteria. In summary, this study found that AMP delayed brain aging in mice by inhibiting inflammatory and regulating intestinal microbes, which providing the possibility for the amelioration and treatment of aging and related metabolic diseases.


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