2. Academic Validation
  3. Simo Tang mitigates mitochondria-dependent apoptosis via PI3K/AKT pathway activation in Chronic atrophic gastritis

Simo Tang mitigates mitochondria-dependent apoptosis via PI3K/AKT pathway activation in Chronic atrophic gastritis

  • J Ethnopharmacol. 2026 May 23:363:121417. doi: 10.1016/j.jep.2026.121417.
Yaqin Hu 1,  Yue Wan 1,  Zijing Lu 1,  Yiduo Wu 1,  Guangyu Liu 1,  Songqi Liu 2,  Gaoshang Li 3,  Jiayin Huang 4,  Yaoxian Chin 1,  Wubo Wan 1,  Yinliang Ge 1,  Dongxue Wang 5
Affiliations

Affiliations

  • 1 College of Food Science and Engineering, Yazhou Bay Innovation Institute, Hainan Tropical Ocean University, Marine Food Engineering Technology Research Center of Hainan Province, Collaborative Innovation Center of Marine Food Deep Processing, Hainan Key Laboratory of Herpetological Research, Sanya, 572000, China.
  • 2 Sanya Oceanographic Institution, Ocean University of China, Sanya, 572000, China.
  • 3 School of Food Science and Engineering, Ningbo University, Ningbo, 315800, Zhejiang, China.
  • 4 College of Ocean Food and Biological Engineering, Jimei University, Xiamen, 361021, China.
  • 5 College of Food Science and Engineering, Yazhou Bay Innovation Institute, Hainan Tropical Ocean University, Marine Food Engineering Technology Research Center of Hainan Province, Collaborative Innovation Center of Marine Food Deep Processing, Hainan Key Laboratory of Herpetological Research, Sanya, 572000, China. Electronic address: [email protected].
PMID: 41765119 DOI: 10.1016/j.jep.2026.121417
Abstract

Ethnopharmacological relevance: Simo Tang (SMT), a four-herb formula for abdominal distension and dyspepsia, has served for nearly a millennium. Contemporary use remains largely based on empirical tradition and limited clinical observations, leaving the core pharmacological mechanism-particularly the PI3K/Akt pathway-underlying its efficacy against Chronic atrophic gastritis (CAG) yet to be systematically elucidated.

Aim of the study: This study was designed to integrate modern pharmacological, in silico and experimental Validation to systematically decode the therapeutic mechanisms through which SMT counteracts CAG.

Materials and methods: The bioactive ingredients in SMT were identified by UHPLC/MS. Enable network pharmacology to analyze potential active, ingredient targets and pathway enrichment for CAG of SMT therapy for CAG, using computer molecular simulations. Molecular docking and Molecular dynamics (MD) simulations were performed to help verify the binding ability and conceptual stability of the complex. In vitro/vivo experiments, the protective effects of SMT on H2O2-induced gastric mucosal damage were preliminarily analyzed from the perspectives of Apoptosis, inflammation, mitochondrial function and oxidative indicators.

Results: Network pharmacology and inhibitor assays identified Akt1 as a critical mediator of SMT-induced protection. SMT restored the PI3K/Akt pathway, up-regulated the expression of p-GSK3β, Cyclin D1 and Bcl-2, as well as down-regulated the release of Bax, Apaf-1, Cyt-C, and Caspase-9/3. This preserved mitochondrial integrity and reduced Apoptosis in GES-1 cells. Additionally, SMT suppressed IL-6 and TNF-α, increased SOD activity, and lowered ROS and MDA levels in both GES-1 cells and zebrafish larvae. Although LY294002 alone only partially reversed these beneficial effects, combined inhibition of PI3K/Akt and glutathione synthesis (BSO) almost completely abolished protection. Collectively, SMT alleviates CAG progression through concerted actions of ROS scavenging, inflammation resolution and PI3K/Akt re-activation.

Conclusion: By orchestrating the PI3K/Akt cascade, SMT simultaneously elevates antioxidant enzyme activity, maintains mitochondrial homeostasis, suppresses pro-apoptotic and pro-inflammatory signaling, thereby attenuating gastric mucosal injury and retarding CAG progression.

Keywords

Apoptosis; CAG; Mitochondrial; Network pharmacology; PI3K/AKT pathway; SMT.

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