Piwei Peiyuan Pill Ameliorates Chronic Atrophic Gastritis and Intestinal Metaplasia at Least in Part by Inhibiting the Pellino1/IRAK1/NF‐κB Signaling Axis
Findings suggest that PPP mitigates CAG and attenuates IM at least in part by suppressing the Pellino1/IRAK1/NF‐κB signaling pathway, indicating that it may serve as a promising therapeutic strategy for reducing inflammation‐associated gastric carcinogenesis.
Abstract
Chronic atrophic gastritis (CAG) with intestinal metaplasia (IM) is a key precancerous lesion that may progress to intestinal‐type gastric adenocarcinoma. Piwei Peiyuan Pill (PPP) has shown significant clinical efficacy in ameliorating CAG with IM, but its active components and underlying mechanisms remain unclear. High‐performance liquid chromatography (HPLC) and ultra‐high performance liquid chromatography coupled with high‐resolution mass spectrometry (UHPLC‐HRMS) were used to identify the components of PPP and the active ingredients in PPP‐containing serum. The therapeutic efficacy and potential mechanisms of PPP were further investigated via transcriptomic sequencing and experimental validation. UHPLC‐HRMS analysis of PPP‐containing serum identified several bioactive components, including esculin, lithospermic acid, and atractylenolide III. In CAG rats, PPP significantly ameliorated gastric mucosal damage and reduced serum IL‐6 and TNF‐α levels. Transcriptomic results showed that IRAK1 was highly expressed in CAG patients with IM and associated with activation of the NF‐κB pathway. PPP intervention dose‐dependently suppressed hyperactivation of the Pellino1/IRAK1/NF‐κB axis and decreased the expression of intestinal metaplasia markers CDX1 and MUC2. Additionally, PPP improved immune function by increasing the proportion of CD4+ T cells and decreasing the proportion of CD8+ T cells in CAG model rats. Taken together, these findings suggest that PPP mitigates CAG and attenuates IM at least in part by suppressing the Pellino1/IRAK1/NF‐κB signaling pathway, indicating that it may serve as a promising therapeutic strategy for reducing inflammation‐associated gastric carcinogenesis.
It is demonstrated that HEP exerts gastroprotective effects against CAG through coordinated anti-inflammatory, antioxidant, and structure-dependent NF-κB inhibitory actions, supporting its potential as a promising natural agent for CAG intervention.
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Evaluating the preventive and therapeutic effects of RQMJ on CAG and its intervention in the inflammation–cancer transition process highlights the potential pharmacological value and therapeutic prospects of RQMJ in inflammation-driven gastric diseases.
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YWXY alleviates gastric mucosal injury in combined SPEM and SSDS by regulating IL-1β and TNF-α, restoring the miR-7a-5p/Cdr1as axis, and suppressing WFDC2 expression, which indicates coordinated regulation of inflammatory cytokines, ncRNA networks, and metaplastic markers.
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Background Chronic atrophic gastritis (CAG) is a precancerous gastric lesion characterized by persistent inflammatory injury, glandular atrophy, and impairment of gastric mucosal barrier-associated integrity. Huangjin Shuangshen Decoction (HJSS) has shown therapeutic potential in gastritis-related disorders, but its effects on CAG and the underlying mechanism remain unclear. This study investigated whether HJSS alleviates CAG by modulating inflammation-associated barrier dysfunction. Methods CAG was induced in mice by MNNG combined with ranitidine and irregular feeding, followed by treatment with different doses of HJSS, with folic acid as a positive control. Histopathology, gastric function indices, inflammatory mediators, apoptosis-related markers, and barrier-associated molecules were assessed in vivo. MNNG-injured GES-1 cells treated with HJSS-medicated serum were used for in vitro validation. Transcriptomic analysis, network pharmacology, and pharmacological inhibition were integrated to explore the underlying mechanisms. Results HJSS alleviated gastric mucosal atrophy and histopathological injury, improved gastric functional impairment, reduced inflammatory burden, and attenuated apoptosis-associated epithelial injury in experimental CAG. HJSS also promoted the recovery of gastric mucosal barrier-associated molecules, including CFTR, ZO-1, MUC5AC, Occludin, and Claudin-1. Integrated transcriptomic and network pharmacology analyses highlighted an inflammation–barrier framework involving TNF-related signaling and CFTR-associated regulation. In vitro, HJSS mitigated MNNG-induced epithelial injury, whereas CFTR inhibition attenuated the HJSS-associated restoration of CFTR and ZO-1. HJSS was further associated with suppression of TNF/NF-κB signaling and reduced p65 nuclear translocation. Conclusion HJSS alleviates MNNG-induced CAG by attenuating inflammatory injury and promoting the recovery of gastric mucosal barrier-associated molecular features. Its protective effects are associated with suppression of TNF/NF-κB signaling and involvement of CFTR-associated regulation, supporting an inflammation–barrier mechanism underlying the action of HJSS in CAG.
Shuo Zhang, Shuya Zhang, Mengyi Wang et al.· Frontiers in Immunology· 0 citations
Findings indicate that ELKL exerts significant anti-inflammatory effects through the multi-component and multi-target regulation of inflammatory signaling pathways, thereby supporting its therapeutic potential in preventing the progression of CAG and IM.
Yini Tang, Yan Xue, Shigui Xue et al.· Current Computer - Aided Dru...· 0 citations
Hemorrhoids are commonly associated with inflammatory manifestations. Puji Zhichuang suppositories (PJZC) have been widely applied in the treatment of hemorrhoids; however, their underlying therapeutic mechanisms remain insufficiently understood. Therefore, this study investigated the mechanisms of PJZC in inflammatory hemorrhoids using network pharmacology, 16 S rDNA sequencing, and fecal metabolomics analyses. First, the anti-inflammatory effects of PJZC were validated by evaluating perianal diameter, anorectal coefficient, TNF-α and IL-6 levels, intestinal barrier integrity, and damage-associated molecular patterns (DAMPs). Subsequent multi-omics analyses demonstrated that PJZC exert anti-inflammatory effects may involve reduced PI3K-Akt signaling pathway, gut microbiota composition and metabolic profiles. Finally, molecular docking analysis predicted that the core targets and active ingredients may be closely related to ITGB1, EGFR, and bile acids.
Min Yang, Hongbao Liang, Jian Li et al.· Scientific Reports· 0 citations
