Jul 2026· Chinese Medicine· Vol 21· 0 citations· 35 references
Medicine
TL;DR
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.
Abstract
Chronic atrophic gastritis (CAG) is a critical stage in the progression from inflammation to cancer and is closely associated with an increased risk of gastric cancer (GC). Renqing Mangjue (RQMJ), a traditional Tibetan herbal remedy, has shown diverse pharmacological properties, including regulation of gastrointestinal function and anti-inflammatory effects. However, the specific effects and mechanisms by which RQMJ influences the transition from inflammation to cancer remain unclear. This study aimed to evaluate the preventive and therapeutic effects of RQMJ on CAG and its intervention in the inflammation–cancer transition process, with a focus on exploring the underlying molecular mechanisms. RQMJ was chemically characterized by UPLC-Q-TOF–MS/MS and HPLC. A rat model of CAG and its inflammation-cancer transition was established and treated with different doses of RQMJ. The therapeutic effects of RQMJ were evaluated by gross gastric mucosal observation, ELISA, histopathological staining, immunohistochemistry, and Western blot analysis. In vitro, the effects of RQMJ on inflammation and migration of the gastric precancerous cell model (MC cells) were assessed using ELISA, wound-healing, Transwell migration, and Western blot assays. RNA sequencing and molecular biology techniques were then employed to explore the underlying mechanisms, and key targets were further validated in both in vivo and in vitro experiments. Finally, C-type natriuretic peptide (CNP) was used to verify the involvement of the identified signaling pathway. A total of 2780 chemical constituents were identified in RQMJ. A dynamic rat model of CAG and its progression to GC was established. During CAG, persistent inflammation and aberrant PI3K–AKT activation formed a positive-feedback loop, driving FAK overexpression and epithelial–mesenchymal transition (EMT)-related changes, which remained active in GC despite partial reduction of inflammation. RQMJ markedly alleviated gastric mucosal injury, suppressed intestinal metaplasia, and improved gastrointestinal function. It also reduced pro-inflammatory mediators (TNF-α, IL-1β, CRP), increased IL-10, and downregulated tumor-related markers (Ki-67, Vimentin, CA19-9). In vitro, RQMJ inhibited MC cell proliferation and migration, suppressed inflammatory and EMT-related proteins. Mechanistically, RQMJ activated the cGMP–PKG pathway and inhibited the PI3K–AKT signaling pathway, thereby disrupting inflammatory amplification. This further downregulated extracellular matrix (ECM)–receptor interaction molecules (TGF-β, FAK, Itga2), ultimately blocking the inflammation–cancer transition. RQMJ may activate the cGMP–PKG signaling pathway while suppressing aberrant PI3K–AKT activation, thereby reducing inflammatory cytokine levels and inhibiting ECM remodeling and the EMT-associated process, and thus indirectly interrupting the inflammation-cancer cascade. These findings highlight the potential pharmacological value and therapeutic prospects of RQMJ in inflammation-driven gastric diseases.
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 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.
Cheng Zhang, Fei Lu, Ting Ye et al.· Cell Biology International· 0 citations
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.
Ping Li, Jianran Hu, Yan-juan Yang et al.· International Journal of Bio...· 0 citations
Prolonged or high-dose administration of nonsteroidal anti-inflammatory drugs (NSAIDs) can induce gastric mucosal injury (GMI), potentially progressing to gastric ulcer (GU). Studies have shown that oxidative stress and necroptosis were closely associated with GU. Vladimiria souliei, a traditional Chinese herb, has been used to treat digestive disorders, particularly GU, but its pharmacological mechanisms remain unidentified. This study aimed to investigate the pharmacological mechanisms of GMI treatment in this herb. Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to analyze blood-enterable components. Aspirin (ASP) was orally administered to induce GMI in mice. After intervention with Vladimiria souliei extract (VSE), the morphology of gastric tissues was observed, and the levels of pepsin and prostaglandin E2 (PGE2) were detected. Further therapeutic evaluation of VSE in GMI was performed using hematoxylin and eosin (H&E) and periodic acid-schif (PAS) staining. Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) were measured, while immunohistochemistry and Western blot were used to assess nuclear factor erythroid 2-related factor 2 (Nrf2) and receptor interacting protein kinase 1 (RIP1)-related signaling. Six prototype components were identified in the drug-containing serum of the VSE. Moreover, VSE mitigated ASP-induced GMI with shrunken areas of ulcers and promoted gastric mucin secretion, increased the levels of SOD and PGE2, and decreased the levels of pepsin, MDA, IL-1β, IL-6, and TNF-α. Pharmacological studies revealed that VSE upregulated the expression of Nrf2, NAD (P) H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1) and down-regulated the expression of kelch-like ECH-associated protein-1 (Keap1), RIP1, RIP3, mixed lineage kinase domain-like protein (MLKL), phosphoglycerate mutase 5 (PGAM5), and dynamin-related protein 1 (Drp1) in the gastric mucosa. Therefore, VSE alleviated oxidative stress and necroptosis by regulating Nrf2 and RIP1 signaling in ASP-induced GMI mice, providing a theoretical basis for GU treatment and for the development of medicinal resources with this herb.
Bin Zhao, Xinyi Jiang, Xiaojing Wei et al.· Biological and Pharmaceutica...· 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
ETHNOPHARMACOLOGICAL RELEVANCE
Forsythiae Fructus, a classic heat-clearing and detoxifying herb in traditional Chinese medicine (TCM), is widely used for inflammatory conditions. Its primary bioactive component, Forsythoside A (FTA), exhibits potent anti-inflammatory and antioxidant activities. Given that hypertensive nephropathy is characterized by chronic inflammation, oxidative stress, and fibrosis-hallmarks that correspond to "heat" and "toxin" pathologies in TCM theory-Forsythiae Fructus represents a rational candidate for HN therapy. However, the precise mechanisms by which FTA inhibits HN progression remain incompletely elucidated.
AIM OF THE STUDY
This study aims to investigate the protective effects of FTA against Ang II-induced HN and to elucidate the underlying signaling mechanisms.
MATERIALS AND METHODS
We established HN models in C57BL/6 mice and NRK-52E cells using Ang II. The effects of FTA on renal injury were investigated through renal dysfunction indicators and tissue staining. RNA sequencing, molecular docking, CETSA and SPR technologies were employed to explore potential target sites and mechanisms of FTA in renal injury.
RESULTS
FTA mitigated Ang II-induced renal injury by reducing renal dysfunction markers (Cr, BUN and Alb/Cr), restoring renal tissue architecture, and decreasing inflammatory markers (Ilb, Il6, Tnf), without exerting antihypertensive effects. RNA sequencing revealed associations with mTOR and ASCL1.Taken together, our in vivo and in vitro data reveal that FTA binds to ASCL1 and inhibits its activity, subsequently blocking the downstream CCNB1/mTOR pathway to confer renal protection. This inhibition promotes mitophagy and inhibits ferroptosis, ultimately alleviating renal injury.
CONCLUSIONS
This study confirmed that FTA can bind to ASCL1, targeting the ASCL1-CCNB1/mTOR pathway to protect the kidney from Ang II-induced injury, offering broad therapeutic prospects for the treatment of HN.
Xiaoli Cui, Die Yang, Zhi-Hong Zhang et al.· Journal of Ethnopharmacology· 0 citations