Qing-Chang-Hua-Shi granule ameliorates DSS-induced colitis by activating NLRP6 signaling and regulating Th17/Treg balance

Cheng, Cheng; Hu, Jingyi; Li, Yanan; Ji, Yuejin; Lian, Ziyu; Au, Ryan; Xu, Feng; Li, Weiyang; Shen, Hong; Zhu, Lei

doi:10.1016/j.phymed.2022.154452

Cited by 20 publications

(4 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An imbalance in the ratio of Treg to Th17 cells in the gut is a common characteristic typical of colitis. Therefore, upregulating Treg cells in the gut to restore balance between Treg and Th17 cells has been identified as a viable strategy for managing colitis [ 12 – 15 ]. It has been reported that MSCs induce Treg cell differentiation, which in turn limits the inflammatory response [ 16 , 17 ].…”

Section: Introductionmentioning

confidence: 99%

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-β1 in colitis treatment

Zhang,

Zeng,

Wei

et al. 2024

Stem Cell Res Ther

View full text Add to dashboard Cite

Background Mesenchymal stem cells (MSCs) demonstrate a wide range of therapeutic capabilities in the treatment of inflammatory bowel disease (IBD). The intraperitoneal injection of MSCs has exhibited superior therapeutic efficacy on IBD than intravenous injection. Nevertheless, the precise in vivo distribution of MSCs and their biological consequences following intraperitoneal injection remain inadequately understood. Additional studies are required to explore the correlation between MSCs distribution and their biological effects. Methods First, the distribution of human umbilical cord MSCs (hUC-MSCs) and the numbers of Treg and Th17 cells in mesenteric lymph nodes (MLNs) were analyzed after intraperitoneal injection of hUC-MSCs. Subsequently, the investigation focused on the levels of transforming growth factor beta1 (TGF-β1), a key cytokine to the biology of both Treg and Th17 cells, in tissues of mice with colitis, particularly in MLNs. The study also delved into the impact of hUC-MSCs therapy on Treg cell counts in MLNs, as well as the consequence of TGFB1 knockdown hUC-MSCs on the differentiation of Treg cells and the treatment of IBD. Results The therapeutic effectiveness of intraperitoneally administered hUC-MSCs in the treatment of colitis was found to be significant, which was closely related to their quick migration to MLNs and secretion of TGF-β1. The abundance of hUC-MSCs in MLNs of colitis mice is much higher than that in other organs even the inflamed sites of colon. Intraperitoneal injection of hUC-MSCs led to a significant increase in the number of Treg cells and a decrease in Th17 cells especially in MLNs. Furthermore, the concentration of TGF-β1, the key cytokine for Treg differentiation, were also found to be significantly elevated in MLNs after hUC-MSCs treatment. Knockdown of TGFB1 in hUC-MSCs resulted in a noticeable reduction of Treg cells in MLNs and the eventually failure of hUC-MSCs therapy in colitis. Conclusions MLNs may be a critical site for the regulatory effect of hUC-MSCs on Treg/Th17 cells and the therapeutic effect on colitis. TGF-β1 derived from hUC-MSCs promotes local Treg differentiation in MLNs. This study will provide new ideas for the development of MSC-based therapeutic strategies in IBD patients.

show abstract

Section: Introductionmentioning

confidence: 99%

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-β1 in colitis treatment

Zhang,

Zeng,

Wei

et al. 2024

Stem Cell Res Ther

View full text Add to dashboard Cite

show abstract

“…Aliquots of QTF samples were thawed and prepared for UPLC-MS analysis as described in a previous publication. 24 A 5 μL aliquot of prepared QTF was filtered through a 0.22 µm filter and analyzed using a UPLC-ESI-Q-orbitrap-MS system, consisting of the Shimadzu Nexera X2 LC-30AD and the Q Exactive™ Plus Hybrid Quadrupole-Orbitrap™ Mass Spectrometer by Thermo Scientific, San Jose, USA. ACQUITY UPLC ® high strength silica (HSS) T3 columns (2.1×100 mm, 1.8μm) from Waters, Milford, MA, USA, were employed for liquid chromatography separation with a flow rate of 0.3 mL/min.…”

Section: Methodsmentioning

confidence: 99%

Therapeutic Effects of Qingchang Tongluo Decoction on Intestinal Fibrosis in Crohn’s Disease: Network Pharmacology, Molecular Docking and Experiment Validation

Li,

Hu,

et al. 2024

DDDT

Self Cite

View full text Add to dashboard Cite

Background Qingchang Tongluo Decoction (QTF) is clinically used for the treatment of intestinal fibrosis in Crohn’s Disease (CD). However, the role of QTF in CD-associated fibrosis and its potential pharmacological mechanism remains unclear. Purpose The objective of this study was to elucidate the potential mechanism of QTF in treating CD-associated fibrosis, employing a combination of bioinformatics approaches — encompassing network pharmacology and molecular docking — complemented by experimental validation. Methods To investigate the material basis and potential protective mechanism of QTF, a network pharmacology analysis was conducted. The core components and targets of QTF underwent molecular docking analysis to corroborate the findings obtained from network pharmacology. In vitro, a colon fibrotic model was established by stimulating IEC-6 cells with 10 ng/mL of transforming growth factor(TGF-β1). In vivo, an intestinal fibrosis model was induced in BALB/c mice by TNBS. The role of QTF in inhibiting the TGF-β1/Smad signaling pathway was investigated through RT-qPCR, Western blotting, immunohistochemistry staining, and immunofluorescence staining. Results Network pharmacology analysis revealed that QTF could exert its protective effect. Bioinformatics analysis suggested that Flavone and Isoflavone might be the key components of the study. Additionally, AKT1, IL-6, TNF, and VEGFA were identified as potential therapeutic targets. Furthermore, experimental validation and molecular docking were employed to corroborate the results obtained from network pharmacology. RT-qPCR, Immunofluorescence, and Western blotting results demonstrated that QTF significantly improved colon function and inhibited pathological intestinal fibrosis in vivo and in vitro. Conclusion Through the application of network pharmacology, molecular docking, and experimental validation, QTF could be confirmed to inhibit the proliferation of intestinal fibroblasts associated with CD and reduce the expression of Collagen I and VEGFA. This effect is achieved through the attenuation of ECM accumulation, primarily via the inhibition of the TGF-β1/Smad signaling pathway.

show abstract

“…The following parameters were applied: sheath gas flow rate, 45 psi; aux gas flow rate, 15 psi; capillary temperature, 400 °C; full ms resolution, 70,000; MS/MS resolution, 17,500; collision energy, 15/30/45 in NCE mode; and spray voltage, 4.0 kV (ESI+) or − 3.6 kV (ESI-). The mass spectrometry fragments of the tested sample XKY were matched with the in-house secondary mass spectrometry database (Shanghai BIOTREE Biotech Co., Ltd) [ 24 ].…”

Section: Methodsmentioning

confidence: 99%

Therapeutic mechanisms of the medicine and food homology formula Xiao-Ke-Yin on glucolipid metabolic dysfunction revealed by transcriptomics, metabolomics and microbiomics in mice

Ding

Peng

et al. 2023

Chin Med

View full text Add to dashboard Cite

Background In recent decades, the prevalence of metabolic diseases, particularly diabetes, hyperlipidemia, obesity, and non-alcoholic fatty liver disease (NAFLD), has increased dramatically, causing great public health and economic burdens worldwide. Traditional Chinese medicine (TCM) serves as an effective therapeutic choice. Xiao-Ke-Yin (XKY) is a medicine and food homology TCM formula consisting of nine “medicine and food homology” herbs and is used to ameliorate metabolic diseases, such as insulin resistance, diabetes, hyperlipidemia and NAFLD. However, despite its therapeutic potential in metabolic disorders, the underlying mechanisms of this TCM remain unclear. This study aimed to evaluate the therapeutic effectiveness of XKY on glucolipid metabolism dysfunction and explore the potential mechanisms in db/db mice. Methods To verify the effects of XKY, db/db mice were treated with different concentrations of XKY (5.2, 2.6 and 1.3 g/kg/d) and metformin (0.2 g/kg/d, a hypoglycemic positive control) for 6 weeks, respectively. During this study, we detected the body weight (BW) and fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), daily food intake and water intake. At the end of the animal experiment, blood samples, feces, liver and intestinal tissue of mice in all groups were collected. The potential mechanisms were investigated by using hepatic RNA sequencing, 16 S rRNA sequencing of the gut microbiota and metabolomics analysis. Results XKY efficiently mitigated hyperglycemia, IR, hyperlipidemia, inflammation and hepatic pathological injury in a dose dependent manner. Mechanistically, hepatic transcriptomic analysis showed that XKY treatment significantly reversed the upregulated cholesterol biosynthesis which was further confirmed by RT-qPCR. Additionally, XKY administration maintained intestinal epithelial homeostasis, modulated gut microbiota dysbiosis, and regulated its metabolites. In particular, XKY decreased secondary bile acid producing bacteria (Clostridia and Lachnospircaeae) and lowered fecal secondary bile acid (lithocholic acid (LCA) and deoxycholic acid (DCA)) levels to promote hepatic bile acid synthesis by inhibiting the LCA/DCA-FXR-FGF15 signalling pathway. Furthermore, XKY regulated amino acid metabolism including arginine biosynthesis, alanine, aspartate and glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and tryptophan metabolism likely by increasing Bacilli, Lactobacillaceae and Lactobacillus, and decreasing Clostridia, Lachnospircaeae, Tannerellaceae and Parabacteroides abundances. Conclusion Taken together, our findings demonstrate that XKY is a promising “medicine food homology” formula for ameliorating glucolipid metabolism and reveal that the therapeutic effects of XKY may due to its downregulation of hepatic cholesterol biosynthesis and modulation of the dysbiosis of the gut microbiota and metabolites.

show abstract

Qing-Chang-Hua-Shi granule ameliorates DSS-induced colitis by activating NLRP6 signaling and regulating Th17/Treg balance

Cited by 20 publications

References 40 publications

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-β1 in colitis treatment

Mesenteric lymph nodes: a critical site for the up-regulatory effect of hUC-MSCs on Treg cells by producing TGF-β1 in colitis treatment

Therapeutic Effects of Qingchang Tongluo Decoction on Intestinal Fibrosis in Crohn’s Disease: Network Pharmacology, Molecular Docking and Experiment Validation

Therapeutic mechanisms of the medicine and food homology formula Xiao-Ke-Yin on glucolipid metabolic dysfunction revealed by transcriptomics, metabolomics and microbiomics in mice

Contact Info

Product

Resources

About