Piwei Peiyuan Pill Ameliorates Chronic Atrophic Gastritis and Intestinal Metaplasia at Least in Part by Inhibiting the Pellino1/IRAK1/NF‐κB Signaling Axis

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.