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The purpose of this study was to investigate the therapeutic effect of berberine (BBR) on MNNG-induced chronic atrophic gastritis (CAG) and the possible mechanism of BBR through TGF-β1/PI3K signal pathway. GES-1 were pretreated with MNNG for 2 h before BBR treatment in all procedures. Cell viability was quantified by cell counting kit-8, and GES-1...
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Background
PTEN-Long is a translational variant of phosphatase and tensin homolog deleted on chromosome 10 (PTEN). This tumor suppressor is frequently lost or mutated and even it has been shown as the determinant in several human tumors. Therefore, we will determine the significant roles of PTEN-Long in the development of liver cancer.
Methods
In...
Citations
... CAG represents a chronic gastric mucosal inflammation related to the loss of gastric glandular cells, replaced by intestinal-type epithelium and fibrous tissue (Tong et al. 2021). H. pylori has a high rate of infection and antibiotic resistance and poses a threat to humans, and TCM has the potential to mitigate drug resistance and facilitate the eradication of H. pylori . ...
... 16,35,36 Notably, TNF-α generated is considered to be one of the most harmful cytokines involved in CAG. 37 IL-1β is a typical pro-inflammatory cytokine that activates specific immune responses and plays an immune surveillance role. 38 Additionally, IL-6 is a multifunctional proinflammatory cytokine produced by various cells. ...
Background
The Zuojin Pill (ZJP) is widely used for treating chronic atrophic gastritis (CAG) in clinical practice, effectively ameliorating symptoms such as vomiting, pain, and abdominal distension in patients. However, the underlying mechanisms of ZJP in treating CAG has not been fully elucidated.
Purpose
This study aimed to clarify the characteristic function of ZJP in the treatment of CAG and its potential mechanism.
Methods
The CAG model was established by alternant administrations of ammonia solution and sodium deoxycholate, as well as an irregular diet. Therapeutic effects of ZJP on body weight, serum biochemical indexes and general condition were analyzed. HE staining and AB-PAS staining were analyzed to characterize the mucosal injury and the thickness of gastric mucosa. Furthermore, network pharmacology and molecular docking were used to predict the regulatory mechanism and main active components of ZJP in CAG treatment. RT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to measure the expression levels of apoptosis-related proteins, gastric mucosal barrier-associated proteins and PI3K/Akt signaling pathway proteins.
Results
The results demonstrated that ZJP significantly improved the general state of CAG rats, alleviated weight loss and gastric histological damage and reduced the serum biochemical indicators. Network pharmacology and molecular docking found that ZJP in treating CAG by inhibiting inflammation, suppressing apoptosis, and protecting the gastric mucosal barrier via the PI3K/Akt signaling pathway. Further experiments confirmed that ZJP obviously modulated the expression of key proteins involved in gastric mucosal cell apoptosis, such as Bax, Bad, Apaf-1, cleaved-caspase-3, cleaved-caspase-9, Cytochrome C, Bcl-2, and Bcl-xl. Moreover, ZJP significantly reversed the protein expression of Occludin, ZO-1, Claudin-4 and E-cadherin.
Conclusion
Our study revealed that ZJP treats CAG by inhibiting the PI3K/Akt signaling pathway. This research provided a scientific basis for the rational use of ZJP in clinical practice.
... other studies have found that autophagy is significantly inhibited in PLGC, and TCM can alleviate PLGC by promoting autophagy [52,53]. Therefore, we speculate that autophagy also plays different regulatory roles in different stages of PLGC, which is similar to gastric cancer. ...
... It is essential to emphasize that prior studies exclusively focused on observing the role of autophagy in PLGC [6,7,[52][53][54][55][56]. However, the exact molecular mechanism of autophagy regulation remains to be further studied. ...
Objectives
Celastrus orbiculatus ethyl acetate extract (COE) is the main extract of the stem of the Chinese herbal C. orbiculatus, which has anti-tumor and anti-inflammatory biological effects. Our previous study showed that COE had a certain reversal effect on the precancerous lesions of gastric cancer (PLGC) in rats, but the exact mechanism of action remains elusive. We aimed to explore the therapeutic effects of COE on PLGC and the potential mechanisms.
Methods
The PLGC rat model was successfully constructed by N-methyl-N´-nitro-N-nitrosoguanidine (MNNG) multifactorial induction method. Then, COE was prepared to treat the PLGC rat model. Hematoxylin & eosin staining was used to observe gastric mucosal lesions in rats, AB-PAS and HID-AB staining were used to observe intestinal metaplasia. PDCD4-ATG5 signaling pathway was detected by immunohistochemistry (IHC) and reverse transcription polymerase chain reaction (RT-PCR) in vivo, and autophagy level was detected by IHC, transmission electron microscopy, and RT-PCR in vivo. Besides, the PLGC (MC) cell model was successfully constructed by treating GES-1 cells with MNNG. Then, the morphology, proliferation, and apoptosis of MC cells, and the role of the PDCD4-ATG5 signaling pathway and autophagy in MC cells were evaluated by COE and after the overexpression of PDCD4 treatment.
Key findings
COE significantly improved gastric mucosal injury and cellular heteromorphism and retarded the progression of PLGC in rats. Further studies indicated COE not only inhibited the level of autophagy but also interfered with the PDCD4-ATG5 signaling pathway in vivo. On the other hand, COE treatment could effectively reverse MC cell damage, inhibit MC cell proliferation, and promote MC cell apoptosis. Furthermore, COE also promoted PDCD4 and inhibited ATG5 expression in vitro, and the inhibitory effect of COE on ATG5-mediated autophagy was further enhanced after the overexpression of PDCD4.
Conclusions
The study revealed that COE could regulate the PDCD4-ATG5 signaling pathway to inhibit autophagy in gastric epithelial cells, which contributes to reversing the progression of PLGC.
... However, the reversal rate following eradication is influenced by the severity and extent of atrophy 15 . In recent years, traditional Chinese medicine (TCM) has gained increasing attention as a potential treatment for CAG [16][17][18] www.nature.com/scientificreports/ www.nature.com/scientificreports/ ...
Previous studies have demonstrated the rejuvenating and restorative actions of mesenchymal stem cells (MSCs) in multiple diseases, but their role in reversing chronic atrophic gastritis (CAG) is not well understood owing to their low efficiency in homing to the stomach. In this work, we investigated the therapeutic effect of umbilical cord-derived MSCs (UC-MSCs) on CAG by endoscopic submucosal injection and preliminarily explored possible mechanisms in vitro. MSCs and normal saline (NS) were injected into the submucosa of the stomach in randomly grouped CAG rabbits. Therapeutic effects on serum indices and histopathology of the gastric mucosa were analyzed in vivo at 30 and 60 days after MSCs injection. GES-1 cells were co-cultured with MSCs in vitro using a Transwell system and cell viability, proliferation, and migration ability were detected. Additionally, in view of the potential mechanisms, the relative protein expression levels of apoptosis, autophagy and inflammation in vitro were explored by Western Blotting. We found that submucosal injection of MSCs up-regulated serum indices (G-17, PGI and PGI/PGII) and alleviated histopathological damage to the gastric mucosa in CAG rabbits. Co-culture of GES-1 cells with MSCs improved cell viability, proliferation, and migration ability, while suppressing apoptosis. We also observed a reduction in the expression of apoptosis indicators, including Bax and cleaved caspase-3, in GES-1 cells after co-culture with MSCs in vitro. Our findings suggest that submucosal injection of MSCs is a promising approach for reversing CAG, and attenuating apoptosis plays a potential role in this process.
... 33 Berberine may play a role in treating chronic atrophic gastritis by regulating TGF-β1/PI3K/Akt signal pathway. 34 Jatrorrhizine and columbamine, two hydrogenation metabolites of berberine, exert anti-inflammatory and antioxidant activity. 35,36 Palmatine has been shown to possess gastroprotective, anti-inflammatory, and antioxidant effects. ...
CHEN Zhiyong，LI Ye．Deciphering the chemical profile and pharmacological mechanism of Jinlingzi powder (金铃子散) against bile reflux gastritis using ultra-high performance liquid chromatography coupled with Q Exactive Focus mass spectrometry， network pharmacology， and molecular docking[J/OL]．Journal of Traditional Chinese Medicine.
... The in vitro gastric-mucosal cell damage model was established via MNNG treatment of GES-1 cells, and consequently, the morphology and growth characteristics of the model cells changed, compared with normal GES-1 cells. The proliferation, differentiation, and epithelial regeneration of GES-1 model cells are known to be regulated by the SHH signaling pathway [23,27]. The severity of gastric atrophy may be influenced by the inhibition of the SHH signaling pathway by IL-1β, which may inhibit gastric-acid secretion and intracellular calcium release ( Figure 10). ...
CAG is a burdensome and progressive disease. Numerous studies have shown the effectiveness of RUT in digestive system diseases. The therapeutic effects of RUT on MNNG-induced CAG and the potential mechanisms were probed. MNNG administration was employed to establish a CAG model. The HE and ELISA methods were applied to detect the treatment effects. WB, qRT-PCR, immunohistochemistry, TUNEL, and GES-1 cell flow cytometry approaches were employed to probe the mechanisms. The CAG model was successfully established. The ELISA and HE staining data showed that the RUT treatment effects on CAG rats were reflected by the amelioration of histological damage. The qRT-PCR and WB analyses indicated that the protective effect of RUT is related to the upregulation of the SHH pathway and downregulation of the downstream of apoptosis to improve gastric cellular survival. Our data suggest that RUT induces a gastroprotective effect by upregulating the SHH signaling pathway and stimulating anti-apoptosis downstream.
... Jianpiyiqi formula [53] inhibit proliferation Reduce the expression of Wnt1, β-catenin, and cyclin D1 and increase the expression of GSK-3β Huazhuojiedu [54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69][70] promote apoptosis and inhibit proliferation Inhibit AKT1 and downregulate the lnc 517368 ...
... Zuojin Pill [59] Induce autophagy increase the expression levels of PTEN, LC3-II, and Beclin-1 Berberine [60] Induce autophagy promote autophagy-related LC3-II and Beclin-1 and inhibit the PI3K/AKT signaling pathway Weipingshu [61] Induce autophagy increase the number of autophagosomes Anwei decoction [71] Induce autophagy increase the expression levels of ULK1、Atg13、beclin-1, and LC3 Huatan Xiaoyu formula [72] Induce autophagy promote autophagy-related LC3II/LCI and Beclin-1, reduce P62 the patients were significantly decreased after the combined use of the two drugs. Additionally, the study also found that the serum levels of G-17, PG I, and PG II in the experimental group were decreased [26]. ...
... Berberine is an isoquinoline alkaloid found in many herbs, including Coptidis Rhizoma and Phellodendri Chinrnsis Cortex. It can alleviate the inflammatory response of CAG by promoting autophagy-related LC3-II and Beclin-1 and inhibiting the PI3K/AKT signaling pathway [60]. Weipingshu Capsule is a prescription from Xi'an Hospital of TCM for the treatment of precancerous lesions of gastric cancer. ...
Chronic gastritis (CG) is a persistent inflammation of the gastric mucosa that can cause uncomfortable symptoms in patients. Traditional Chinese medicine (TCM) has been widely used to treat CG due to its precise efficacy, minimal side effects, and holistic approach. Clinical studies have confirmed the effectiveness of TCM in treating CG, although the mechanisms underlying this treatment have not yet been fully elucidated. In this review, we summarized the clinical research and mechanisms of TCM used to treat CG. Studies have shown that TCM mechanisms for CG treatment include H. pylori eradication, anti-inflammatory effects, immune modulation, regulation of gastric mucosal cell proliferation, apoptosis, and autophagy levels.
... These effects may be related to kaempferol's inhibition of oxidative stress and attenuation of inflammatory factors, such as tumor necrosis factoralpha (TNF-α), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), and nuclear factor κB (NF-κB) and the modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways (26). Berberine is an alkaloid that reduces the expression of TNF-α, IL1β, and IL8 genes and the occurrence of intestinal inflammation through inhibiting the expression of TLR4 and NOD1 genes in intestinal mucosa (27,28). Epiberberine is an isomer of berlambine; it exhibits anti-adipogenesis effects by modulating the Akt and ERK pathways, anti-dyslipidemia effects by inhibition on cholesterol synthesis, anti-cancer effects by impacting the p53/Bax apoptosis pathway, and antibacterial activities (29). ...
Wumei San (WMS) is a traditional Chinese medicine that has been widely applied in the treatment of piglet diarrhea (PD). However, the mechanism of WMS in PD has not been investigated. In this study, the main active compounds of WMS and the target proteins were obtained from the Traditional Chinese Medicine Systematic Pharmacology, PubChem, and SwissTargetPrediction databases. The molecular targets of PD were identified using GeneCards, OMIM, and NCBI databases. The common targets of WMS and PD were screened out and converted into UniProt gene symbols. PD-related target genes were constructed into a protein-protein interaction network, which was further analyzed by the STRING online database. Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed to construct the component-target gene-disease network. Molecular docking was then used to examine the relationship between the core compounds and proteins. As a result, a total of 32 active compounds and 638 target genes of WMS were identified, and a WMS-compound-target network was successfully constructed. Through network pharmacology analysis, 14 core compounds in WMS that showed an effect on PD were identified. The targets revealed by GO and KEGG enrichment analysis were associated with the AGE-RAGE signaling pathway, PI3K-Akt signaling pathway, TNF signaling pathway, NOD-like receptor signaling pathway, IL-17 signaling pathway, and other pathways and physiological processes. Molecular docking analysis revealed that the active compounds in WMS spontaneously bind to their targets. The results indicated that WMS may regulate the local immune response and inflammatory factors mainly through the TNF signaling pathway, IL-17 signaling pathway, and other pathways. WMS is a promising treatment strategy for PD. This study provides new insights into the potential mechanism of WMS in PD.
... TCM can not only improve clinical symptoms but also control and block the progression of CAG and improve gastric mucosal precancerous lesions, thereby reducing the incidence and mortality of gastric cancer [3,4]. e stimulation of inflammatory factors promotes the infiltration of inflammatory cells, activates cytokines, changes the cellular microenvironment, and maintains chronic inflammation in the stomach [5,6]. Changes in the microenvironment caused by chronic stimulation can further induce DNA damage, increase the frequency of gene mutations, and induce cell carcinogenesis, leading to gastric cancer. ...
CAG is the most common precancerous disease of gastric cancer, which belongs to a kind of chronic gastritis. CAG is in close association with gastric cancer, which makes itself a critical node clinically in cancer prevention and treatment. Curcumol is a main active monomer in Fuzheng Huowei decoction, which has the properties of antioxidant, antiviral, and antitumor. In this study, the expression of SDF-1α/CXCR4/NF-κB was detected by in vivo and in vitro methods. Then, we found that the expressions of NF-κB, SDF-1α, CXCR4, and p-NF-κB were decreased in the curcumol treatment group. Curcumol inhibited gastric cancer cells’ viability, migration, and invasion and induced their apoptosis. After adding the lentivirus overexpressing SDF-1α to the curcumol treatment group, it was found that SDF-1α, CXCR4, NF-κB, and p-NF-κB protein expressions were all increased, and the effect of curcumol on gastric cancer cells was reversed. In the nude mouse experiment, the tumor volume in the curcumol + SDF-1α group was the largest, and the tumor volume in the Fuzheng Huowei decoction + NC group was the smallest. In conclusion, curcumol effectively protects gastric tissue and inhibits the viability of gastric cancer cells, and curcumol regulates SDF-1α/CXCR4/NF-κB to play a therapeutic role in chronic atrophic gastritis and gastric cancer.
... Traditional Chinese medicine (TCM) has been prevalently acknowledged as the treasure trove of natural compounds with pronounced clinical efficacy [6]. As reported before, many TCMs can improve CAG, such as berberine [7] and Jianpiyiqi formula [8]. Banxia Xiexin decoction (BXD), as a classic prescription Treatise on Febrile Diseases (Shanghan Lun), has been applied for two thousand years and is considered an effective therapy for functional dyspepsia, gastroesophageal reflux disease, and colon cancer [9][10][11]. ...
Chronic atrophic gastritis (CAG) is a common chronically digestive disease which is notoriously characterized by atrophy of the epithelium and glands of the gastric mucosa, reduced number, thinning of the gastric mucosa, thickening of the mucosal base, or pyloric glandular hyperplasia and intestinal glandular hyperplasia, or with atypical hyperplasia. Banxia Xiexin decoction (BXD) has been applied for two thousand years and is considered an effective therapy for functional dyspepsia, gastroesophageal reflux disease and colon cancer. In this current study, to probe into the underlying mechanism of BXD on CAG, network pharmacology was conducted to collect druggable ingredients and predicted targets of BXD and the CAG-associated targets were harvested to take intersection with druggable ingredients from BXD predicted targets to obtain potential critical action targets. Subsequently, GO enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were conducted to elucidate the underlying mechanisms and roles from the perspective of overall pathways and cellular functions. Eventually, molecular docking integrated with molecular dynamics simulations was conducted to further investigate the mechanism of action of BXD active ingredients on CAG from drug molecule-target interactions and to provide a theoretical basis for BXD drug development.
