J Ethnopharmacol. 2026 Sep 5;374(Pt 1):122370. doi: 10.1016/j.jep.2026.122370. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Wuwei Huanglian Wan (WWHLW) is a traditional Tibetan medicine formula developed by Tibetan physician Takpe Pingcuo and officially documented in the Ministry of Health Drug Standards for Tibetan Medicines (Volume I, 1995). It has long been used for the treatment of gastrointestinal disorders, particularly conditions associated with gastrointestinal discomfort and inflammation. Given the overlap between its traditional indications and the clinical manifestations of H. pylori-associated gastritis (HAG), WWHLW represents a promising candidate for the management of H. pylori infection and related gastric inflammation. In addition, several constituent herbs of WWHLW have demonstrated anti-H. pylori and anti-inflammatory activities, providing a pharmacological basis for further investigating its therapeutic effects.

AIM OF THE STUDY: This study aimed to systematically evaluate the therapeutic effects of WWHLW against H. pylori infection and HAG, and to explore the biological processes associated with these effects through integrated multi-omics and experimental validation.

MATERIALS AND METHODS: The therapeutic effects of WWHLW were evaluated through in vitro antibacterial assays and an H. pylori-infected mouse model. UHPLC-HRMS/MS was employed for chemical profiling and identification of serum-absorbed constituents. Serum metabolomics, 16S rRNA gene sequencing, network pharmacology analysis, molecular docking analysis, and molecular biological analyses were integrated to investigate the metabolic, microbial, and signaling changes associated with its therapeutic activity.

RESULTS: WWHLW exhibited anti-H. pylori activity, with minimum inhibitory concentrations (MICs) of 0.2-0.5 mg/mL against both standard strains and multidrug-resistant clinical isolates. At MIC concentrations, WWHLW treatment altered the expression of multiple virulence-associated genes and reduced gastric H. pylori colonization by 93.8% in infected mice. UHPLC-HRMS/MS analysis putatively annotated 121 compounds in the WWHLW extracts, of which 10 prototype constituents were detected in serum after oral administration. Integrated metabolomics and network pharmacology analyses revealed alterations in lipid and amino acid-related metabolic pathways following WWHLW treatment. Gut microbiota analysis showed that WWHLW was associated with less pronounced alterations in microbial diversity and composition than antibiotic treatment. Correlation analysis further revealed statistical associations between microbial taxa and lipid and amino acid-related features. Experimental validation showed that WWHLW reduced inflammatory cytokine expression and suppressed STAT3 phosphorylation, consistent with altered IL-6/STAT3-related molecular changes.

CONCLUSIONS: WWHLW exhibits therapeutic potential against H. pylori infection and HAG through combined antibacterial, anti-inflammatory and metabolic regulatory effects. The protective activity of WWHLW was associated with reduced IL-6/STAT3 signaling, providing pharmacological evidence supporting its traditional use in gastrointestinal disorders.

PMID:42700849 | DOI:10.1016/j.jep.2026.122370

Ther Adv Med Oncol. 2026 Aug 31;18:17588359261481797. doi: 10.1177/17588359261481797. eCollection 2026.

ABSTRACT

BACKGROUND: Hepatocellular carcinoma (HCC) is driven by extensive metabolic reprogramming, vascular remodeling, and immune microenvironmental dysfunction. Although numerous stratification signatures have been proposed, few are grounded in clinically derived serum multi-omics and biologically linked to endothelial remodeling, endothelial regulation, and immune exclusion.

OBJECTIVES: This study aimed to identify a serum-derived lipid-endothelial program associated with immune exclusion and clinical stratification in HCC.

DESIGN: A translational multi-omics study integrating clinically collected serum samples, public transcriptomic cohorts, single-cell RNA sequencing, and experimental validation.

METHODS: Proteomic and metabolomic sequencing was performed on serum samples from patients with HCC and normal controls. Dysregulated pathways were integrated with transcriptomic data from TCGA-LIHC and ICGC-LIRI-JP cohorts to identify genes jointly associated with lipid metabolism and leukocyte transendothelial migration. A risk score was calculated using the expression of PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA. Higher expression of TXNRD1, CLDN4, CLDN6, and CTSA contributed to a higher risk score, whereas PON1 and CYP2C9 contributed protective coefficients. Immune contexture, tumor mutation burden, and exploratory therapeutic sensitivity patterns were further evaluated using transcriptome-based drug sensitivity prediction, followed by single-cell RNA sequencing and experimental expression validation.

RESULTS: Serum multi-omics analysis revealed prominent dysregulation of lipid metabolic pathways and leukocyte transendothelial migration-related processes in HCC. Integrative analysis identified a six-gene lipid-endothelial signature (PON1, TXNRD1, CLDN4, CLDN6, CYP2C9, and CTSA) that stratified patients into high- and low-risk groups. In the TCGA-LIHC cohort, high-risk patients had significantly poorer overall survival than low-risk patients (log-rank P < 0.0001), and this survival-stratifying association was externally supported in the ICGC-LIRI-JP cohort (log-rank P = 0.016). The high-risk phenotype was associated with immune-excluded features, distinct somatic mutation patterns, and altered predicted sensitivity to several selected anticancer agents. Single-cell analysis and experimental assays further supported the association between the six-gene program, malignant epithelial states, endothelial-related remodeling, and immune microenvironmental heterogeneity.

CONCLUSION: This study defines a clinically derived lipid-endothelial program associated with immune exclusion, adverse prognosis, and potential differences in therapeutic vulnerability in HCC. The proposed signature provides a biologically informed framework for prognostic assessment and may support future evaluation of targeted interventions in HCC.

PMID:42682961 | PMC:PMC13530516 | DOI:10.1177/17588359261481797