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Zhou J, Li N, Li X, Ye J, Wang M, Sun G. Review on recent advancements in understanding acetylsalicylic acid-induced gastrointestinal injury: mechanisms, medication, and dosage refinement. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2025; 398:3297-3320. [PMID: 39545984 DOI: 10.1007/s00210-024-03521-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/02/2024] [Accepted: 10/06/2024] [Indexed: 11/17/2024]
Abstract
Acetylsalicylic acid (ASA) is a clinical drug with multiple effects, including prevention of cardiovascular adverse events and anti-cancer effects. However, gastrointestinal side effects, such as gastrointestinal ulcers and bleeding, limit the use of ASA and reduce patient compliance. Various studies have investigated the mechanisms of ASA-induced gastrointestinal injury, and many medicines have been reported to be effective in preventing and treating the adverse gastrointestinal effects of ASA. New formulations of ASA have demonstrated milder gastrointestinal injury than ASA alone. In this article, we summarized the mechanisms of ASA-induced gastrointestinal injury, drugs that resist gastrointestinal side effects of ASA, and progress in research on formulation improvement of ASA to help resolve the clinical dilemma of ASA usage.
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Affiliation(s)
- Jiahui Zhou
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Na Li
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Xinzhong Li
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China
| | - Jingxue Ye
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China.
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China.
| | - Min Wang
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China.
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China.
| | - Guibo Sun
- Beijing Key Laboratory of Innovative Drug Discovery of Traditional Chinese Medicine (Natural Medicine) and Translational Medicine, Institute of Medicinal Plant Development, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
- Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100193, China.
- NMPA Key Laboratory for Research and Evaluation of Pharmacovigilance, Beijing, China.
- Key Laboratory of New Drug Discovery Based On Classic Chinese Medicine Prescription, Chinese Academy of Medical Sciences, Beijing, China.
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Liang TY, Deng RM, Li X, Xu X, Chen G. The role of nitric oxide in peptic ulcer: a narrative review. Med Gas Res 2021; 11:42-45. [PMID: 33642337 PMCID: PMC8103973 DOI: 10.4103/2045-9912.310059] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2019] [Revised: 12/11/2019] [Accepted: 12/11/2019] [Indexed: 12/16/2022] Open
Abstract
Peptic ulcer refers to the inflammatory response and necrotic lesions of the mucosa under the action of various pathogenic factors, which goes deeply into the mucosal muscle layer and often occurs to the gastrointestinal mucosa related to gastric acid secretion, among which the stomach and duodenum are the most common. The clinical manifestations include slow onset, prolonged course and weekly upper abdominal pain. Nitric oxide (NO) is an intracellular and intercellular signaling molecule that plays an important role in many physiological and pathological processes. Studies have found that a small amount of NO produced in vivo plays a role in many physiological homeostasis, such as regulating blood pressure, platelet aggregation, nitrogenization of hemoglobin, and regulating proliferation and differentiation of stem cells. However, under the action of some cytokines and oxidative stress, intracellular NO synthase will catalyze the synthesis of large amounts of NO and participate in the inflammatory response, causing beneficial or harmful effect on the body. Numerous basic studies have focused on the relationship between NO and peptic ulcer. The purpose of this review is to summarize the role of NO in peptic ulcer and its possible mechanism.
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Affiliation(s)
- Tian-Yu Liang
- Department of Neurosurgery & Brain and Nerve Research Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Ru-Ming Deng
- Department of Neurosurgery & Brain and Nerve Research Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Xiang Li
- Department of Neurosurgery & Brain and Nerve Research Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Xiang Xu
- Department of Neurosurgery & Brain and Nerve Research Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
| | - Gang Chen
- Department of Neurosurgery & Brain and Nerve Research Laboratory, the First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
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Anter HM, Abu Hashim II, Awadin W, Meshali MM. Novel chitosan oligosaccharide-based nanoparticles for gastric mucosal administration of the phytochemical "apocynin". Int J Nanomedicine 2019; 14:4911-4929. [PMID: 31456637 PMCID: PMC6620830 DOI: 10.2147/ijn.s209987] [Citation(s) in RCA: 31] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2019] [Accepted: 05/14/2019] [Indexed: 02/06/2023] Open
Abstract
Background: Apocynin (APO) is a bioactive phytochemical with prominent anti-inflammatory and anti-oxidant activities. Designing a nano-delivery system targeted to potentiate the gastric antiulcerogenic activity of APO has not been investigated yet. Chitosan oligosaccharide (COS) is a low molecular weight chitosan and its oral nanoparticulate system for potentiating the antiulcerogenic activity of the loaded APO has been described here. Methods: COS-nanoparticles (NPs) loaded with APO (using tripolyphosphate [TPP] as a cross-linker) were prepared by ionic gelation method and fully characterized. The chosen formula was extensively evaluated regarding in vitro release profile, kinetic analysis, and stability at refrigerated and room temperatures. Ultimately, the in vivo antiulcerogenic activity against ketoprofen (KP)-induced gastric ulceration in rats was assessed by macroscopic parameters including Paul's index and antiulcerogenic activity, histopathological examination, immunohistochemical (IHC) evaluation of cyclooxygenase-2 (COX-2) expression level in ulcerated gastric tissue, and biochemical measurement of oxidative stress markers and nitric oxide (NO) levels. Results: The selected NPs formula with COS (0.5 % w/v) and TPP (0.1% w/v) was the most appropriate one with drug entrapment efficiency percentage of 35.06%, particle size of 436.20 nm, zeta potential of +38.20 mV, and mucoadhesive strength of 51.22%. It exhibited a biphasic in vitro release pattern as well as high stability at refrigerated temperature for a 6-month storage period. APO-loaded COS-NPs provoked marvelous antiulcerogenic activity against KP-induced gastric ulceration in rats compared with free APO treated group, which was emphasized by histopathological, IHC, and biochemical studies. Conclusion: In conclusion, APO-loaded COS-NPs could be considered as a promising oral phytopharmaceutical nanoparticulate system for management of gastric ulceration.
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Affiliation(s)
- Hend Mohamed Anter
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia35516, Egypt
| | - Irhan Ibrahim Abu Hashim
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia35516, Egypt
| | - Walaa Awadin
- Department of Pathology, Faculty of Veterinary Medicine, Mansoura University, Mansoura, Dakahlia35516, Egypt
| | - Mahasen Mohamed Meshali
- Department of Pharmaceutics, Faculty of Pharmacy, Mansoura University, Mansoura, Dakahlia35516, Egypt
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Al Asmari A, Al Shahrani H, Al Masri N, Al Faraidi A, Elfaki I, Arshaduddin M. Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation. Toxicol Rep 2015; 3:105-113. [PMID: 28959528 PMCID: PMC5615375 DOI: 10.1016/j.toxrep.2015.11.001] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/27/2015] [Revised: 11/01/2015] [Accepted: 11/06/2015] [Indexed: 02/07/2023] Open
Abstract
Vanillin is commonly used as an additive in food, medicine and cosmetics, but its effect has not yet been studied in gastric injury. Therefore the effect of vanillin was studied in experimental gastric ulcer. Gastric secretion and acidity were studied in pylorus ligated rats. Ulcer index, levels of gastric mucus, malondialdehyde (MDA), myeloperoxidase activity (MPO), expression of nuclear factor kappa B (NF-κB) p65, and histopathological changes were determined in ethanol induced gastric ulcer. Pre treatment with vanillin significantly reduced gastric secretion (P < 0.001) and acidity (P < 0.0001) and gastric ulcer index scores (P < 0.001). and augmented the gastric mucosal defense. Vanillin significantly restored the depleted gastric wall mucus levels (P < 0.0001) induced by ethanol and also significantly attenuated ethanol induced inflammation and oxidative stress by the suppression of gastric MPO activity (P < 0.001), reducing the expression of NF-κB p65 and the increased MDA levels (P < 0.001). Vanillin was also effective in alleviating the damage to the histological architecture and the activation of mast cells induced by ethanol. Together the results of this study highlight the gastroprotective activity of vanillin in gastric ulcers of rats through multiple actions that include inhibition of gastric secretion and acidity, reduction of inflammation and oxidative stress, suppression of expression of NF-κB, and restoration of the histological architecture.
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Affiliation(s)
| | - Hamoud Al Shahrani
- Department of Ophthalmology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Nasser Al Masri
- Department of Gastroenterology, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Ahmed Al Faraidi
- Department of Psychiatry, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
| | - Ibrahim Elfaki
- Research Center, Prince Sultan Military Medical City, Riyadh, Saudi Arabia
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Halder S, Kar R, Galav V, Mehta AK, Bhattacharya SK, Mediratta PK, Banerjee BD. Cadmium exposure during lactation causes learning and memory-impairment in F1 generation mice: amelioration by quercetin. Drug Chem Toxicol 2015; 39:272-8. [PMID: 26446883 DOI: 10.3109/01480545.2015.1092042] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
Cadmium (Cd) is a known pollutant present in the environment at low levels and is reported to affect reproduction in many ways. The present study was undertaken to explore the effect of Cd in F1 generation mice on cognitive parameters, and to further investigate whether quercetin could modulate these effects. In this study, female lactating mice were exposed to cadmium for seven days just after delivery. The new born pups in their adulthood were tested for learning and memory parameters by passive avoidance task and Morris water maze (MWM) test. It was observed that pups exposed to Cd showed significant impairment of memory in step down latency test, which was reversed by quercetin (100 mg/kg). In MWM test for spatial memory, animals exposed to Cd exhibited increased escape latency, which was reversed by quercetin (50 mg/kg) significantly. Quercetin alone (50 and 100 mg/kg) also demonstrated improved spatial memory, and showed improved retention memory in the passive avoidance paradigm at dose 50 mg/kg. On testing oxidative stress parameters, we observed significantly increased malondialdehyde (MDA) levels in brain tissue of Cd-treated mice. Moreover, co-treatment with quercetin (50 mg/kg) and Cd significantly reduced these MDA levels. The other doses (25 and 100 mg/kg) also showed reduction in MDA levels as compared to the group exposed to Cd alone, though the difference was not statistically significant. Hence, this study highlights the possibility of cognitive impairment in adulthood if there is Cd exposure during lactation and oxidative stress could possibly attribute to this effect.
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Affiliation(s)
- Sumita Halder
- a Department of Pharmacology , University College of Medical Sciences and G. T. B. Hospital , New Delhi , India
| | - Rajarshi Kar
- b Department of Biochemistry , University College of Medical Sciences and G. T. B. Hospital , New Delhi , India
| | - Vikas Galav
- c Central Animal House, University College of Medical Sciences and G. T. B. Hospital , New Delhi , India
| | - Ashish K Mehta
- d Department of Pharmacology , Vardhman Mahavir Medical College, Safdarjung Hospital , New Delhi , India , and
| | - Swapan K Bhattacharya
- a Department of Pharmacology , University College of Medical Sciences and G. T. B. Hospital , New Delhi , India
| | - Pramod K Mediratta
- e Department of Pharmacology , School of Medical Sciences and Research, Sharda University , Greater Noida, Uttar Pradesh , India
| | - Basu D Banerjee
- b Department of Biochemistry , University College of Medical Sciences and G. T. B. Hospital , New Delhi , India
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Farzaei MH, Abdollahi M, Rahimi R. Role of dietary polyphenols in the management of peptic ulcer. World J Gastroenterol 2015; 21:6499-6517. [PMID: 26074689 PMCID: PMC4458761 DOI: 10.3748/wjg.v21.i21.6499] [Citation(s) in RCA: 94] [Impact Index Per Article: 9.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Revised: 02/22/2015] [Accepted: 04/03/2015] [Indexed: 02/06/2023] Open
Abstract
Peptic ulcer disease is a multifactorial and complex disease involving gastric and duodenal ulcers. Despite medical advances, the management of peptic ulcer and its complications remains a challenge, with high morbidity and death rates for the disease. An accumulating body of evidence suggests that, among a broad reach of natural molecules, dietary polyphenols with multiple biological mechanisms of action play a pivotal part in the management of gastric and duodenal ulcers. The current review confirmed that dietary polyphenols possess protective and therapeutic potential in peptic ulcer mediated by: improving cytoprotection, re-epithelialization, neovascularization, and angiogenesis; up-regulating tissue growth factors and prostaglandins; down-regulating anti-angiogenic factors; enhancing endothelial nitric oxide synthase-derived NO; suppressing oxidative mucosal damage; amplifying antioxidant performance, antacid, and anti-secretory activity; increasing endogenous mucosal defensive agents; and blocking Helicobacter pylori colonization associated gastric morphological changes and gastroduodenal inflammation and ulceration. In addition, anti-inflammatory activity due to down-regulation of proinflammatory cytokines and cellular and intercellular adhesion agents, suppressing leukocyte-endothelium interaction, inhibiting nuclear signaling pathways of inflammatory process, and modulating intracellular transduction and transcription pathways have key roles in the anti-ulcer action of dietary polyphenols. In conclusion, administration of a significant amount of dietary polyphenols in the human diet or as part of dietary supplementation along with conventional treatment can result in perfect security and treatment of peptic ulcer. Further well-designed preclinical and clinical tests are recommended in order to recognize higher levels of evidence for the confirmation of bioefficacy and safety of dietary polyphenols in the management of peptic ulcer.
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