Berberine Attenuates Chronic Atrophic Gastritis Induced by MNNG and Its Potential Mechanism

Main Recommendations Patients with chronic atrophic gastritis or intestinal metaplasia (IM) are at risk for gastric adenocarcinoma. This underscores the importance of diagnosis and risk stratification for these patients. High definition endoscopy with chromoendoscopy (CE) is better than high definition white-light endoscopy alone for this purpose. Virtual CE can guide biopsies for staging atrophic and metaplastic changes and can target neoplastic lesions. Biopsies should be taken from at least two topographic sites (antrum and corpus) and labelled in two separate vials. For patients with mild to moderate atrophy restricted to the antrum there is no evidence to recommend surveillance. In patients with IM at a single location but with a family history of gastric cancer, incomplete IM, or persistent Helicobacter pylori gastritis, endoscopic surveillance with CE and guided biopsies may be considered in 3 years. Patients with advanced stages of atrophic gastritis should be followed up with a high quality endoscopy every 3 years. In patients with dysplasia, in the absence of an endoscopically defined lesion, immediate high quality endoscopic reassessment with CE is recommended. Patients with an endoscopically visible lesion harboring low or high grade dysplasia or carcinoma should undergo staging and treatment. H. pylori eradication heals nonatrophic chronic gastritis, may lead to regression of atrophic gastritis, and reduces the risk of gastric cancer in patients with these conditions, and it is recommended. H. pylori eradication is also recommended for patients with neoplasia after endoscopic therapy. In intermediate to high risk regions, identification and surveillance of patients with precancerous gastric conditions is cost-effective.

A global consensus meeting was held to review current evidence and knowledge gaps and propose collaborative studies on population-wide screening and eradication of Helicobacter pylori for prevention of gastric cancer (GC). 28 experts from 11 countries reviewed the evidence and modified the statements using the Delphi method, with consensus level predefined as ≥80% of agreement on each statement. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach was followed. Consensus was reached in 26 statements. At an individual level, eradication of H. pylori reduces the risk of GC in asymptomatic subjects and is recommended unless there are competing considerations. In cohorts of vulnerable subjects (eg, first-degree relatives of patients with GC), a screen-and-treat strategy is also beneficial. H. pylori eradication in patients with early GC after curative endoscopic resection reduces the risk of metachronous cancer and calls for a re-examination on the hypothesis of ‘the point of no return’. At the general population level, the strategy of screen-and-treat for H. pylori infection is most cost-effective in young adults in regions with a high incidence of GC and is recommended preferably before the development of atrophic gastritis and intestinal metaplasia. However, such a strategy may still be effective in people aged over 50, and may be integrated or included into national healthcare priorities, such as colorectal cancer screening programmes, to optimise the resources. Reliable locally effective regimens based on the principles of antibiotic stewardship are recommended. Subjects at higher risk of GC, such as those with advanced gastric atrophy or intestinal metaplasia, should receive surveillance endoscopy after eradication of H. pylori . Evidence supports the proposal that eradication therapy should be offered to all individuals infected with H. pylori . Vulnerable subjects should be tested, and treated if the test is positive. Mass screening and eradication of H. pylori should be considered in populations at higher risk of GC.

Pectolinarigenin (PEC), a natural flavonoid present in Cirsium chanroenicum and in some species of Citrus fruits, has various pharmacological benefits such as anti-inflammatory and anti-cancer activities. In the present study, we investigated the anti-cancer mechanism of PEC induced cell death caused by autophagy and apoptosis in AGS and MKN28 human gastric cancer cells. The PEC treatment significantly inhibited the AGS and MKN28 cell growth in a dose-dependent manner. Further, PEC significantly elevated sub-G1 phase in AGS cells and G2/M phase cell cycle arrest in both AGS and MKN28 cells. Apoptosis was confirmed by Annexin V and Hoechst 33342 fluorescent staining. Moreover, Immunoblotting results revealed that PEC treatment down-regulated the inhibitor of apoptosis protein (IAP) family protein XIAP that leads to the activation of caspase-3 thereby cleavage of PARP (poly-ADP-ribose polymerase) in both AGS and MKN28 cells in a dose-dependent manner. The autophagy-inducing effect was indicated by the increased formation of acidic vesicular organelles (AVOs) and increased protein levels of LC3-II conversion in both AGS and MKN28 cells. PEC shows the down regulation of PI3K/AKT/mTOR pathway which is a major regulator of autophagic and apoptotic cell death in cancer cells that leads to the down-regulation of p-4EBP1, p-p70S6K, and p-eIF4E in PEC treated cells when compared with the untreated cells. In conclusion, PEC treatment might have anti-cancer effect by down-regulation of PI3K/AKT/mTOR pathway leading to G2/M phase cell cycle arrest, autophagic and apoptotic cell death in human gastric cancer cells. Further studies of PEC treatment can support to develop as a potential alternative therapeutic agent for human gastric carcinoma.