J Ethnopharmacol. 2026 Aug 29;373:122318. doi: 10.1016/j.jep.2026.122318. Online ahead of print.

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Helicobacter pylori (H. pylori) infection is a leading risk factor for chronic gastritis, peptic ulcers, and gastric cancer. The escalating antibiotic resistance of H. pylori and adverse effects arising from standard antibiotic regimens have underscored an urgent need for natural, food-complementary therapeutic alternatives. Terminalia chebula Retz., commonly named "Hezi" in traditional Chinese medicine and "Haritaki" in Ayurveda, is a well-recognized edible fruit with a long history of use in alleviating gastrointestinal disorders.

AIM OF THE STUDY: While it has been traditionally recognized for its anti-inflammatory and antimicrobial properties, its anti-adhesive efficacy against H. pylori and the metabolic mechanisms underlying its in vivo effects remain largely unexplored.

MATERIALS AND METHODS: This study adopted multiple analytical and experimental approaches: ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), RNA-seq, cell viability and adhesion assays, western blotting, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), metabolomics, and proteomics.

RESULTS: In this study, 15 primary compounds in T. chebula aqueous extract were identified, predominantly tannins. Multi-omics analyses (transcriptomics, metabolomics, and proteomics) revealed that T. chebula aqueous extract significantly inhibited H. pylori adhesion and enriched the lysine degradation pathway. Notably, N-alpha-acetyl-L-lysine was characterized as a key metabolite in fecal metabolomic profiling, which was associated with glycosphingolipid biosynthesis, ferroptosis, HIF-1 signaling, lysosomal function, and arginine metabolism. In vitro assays confirmed that N-alpha-acetyl-L-lysine reduced H. pylori adhesion to GES-1 cells, reversed H. pylori-induced cellular damage, and suppressed the secretion of pro-inflammatory cytokines (IL-6 and TNF-α). In vivo, T. chebula aqueous extract administration markedly alleviated H. pylori-induced gastric inflammation by downregulating IL-6, IL-1β, TNF-α, TGF-β, and IFN-γ. Collectively, these findings demonstrate that T. chebula aqueous extract exerts anti-H. pylori effects by regulating lysine metabolism, with N-alpha-acetyl-L-lysine serving as a key metabolite via fecal metabolomics.

CONCLUSION: These findings highlight T. chebula's promising potential as a functional food ingredient or adjunctive therapy for H. pylori-related diseases, providing a natural, mechanism-based option for clinical intervention.

PMID:42665167 | DOI:10.1016/j.jep.2026.122318

Nat Commun. 2026 Mar 20;17(1):2655. doi: 10.1038/s41467-026-70193-w.

ABSTRACT

Pulmonary fibrosis represents a progressive interstitial lung disease marked by excessive extracellular matrix deposition and architectural distortion. Vascular endothelial cells critically contribute to fibrogenesis through paracrine secretion of pro-fibrotic mediators, yet their mechanobiological regulation remains elusive. Using integrated single-cell multi-omics profiling of human pulmonary fibrosis specimens and experimental fibrosis models induced by bleomycin or silica, we identify mechanosensitive Piezo1 upregulation in Endothelial cells as a hallmark of fibrotic progression. Endothelial-specific Piezo1 knockout significantly attenuates Bleomycin-induced fibrotic remodeling in male mice, establishing its pathogenic necessity. Mechanistically, PIEZO1 activation promotes pulmonary fibrosis development via CAPN2-mediated STAT3 phosphorylation, which may regulate the secretion of the pro-fibrotic molecule interleukin-33. These findings suggest that the endothelial PIEZO1-CAPN2-STAT3-IL33 axis is a potential therapeutic target for PF intervention.

PMID:41862476 | PMC:PMC13004862 | DOI:10.1038/s41467-026-70193-w

Redox Biol. 2026 Jan 14;92:104026. doi: 10.1016/j.redox.2026.104026. Online ahead of print.

ABSTRACT

Primary graft dysfunction (PGD) caused by ischemia-reperfusion injury (IRI) is a major complication after lung transplantation, yet its underlying mechanisms remain unclear. Triggering receptor expressed on myeloid cells 1 (Trem1) is an important mediator of inflammation, but its role in neutrophil function and metabolic reprogramming during lung IRI is not well understood. In this study, we used a murine orthotopic lung transplantation model with cold ischemia and reperfusion, and Trem1 knockout (Trem1-/-) and myeloid-specific Trem1 conditional knockout mice (Lysm^CreTrem1^fl) to explore the role of Trem1 in neutrophil recruitment, neutrophil extracellular trap (NET) formation, and metabolism. Our results show that Trem1 expression increases in both mouse and human lungs after reperfusion and correlates with neutrophil infiltration and lung injury. Trem1 deficiency significantly reduced neutrophil and macrophage recruitment, NET formation, and tissue damage. Multi-omics analysis revealed that Trem1 deletion suppressed oxidative phosphorylation (OXPHOS) and induced a metabolic shift in neutrophils toward glycolysis. In clinical samples, the abundance of TREM1+ neutrophils was correlated with PGD severity and OXPHOS activity. These findings identify Trem1 as a key regulator of neutrophil metabolism and recruitment in lung IRI, and suggest that targeting Trem1 may provide a novel therapeutic strategy to mitigate PGD and improve lung transplant outcomes.

PMID:41861599 | DOI:10.1016/j.redox.2026.104026