Banxia Xiexin Decoction modulates short-chain fatty acid metabolism and mitigates ulcerative colitis by reshaping the intestinal microbiota.

Anti-inflammatory activity and mechanism of action of Banxia Xiexin Decoction on DSS-induced ulcerative colitis in mice.

The aim of this paper was to investigate the effect of Banxia Xiexin Decoction(BXD) on inflammatory factors and intestinal flora in a dextran sulfate sodium induced ulcerative colitis(DSS-UC) mouse model, and to explore the mechanism of BXD in treating ulcerative colitis from the perspective of flora disorder. Forty C57 BL/6 J mice were randomly divided into control group, model group and BXD group. A 2.5% DSS-induced ulcerative colitis model was established. On the 8 th day, normal saline, normal saline, and BXD were given daily for 14 days. After 14 days, HE staining was used to observe histopathological changes of the colon. Serum inflammatory factor content was detected by ELISA, and the change of intestinal flora in mice feces was detected by 16 S rRNA sequencing technology. Compared with control group, the colonic tissue of mice in model group was damaged seriously, and the contents of IL-6 and TNF-α in serum were significantly increased(P<0.05). Compared with model group, mice in BXD group had less colonic damage, and the contents of IL-6, TNF-α in serum were decreased significantly(P<0.05). After creation, the richness of Patescibacteria was increased significantly at the phylum level(P<0.05). At the same time, the richness of Faecalibaculum(P<0.01), norank_f_Muribaculaceae(P<0.01) were decreased significantly at the genus level, while the richness of Turicibacter(P<0.01), Romboutsia(P<0.01), Clostridium_sensu_stricto_1(P<0.01) were increased significantly. After the intervention with BXD, the content of Patescibacteria was significantly reduced at the phylum level(P<0.05), and the contents of Lactobacillus(P<0.01), Clostri-dium_sensu_stricto_1(P<0.01), Enterorhabdus(P<0.01), Candidatus_Saccharimonas(P<0.05), Eubacterium_fissicatena_group(P<0.05) were decreased significantly at the genus level, while the contents of Dubosiella, Bacteroides and Allobaculum were increased significantly. Therefore, BXD could significantly improve the symptoms of DSS-UC mice. It not only could reduce the contents of IL-6 and TNF-α, but also could reduce the richness of Patescibacteria at the phylum level, and those of Clostridium_sensu_stricto_1, Candidatus_Saccharimonas, Eubacterium_fissicatena_group at the genus level. Inaddition, BXD could increase the richness of Bacteroides and Bifidobacterium. It suggested that BXD could play a role in the treatment of ulcerative colitis partially through reducing inflammatory factors and regulating the structure of the gut microbiota.

Banxia Xiexin decoction (BXD), a traditional Chinese medicine, was widely used in treating ulcerative colitis (UC). However, the active components of BXD and its mechanism in UC remain elusive. Therefore, we used network pharmacology in vivo experiments, molecular docking, and surface plasmon resonance strategy (SPR) to uncover BXD's potential mechanism. A UC rat model was established by orally administering 7% dextran sulfate sodium (DSS) in drinking water, BXD and palmatine were orally administered for 7days. Network pharmacology was used to investigate the main bioactive components and crucial targets of BXD in treating UC. Molecular docking was used to investigate interactions between components and crucial targets, verifying the results by SPR. By network pharmacology predicting, 20 active components and 44 candidate anti-UC targets of BXD were identified, and the crucial proteins were screeded from PPI network, including extracellular regulated protein kinases (ERK), AKT1, and tumor necrosis factor-α (TNF). In addition, some key active components (palmatine, sexangularetin, and skullcapflavone II) were screened out from the active components-targets network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and in vivo experiments showed that protein-serine-threonine kinase (Akt)/MAPK pathway was involved in BXD treatment for UC; BXD and palmatine significantly ameliorated the severity of DSS-induced UC in rats. Our study might assist in further investigation of the active components in Chinese medicine.

Banxia Xiexin Decoction prevents colitis by modulating gut microbiota and enhancing defensin and immunoglobulin A production.

PurposePrevious studies have highlighted a strong association between programmed cell death and ulcerative colitis (UC). Banxia Xiexin decoction (BXD) is a thoroughly validated formula with an extensive history of clinical application for treating UC. However, it remains unclear whether BXD regulates pyroptosis and necroptosis in UC. This study focused on pyroptosis and necroptosis to investigate the underlying mechanisms of BXD on UC.Material and MethodsThe therapeutic effects of BXD were evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model. To identify key signaling pathways, transcriptomics and proteomics were performed, followed by the validation of these pathways using Western blotting, immunohistochemistry, and immunofluorescence in vivo and in vitro. The bioactive components of BXD were screened through pharmacodynamic experiments, molecular docking, and surface plasmon resonance (SPR) analysis.ResultsBXD significantly alleviated UC symptoms by reducing inflammatory levels and improving intestinal barrier function. Multi-omics analyses demonstrated a significant alteration in pyroptosis- and necroptosis-related signaling pathways following BXD intervention. BXD suppressed pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway in the colons of UC model mice and in LPS+TNF-α-induced NCM460 cells. The screening of active ingredients revealed that baicalin and glycyrrhizic acid significantly affected LDH release and IL-1β levels. Molecular docking and SPR analyses demonstrated that baicalin targeted P2RX7 with high affinity and that glycyrrhizic acid targeted TNFR1 with moderate affinity.ConclusionBXD ameliorates inflammation and intestinal barrier dysfunction in UC by suppressing pyroptosis through the P2RX7/NEK7 pathway and necroptosis via the TNFR1/RIPK3 pathway. Baicalin and glycyrrhizic acid are identified as the pharmacodynamic components responsible for these therapeutic effects. These findings can provide molecular mechanisms and a material basis for the clinical application of BXD in the treatment of UC.

Banxia Xiexin Decoction inhibits colitis-associated colorectal cancer development by modulating STAT3 signaling and gut microbiota

Banxia Xiexin Decoction delays colitis-to-cancer transition by inhibiting E-cadherin/β-catenin pathway via Fusobacterium nucleatum FadA

ABSTRACTThe development of new therapeutic strategies for ulcerative colitis (UC) requires the targeting of multiple pathogenic factors, including disruption of the colonic mucosal barrier, dysregulated inflammation, and gut microbiota imbalance. This study aimed to investigate the protective mechanisms of almond polysaccharide (AP1) against dextran sulfate sodium (DSS)‐induced UC in mice. Administration of AP1 significantly restored DSS‐induced reductions in goblet cells and inhibited epithelial apoptosis, thereby preserving colonic mucosal barrier integrity. In addition, AP1 decreased the levels of proinflammatory cytokines and oxidative stress markers in colonic tissues. Gut microbiota analysis revealed that AP1 effectively restored microbial composition and diversity. Furthermore, AP1 increased the relative abundance of beneficial bacteria while reducing pathogenic taxa, thereby contributing to the restoration of intestinal microbial balance in UC mice. Metabolomic analysis of short‐chain fatty acids (SCFAs) demonstrated that DSS‐induced UC significantly depleted major SCFAs (acetic acid, propionic acid, n‐butyric acid) and disrupted branched‐chain fatty acid (i‐butyric acid and i‐valeric acid) metabolism, whereas AP1 intervention reestablished SCFA profiles. Correlation analysis showed Bacteroides negatively correlated with multiple SCFAs, whereas Alistipes positively correlated with propionic acid. Collectively, these findings underscore the role of AP1 in rescuing microbiota‐derived SCFA metabolism. In summary, AP1 was shown to alleviate UC symptoms through multiple mechanisms, including the preservation of mucosal barrier integrity, suppression of oxidative stress and inflammation, and modulation of gut microbiota composition and the intestinal microenvironment. These results support the therapeutic potential of AP1 as a natural polysaccharide‐based agent for UC treatment.

To clarify the potential mechanism of Banxia Xiexin Decoction (BXD) on colorectal cancer (CRC) from the perspective of metabolomics. Forty male C57BL/6 mice were randomly divided into normal control (NC), azoxymethane/dextran sulfate sodium (AOM/DSS) model, low-dose BXD (L-BXD), high-dose BXD (H-BXD) and mesalamine (MS) groups according to a random number table, 8 mice in each group. Colorectal cancer model was induced by AOM/DSS. BXD was administered daily at doses of 3.915 (L-BXD) and 15.66 g/kg (H-BXD) by gavage for consecutive 21 days, and 100 mg/kg MS was used as positive control. Following the entire modeling cycle, colon length of mice was measured and quantity of colorectal tumors were counted. The spleen and thymus index were determined by calculating the spleen/thymus weight to body weight. Inflammatory cytokine and changes of serum metabolites were analyzed by enzyme-linked immunosorbent assay kits and ultra performance liquid chromatography-quadrupole/time-of-flight mass spectrometry (UPLC-Q/TOF-MS), respectively. Notably, BXD supplementation protected against weight loss, mitigated tumor formation, and diminished histologic damage in mice treated with AOM/DSS (P<0.05 or P<0.01). Moreover, BXD suppressed expression of serum inflammatory enzymes, and improved the spleen and thymus index (P<0.05). Compared with the normal group, 102 kinds of differential metabolites were screened in the AOM/DSS group, including 48 potential biomarkers, involving 18 main metabolic pathways. Totally 18 potential biomarkers related to CRC were identified, and the anti-CRC mechanism of BXD was closely related to D-glutamine and D-glutamate metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arginine biosynthesis, nitrogen metabolism and so on. BXD exerts partial protective effects on AOM/DSS-induced CRC by reducing inflammation, protecting organism immunity ability, and regulating amino acid metabolism.

Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model

Sea buckthorn berries alleviate ulcerative colitis via regulating gut Faecalibaculum rodentium-mediated butyrate biosynthesis.

Background: Inflammation-related NLRP3/Caspase-1/GSDMD-mediated pyroptosis is involved in the progression of ulcerative colitis (UC). β-sitosterol (SIT) was reported to have anti-inflammatory effects on experimental colitis, while the regulation of SIT on pyroptosis is unclear. Therefore, the present study aimed to define the protective and healing effects of SIT on dextran sulfate sodium (DSS)-induced experimental UC rats and human epithelial colorectal adenocarcinoma cells (Caco-2) and explore the underlying mechanisms that are responsible for its effects on NLRP3/Caspase-1/GSDMD-mediated pyroptosis in UC. Methods: UC model rats were established by oral 4% DSS. Following colitis injury, the animals received SIT (doses of 50, 100, and 200mg/kg) treatment for 2 weeks. For in vitro study, we exposed Caco-2-50mg/mL DSS with or without SIT (concentrations of 8 and 16μg/mL). Disease activity index (DAI) and histopathological injury were assessed in vivo. Activation proteins of nuclear factor kappa B (NF-κB) signaling axis, and tight junction-related proteins of zonula occludens-1 (ZO-1) and occludin were detected in colon tissues. TNF-α, IL-1β, and IL-18 in serum and cell supernatant were measured by enzyme-linked immunosorbent assay (ELISA). Changes in NLRP3/Caspase-1/GSDMD-mediated pyroptosis signaling pathway activation were analyzed both in tissues and cells. Results: Our findings suggested that SIT treatment attenuated the severity of 4% DSS-induced UC by protecting rats from weight and colon length loss, and macroscopic damage. SIT also reduced proinflammatory factors production (TNF-α, IL-1β, and IL-18) in serum and cell supernatant. Mechanistically, SIT downregulated the expression levels of pyroptosis-related proteins including Caspase-1, cleaved-Caspase-1, NLRP3, GSDMD, and GSDMD-N in colon tissues and Caco-2 cells. Further analysis indicated that SIT maintained the colonic barrier integrity by enhancing the protein expression of ZO-1 and occludin. Conclusion: We confirmed that SIT exerts protective and therapeutic effects on DSS-induced colitis injury by suppressing NLRP3/Caspase-1/GSDMD-mediated pyroptosis and inflammation response. These findings demonstrated that SIT could be a potential medication for UC treatment.

Banxia Xiexin Decoction (hereinafter referred to as BXD), is a classic Chinese medicine prescription, the whole prescription group of medicines is strict and concise, reflecting the essence of xin opening bitter lowering, calming cold and heat, tonifying and purgating. The spleen and stomach are the main organs of the human digestive system, which are located in the middle of the focal point and are mainly responsible for the operation of the whole body qi machinery and the biochemistry of Qi and blood. Banxia Xiexin Decoction total Yin and Yang deficiency and fullness, with the spleen and stomach physiological characteristics coincide, widely used in all kinds of digestive system diseases, such as: chronic gastritis, functional dyspepsia, reflux esophagitis, ulcerative colitis and so on. In this paper, the results of modern experimental studies on BXD and the experience of various doctors in treating digestive diseases with Banxia Xiexin Decoction in recent years are reviewed.

Rhubarb Peony Decoction ameliorates ulcerative colitis in mice by regulating gut microbiota to restoring Th17/Treg balance

DIREN mitigates DSS-induced colitis in mice and attenuates collagen deposition via inhibiting the Wnt/β-catenin and focal adhesion pathways