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      Protective Effect and Potential Mechanism of the Traditional Chinese Medicine Shaoyao-Gancao Decoction on Ethanol-Induced Gastric Ulcers in Rats

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          Abstract

          Background

          Shaoyao-Gancao decoction (SGD) is a classic prescription in traditional Chinese medicine. SGD is effective in the treatment of gastric and duodenal ulcers. However, the biological activity and possible mechanisms of SGD in the treatment of gastric ulcers have not been fully elucidated. The purpose of this study was to scientifically evaluate the protective effect and potential mechanism of SGD against ethanol-induced gastric ulcers in rats.

          Methods

          A single gavage of 10 mL/kg of 75% ethanol was used to establish a rat gastric ulcer model. A histopathological examination of the gastric tissue was performed. The levels of TNF- α, EGF, PGE 2, SOD, and TBARS in gastric tissue were measured by ELISA. Cellular apoptosis in gastric tissues was assessed by TUNEL assay. The expression levels of caspase-3 and Bcl-2 were determined by immunohistochemistry. The potential mechanism of SGD in treating gastric ulcers was further studied using a network pharmacology research method.

          Results

          The gastric tissue of rats with ethanol-induced gastric ulcers had obvious injury throughout the mucosal layer, which was significantly weakened in rats treated with SGD. Furthermore, treatment with SGD significantly increased the levels of EGF, PGE 2, SOD, and Bcl-2 and decreased the levels of TNF- α, TBARS, and caspase-3 in the gastric tissue of rats with ethanol-induced gastric ulcers. SGD reduced ethanol-induced cell apoptosis in gastric tissue from rats with gastric ulcers. A traditional Chinese medicine-based network pharmacology study revealed that SGD exerts its anti-gastric ulcer effect by acting on multiple pathways.

          Conclusions

          The above results indicate that SGD can improve gastric ulcers induced by ethanol. Moreover, this study demonstrated multicomponent, multitarget, and multipathway characteristics of SGD in the treatment of gastric ulcers and provided a foundation for further drug development research.

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          Rb inactivation promotes genomic instability by uncoupling cell cycle progression from mitotic control.

          Loren Michel, Carlos Cordon Cardo, Gloria Juan … (2004)
          Advanced human cancers are invariably aneuploid, in that they harbour cells with abnormal chromosome numbers. However, the molecular defects underlying this trait, and whether they are a cause or a consequence of the malignant phenotype, are not clear. Mutations that disable the retinoblastoma (Rb) pathway are also common in human cancers. These mutations promote tumour development by deregulating the E2F family of transcription factors leading to uncontrolled cell cycle progression. We show that the mitotic checkpoint protein Mad2 is a direct E2F target and, as a consequence, is aberrantly expressed in cells with Rb pathway defects. Concordantly, Mad2 is overexpressed in several tumour types, where it correlates with high E2F activity and poor patient prognosis. Generation of Rb pathway lesions in normal and transformed cells produces aberrant Mad2 expression and mitotic defects leading to aneuploidy, such that elevated Mad2 contributes directly to these defects. These results demonstrate how chromosome instability can arise as a by-product of defects in cell cycle control that compromise the accuracy of mitosis, and suggest a new model to explain the frequent appearance of aneuploidy in human cancer.
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            Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori: a population-based study

            Ka Shing Cheung, Esther W Chan, Angel Y S Wong … (2017)
            Objective Proton pump inhibitors (PPIs) is associated with worsening of gastric atrophy, particularly in Helicobacter pylori (HP)-infected subjects. We determined the association between PPIs use and gastric cancer (GC) among HP-infected subjects who had received HP therapy. Designs This study was based on a territory-wide health database of Hong Kong. We identified adults who had received an outpatient prescription of clarithromycin-based triple therapy between year 2003 and 2012. Patients who failed this regimen, and those diagnosed to have GC within 12 months after HP therapy, or gastric ulcer after therapy were excluded. Prescriptions of PPIs or histamine-2 receptor antagonists (H2RA) started within 6 months before GC were excluded to avoid protopathic bias. We evaluated GC risk with PPIs by Cox proportional hazards model with propensity score adjustment. H2RA was used as a negative control exposure. Result Among the 63 397 eligible subjects, 153 (0.24%) developed GC during a median follow-up of 7.6 years. PPIs use was associated with an increased GC risk (HR 2.44, 95% CI 1.42 to 4.20), while H2RA was not (HR 0.72, 95% CI 0.48 to 1.07). The risk increased with duration of PPIs use (HR 5.04, 95% CI 1.23 to 20.61; 6.65, 95% CI 1.62 to 27.26 and 8.34, 95% CI 2.02 to 34.41 for ≥1 year, ≥2 years and ≥3 years, respectively). The adjusted absolute risk difference for PPIs versus non-PPIs use was 4.29 excess GC (95% CI 1.25 to 9.54) per 10 000 person-years. Conclusion Long-term use of PPIs was still associated with an increased GC risk in subjects even after HP eradication therapy.
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              History of Helicobacter pylori, duodenal ulcer, gastric ulcer and gastric cancer.

              David Graham (2014)
              Helicobacter pylori (H. pylori) infection underlies gastric ulcer disease, gastric cancer and duodenal ulcer disease. The disease expression reflects the pattern and extent of gastritis/gastric atrophy (i.e., duodenal ulcer with non-atrophic and gastric ulcer and gastric cancer with atrophic gastritis). Gastric and duodenal ulcers and gastric cancer have been known for thousands of years. Ulcers are generally non-fatal and until the 20th century were difficult to diagnose. However, the presence and pattern of gastritis in past civilizations can be deduced based on the diseases present. It has been suggested that gastric ulcer and duodenal ulcer both arose or became more frequent in Europe in the 19th century. Here, we show that gastric cancer and gastric ulcer were present throughout the 17th to 19th centuries consistent with atrophic gastritis being the predominant pattern, as it proved to be when it could be examined directly in the late 19th century. The environment before the 20th century favored acquisition of H. pylori infection and atrophic gastritis (e.g., poor sanitation and standards of living, seasonal diets poor in fresh fruits and vegetables, especially in winter, vitamin deficiencies, and frequent febrile infections in childhood). The latter part of the 19th century saw improvements in standards of living, sanitation, and diets with a corresponding decrease in rate of development of atrophic gastritis allowing duodenal ulcers to become more prominent. In the early 20th century physician's believed they could diagnose ulcers clinically and that the diagnosis required hospitalization for "surgical disease" or for "Sippy" diets. We show that while H. pylori remained common and virulent in Europe and the United States, environmental changes resulted in changes of the pattern of gastritis producing a change in the manifestations of H. pylori infections and subsequently to a rapid decline in transmission and a rapid decline in all H. pylori-related diseases.
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                Author and article information

                Contributors
                Wen Liu:
                ORCID: https://orcid.org/0000-0002-4850-6719
                Journal
                Journal ID (nlm-ta): Evid Based Complement Alternat Med
                Journal ID (iso-abbrev): Evid Based Complement Alternat Med
                Journal ID (publisher-id): ECAM
                Title: Evidence-based Complementary and Alternative Medicine : eCAM
                Publisher: Hindawi
                ISSN (Print): 1741-427X
                ISSN (Electronic): 1741-4288
                Publication date Collection: 2022
                Publication date (Electronic): 11 April 2022
                Publication date PMC-release: 11 April 2022
                Volume: 2022
                Electronic Location Identifier: 3069089
                Affiliations
                1School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550004, China
                2The Key Laboratory of Chemistry for Natural Products of Guizhou Province, Chinese Academy of Sciences, Guiyang 550014, China
                3The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang 550001, China
                4Provincial Key Laboratory of Pharmaceutics in Guizhou Province, Guizhou Medical University, Guiyang 550004, China
                5School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550004, China
                6Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
                Author notes

                Academic Editor: Isac Medeiros

                Author information
                https://orcid.org/0000-0002-4850-6719
                Article
                DOI: 10.1155/2022/3069089
                PMC ID: 9017495
                SO-VID: 40dc242d-2c12-4505-b1cb-6ab671e3d438
                Copyright © Copyright © 2022 Yang Jin et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 23 July 2021
                Date revision received : 27 February 2022
                Date accepted : 30 March 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 82060704
                Award ID: 81860706
                Funded by: Guizhou Provincial Department of Science and Technology
                Award ID: QKHJC [2018]1016
                Funded by: Department of Education of Guizhou Province
                Award ID: QJHKYZ [2017]040
                Categories
                Subject: Research Article

                ScienceOpen disciplines: Complementary & Alternative medicine
                Data availability:
                ScienceOpen disciplines: Complementary & Alternative medicine

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