<p>Stress is a key trigger of gastric dysmotility, partly via mitochondrial dysfunction and disordered gut–brain hormonal signaling. Xinwei Tang (XWT) is a multi-herb formula used empirically for upper gastrointestinal symptoms, but its mechanisms remain unclear. This study aimed to determine whether XWT alleviates water-immersion restraint stress (WIRS)–induced gastric dysmotility and to delineate underlying mitochondrial and metabolic pathways using integrated in vivo, in vitro and multi-omics approaches. Male rats underwent 7-d WIRS and received vehicle, domperidone (3&#xa0;mg/kg) or XWT (3, 6, 12&#xa0;g/kg). Gastric emptying, serum motilin/gastrin, oxidative stress indices and PINK1/Parkin–LC3/p62 proteins were assessed, and H₂O₂-injured GES-1 cells were treated with XWT-medicated serum. Gastric antra from MOD and XWT-H rats were analyzed by RNA-seq and DIA proteomics (<i>n</i> = 3/group). WIRS reduced gastric emptying by roughly half and lowered motilin/gastrin, increased ROS/MDA and disrupted PINK1/Parkin–LC3/p62 profiles; XWT dose-dependently reversed these changes, with XWT-H approximating domperidone. Omics revealed XWT-associated downregulation of inflammatory/protease and acute-phase genes/proteins and enrichment of oxidative phosphorylation, tricarboxylic-acid cycle and other metabolic pathways, without global activation of canonical autophagy/mitophagy gene sets. These preclinical data indicate that XWT ameliorates stress-induced gastric dysmotility via mitochondria- and metabolism-centred protection with selective tuning of mitophagy-related proteins.</p>

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Mechanisms of Xinwei Tang in stress-induced gastric dysmotility: evidence from rat and In Vitro models

  • Man Tian,
  • Honghui Xiao,
  • Yingbing Mei,
  • Xinyu Zhang,
  • Zhengliang Qi

摘要

Stress is a key trigger of gastric dysmotility, partly via mitochondrial dysfunction and disordered gut–brain hormonal signaling. Xinwei Tang (XWT) is a multi-herb formula used empirically for upper gastrointestinal symptoms, but its mechanisms remain unclear. This study aimed to determine whether XWT alleviates water-immersion restraint stress (WIRS)–induced gastric dysmotility and to delineate underlying mitochondrial and metabolic pathways using integrated in vivo, in vitro and multi-omics approaches. Male rats underwent 7-d WIRS and received vehicle, domperidone (3 mg/kg) or XWT (3, 6, 12 g/kg). Gastric emptying, serum motilin/gastrin, oxidative stress indices and PINK1/Parkin–LC3/p62 proteins were assessed, and H₂O₂-injured GES-1 cells were treated with XWT-medicated serum. Gastric antra from MOD and XWT-H rats were analyzed by RNA-seq and DIA proteomics (n = 3/group). WIRS reduced gastric emptying by roughly half and lowered motilin/gastrin, increased ROS/MDA and disrupted PINK1/Parkin–LC3/p62 profiles; XWT dose-dependently reversed these changes, with XWT-H approximating domperidone. Omics revealed XWT-associated downregulation of inflammatory/protease and acute-phase genes/proteins and enrichment of oxidative phosphorylation, tricarboxylic-acid cycle and other metabolic pathways, without global activation of canonical autophagy/mitophagy gene sets. These preclinical data indicate that XWT ameliorates stress-induced gastric dysmotility via mitochondria- and metabolism-centred protection with selective tuning of mitophagy-related proteins.