Xianjing Hu

Inflammatory bowel disease (IBD) is a chronic disorder characterized by recurrent intestinal inflammation and gut microbiota dysbiosis. Huanglian-Wendan Decoction (HLWDD) has been clinically used for IBD treatment; however, its underlying mechanisms remain unclear. In this study, a dextran sulfate sodium (DSS, 2.25%)-induced IBD mouse model was established to evaluate the therapeutic effects of HLWDD. The protective mechanisms were investigated in colon tissues of DSS-induced mice using ELISA, immunoblotting, histological, and immunohistochemical analyses. In addition, the impact of HLWDD on gut microbiota dysbiosis was analyzed using 16S rRNA sequencing. Antibiotic treatment was applied before DSS administration to deplete gut microbiota and verify the role of microbial modulation. Furthermore, the phytochemical constituents of HLWDD were characterized using liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (LC-QTOF-MS/MS). The results demonstrated that HLWDD markedly alleviated DSS-induced colitis, as evidenced by reduced body weight loss, rectal bleeding, colon shortening, and disease activity index (DAI) scores. Mechanistically, HLWDD suppressed inflammatory responses in colon tissues by inhibiting the TLR4/MyD88/NF-κB and IL-6/JAK2/STAT3 signaling pathways, while enhancing epithelial barrier integrity through upregulation of ZO-1, Occludin, Claudin-1, and Mucin-2. In addition, HLWDD attenuated endoplasmic reticulum stress (ERS) and apoptosis by downregulating CHOP, phospho-eIF2α, cleaved caspase-3, and Bax, while increasing Bcl-2 expression in colonic tissues. Microbiota analysis revealed an increased abundance of beneficial bacterial genera such as Akkermansia and Escherichia-Shigella-related commensals, along with enrichment of beneficial bacterial families including Ruminococcaceae, Lachnospiraceae, and Verrucomicrobiaceae, whereas potentially harmful taxa such as Escherichia and Paraprevotella were reduced. HLWDD also increased the production of short-chain fatty acids (SCFAs), including acetate, butyrate, and isobutyrate, thereby promoting intestinal homeostasis. Importantly, the protective effects of HLWDD were largely abolished following antibiotic-mediated gut microbiota depletion, confirming the essential role of microbial modulation in its therapeutic action. Collectively, these findings suggest that HLWDD ameliorates IBD by regulating gut microbiota composition and function, thereby inhibiting colonic ER stress and apoptosis and restoring intestinal barrier integrity. This study provides mechanistic evidence supporting the potential clinical application of HLWDD as a novel therapeutic strategy for IBD.

1. The global burden of chronic and multifactorial disease continues to rise, and the need for effective and safe targeted management has never been greater. Their potential to modulate diverse mol...

This study aims to investigate the molecular mechanism by which sulfurized garlic (SAC) inhibits ferroptosis through targeting Keap1/Nrf2/GPX4 signaling pathway, thereby restoring intestinal epithelial cell barrier function and alleviating ulcerative colitis (UC). Oxidative stress was induced in cells using H₂O₂ and detected by DCFH-DA. CETSA and Western blotting were employed to assess SAC-target protein binding and antioxidant capacity using DPPH and total antioxidant assays. In vivo, C57BL/6 mice were divided into control, DSS, and SAC groups. DAI was scored based on weight loss, stool consistency, and bleeding. Histology (H&E), IHC (MUC2 and Nrf2), ROS (ELISA), gene expression (qRT-PCR), and protein levels (Western blotting) were analyzed in colon tissues. Serum metabolite profiles were assessed by UHPLC-QTOF-MS for differential metabolite identification and KEGG pathway enrichment. SAC can effectively alleviate UC, which is based on SAC elevating the expression of antioxidant enzymes like GPX4 and NQO1, while reducing ROS and MDA levels. Molecular docking and CETSA analyses revealed that SAC interacts with Keap1 and GPX4 proteins, activating the Keap1/Nrf2/GPX4 pathway. Metabolomics enrichment indicated that SAC modulates the glutathione metabolism pathway by regulating GSH levels, thereby influencing GPX4 stability and activity. SAC can regulate glutathione metabolism through Keap1/Nrf2/GPX4 signaling pathway, inhibit ferroptosis, alleviate intestinal epithelial cell damage, and repair intestinal barrier function.

Colitis-associated cancer (CAC) arises from persistent intestinal inflammation, immune dysregulation, and microbiota-driven epithelial injury, representing a major link between inflammatory bowel disease and colorectal malignancy. Despite advances in therapy, colon cancer remains one of the leading causes of cancer-related mortality worldwide, underscoring the urgent need for effective preventive and immunomodulatory interventions. Ardisiacrispin B (AB), a bioactive triterpenoid isolated from the Ardisia genus, has been reported to suppress tumor growth by regulating apoptosis and ferroptosis; however, its role in inflammation-driven colorectal tumorigenesis remains unexplored. In this study, we investigated the protective and antitumor effects of AB in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced CAC mouse model, with a focus on inflammatory signaling pathways, epithelial remodeling, and gut microbiota modulation. AB administration markedly alleviated disease severity, as evidenced by a significant reduction in disease activity index, including body weight loss, diarrhea, and rectal bleeding. Histopathological evaluation revealed preserved colonic mucosal architecture, diminished inflammatory cell infiltration, and a pronounced reduction in tumor number and size. AB treatment partially modulated the gut microbiota, with a trend toward enrichment of beneficial taxa and a reduction in inflammation-associated bacterial populations. Concurrently, AB robustly downregulated the colonic expression of pro-inflammatory cytokines and chemokines. AB treatment was associated with increased expression of pro-apoptotic markers, indicative of enhanced apoptotic signaling in colonic epithelial cells, as indicated by increased expression of cleaved PARP, cleaved caspase-3, p53, and BAX, while markedly inhibiting cellular proliferation through suppression of Ki-67. Mechanistically, AB was associated with attenuation of key inflammatory and oncogenic signaling pathways, including IL-6/JAK2/STAT3, LPS/TLR4/MyD88/NF-κB, and MAPK cascades. Collectively, Ardisiacrispin B attenuates colitis-associated cancer by rebalancing gut microbiota, suppressing inflammation, and inducing tumor cell apoptosis through inhibition of key oncogenic signaling pathways. Graphical Abstract

Ardisiacrispin B (AB) has demonstrated anti-inflammatory and anti-tumor activities, yet its therapeutic potential in inflammatory bowel disease (IBD) remains unexplored. This study evaluated the efficacy of AB in dextran sulfate sodium (DSS)-induced IBD in mice by monitoring body weight, disease activity index, stool consistency, rectal bleeding, and colon length. Intestinal barrier integrity and inflammatory responses were assessed via ELISA, FITC-dextran permeability, Western blot, and immunohistochemistry. Gut microbiota composition was profiled using 16S rRNA sequencing, along with bioinformatics to predict potential mechanisms, which were subsequently validated through immunofluorescence and flow cytometry. The results showed that AB significantly mitigated body weight loss, DAI scores, colon length shortening, and splenomegaly in mice, and alleviated the pathological damage to the colon. AB strengthened intestinal barrier integrity by increasing ZO-1, Occludin, claudin-1, MUC2, and EPO levels, and reducing ET-1 and DAO levels. AB suppressed inflammation by reducing IL-1β, IL-6, and TNF-α levels, and inhibiting JAK2/STAT3 and TLR4/MyD88/NF-κB pathways. Additionally, AB rebalanced the gut microbiota by increasing beneficial bacteria (Akkermansia) and decreasing pathogenic bacteria (Bacteroides and Helicobacter). Interestingly, AB rebalanced Th17/Treg by decreasing the colonic IL-17 level, increasing IL-10, IL-22, and TGF-β levels, and reversing the proportion of Th17/Treg cells in the blood, mesenteric lymph nodes, and spleen of IBD mice. These findings demonstrate that AB mitigates DSS-induced IBD through coordinated regulation of intestinal barrier integrity, gut microbiota composition, and Th17/Treg immune balance, identifying AB as a promising candidate for IBD therapy.

Chronic inflammation plays a key role in the development of hepatocellular carcinoma (HCC), one of the most prevalent and lethal forms of liver cancer. This study aimed to evaluate the anti‐HCC potential of the petroleum ether extract of Ficus pandurata Hance (FPHPE), a traditional hepatoprotective herb, focusing on its pro‐apoptotic and anti‐inflammatory actions via the JAK2/STAT3 signaling pathway. In vitro experiments demonstrated significant growth inhibition of HepG2, SMMC7721, and Hep3B cells following FPHPE treatment. GC–MS profiling identified 26 phytoconstituents, including friedelane, seseline, bergaptan, and tocopherols, many with known bioactivity. In a xenograft mouse model, FPHPE markedly suppressed tumor growth without causing systemic toxicity. Mechanistic analyses demonstrated that FPHPE activated mitochondria‐mediated apoptosis, as confirmed by Annexin V/PI flow cytometry, Western blot quantification from three biological replicates, TEM imaging showing disrupted cristae, and JC‐1 staining revealing mitochondrial membrane depolarization. Concurrently, FPHPE downregulated phosphorylated and total JAK2/STAT3, inhibited STAT3 nuclear translocation, and suppressed key downstream effectors (iNOS, COX2, c‐Myc, Vimentin, and Slug). ELISA further confirmed a reduction of pro‐inflammatory cytokines TNF‐α and IL‐1β in tumor tissues. Together, these findings establish FPHPE as a dual‐action phytotherapeutic candidate that interrupts both survival and inflammatory pathways, positioning F. pandurata as a promising source for nutraceuticals or complementary therapies against inflammation‐driven liver cancer.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease frequently accompanied by intestinal barrier dysfunction and gut microbiome dysbiosis. Emerging evidence suggests that these impairments can contribute to secondary liver injury (SLI) by disrupting the gut–liver axis and promoting hepatic inflammation. Gentiopicroside (GPS), a natural iridoid glycoside, possesses antimicrobial, anti-inflammatory, and hepatoprotective properties. This study aimed to evaluate the protective effects and underlying mechanisms of GPS in a dextran sulfate sodium (DSS)-induced mouse model of UC and associated SLI. Mice were evaluated for body weight, Disease Activity Index (DAI), colon length, histopathology, tight junction protein expression, gut microbiota composition, inflammatory cytokine levels, and liver function biomarkers. GPS significantly alleviated weight loss, reduced DAI scores, restored intestinal tight junction protein expression, and improved colonic permeability. GPS also modulated the gut microbiota, notably increasing beneficial Bacteroides and Clostridium cluster IV. Mechanistically, GPS suppressed colonic and hepatic inflammation by inhibiting the TLR4/MyD88/NF-κB and JAK2/STAT3 signaling pathways. Moreover, GPS improved liver function and reduced hepatic inflammatory markers, indicating mitigation of SLI. In conclusion, GPS exerts protective effects against DSS-induced UC and SLI by enhancing intestinal barrier integrity, modulating the gut microbiome, and attenuating inflammation via the gut–liver axis.