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

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.