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Araújo RPN, da Silva Freitas FV, Nunes DB, da Silva Brito AK, da Costa DS, de Sousa DP, de Cássia Meneses Oliveira R, Dos Santos RF. Investigating the pharmacological potential of phytol on experimental models of gastric ulcer in rats. NAUNYN-SCHMIEDEBERG'S ARCHIVES OF PHARMACOLOGY 2024; 397:7757-7766. [PMID: 38717706 DOI: 10.1007/s00210-024-03085-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/30/2023] [Accepted: 04/04/2024] [Indexed: 10/04/2024]
Abstract
Phytol is a diterpene constituent of many essential oils, belonging to the group of unsaturated acyclic alcohols. Although phytol possesses antimycobacterial and anti-inflammatory effects, no reports of a gastrointestinal action are available from the literature. Due to the well-known shortcomings of classical anti-ulcer drugs (e.g. side effects or relapses), natural products may offer an attractive alternative. In this study, a potential gastroprotective activity of phytol was evaluated using acute and chronic ulcer models in rats. Phytol 12.5, 25 and 50 mg/kg, administered orally 1 h prior to induction of gastric lesions by absolute ethanol, inhibited the lesion area by 96, 90 and 95%, respectively. When lesions were induced by ischemia and reperfusion, phytol 12.5 and 25 mg/kg per os decreased the lesion areas by 89 and 46%, respectively. In the third acute ulcer model (lesions induced by ibuprofen), phytol 12.5 mg/kg reduced the lesion area by 55%. Phytol restored the decreased level of reduced glutathione, the increased levels of myeloperoxidase and malondialdehyde and the decreased levels of catalase and superoxide dismutase in rats with gastric ulcer induced by ethanol to levels obtained in vehicle group. Finally, in a chronic model in which gastric ulcer was induced by acetic acid directly instilled into the stomach, phytol administered orally over a time period of 7 days at 12.5, 25, 50 and 100 mg/kg reduced lesion areas by 84, 81, 83 and 68%. Our data suggest a gastroprotective and cicatrizing effect of phytol, possibly associated with its antioxidant effect.
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Affiliation(s)
- Ruan Pablo Nunes Araújo
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
| | - Francilene Vieira da Silva Freitas
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
| | - Daniel Barbosa Nunes
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
| | - Ana Karoline da Silva Brito
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
| | - Douglas Soares da Costa
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
| | - Damião Pergentino de Sousa
- Pharmaceutical Sciences Department, Federal University of Paraíba, Campus I Lot. Cidade Universitaria, João Pessoa, Paraíba, CEP 58051-900, Brazil
| | - Rita de Cássia Meneses Oliveira
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil.
| | - Rosimeire Ferreira Dos Santos
- Medicinal Plants Research Center, Graduate Program in Pharmacology, Center of Health Sciences, Federal University of Piauí, Nossa Sra. de Fátima Avenue - Fátima, Teresina, Piauí, CEP 64049-550, Brazil
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Zhang M, Xu L, Chen L, Wu H, Jia L, Zhu H. Dendrobium officinale Polysaccharides as a Natural Functional Component for Acetic-Acid-Induced Gastric Ulcers in Rats. Molecules 2024; 29:880. [PMID: 38398633 PMCID: PMC10891678 DOI: 10.3390/molecules29040880] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2023] [Revised: 02/10/2024] [Accepted: 02/12/2024] [Indexed: 02/25/2024] Open
Abstract
Dendrobium officinale is an important edible and medicinal plant, with the Dendrobium officinale polysaccharide (DOP) being its primary active constituent, known for its diverse biological activities. In this study, DOP was extracted and characterized for its structural properties. The potential of DOP to ameliorate gastric ulcers (GUs) was investigated using an acetic-acid-induced GU model in rats. The results demonstrated that DOP exerted a multifaceted protective effect against GU, mitigating the deleterious impact on food intake and body weight in rats. DOP exhibited its protective action by attenuating cellular damage attributed to oxidative stress and inflammatory reactions mediated by enhanced activities of SOD, GSH, and GSH-PX, coupled with a downregulation in the expression of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α. Furthermore, DOP effectively inhibited apoptosis in gastric mucosa cells of acetic-acid-induced GU rat models and facilitated the self-repair of damaged tissues. Remarkably, the DOP-200 and DOP-400 groups outperformed omeprazole in reducing the expression of IL-6 and malondialdehyde (MDA) in tissues, as well as IL-1β, IL-6, and TNF-α in serum. These groups also exhibited an improved expression of SOD in tissues and SOD, GSH, and GSH-PX in serum. A Western blot analysis of gastric mucosa demonstrated that the DOP-200 and DOP-400 groups significantly reduced the expression of NF-κBp65, phosphorylated NF-κBp65, FoxO3a, and Bim. The observed antagonism to GU appeared to be associated with the NF-κB cell pathway. Additionally, qRT-PCR results indicate that DOP reduced the mRNA transcription levels of IL-6, and TNF-α, which shows that the healing of GU is related to the reduction in the inflammatory reaction by DOP. However, the expression of EGF and VEGF decreased, suggesting that the mechanism of DOP inhibiting GU may not be directly related to EGF and VEGF, or there is an uncertain competitive relationship between them, so further research is needed.
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Affiliation(s)
- Miao Zhang
- School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China; (M.Z.); (L.J.)
- Guangxi Science Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China; (L.X.); (L.C.); (H.W.)
| | - Liba Xu
- Guangxi Science Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China; (L.X.); (L.C.); (H.W.)
| | - Long Chen
- Guangxi Science Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China; (L.X.); (L.C.); (H.W.)
- Department of Analytical Chemistry and Food Science, Faculty of Food Science and Technology, University of Vigo, 36310 Vigo, Spain
| | - Huan Wu
- Guangxi Science Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China; (L.X.); (L.C.); (H.W.)
| | - Li Jia
- School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China; (M.Z.); (L.J.)
| | - Hua Zhu
- School of Chemistry and Chemical Engineering, Guangxi Minzu University, Nanning 530006, China; (M.Z.); (L.J.)
- Guangxi Science Research Center of Traditional Chinese Medicine, Guangxi University of Chinese Medicine, Nanning 530200, China; (L.X.); (L.C.); (H.W.)
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Zhen BX, Cai Q, Li F. Chemical components and protective effects of Atractylodes japonica Koidz. ex Kitam against acetic acid-induced gastric ulcer in rats. World J Gastroenterol 2023; 29:5848-5864. [PMID: 38074916 PMCID: PMC10701307 DOI: 10.3748/wjg.v29.i43.5848] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Revised: 10/21/2023] [Accepted: 11/08/2023] [Indexed: 11/20/2023] Open
Abstract
BACKGROUND Atractylodes japonica Koidz. ex Kitam. (A. japonica, Chinese name: Guan-Cangzhu, Japanese name: Byaku-jutsu), a perennial herb, which is mainly distributed in northeast area of China, it’s often used to treat digestive system diseases such as gastric ulcer (GU). However, the mechanism of its potential protective effects against GU remains unclear.
AIM To investigate the protective effects of A. japonica on acetic acid-induced GU rats.
METHODS The chemical constituents of A. japonica were determined by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) analysis. The rat model of GU was simulated by acetic acid method. The pathological changes of gastric tissues were evaluated by hematoxylin-eosin stain, the levels of epidermal growth factor (EGF), EGF receptor (EGFR), nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-10, Na+-K+-ATPase (NKA) in serum and gastric tissues were determined by enzyme-linked immunosorbent assay, and the mRNA expressions of EGFR, NF-κBp65, IkappaBalpha (IκBα) and Zonula Occludens-1 (ZO-1) in gastric tissues were determined by real-time reverse transcription polymerase chain reaction, and the efficacy was observed. Then, plasma metabolomic analysis was performed by UPLC-MS/MS to screen the specific potential biomarkers, metabolic pathways and to explore the possible mechanisms.
RESULTS 48 chemical constituents were identified. Many of them have strong pharmacological activity, the results also revealed that A. japonica significantly improved the pathological damage of gastric tissues, increased the expression levels of IL-10, IκBα related to anti-inflammatory factors, decreased the expression levels of IL-1β, NF-κB, NF-κBp65, related to proinflammatory factors, restored the levels of factors about EGF, EGFR, ZO-1 associated with ulcer healing and the levels of factors about NKA associated with energy metabolism. Metabolomic analysis identified 10 potential differential metabolites and enriched 7 related metabolic pathways.
CONCLUSION These findings contribute to the understanding of the potential mechanism of A. japonica to improve acetic acid-induced GU, and will be of great importance for the development and clinical application of natural drugs related to A. japonica.
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Affiliation(s)
- Bi-Xian Zhen
- Department of Medicine, Liaoning University of Traditional Chinese Medicine, Dalian 116600, Liaoning Province, China
| | - Qian Cai
- Department of Medicine, Liaoning University of Traditional Chinese Medicine, Dalian 116600, Liaoning Province, China
| | - Feng Li
- Department of Medicine, Liaoning University of Traditional Chinese Medicine, Dalian 116600, Liaoning Province, China
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Meurer M, de Oliveira BMM, Cury BJ, Jerônimo DT, Venzon L, França TCS, Mariott M, Silva-Nunes R, Santos AC, Roman-Junior WA, Oliveira RG, Arunachalam K, Santin JR, Benvenutti L, Souza P, Aldana-Mejía JA, da Silva L. Extract of Tagetes erecta L., a medicinal plant rich in lutein, promotes gastric healing and reduces ulcer recurrence in rodents. JOURNAL OF ETHNOPHARMACOLOGY 2022; 293:115258. [PMID: 35378194 DOI: 10.1016/j.jep.2022.115258] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 02/09/2022] [Accepted: 03/29/2022] [Indexed: 06/14/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Tagetes erecta L. (Asteraceae), popularly known as Aztec Marigold, is used in South America to treat several ailments. Despite reports that T. erecta flowers are used in folk medicine to treat gastrointestinal diseases, there is no study regarding its gastric healing effects. AIM OF THE STUDY The effect of dry extract of T. erecta L. (DETe) in gastric healing and gastric ulcer recurrence was evaluated, contributing to the validation of the antiulcer potential of this medicinal plant. METHODS Rats were treated orally with vehicle (1 ml/kg), omeprazole (20 mg/kg), or DETe (3, 30 or 300 mg/kg) for 7 days, twice a day. The lesion area was evaluated, and the levels of reduced glutathione (GSH) and lipoperoxides (LOOH) and the activity of the superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and myeloperoxidase (MPO) were measured. The ulcer recurrence was evaluated in mice and induced by interleukin (IL)-1β (1 μg/kg, i.p). The recurred area, gastric wall thickness, GSH and cytokines levels, MPO and N-acetylglucosaminidase (NAG) activities were measured. RESULTS DETe accelerated the healing of gastric ulcers only at 300 mg/kg, reducing the ulcerated area by 66%. In parallel, DETe reduced LOOH levels, SOD, CAT and MPO activities, while increasing GST activity and mucin amount. In the recurrence model, DETe reduced the lesion area by 94%, and in parallel decreased the gastric wall thickness and TNF levels, while increasing IL-10 amount. CONCLUSIONS Corroborating the popular use of T. erecta, DETe favors the antioxidant system and reduce gastric inflammation, accelerating the gastric healing process and reducing the ulcer recurrence.
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Affiliation(s)
- Mariane Meurer
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Beatriz M M de Oliveira
- Postgraduate Program in Health Sciences, Community University of Chapecó Region, Chapecó, SC, 89809-900, Brazil
| | - Benhur J Cury
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Daniele T Jerônimo
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Larissa Venzon
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Tauani C S França
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Marihá Mariott
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Ruan Silva-Nunes
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Ana C Santos
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Walter A Roman-Junior
- Postgraduate Program in Health Sciences, Community University of Chapecó Region, Chapecó, SC, 89809-900, Brazil
| | - Ruberlei G Oliveira
- Postgraduate Program in Master's Degree in Sciences Applied to Hospital Care Júlio Müller University Hospital, Federal University of Mato Grosso, Cuiabá, Brazil
| | - Karuppusamy Arunachalam
- Key Laboratory of Economic Plants and Biotechnology and the Yunnan Key Laboratory for Wild Plant Resources, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, People's Republic of China
| | - José Roberto Santin
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Larissa Benvenutti
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Priscila Souza
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil
| | - Jennyfer A Aldana-Mejía
- Postgraduate Program in Pharmaceutical Sciences, University of São Paulo, Campus Ribeirão Preto, Ribeirão Preto, Brazil
| | - Luisa da Silva
- Postgraduate Program in Pharmaceutical Sciences, Chemical Pharmaceutical Research Nucleus (NIQFAR), University of Vale Do Itajaí, Itajaí, SC, 89809-900, Brazil.
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Mohammed MA, Hamed MA, El-Gengaihi SE, Enein AMA, Kachlicki P, Hassan EM. Profiling of secondary metabolites and DNA typing of three different Annona cultivars grown in Egypt. Metabolomics 2022; 18:49. [PMID: 35781851 PMCID: PMC9252975 DOI: 10.1007/s11306-022-01911-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 06/15/2022] [Indexed: 11/28/2022]
Abstract
OBJECTIVES Natural products are often efficacious and safe alternatives to synthetic drugs. This study explored secondary leaves and bark metabolites profiles in extracts of a new Egyptian hybrid, Annona cherimola × Annona squamosa, known as Abdel Razek. This hybrid exhibited 100% similarity with A. cherimola as evidenced by random amplified polymorphic DNA (RAPD) and inter-simple sequence repeat (ISSR) analyses. METHODS Primary constituents in methanol extracts of different plant organs were identified. Extracts richest in alkaloids and polyphenolics were assessed for in vitro antioxidant activity and the most potent were further studied in vivo for treating gastric ulcer in rats. The latter activity was assessed histopathologically. RESULTS Structural analysis with HPLC/ESI-MSn, and UPLC/HESI-MS/MS identified 63 metabolites, including seven amino acids, 20 alkaloids, 16 flavonoids, eight phenolics and other compounds. Severe stomach alteration was observed after ethanol induction in rats. Ulcer score, oxidative stress biomarkers, cell organelles biomarker enzymes, and gastrointestinal histological features improved to variable degrees after treatment with Annona Abdel Razek hybrid leaves and bark methanol extracts. CONCLUSION Extracts of Annona Abdel Razek had showed in vitro antioxidant effect and may be promising for the treatment of gastric ulcers.
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Affiliation(s)
- Mona Arafa Mohammed
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12311, Egypt.
| | - Manal A Hamed
- Department of Therapeutic Chemistry, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12311, Egypt.
| | - Souad Eisawy El-Gengaihi
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12311, Egypt
| | | | - Piotr Kachlicki
- Institute of Plant Genetics of the Polish Academy of Sciences (Metabolomics Group), Poznan, Poland
| | - Emad Mohamed Hassan
- Medicinal and Aromatic Plants Research Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Dokki, Cairo, 12311, Egypt
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da Silveira Vasconcelos M, de Souza TDFG, Nunes-Pinheiro DCS, da Silva Mendes FR, de Sousa FD, de Siqueira Oliveira L, de Paula PC, Gurgel DC, Silva AS, Nabavi SM, de Melo DF. Antioxidants and gastric lesions. ANTIOXIDANTS EFFECTS IN HEALTH 2022:681-718. [DOI: 10.1016/b978-0-12-819096-8.00056-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Yuan E, Liu L, Huang M, Chang B, Qi C, Gou N, Ren J. Effects of complex extracts of traditional Chinese herbs on gastric mucosal injury in rats and potential underlying mechanism. FOOD FRONTIERS 2021; 2:305-315. [DOI: 10.1002/fft2.73] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/21/2025] Open
Abstract
AbstractFive complex extracts (CEs) of seven Chinese herbs (Astragalus, Poria cocos, Alpinia officinarum Hance, Radix Puerariae, Ginseng, Licorice, Hericium erinaceus) were prepared by hot water extraction and evaluated for their effect on gastric ulcer in rats. In rats with acetic acid‐induced chronic gastric ulcer, gross and microscopic appearance showed that gastric mucosal injury index and lesion inhibition rate were improved after CEs gavage for 21 days. Pretreatment with CEs for 21 days in rats with acute gastric ulcer could also improve the gastric mucosal injury by ethanol. CE1, CE4, and CE5 showed more obvious effect in two models. The cell experiments results showed that CE1, CE4, and CE5 effectively inhibited Wnt signaling activity. Thus, they could protect gastric mucosa through inhibiting Wnt signaling pathway. These results indicated that CE1, CE4, and CE5 had significant protective effects on gastric mucosal injury by inhibiting Wnt signalling pathway and could be developed into safe functional products.
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Affiliation(s)
- Erdong Yuan
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Liangyun Liu
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Min Huang
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Bo Chang
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Chunli Qi
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Na Gou
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
| | - Jiaoyan Ren
- School of Food Science and Technology South China University of Technology Wushan Road 381 Guangzhou Guangdong 510000 China
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Taxifolin and gastro-adhesive microparticles containing taxifolin promotes gastric healing in vivo, inhibits Helicobacter pylori in vitro and proton pump reversibly in silico. Chem Biol Interact 2021; 339:109445. [PMID: 33741339 DOI: 10.1016/j.cbi.2021.109445] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Revised: 02/22/2021] [Accepted: 03/10/2021] [Indexed: 01/02/2023]
Abstract
Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H+/K+-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm2). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H+/K+-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 μg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H+/K+-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.
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Salami AT, Adebimpe MA, Olagoke OC, Iyiola TO, Olaleye SB. Potassium bromate cytotoxicity in the Wister rat model of chronic gastric ulcers: Possible reversal by protocatechuic acid. J Food Biochem 2020; 44:e13501. [PMID: 33025593 DOI: 10.1111/jfbc.13501] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Revised: 09/09/2020] [Accepted: 09/15/2020] [Indexed: 12/13/2022]
Abstract
The interaction between ingested xenobiotics and the gastrointestinal epithelium influences the possibility of gut epithelial cytotoxicity and systemic toxicity. Potassium bromate (KBrO3 ) has been shown to perturb the central nervous system and it may be carcinogenic, albeit it is used as a food additive. This highlights the need to understand KBrO3 's effect on the stomach epithelium. Here, we report the cytotoxic potential of KBrO3 in an ulcerated stomach, as well as possible cytoprotection by the polyphenol - protocatechuic acid. Potassium bromate (12.5 mg/kg) and protocatechuic acid (120 mg/kg) were administered orally while omeprazole (20 mg/kg) was used as standard. Potassium bromate exacerbated gastric ulcers, increased malonaldehyde levels, catalase, and sodium pump activities, but reduced nitric oxide levels. Potassium bromate further increased mast cell count in the muscularis mucosa, while inducing chronic inflammation and moderate angiogenesis in the gastric mucosa. Our results delineate KBrO3 -induced gastric epithelial cytotoxicity that is ameliorated by protocatechuic acid. PRACTICAL APPLICATIONS: Potassium bromate is a known food additive in the baking, brewing, and cheese-making process. Conversely, protocatechuic acid (3,4-dihydroxybenzoic acid) is the polyphenolic content of plants like Hibiscus sabdariffa L that are commonly consumed as herbal drink, food, spices, and used in folk medicine. This study reports the cytoprotective effect of protocatechuic acid against gastric mucosa ulceration that has been aggravated by potassium bromate.
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Affiliation(s)
- Adeola T Salami
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Mayokun A Adebimpe
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
| | - Olawande C Olagoke
- Departamento de Bioquímica e Biologia Molecular, Centro de Ciências Naturais e Exatas (CCNE), Universidade Federal de Santa Maria, Santa Maria, Brasil
| | - Toluwalope O Iyiola
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria.,Department of Physiology, Faculty of Basic Medical Sciences, Adeleke University, Ede, Nigeria
| | - Samuel B Olaleye
- Department of Physiology, College of Medicine, University of Ibadan, Ibadan, Nigeria
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Mishra AP, Bajpai A, Chandra S. A Comprehensive Review on the Screening Models for the Pharmacological Assessment of Antiulcer Drugs. ACTA ACUST UNITED AC 2020; 14:175-196. [PMID: 30864527 DOI: 10.2174/1574884714666190312143846] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Revised: 02/15/2019] [Accepted: 02/27/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Due to inappropriate diet, smoking, alcohol consumption, regular use of drugs like NSAIDs and sedentary lifestyle, one may feel upper abdominal pain which may be the predictor of the gastrointestinal disorder called Peptic Ulcer. When an imbalance occurs between the defensive factor and aggressive factor of the stomach, ulcer formation in the esophageal lining, stomach, or duodenum takes place. This leads to the formation of small sores that cause pain. Another condition that synergizes the abdominal pain is vomiting materials which look like coffee grounds, blood in the stool, black or tarry stools. This pain may increase after lunch or dinner. This problem persists, that often leads to the gastroenterologist's consultation. OBJECTIVE There are many antiulcer screening models present for the determination of antiulcer activity of the drug molecule. The main objective of this study is to find which model is best for the determination of antiulcer activity. METHODS A literature search was conducted on the databases namely Science direct and PubMed with the help of different keywords such as "Anti-ulcer", "In-vitro models" and "In-vivo models". The search was customized by applying the appropriate filters so as to get the most relevant articles to meet the objective of this review article. RESULT There are different research and review papers based on the antiulcer screening models for the determination of antiulcer activity of new drug molecules. CONCLUSION On the basis of our study, we found some useful models for the antiulcer activity of drugs and suggested that, if we use in-vitro and in-vivo methods together, then we may obtain the most relevant result in our research area.
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Affiliation(s)
- Abhinav P Mishra
- Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur - Agra - Delhi National Highway -2, Bhauti, Kanpur, Uttar Pradesh 209305, India
| | - Ankit Bajpai
- Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur - Agra - Delhi National Highway -2, Bhauti, Kanpur, Uttar Pradesh 209305, India
| | - Suresh Chandra
- Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur - Agra - Delhi National Highway -2, Bhauti, Kanpur, Uttar Pradesh 209305, India
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Kim YS, Nam Y, Song J, Kim H. Gastroprotective and Healing Effects of Polygonum cuspidatum Root on Experimentally Induced Gastric Ulcers in Rats. Nutrients 2020; 12:nu12082241. [PMID: 32727104 PMCID: PMC7468921 DOI: 10.3390/nu12082241] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Revised: 07/20/2020] [Accepted: 07/23/2020] [Indexed: 12/22/2022] Open
Abstract
Polygonum cuspidatum is widely used as food and medicine in Korea, China, and Japan. Its major bioactive components, resveratrol and emodin, reportedly protect against gastric lesions. We therefore aimed to investigate: (1) the gastroprotective effects of P. cuspidatum roots in hydrochloric acid/ethanol (HCl/EtOH)- and indomethacin-induced acute gastric ulcer rat models; (2) the healing effects in an acetic acid-induced ulcer model; and (3) potential mechanisms by measuring gastric acid secretion-related parameters in a pyloric ligation-induced ulcer model, and by measuring antioxidant enzyme and prostaglandin E2 levels in the gastric tissue of HCl/EtOH-treated rats. Oral administration of P. cuspidatum extract (PCE) at doses of 100 and 300 mg/kg significantly decreased HCl/EtOH- and indomethacin-induced gastric lesions. PCE at 300 mg/kg significantly reduced gastric lesions in acetic acid-induced ulcers. PCE increased superoxide dismutase (SOD)activity and glutathione(GSH) and prostaglandin E2 levels in gastric tissue, whereas it did not alter gastric acid secretion-related parameters. Our findings indicate that PCE has gastroprotective effects against HCl/EtOH and non-steroidal anti-inflammatory drugs(NSAIDs) and promotes healing of acetic acid-induced ulcers. These gastric mucosal protection and ulcer healing effects are associated with antioxidant effects and the augmentation of prostaglandin E2 and suggest that P. cuspidatum might be a promising preventive and therapeutic agent for treating gastric ulcers.
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Affiliation(s)
| | | | - Jungbin Song
- Correspondence: (J.S.); (H.K.); Tel.: +82-2-961-9394 (J.S.); +82-2-961-0419 (H.K.)
| | - Hocheol Kim
- Correspondence: (J.S.); (H.K.); Tel.: +82-2-961-9394 (J.S.); +82-2-961-0419 (H.K.)
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12
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Bang BW, Park D, Kwon KS, Lee DH, Jang MJ, Park SK, Kim JY. BST-104, a Water Extract of Lonicera japonica, Has a Gastroprotective Effect via Antioxidant and Anti-Inflammatory Activities. J Med Food 2019; 22:140-151. [DOI: 10.1089/jmf.2018.4231] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Affiliation(s)
- Byoung Wook Bang
- Division of Gastroenterology, Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
| | - Dongsun Park
- Department of Biology Education, Korea National University of Education, Cheongju, South Korea
| | - Kye Sook Kwon
- Division of Gastroenterology, Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
| | - Don Haeng Lee
- Division of Gastroenterology, Department of Internal Medicine, Inha University College of Medicine, Incheon, South Korea
| | - Min-Jung Jang
- Department of Research, GREEN CROSS Wellbeing Co., Ltd., Seongnam, South Korea
| | - Sun Kyu Park
- Department of Research, GREEN CROSS Wellbeing Co., Ltd., Seongnam, South Korea
| | - Jeom-Yong Kim
- Department of Research, GREEN CROSS Wellbeing Co., Ltd., Seongnam, South Korea
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Bhattamisra S, Hooi L, Shyan L, Chieh L, Candasamy M, Sahu P. Effect of geraniol and clarithromycin combination against gastric ulcers induced by acetic acid and Helicobacter pylori in rats. Pharmacognosy Res 2019. [DOI: 10.4103/pr.pr_21_19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
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Protective activity of geraniol against acetic acid and Helicobacter pylori- induced gastric ulcers in rats. J Tradit Complement Med 2018; 9:206-214. [PMID: 31193983 PMCID: PMC6544613 DOI: 10.1016/j.jtcme.2018.05.001] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 04/26/2018] [Accepted: 05/05/2018] [Indexed: 12/11/2022] Open
Abstract
Geraniol, an active constituent of rose and palmarosa essential oils, possesses several pharmacological properties, including antioxidant, antibacterial and antiulcer activity. Geraniol was therefore investigated for its antiulcer and anti-Helicobacter pylori activity in rats. Ulcers were induced by injecting acetic acid into the sub-serosal layer of the stomach followed by orogastric inoculation of H. pylori for 7 days. Geraniol (15 and 30 mg/kg), vehicle and a standard drug combination (amoxicillin, 50 mg/kg; clarithromycin, 25 mg/kg and omeprazole, 20 mg/kg) were administered twice daily for 14 days. All the parameters were measured at the end of treatment. The ulcer index was significantly (P < 0.05) lowered in geraniol and standard drug-treated rats as compared to the H. pylori control group (4.13 ± 0.43). Treatment with geraniol (30 mg/kg) significantly (P < 0.01) increased the gastric pH along with a reduction in total acidity and gastric juice volume. Geraniol significantly (P < 0.05) attenuated the myeloperoxidase activity and augmented the total glutathione level in gastric mucosa. The extent of damage in the stomach was measured using a histopathological score. The score in H. pylori control, geraniol (30 mg/kg) and standard drugs was 9, 3.5 and 2.0 respectively. In the rapid urease test, treatment with geraniol (30 mg/kg) and the standard drugs produced a 33% and 67% cure respectively from H. pylori infection. Further, the reduction in bacterial load in the gastric mucosa was confirmed using modified Giemsa staining. Geraniol was observed to exhibit significant antiulcer and anti-H. pylori activity in a rodent model.
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Chen YC, Ho CC, Yi CH, Liu XZ, Cheng TT, Lam CF. Exendin-4, a glucagon-like peptide-1 analogue accelerates healing of chronic gastric ulcer in diabetic rats. PLoS One 2017; 12:e0187434. [PMID: 29095895 PMCID: PMC5667749 DOI: 10.1371/journal.pone.0187434] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2017] [Accepted: 10/19/2017] [Indexed: 12/30/2022] Open
Abstract
Background Diabetes mellitus is an independent risk factor for impaired healing of peptic ulcers, and there are currently no supplementary therapeutics other than the standard antipeptic medicine to improve the ulcer healing in diabetes. This study examined the potential pleiotropic effect of a glucagon-like peptide (Glp)-1 analogue exendin (Ex)-4 on the regeneration of gastric ulcer in streptozotocin-induced diabetic rats. Methods and results Chronic ulcer was created in rat stomach by submucosal injection of acetic acid and peri-ulcer tissues were analyzed 7 days after operation. Ulcer wound healing was impaired in diabetic rats with suppressed tissue expression of eNOS and enhanced levels of pro-inflammatory reactions. Treatment with intraperitoneal injection of Ex4 (0.5 μg/kg/d) significantly reduced the area of gastric ulcer without changing blood glucose level. Ex-4 restored the expression of pro-angiogenic factors, and attenuated the generation of regional inflammation and superoxide anions. The improvement of ulcer healing was associated with increased expression of MMP-2 and formation of granulation tissue in the peri-ulcer area. Conclusion Administration of Ex4 may induce pro-angiogenic, anti-inflammatory and anti-oxidative reactions in the peri-ulcer tissue of diabetic rats that eventually enhances tissue granulation and closure of ulcerative wounds. Our results support the potential clinical application of Glp-1 analogues as supplementary hypoglycemic agents in the antipeptic ulcer medication in diabetes.
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Affiliation(s)
- Yen-Cheng Chen
- Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Ching-Chun Ho
- Department of Surgery, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Chih-Hsun Yi
- Department of Internal Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan
| | - Xiu-Zhu Liu
- Department of Anesthesiology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan
| | - Tzu-Ting Cheng
- Department of Anesthesiology, E-Da Hospital/E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
| | - Chen-Fuh Lam
- Department of Anesthesiology, Buddhist Tzu-Chi General Hospital, Hualien, Taiwan
- Department of Anesthesiology, E-Da Hospital/E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan
- * E-mail:
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16
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Wang Y, Wang S, Bao Y, Li T, Chang X, Yang G, Meng X. Multipathway Integrated Adjustment Mechanism of Glycyrrhiza Triterpenes Curing Gastric Ulcer in Rats. Pharmacogn Mag 2017; 13:209-215. [PMID: 28539709 PMCID: PMC5421414 DOI: 10.4103/0973-1296.204550] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2016] [Revised: 03/02/2016] [Indexed: 12/17/2022] Open
Abstract
Background: Gastric ulcer is a common chronic disease in human digestive system, which is difficult to cure, easy to relapse, and endangers human health seriously. Compared with western medicine, traditional Chinese medicine has a unique advantage in improving the general situation, stablizing medical condition, and with little side effects. Glycyrrhiza known as “king of all the medicine”, has a range of pharmacological activities and is commonly used in a variety of proprietary Chinese medicines and formulations. Objective: On the basis of explicit antiulcer effect of Glycyrrhiza triterpenes, the molecular mechanisms of its therapeutic effect on acetic acid induced gastric ulcer in rats were explored. Materials and Methods: Acetic acid induced gastric ulcer model in rats was established to evaluate the curing effect of G. triterpenes and all of the rats were randomised into six groups: Control group, model group, omeprazole group (0.8 mg/mL), triterpenes high dose group (378.0 mg/mL), triterpenes middle dose group (126.0 mg/mL), and triterpenes low dose group (42.0 mg/mL). All rats in groups were orally administered the active group solution 1.5 mL once daily (model and control groups with saline) for 7 days. HPLC-TOF-MS analysis method was performed to obtain the plasma metabolites spectrums of control group, model group, triterpenes high, middle and low dose groups. Results: A total of 11 differential endogenous metabolites related to the therapeutic effect of G. triterpenes were identified, including tryptophan, phingosine-1-phosphate, pantothenic acid, and so on, among which tryptophan and phingosine-1-phosphate are related with the calcium signaling pathway and arachidonic acid (AA) metabolism. At the same time, in order to verify the above results, quantitative real time polymerase chain reaction were performed to evaluate the expression of H+-K+-ATPase alpha mRNA and phospholipase a 2 mRNA in relational signaling pathways. Combined with statistical analysis of plasma metabolic spectrum and gene expression in tissue, it is suggested that G. triterpenes has antiulcer effect on gastric ulcer in rats. Conclusion: G. triterpenes has a certain regulating effect on the metabolism of tryptophan, AA, sphingosine, and other endogenous metabolites, and we speculated that the antiulcer potential of G. triterpenes can be primarily attributed to its inhibiting gastric acid secretion, reducing the release of inflammatory mediators, and protecting gastric mucosa effects to prevent the further development of gastric ulcer. SUMMARY
G. triterpenes can obviously relieve the symptoms of gastric ulcer, especially the low dose group. G. triterpenes can effectively regulate the amount of small molecule metablism in gastric ulcer rats in vivo, including tryptophan, phingosine-1-phosphate, etc. G. triterpenes resisting gastric ulcer is probably by regulating arachidonic acid metabolism, sphingosine metabolism, etc. Down-regulation of H+-K+-ATPase alpha subunit mRNA and up-regulation of PLA2 mRNA in gastric tissue of dose group validated the possible mechanisms of G. triterpenes for the treatment of gastric ulcer Abbreviations used: HP: Helicobacter pylori, ECL: enterochromaffinlike, TCM: Traditional Chinese medicine; HPLC: High Performance Liquid Chromatography, HPLC/MS: High Performance Liquid chromatography Mass Spectrometry, HPLC-TOF-MS: High Performance Liquid Chromatography and Tof Mass Spectrometry, SD: Sprague Dawley, PCDL: Personal Compound Database and Library, MPP: Mass Profiler Professiona; PCA: principal component analysis, RT-PCR: real time polymerase chain reaction, PGE 2: Prostaglandin E2, COX1: cyclooxygenase 1 S1P: Sphingosine-1-phosphate, AA: Arachidonic acid, 5-HT: 5- hydroxytryptamine.
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Affiliation(s)
- Ying Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China
| | - Shuai Wang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China.,Component Medicine Engineering Research Center of Liaoning Province, Dalian, People's Republic of China.,Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, People's Republic of China
| | - Yongrui Bao
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China.,Component Medicine Engineering Research Center of Liaoning Province, Dalian, People's Republic of China.,Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, People's Republic of China
| | - Tianjiao Li
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China.,Component Medicine Engineering Research Center of Liaoning Province, Dalian, People's Republic of China.,Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, People's Republic of China
| | - Xin Chang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China
| | - Guanlin Yang
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China
| | - Xiansheng Meng
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian, People's Republic of China.,Component Medicine Engineering Research Center of Liaoning Province, Dalian, People's Republic of China.,Liaoning Province Modern Chinese Medicine Research Engineering Laboratory, Dalian, People's Republic of China
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Wang L, Wang X, Zhang SL, Zhu XM, Liu YQ, Song ZJ, Du WJ, Ji J, Cui CL, He X, Zhang CF, Guo CR, Wang CZ, Yuan CS. Gastroprotective effect of palmatine against acetic acid-induced gastric ulcers in rats. J Nat Med 2016; 71:257-264. [DOI: 10.1007/s11418-016-1057-2] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 10/20/2016] [Indexed: 10/20/2022]
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18
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Beta-cyclodextrin enhanced gastroprotective effect of (−)-linalool, a monoterpene present in rosewood essential oil, in gastric lesion models. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:1245-1251. [PMID: 27629579 DOI: 10.1007/s00210-016-1298-3] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2016] [Accepted: 09/02/2016] [Indexed: 12/18/2022]
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Lee BH, Kim N, Nam RH, Lee JY, Lee HS, Lee CH, Park JH, Lee DH. Difficult establishment of a chronic nonsteroidal anti-inflammatory drugs induced gastric inflammation rat model due to gastric adaptation and small bowel damage. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2016; 63:341-7. [PMID: 24953610 DOI: 10.4166/kjg.2014.63.6.341] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
BACKGROUND/AIMS The prevalence of peptic ulcer disease has not decreased mainly due to an increase in the use of NSAIDs. This study was conducted in order to determine whether a chronic NSAID-induced gastric inflammation model could be established by repeated administration of NSAID. METHODS Indomethacin (10 mg/kg) was administered once per week for six weeks in 8- and 26-week rats and animals were sacrificed every week after administration. Gross ulcer index, histologic damage index, myeloperoxidase (MPO) activity, and mucus (glucosamine) levels were measured. Small bowel damage was also evaluated. RESULTS Gross gastric damage index showed a peak level at three weeks and then decreased slowly in the 26-week indomethacin group. Gastric mucosal glucosamine level increased in both the 8-week (p=0.038) and 26-week groups (p=0.007). In addition, gastric mucosal MPO level decreased in the 8-week group (p=0.018) but did not show a decrease in the 26-week group. Small bowel damage began to occur at three weeks during the schedule and eight of 36 rats (22.2%) died due to perforation or peritonitis of the small bowel in the 8- and 26-week indomethacin groups, respectively. CONCLUSIONS Due to gastric adaptation and small bowel damage, repeated administration of NSAID to experimental animals may not be an adequate method for establishment of the chronic gastric inflammation model.
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Affiliation(s)
- Byoung Hwan Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro 173beon-gil, Bundang-gu, Seongnam 463-707, Korea
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Diminazene aceturate, an angiotensin-converting enzyme II activator, prevents gastric mucosal damage in mice: Role of the angiotensin-(1-7)/Mas receptor axis. Biochem Pharmacol 2016; 112:50-9. [PMID: 27241079 DOI: 10.1016/j.bcp.2016.05.010] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2016] [Accepted: 05/24/2016] [Indexed: 01/15/2023]
Abstract
The angiotensin (Ang) II converting enzyme (ACE II) pathway has recently been shown to be associated with several beneficial effects in various organisms, including gastroprotection. ACE II is responsible for converting Ang II into an active peptide, Ang-(1-7), which in turn binds the Mas receptor. Recent studies have shown that diminazene aceturate (Dize) a trypanocidal used in animals, activates ACE II. Thus, in this study, we aimed to evaluate the gastroprotective effects of Dize via the ACE II/Ang-(1-7)/Mas receptor pathway against gastric lesions induced by ethanol and acetic acid in mice. The results showed that Dize could promote gastric protection via several mechanisms, including increased levels of antioxidants and anti-inflammatory factors (e.g., decreasing tumor necrosis factor and interleukin-6 expression and reducing myeloperoxidase activity), maturation of collagen fibers, and promotion of re-epithelialization and regeneration of gastric tissue in different injury models. Thus, Dize represents a novel potential gastroprotective agent.
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Mohod SM, Kandhare AD, Bodhankar SL. Gastroprotective potential of Pentahydroxy flavone isolated from Madhuca indica J. F. Gmel. leaves against acetic acid-induced ulcer in rats: The role of oxido-inflammatory and prostaglandins markers. JOURNAL OF ETHNOPHARMACOLOGY 2016; 182:150-159. [PMID: 26906969 DOI: 10.1016/j.jep.2016.02.026] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/25/2015] [Revised: 01/30/2016] [Accepted: 02/19/2016] [Indexed: 06/05/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Madhuca indica J. F. Gmel. (Sapotaceae) has shown antioxidant, anti-inflammatory, analgesic, anti-diabetic and hepatoprotective potential. It has been traditionally used as laxative, tonic, anti-burn, anti-earthworm, wound healing and headache. AIM OF THE STUDY To investigate the efficacy and possible mechanism of Madhuca indica J. F. Gmel. leaves methanolic extract (MI-ALC) and its isolated chloroform fraction (D3) against experimental induced gastric ulcers. MATERIALS AND METHODS D3 was isolated from MI-ALC, well characterized (HPTLC, FT-IR, (1)H-NMR and LC-MS) and evaluated for its gastroprotective activity by using acetic acid induced ulcer in male Wistar rats (150-200g). D3 (2.5, 5 and 10mg/kg, p.o.) were administered for the period of 14 days. At the end of treatment, rats were sacrificed to collect the stomach sample for evaluation of antioxidant (SOD, GSH, and MDA) enzyme, oxido-inflammatory (TNF-α, IL-1, iNOs) and prostaglandins (COX-II) markers by using RT-PCR. RESULTS The structure and molecular weight (MW) of the isolated compound (D3) were confirmed by 1D and 2D spectral data and characterized as 3,5,7,3',4'-Pentahydroxy flavone with MW C15H10O7. Administration of 3,5,7,3',4'-Pentahydroxy flavone (5 and 10mg/kg) significantly and dose-dependently inhibited (P<0.01 and P<0.001) acetic acid induced an alteration in the antioxidant enzyme. It also significantly and dose-dependently down-regulated gastric oxido-inflammatory and prostaglandins markers. Histopathological aberration induced in the stomach also attenuated by 3,5,7,3',4'-Pentahydroxy flavone treatment. CONCLUSION Finding of present investigation suggests that MI-ALC possessed potent antiulcer activity due to the presence of 3,5,7,3',4'-Pentahydroxy flavone via its oxido-inflammatory and prostaglandins modulatory potential.
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Affiliation(s)
- Smeeta M Mohod
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Paud Road, Erandwane, Pune 411038, Maharashtra, India
| | - Amit D Kandhare
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Paud Road, Erandwane, Pune 411038, Maharashtra, India
| | - Subhash L Bodhankar
- Department of Pharmacology, Poona College of Pharmacy, Bharati Vidyapeeth Deemed University, Paud Road, Erandwane, Pune 411038, Maharashtra, India.
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de Barros M, Mota da Silva L, Boeing T, Somensi LB, Cury BJ, de Moura Burci L, Santin JR, de Andrade SF, Monache FD, Cechinel-Filho V. Pharmacological reports about gastroprotective effects of methanolic extract from leaves of Solidago chilensis (Brazilian arnica) and its components quercitrin and afzelin in rodents. Naunyn Schmiedebergs Arch Pharmacol 2016; 389:403-17. [PMID: 26758066 DOI: 10.1007/s00210-015-1208-0] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2015] [Accepted: 12/29/2015] [Indexed: 12/28/2022]
Abstract
Solidago chilensis Meyenmost (Asteraceae), popularly known as "Brazilian arnica" or "arnica-do-campo," is widely used in the folk medicine to treat gastric disorders. Based on this, the gastroprotective activity of S. chilensis methanolic extract was investigated. Besides, a phytochemical study allowed isolation of two flavonoids (quercitrin and afzelin). The gastroprotective effects were investigated in acute gastric ulcer models, and the antisecretory activity was assessed in vivo and in vitro. The adhered mucus levels, reduced glutathione (GSH) content and myeloperoxidase (MPO) activity were quantified in ulcerated tissues. The contribution of isolated compounds in extract effects was evaluated, and its doses were calculated according to its yield. To evaluate the in vivo healing properties of S. chilensis methanolic extract, a chronic gastric ulcer was induced in mice by 10 % acetic acid. Evaluation of tumor necrosis factor (TNF) levels was also performed at the site of the acetic acid-induced gastric ulcer. In parallel, effects on cell viability and cell proliferation of fibroblasts (L929 cells) were determined by in vitro trials. Firstly, the S. chilensis methanolic extract (100 or 300 mg/kg) reduced the ulcer area induced by ethanol/HCl in mice when compared to the vehicle group. Moreover, the S. chilensis extract (300 mg/kg) prevented the mucus depletion, the increase in MPO activity and the decrease in the GSH levels in the ulcerated gastric tissue. The S. chilensis extract also was able to decrease the indomethacin-induced gastric ulcer in rats at a dose of 100 mg/kg. The antisecretory effect of the extract (100 mg/kg, intraduodenal (i.d.)) was confirmed by the reduction in the volume and acidity in parallel to an increase in the pH of gastric content. In addition, quercitrin (1.38 mg/kg, but not 0.46 mg/kg) and afzelin (0.026 and 0.078 mg/kg) decreased the ethanol/HCl-induced gastric ulcer. In this model, quercitrin (1.38 mg/kg) prevented the depletion of gastric GSH content and both quercitrin (1.38 mg/kg) and afzelin (0.078 mg/kg) reduced the MPO activity. These compounds also inhibited the H(+),K(+)-ATPase activity at a concentration of 1-100 μg/ml. In addition, the participation of quercitrin and afzelin in these effects also was confirmed. Furthermore, after 4 days of the treatment, an oral administration of S. chilensis methanolic extract (100 mg/kg) reduced the area of the gastric ulcer induced by acetic acid and the regeneration of the gastric mucosa was accompanied by a reduction in gastric TNF levels. The healing properties of the extract also were confirmed by enhancement of proliferation and coverage of scratched wounds in a fibroblast monolayer. Together, our results confirmed the gastroprotective effect of S. chilensis methanolic extract as well as its gastric healing potential and provided some support to the traditional use of S. chilensis for prevention and treatment of gastric lesions in complementation to its known anti-inflammatory properties.
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Affiliation(s)
- Mariel de Barros
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Luisa Mota da Silva
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Ligia de Moura Burci
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade Federal do Paraná (UFPR), Centro Politécnico, Jardim das Américas, 81531-970, Curitiba, PR, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil.
| | - Franco Delle Monache
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
| | - Valdir Cechinel-Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Rua Uruguai, 458, Centro, 88302-202, Itajaí, SC, Brazil
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Herling AW. Pharmacological Effects on Gastric Function. DRUG DISCOVERY AND EVALUATION: PHARMACOLOGICAL ASSAYS 2016:2341-2413. [DOI: 10.1007/978-3-319-05392-9_56] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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da Silva LM, Boeing T, Somensi LB, Cury BJ, Steimbach VMB, Silveria ACDO, Niero R, Cechinel Filho V, Santin JR, de Andrade SF. Evidence of gastric ulcer healing activity of Maytenus robusta Reissek: In vitro and in vivo studies. JOURNAL OF ETHNOPHARMACOLOGY 2015; 175:75-85. [PMID: 26364940 DOI: 10.1016/j.jep.2015.09.006] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 08/31/2015] [Accepted: 09/05/2015] [Indexed: 05/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Maytenus robusta Reissek (Celastraceae) is traditionally used in Brazilian folk medicine to treat gastric ulcer, as a substitute for M. ilicifolia, which is almost extinct. The gastroprotective properties of M. robusta were demonstrated previously using only preventive approaches, such as acute gastric ulcer models. However, the healing effect of M. robusta in gastric ulcers remains unclear. AIM OF THE STUDY The current study was carried out to investigate the healing effectiveness of M. robusta hydroalcoholic extract (HEMR) from aerial parts in the acetic acid-induced chronic ulcer model and to determine its effect on cell proliferation, scavenging free radicals, and inflammatory and oxidative damage. MATERIAL AND METHODS To evaluate the healing properties of HEMR in vivo, chronic gastric ulcer was induced in rats by 80% acid acetic. Next, different groups of animals (n=6) were treated orally with vehicle (water plus 1% tween, 1 ml/kg), omeprazole (20mg/kg), or HEMR (1-10mg/kg), twice daily for 7 days. At the end of the treatment, the total ulcer area (mm(2)) was measured and a sample of gastric tissue was taken for histological and histochemical analysis. Evaluation of GSH and LOOH levels, GST, SOD, CAT and MPO activity was also performed at the site of the lesion. In parallel, radical scavenging activity, cytoprotective effect, and cell proliferation activity in fibroblasts (L929 cells) were determined by in vitro trials. The antisecretory properties were evaluated using the pylorus ligature model in rats, and the anti-Helicobacter pylori activity was determined in vitro. Acute toxicity was evaluated by relative organ weight and biochemical parameters in serum. The prokinetic properties were also evaluated in mice. RESULTS Oral administration of HEMR (10mg/kg) reduced the gastric ulcer area by 53%, compared to the vehicle group (120.0 ± 8.3mm(2)), the regeneration of gastric mucosa was evidenced in histological analysis. Moreover, HEMR treatment increased gastric mucin content and reduced oxidative stress and inflammatory parameters at the site of the ulcer. In vitro, HEMR (1-1000 µg/ml) was able to scavenge free radical DPPH and promote cytoprotection against H2O2 in fibroblasts at 0.1-100 µg/ml. Moreover, HEMR healing properties also were confirmed by enhancement of proliferation and coverage of scratched wounds in fibroblast monolayer. However, HEMR (10mg/kg) by the intraduodenal route did not promote changes in volume, pH, total acidity or pepsin activity in the pylorus ligature model, and HEMR up to 2000 µg/ml also did not present considerable activity against H. pylori. In relation to gastrointestinal motility, HEMR (10mg/kg, p.o) did not provoke alterations. It is also important to mention that oral administration of HEMR did not produce any sign of acute toxicity in animals. CONCLUSIONS The data here obtained show that M. robusta has evident ulcer healing potential, mainly through the strengthening of protective factors of gastric mucosa, such as mucus layer, antioxidant defenses and cell proliferation. Taking into account the advantages of cultivation and harvesting of M. robusta compared to M. ilicifolia, and the evidence presented here, it is plausible to conclude that hydroalcoholic extract obtained from aerial parts of M. robusta is an interesting source for the development of a phytotherapeutic formulation to treat gastric ulcer.
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Affiliation(s)
- Luisa Mota da Silva
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil.
| | - Thaise Boeing
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Lincon Bordignon Somensi
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Benhur Judah Cury
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | | | | | - Rivaldo Niero
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Valdir Cechinel Filho
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciência s Farmacêuticas (PPGCF), Universidade do Vale do Itajaí (UNIVALI), Itajaí, SC, Brazil
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Estrogen alleviates acetic acid-induced gastric or colonic damage via both ERα- and ERβ-mediated and direct antioxidant mechanisms in rats. Inflammation 2015; 37:694-705. [PMID: 24323397 DOI: 10.1007/s10753-013-9786-9] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
In order to demonstrate the possible protective effects of estrogen receptor (ER)-α and ERβ receptor subtypes in the pathogenesis of colonic and gastric oxidant damage, experimental ulcer and colitis were induced by acetic acid, and the animals were randomly divided as colitis, ulcer, and their corresponding non-ulcer and non-colitis control groups. Each group of rats was treated intramuscularly with the vehicle, selective ERα agonist propylpyrazole-triol (1 mg/kg), ERβ agonist diarylpropionitrile (1 mg/kg), non-selective ER agonist 17β estradiol (E2; 1 mg/kg), or E2 plus non-selective ER antagonist ICI-182780 (1 mg/kg). The results revealed that induction of ulcer or colitis resulted in systemic inflammation as assessed by increased levels of plasma TNF-α and IL-6 levels. In both tissues, the presence of oxidant damage was verified by histological analysis and elevated myleoperoxidase activity. In the colitis and ulcer groups, both ER agonists and the non-selective E2 reversed the oxidative damage in a similar manner. These findings indicate that estrogen acts via both ERα- and ERβ-mediated and direct antioxidant mechanisms, where both ER subtypes play equal and efficient roles in the anti-inflammatory action of estrogen, in limiting the migration of neutrophils to the inflamed tissue, reducing the release and activation of cytokines and thereby alleviating tissue damage.
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Yu Y, Jia TZ, Cai Q, Jiang N, Ma MY, Min DY, Yuan Y. Comparison of the anti-ulcer activity between the crude and bran-processed Atractylodes lancea in the rat model of gastric ulcer induced by acetic acid. JOURNAL OF ETHNOPHARMACOLOGY 2015; 160:211-218. [PMID: 25481080 DOI: 10.1016/j.jep.2014.10.066] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/13/2014] [Revised: 09/20/2014] [Accepted: 10/13/2014] [Indexed: 06/04/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The rhizome of Atractylodes lancea (AL, Compositae, Chinese name: Cangzhu; Japanese name: Sou-ju-tsu) has been used traditionally for the treatment of various diseases such as digestive disorders, rheumatic diseases, and influenza in China, Korea and Japan. The crude AL and AL bran-processed are both listed in the Chinese Pharmacopoeia. However, the differences between the effects of the crude and AL bran-processed on gastric ulcer were poorly understood, and the mechanisms for the treatment of gastric ulcer were not clear. This study aimed at comparing the anti-ulcer effects between the crude AL and AL processed in acetic acid induced model in rats and evaluating the mechanisms of action involved in the anti-ulcer properties of AL. MATERIALS AND METHODS The model of gastric ulcer was imitated by acetic acid in rats, and AL was gavaged. The serum and gastric tissues were collected. The levels of epidermal growth factor (EGF), trefoil factor2 (TFF2), tumor necrosis factor-α (TNF-α), interleukin 6, 8 (IL-6, 8) and prostaglandin E2 (PGE2) in serum and gastric tissues were determined by the double-antibody sandwich enzyme-linked immunosorbent assay (ELISA), and the mRNA expressions of EGF, TFF2, TNF-α, and IL-8 in stomach were analyzed by quantitative real-time reverse transcription polymerase chain reaction (RT-PCR). Meanwhile, histopathological changes were evaluated by hematoxylin and eosin (HE) stain. The protein expressions of EGF, TFF2, TNF-α, and IL-8 were examined by immunohistochemistry in stomach. RESULTS The results demonstrated that the damage of gastric tissue was obviously alleviated and the productions of TNF-α, IL-8, IL-6, and PGE2 and the mRNA expressions of TNF-α, and IL-8 were notably inhibited. Furthermore, the productions of EGF and TFF2 and the mRNA expressions of EGF and TFF2 were significantly stimulated by both crude AL and AL processed in a dose-dependent manner. Compared with the crude AL, the processed AL was more effective. CONCLUSION The AL processed had more satisfactory effects in treatment of gastric-ulcer than the crude AL. The anti-ulcer effects of AL could be attributed to the anti-inflammatory properties via down-regulating TNF-α, IL-8, IL-6 and PGE2 and to the gastroprotective effects via up-regulating EGF and TFF2.
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Affiliation(s)
- Yan Yu
- Experimental Center of Traditional Chinese Medicine, The Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China; School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China
| | - Tian-Zhu Jia
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
| | - Qian Cai
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China.
| | - Ning Jiang
- Laboratory of Molecular Biology, School of Basic Medical Science, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China
| | - Ming-Yue Ma
- School of Pharmacy, Liaoning University of Traditional Chinese Medicine, Dalian 116600, China
| | - Dong-Yu Min
- Experimental Center of Traditional Chinese Medicine, The Affiliated Hospital, Liaoning University of Traditional Chinese Medicine, Shenyang 110847, China
| | - Yuan Yuan
- Institute of Traditional Chinese Medicine of Liaoning Province, Shenyang 110034, China
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Protective Effect of Flos Lonicerae against Experimental Gastric Ulcers in Rats: Mechanisms of Antioxidant and Anti-Inflammatory Action. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2014; 2014:596920. [PMID: 25610477 PMCID: PMC4290635 DOI: 10.1155/2014/596920] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/22/2014] [Revised: 11/21/2014] [Accepted: 12/11/2014] [Indexed: 02/06/2023]
Abstract
Flos Lonicerae is one of the oldest and most commonly prescribed herbs in Eastern traditional medicine to treat various inflammatory diseases. In the present study, we investigated the effects of ethyl acetate fraction of Flos Lonicerae (GC-7101) on experimental gastric ulcer models and its mechanisms of action in gastric ulcer healing. The pharmacological activity of GC-7101 was investigated in rats on HCl/EtOH, indomethacin, water immersion restraint stress induced acute gastric ulcer, and acetic-acid-induced subchronic gastric ulcer. To determine its gastroprotective mechanisms, gastric wall mucus secretion, mucosal PGE2, mucosal NO content, nuclear translocation of NF-κB, mRNA expression of inflammatory cytokines, lipid peroxidation and glutathione content, and superoxide dismutase and catalase activities were measured. GC-7101 significantly attenuated development of acute gastric ulcer and accelerated the healing of acetic-acid-induced subchronic gastric ulcer. In HCl/EtOH-induced gastric ulcer, GC-7101 markedly enhanced gastric wall mucus content which was accompanied by increased mucosal PGE2 and NO production. Furthermore, treatment of GC-7101 exhibited anti-inflammatory and antioxidant activities as evidenced by decreased myeloperoxidase activity, NF-κB translocation, inflammatory cytokines mRNA expression, and lipid peroxidation and increased glutathione content and superoxide dismutase and catalase activities. These results demonstrated that GC-7101 possesses strong antiulcerogenic effect by modulating oxidative stress and proinflammatory mediators.
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Zhao K, Fan Q, Chen Y, Li J, Tang HL, Jia M, Wang JC, Yang CM. Effect of positive acceleration on gastric mucosal blood flow in rats with experimental gastric ulcer. Shijie Huaren Xiaohua Zazhi 2014; 22:3947-3952. [DOI: 10.11569/wcjd.v22.i26.3947] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To assess the effect of positive acceleration (+Gz) on gastric mucosal blood flow (GMBF) in rats with experimental gastric ulcer.
METHODS: Forty male SD rats were randomly and equally divided into four groups: A, B, C and D. Group A was normal rats without exposure to constant +Gz. Gastric ulcer was induced with acetic acid in rats of groups B, C and D. After 3 d, rats of groups B, C and D were exposed to constant +1 Gz, +5 Gz and +10 Gz for 5 min (once every other day, 4 times in all), respectively. After 1 wk, GMBF was measured with the MoorVMS-LDF2 laser Doppler blood flow meter, and the stomach was removed and observed macroscopically to measure the area of ulcer with a vernier caliper.
RESULTS: Gastric mucosa tissue of rats of group A were intact. Different sized ulcer lesions were observed in the gastric lesser curvature of rats of groups B-D. The higher the +Gz value, the larger the ulcer area. Compared with group B (1.602 mm2 ± 0.490 mm2), the ulcer area of rats of group C (6.239 mm2 ± 0.597 mm2) was significantly larger (P < 0.01). The ulcer area of rats of group D (9.511 mm2 ± 1.857 mm2) was significantly bigger than that of rats of group C (P < 0.05). Compared with group A (432.919 pu ± 11.598 pu), the GMBF of rats of group B (367.602 pu ± 10.133 pu) was significantly lower (P < 0.01). After exposure to +Gz, GMBF of rats of groups C (303.925 pu ± 16.417 pu) and D (246.750 pu ± 22.815 pu) was significantly lower than that of group B (P < 0.01). GMBF of rats of group D was significantly lower than that of group C (P < 0.05). There was a significant negative correlation between gastric ulcer area and volume of GMBF (r = -0.911, P < 0.05).
CONCLUSION: Exposure to +Gz delays gastric ulcer healing in rats, which is closely related to GMBF. The decrease of GMBF is probably one of the most direct factors affecting ulcer healing.
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Zhao K, Yang CM, Chen Y, Li J, Tang HL. Progress in understanding effects of positive acceleration on quality of ulcer healing in rats with experimental gastric ulcer. Shijie Huaren Xiaohua Zazhi 2014; 22:1359-1364. [DOI: 10.11569/wcjd.v22.i10.1359] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Injuries associated with high-performance fighter aircrafts and spacecrafts are bringing serious challenges to pilots. Exposure to positive acceleration (+Gz) can increase the incidence and recurrence of peptic ulcer. Recurrence of ulcer is closely related to quality of ulcer healing (QOUH), and improving QOUH is considered to be the third leap of understanding of peptic ulcer and has become a hotspot of aerospace medicine research. In this paper, we review the recent advances in understanding the effects of +Gz exposure on QOUH in rats with experimental gastric ulcer in terms of animal model development, QOUH assessment, and influencing factors for QOUH, with an aim to improve the protection against injuries caused by +Gz exposure, strengthen the pilot's overall ability to resist +Gz, and enhance the safety of flight.
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Tianjiao L, Shuai W, Xiansheng M, Yongrui B, Shanshan G, Bo L, Lu C, Lei W, Xiaorong R. Metabolomics coupled with multivariate data and pathway analysis on potential biomarkers in gastric ulcer and intervention effects of Corydalis yanhusuo alkaloid. PLoS One 2014; 9:e82499. [PMID: 24454691 PMCID: PMC3893072 DOI: 10.1371/journal.pone.0082499] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2013] [Accepted: 10/24/2013] [Indexed: 12/17/2022] Open
Abstract
Metabolomics, the systematic analysis of potential metabolites in a biological specimen, has been increasingly applied to discovering biomarkers, identifying perturbed pathways, measuring therapeutic targets, and discovering new drugs. By analyzing and verifying the significant difference in metabolic profiles and changes of metabolite biomarkers, metabolomics enables us to better understand substance metabolic pathways which can clarify the mechanism of Traditional Chinese Medicines (TCM). Corydalis yanhusuo alkaloid (CA) is a major component of Qizhiweitong (QZWT) prescription which has been used for treating gastric ulcer for centuries and its mechanism remains unclear completely. Metabolite profiling was performed by high-performance liquid chromatography combined with time-of-flight mass spectrometry (HPLC/ESI-TOF-MS) and in conjunction with multivariate data analysis and pathway analysis. The statistic software Mass Profiller Prossional (MPP) and statistic method including ANOVA and principal component analysis (PCA) were used for discovering novel potential biomarkers to clarify mechanism of CA in treating acid injected rats with gastric ulcer. The changes in metabolic profiling were restored to their base-line values after CA treatment according to the PCA score plots. Ten different potential biomarkers and seven key metabolic pathways contributing to the treatment of gastric ulcer were discovered and identified. Among the pathways, sphingophospholipid metabolism and fatty acid metabolism related network were acutely perturbed. Quantitative real time polymerase chain reaction (RT-PCR) analysis were performed to evaluate the expression of genes related to the two pathways for verifying the above results. The results show that changed biomarkers and pathways may provide evidence to insight into drug action mechanisms and enable us to increase research productivity toward metabolomics drug discovery.
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Affiliation(s)
- Li Tianjiao
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
| | - Wang Shuai
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, P. R. China
| | - Meng Xiansheng
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, P. R. China
- * E-mail: (MX); (XR)
| | - Bao Yongrui
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
| | - Guan Shanshan
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
| | - Liu Bo
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
| | - Chen Lu
- Liaoning University of Traditional Chinese Medicine, Dalian, P. R. China
| | - Wang Lei
- Agilent Technologies Co, Ltd., Beijing, P. R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, P. R. China
| | - Ran Xiaorong
- Agilent Technologies Co, Ltd., Beijing, P. R. China
- Liaoning University of Traditional Chinese Medicine-Agilent Technologies Modern TCM and Multi-omics Research Collaboration Lab, Dalian, P. R. China
- * E-mail: (MX); (XR)
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Onasanwo SA, Emikpe BO, Ajah AA, Elufioye TO. Anti-ulcer and ulcer healing potentials of Musa sapientum peel extract in the laboratory rodents. Pharmacognosy Res 2013; 5:173-8. [PMID: 23900937 PMCID: PMC3719258 DOI: 10.4103/0974-8490.112423] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2012] [Revised: 09/07/2012] [Accepted: 05/22/2013] [Indexed: 12/11/2022] Open
Abstract
Background: This study investigated the anti-ulcer and ulcer healing potentials of the methanol extract of Musa sapientum peel in the laboratory rats. Materials and Methods: Methanol extract of the peels on Musa sapientum (MEMS) was evaluated for its anti-ulcer using alcohol-induced, aspirin-induced, and pyloric ligation-induced models, and for its ulcer healing employing acetic acid-induced ulcer models in rats. Results: The findings from this experiment showed that MEMS (50, 100 and 200 mg/kg, b.w.) anti-ulcer and ulcer healing activity (P ≤ 0.05) is dose-dependent. Also, MEMS exhibited healing of the ulcer base in all the treated groups when compared with the control group. Conclusion: The outcomes of this experiment revealed that the anti-ulcer effect of MEMS may be due to its anti-secretory and cyto-protective activity. The healing of the ulcer base might not be unconnected with basic fibroblast growth factors responsible for epithelial regeneration.
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Affiliation(s)
- Samuel Adetunji Onasanwo
- Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, Ibadan, Nigeria
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Chen L, Chen Y, Fan Q, Han QL, Tang HL, Li J, Yang CM. Effect of persistent positive acceleration on the quality of ulcer healing in rats with experimental gastric ulcer. Shijie Huaren Xiaohua Zazhi 2013; 21:1841-1846. [DOI: 10.11569/wcjd.v21.i19.1841] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of positive acceleration (+Gz) on gastric ulcer healing in rats and to explore the possible mechanisms involved.
METHODS: Thirty-two male SD rats were randomly and equally divided into a control group, a +5Gz exposure group, a +10Gz exposure group, and a +10Gz exposure plus KangFuXin solution group. Gastric ulcer was induced in rats with acetic acid. After 3 d, rats in the latter three groups were exposed to +Gz each other day for 1 wk (four times in all, five minutes each time). The rats in the +10Gz exposure plus KangFuXin solution group were additionally gavaged with 2 mL of KangFuXin solution every day for 1 wk. Tissue and bloods samples were taken to detect the contents of prostaglandin E2 (PGE2) in the gastric mucosa and calcitonin gene-related peptide (CGRP) in blood by radioimmunoassay and the content of nitric oxide (NO) in blood by nitrate reductase assay.
RESULTS: The higher +Gz, the thinner restored mucosa thickness and the more the number of cystically dilated glands. The contents of PGE2 in the gastric mucosa were significantly lower in the +10Gz exposure group than in the +5Gz exposure group, control group, and +10Gz exposure plus KangFuXin solution group (3.438 pg/mL ± 0.908 pg/mL vs 5.147 pg/mL ± 0.652 pg/mL, 6.986 pg/mL ± 0.743 pg/mL, 6.133 pg/mL ± 0.545 pg/mL, all P < 0.01). The contents of CGRP in blood were significantly lower in the +10Gz exposure group than in the +5Gz exposure group, control group, and +10Gz exposure plus KangFuXin solution group (62.254 pg/mL ± 15.943 pg/mL vs 78.333 pg/mL ± 11.290 pg/mL, 82.583 pg/mL ± 11.788 pg/mL, 78.455 pg/mL±12.645 pg/mL, all P < 0.05). The contents of NO in blood were significantly lower in the +10Gz exposure group than in the +5Gz exposure group, control group, and +10Gz exposure plus KangFuXin solution group (44.773 μmol/L ± 6.858 μmol/L vs 47.783 μmol/L ± 2.847 μmol/L, 53.806 μmol/L ± 9.272 μmol/L, 53.853 μmol/L ± 7.372 μmol/L, all P < 0.05).
CONCLUSION: Positive acceleration delays gastric ulcer healing in rats, and treatment with KangFuXin Solution can improve the quality of ulcer healing.
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Klein-Júnior LC, Santin JR, Lemos M, Silveira ACDO, Rocha JAR, Beber AP, Wagner TM, Bresolin TMB, Bella-Cruz A, Cechinel-Filho V, Faloni de Andrade S. Role of gastric mucus secretion, oxinitrergic system and sulfhydryl groups on the gastroprotection elicited by Polygala cyparissias (Polygalaceae) in mice. J Pharm Pharmacol 2013; 65:767-76. [DOI: 10.1111/jphp.12038] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2012] [Accepted: 01/06/2013] [Indexed: 12/11/2022]
Abstract
Abstract
Objectives
This study has aimed to assess the mechanisms of action for the gastroprotective effect of the acetone extract (PCAE) and methanol fraction (PCMF) of Polygala cyparissias, as well as to evaluate the activity of 1,3,6,8-tetrahydroxy-2,7-dimethoxyxanthone (1), 1,7-dihydroxy-2,3-dimethoxyxanthone (2) and astragalin (3).
Methods
Gastric secretion and mucus content were determined by pylorus ligation in mice. Nitric oxide (NO) and sulfhydryl group participation were observed by the pretreatment of mice with L-NAME or NEM. Acute ulcer was induced by ethanol/HCl and chronic ulcer by acetic acid. Anti-Helicobacter pylori activity was evaluated by the agar solid dilution assay.
Key findings
Neither PCAE nor PCMF had the ability to reduce H+ concentration. However, both of them enhanced mucus secretion. PCAE demonstrated its gastroprotection in a NO-dependent manner, while PCMF exerted the activity depending on the sulfhydryl group. In chronic ulcer, the curative ratios for the PCAE and PCMF were 67.5 and 58.4%, respectively. No effect over H. pylori was detected. Compounds 1, 2 and 3 were able to reduce lesions in the order of 79.6, 73.8 and 67.6%, respectively.
Conclusions
The data suggested that PCAE and PCMF displayed antiulcer activity due to different mechanisms and with the participation of phenolic compounds obtained from the plant.
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Affiliation(s)
- Luiz Carlos Klein-Júnior
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - José Roberto Santin
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Marivane Lemos
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Alessandro Conrado de Oliveira Silveira
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Curso de Farmácia, Universidade de Blumenau – FURB, Blumenau, Brazil
| | - Jady Alice Rodrigues Rocha
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Ana Paula Beber
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Theodoro Marcel Wagner
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Departamento de Farmácia, Universidade da Região de Joinville, Joinville, Brazil
| | - Tania Mari Bellé Bresolin
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Alexandre Bella-Cruz
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Valdir Cechinel-Filho
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
| | - Sérgio Faloni de Andrade
- Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, Itajaí, Brazil
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Nakashita M, Suzuki H, Miura S, Taki T, Uehara K, Mizushima T, Nagata H, Hibi T. Attenuation of acetic acid-induced gastric ulcer formation in rats by glucosylceramide synthase inhibitors. Dig Dis Sci 2013; 58:354-62. [PMID: 22918683 DOI: 10.1007/s10620-012-2350-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2012] [Accepted: 07/28/2012] [Indexed: 01/26/2023]
Abstract
INTRODUCTION Ceramide has been suggested to play a role in apoptosis during gastric ulcerogenesis. The present study is designed to investigate whether accumulated ceramide could serve as the effector molecules of ulcer formation in a rat model of acetic acid-induced gastric ulcer. METHODS The effect of fumonisin B1, an inhibitor of ceramide synthase, and of d,l,-threo-1-phenyl-2-hexadecanoylamino-3-morpholino-1-propanol (PPMP) and N-butyldeoxynojirimycin (NB-DNJ), both inhibitors of glucosylceramide synthase, on the accumulation of ceramide and formation of gastric ulcer were examined in the rat model of acetic acid-induced gastric ulcer. RESULTS Fumonisin B1 attenuated acetic acid-induced gastric ulcer formation, associated with a decrease in the number of apoptotic cells. Our results showed that it is neither the C18- nor the C24-ceramide itself, but the respective metabolites that were ulcerogenic, because PPMP and NB-DNJ attenuated gastric mucosal apoptosis and the consequent mucosal damage in spite of their reducing the degradation of ceramide. CONCLUSION The ceramide pathway, in particular, the metabolites of ceramide, significantly contributes to acetic acid-induced gastric damage, possibly via enhancing apoptosis. On the other hand, PPMP and NB-DNJ treatment attenuated gastric mucosal apoptosis and ulcer formation despite increasing the ceramide accumulation, suggesting that it was not the ceramides themselves, but their metabolites that contributed to the ulcer formation in the acetic acid-induced gastric ulcer model.
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Affiliation(s)
- Manabu Nakashita
- Division of Gastroentrology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan
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Xue R, Cao Y, Han N, Lin X, Liu Z, Yin J. Activity of DBXX granules on anti-gastric ulcer and decreasing the side effect of chemotherapy in S180 tumor-bearing mice. JOURNAL OF ETHNOPHARMACOLOGY 2011; 137:1156-1160. [PMID: 21810461 DOI: 10.1016/j.jep.2011.07.042] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/15/2011] [Revised: 06/17/2011] [Accepted: 07/17/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE DBXX is a derived prescription from "Banxiaxiexin Tang" in "Shanghan Lun", the representative prescription to regulate spleen and stomach. AIM OF THE STUDY To determine the pharmacodynamics effects of DBXX granules on anti-ulcer and anti-side effect on digestive system induced by chemotherapeutic drugs. MATERIALS AND METHODS Chronic gastric ulcer was induced by an injection of 100% glacial acetic acid into the submucosal layer of the glandular stomach, then the area of all ulcers was added together as the ulcer index and inhibition rate of ulcer was calculated. While S180 tumor-bearing mice were treated with cyclophosphamide as the chemotherapeutic drug, the weight of food-intake after chemotherapy, the loss body weight, tumor weight and spleen index were weighed and calculated. RESULTS In the gastric ulcer bearing mice, DBXX granules showed a dose-dependent reduction of ulcer at the dose 4.87 and 9.73 g/kg. In the S180 tumor-bearing mice, low dose of DBXX granules could significantly improve every investigated index compared with that of control group (p < 0.05). CONCLUSIONS It proved that DBXX granules showed good healing effect on the chronic gastric ulcer mice and significant effect on decreasing the side effect of chemotherapy of S180 tumor-bearing mice.
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Affiliation(s)
- Rui Xue
- Department of Pharmacognosy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China
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Zhang W, Li J, Han QL, Chen Y, Tang HL, Du B, Yang CM. Effect of simulated weightlessness on the healing of experimental gastric ulcer in rats. Shijie Huaren Xiaohua Zazhi 2011; 19:2863-2868. [DOI: 10.11569/wcjd.v19.i27.2863] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of simulated weightlessness on the healing of acetic acid-induced experimental gastric ulcer in rats and to explore the potential mechanisms involved.
METHODS: Thirty-two SD rats were randomly and equally divided into four groups: 7 d tail suspension group, 7 d control group,14 d tail suspension, and 14 d control group. Gastric ulcer was induced in rats with acetic acid. Tail suspension was used to simulate the weightlessness condition 3 days after ulcer induction. The gastric ulcer area was measured with a vernier caliper. The ultrastructure of regenerative mucosa was observed by electronic microscopy. Epidermal growth factor (EGF) level in gastric juice was determined by radioimmunoassay (RIA). The staging of ulcer healing was performed.
RESULTS: Compared to the 7 d control group, the ulcer area significantly increased (6.0 mm2 ± 1.7 mm2 vs 2.2 mm2 ± 0.7 mm2, t = 5.661, P < 0.01) and the stage of ulcer significantly decreased (χ2 = 12.771, P < 0.01) in the 7d suspension group. Compared to the 14 d control group, the ulcer area and EGF level increased (3.0 mm2 ± 1.2 mm2 vs 1.1 mm2 ± 0.4 mm2, t = 4.233, P < 0.01; 0.155 ng/mL ± 0.052 ng/mL vs 0.103 ng/mL ± 0.019 ng/mL, t = 2.635, P < 0.05) in the 14 d suspension group. Compared to the 7 d suspension group, the ulcer area, EGF level and stage of ulcer significantly decreased (3.0 mm2 ± 1.2 mm2 vs 6.0 mm2 ± 1.7 mm2, t = 3.805, P < 0.01; 0.155 ng/mL ± 0.052 ng/mL vs 0.434 ng/mL ± 0.137 ng/mL, t = 5.657, P < 0.01; χ2 = 12.953, P < 0.01) in the 14 d suspension group. The ultrastructural restoration and histological maturity of healed ulcer in the 7 d and 14 d suspension groups were inferior to those in the 7 d and 14 d control groups.
CONCLUSION: Simulated weightlessness may depress the structure of regenerative gastric mucosa, delay the healing of ulcer, and increase EGF level in gastric juice.
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Protective effect of leaves of Raphinus sativus Linn on experimentally induced gastric ulcers in rats. Saudi Pharm J 2011; 19:171-6. [PMID: 23960756 DOI: 10.1016/j.jsps.2011.03.003] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2010] [Accepted: 03/05/2011] [Indexed: 11/20/2022] Open
Abstract
Raphinus sativus Linn (Cruciferae) commonly known as 'Radish' is a multipurpose herb cultivated in different parts of the world for its edible roots and leaves. The present study was aimed to evaluate the antiulcer activity of leaf extracts of R. sativus Linn on acetic acid induced chronic gastric ulcer and pylorus ligation induced gastric ulcer in rats. The acute oral toxicity study revealed that all the extracts were safe up to 2000 mg/kg per oral dose; hence one-tenth of this dose was selected for evaluation of antiulcer activity. In acetic acid induced gastric ulcer models, the ERS, CRS, EARS and AQRS have offered significant protection against acetic acid induced ulcers when compared to control group. While in pylorus ligation induced ulcer model the ERS, EARS and AQRS showed significant protection by decreasing the ulcer index, total acidity and free acidity. In conclusion the leaf extracts of R. sativus Linn are found to possess antiulcer property in the experimental animal models of gastric ulcers, which is consistent with the literature report in the folk medicine.
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Potrich FB, Allemand A, da Silva LM, Dos Santos AC, Baggio CH, Freitas CS, Mendes DAGB, Andre E, Werner MFDP, Marques MCA. Antiulcerogenic activity of hydroalcoholic extract of Achillea millefolium L.: involvement of the antioxidant system. JOURNAL OF ETHNOPHARMACOLOGY 2010; 130:85-92. [PMID: 20420892 DOI: 10.1016/j.jep.2010.04.014] [Citation(s) in RCA: 78] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/25/2009] [Revised: 03/29/2010] [Accepted: 04/17/2010] [Indexed: 05/29/2023]
Abstract
UNLABELLED Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as "yarrow" and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints. AIM OF THE STUDY In the present study, we evaluated the efficacy of a hydroalcoholic extract from the Achillea millefolium (HE) for gastroprotective properties and additional mechanism(s) involved in this activity. MATERIAL AND METHODS Rats were treated with HE and subsequently exposed to both acute gastric lesions induced by ethanol P.A. and chronic gastric ulcers induced by 80% acetic acid. Following treatment, glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured. The activity of myeloperoxidase (MPO) and histological and immunohistochemical analysis were performed in animals with acetic acid-induced gastric ulcers. RESULTS Oral administration of HE (30, 100 and 300mg/kg) inhibited ethanol-induced gastric lesions by 35, 56 and 81%, respectively. Oral treatment with HE (1 and 10mg/kg) reduced the chronic gastric ulcers induced by acetic acid by 43 and 65%, respectively, and promoted significant regeneration of the gastric mucosa after ulcer induction denoting increased cell proliferation, which was confirmed by PCNA immunohistochemistry. HE treatment prevented the reduction of GSH levels and SOD activity after acetic acid-induced gastric lesions. In addition, HE (10mg/kg) inhibited the MPO activity in acetic acid-induced gastric ulcers. CONCLUSIONS The results of the present study indicate that the antioxidant properties of HE may contribute to the gastroprotective activity of this extract.
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Kang JM, Kim N, Kim B, Kim JH, Lee BY, Park JH, Lee MK, Lee HS, Kim JS, Jung HC, Song IS. Enhancement of gastric ulcer healing and angiogenesis by cochinchina Momordica seed extract in rats. J Korean Med Sci 2010; 25:875-81. [PMID: 20514308 PMCID: PMC2877244 DOI: 10.3346/jkms.2010.25.6.875] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2009] [Accepted: 11/12/2009] [Indexed: 12/13/2022] Open
Abstract
Cochinchina momordica seed is the dried ripe seed of Momordica cochinchinensis, a perennial vine. The antiulcer effect of an extract from cochinchina momordica seeds (SK-MS10) was evaluated in a rat model of acetic acid-induced gastric ulcers. Gastric ulcers were produced by subserosal injection of acetic acid. SK-MS10 (200 mg/kg) or vehicle was administered orally once per day for 14 days after the acetic acid injection. The stomach was removed and the ulcer size measured at day 7 and 14 of the treatment. Expression of vascular endothelial growth factor (VEGF) was assessed by real-time RT-PCR and Western blot analysis. In addition, the microvasculature density (MVD) adjacent to the ulcer margin was examined by immunohistochemistry. The treatment with SK-MS10 for 7 and 14 days significantly accelerated ulcer healing and increased the expression of mRNA (at day 7) as well as VEGF protein (at day 14) compared to the vehicle-treated rats. The MVD for factor VIII was also higher in the SK-MS10 treatment group compared to the vehicle-treated rats; however, these differences were not statistically significant. These results suggest that SK-MS10 treatment accelerates the healing of gastric ulcers via upregulation of VEGF and angiogenesis in an acetic acid rat model.
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Affiliation(s)
- Jung Mook Kang
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | | | - Joo-Hyon Kim
- Life Science R&D Center, SK Chemicals, Suwon, Korea
| | | | - Ji Hyun Park
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Mi Kyoung Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hye Seung Lee
- Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Joo Sung Kim
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Hyun Chae Jung
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - In Sung Song
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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Solmaz A, Sener G, Cetinel S, Yüksel M, Yeğen C, Yeğen BC. Protective and therapeutic effects of resveratrol on acetic acid-induced gastric ulcer. Free Radic Res 2009; 43:594-603. [PMID: 19479585 DOI: 10.1080/10715760902977424] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Sprague Dawley rats of both sexes were injected with either saline or RVT (10 mg/kg) either before or after acetic acid ulcer induction and decapitated 3, 5 or 10 days after ulcer. In the saline-treated ulcer groups, macroscopically evident ulcers were observed, while RVT-pretreated or RVT-treated groups had lower macroscopic ulcer scores. Likewise, the microscopic damage scores were lower for the RVT-administered groups. Gastric myeloperoxidase activity, malondialdehyde, collagen and tumour necrosis factor-alpha levels, as well as luminol- and lucigenin-enhanced chemiluminescence levels that were elevated in the saline-administered ulcer groups, were depressed with both RVT-pretreatment and RVT-treatment. Moreover, depleted glutathione levels in the ulcer groups were increased back to control levels by both pre- and post-treatments of RVT. Results demonstrate that resveratrol has both protective and therapeutic effects on oxidative gastric damage by suppressing pro-inflammatory cascades, including the activation of pro-inflammatory cytokines, accumulation of neutrophils and release of oxygen-derived free radicals.
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Affiliation(s)
- Ali Solmaz
- Department of General Surgery, Marmara University School of Medicine, Istanbul, Turkey
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Souza MDC, Beserra AMS, Martins DC, Real VV, Santos RAND, Rao VS, Silva RMD, Martins DTDO. In vitro and in vivo anti-Helicobacter pylori activity of Calophyllum brasiliense Camb. JOURNAL OF ETHNOPHARMACOLOGY 2009; 123:452-458. [PMID: 19501278 DOI: 10.1016/j.jep.2009.03.030] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/15/2008] [Revised: 03/11/2009] [Accepted: 03/14/2009] [Indexed: 05/27/2023]
Abstract
AIMS OF THE STUDY Calophyllum brasiliense (Camb.) is a medicinal tree that grows particularly in the hilly and forested regions of Brazil. Preparations from its stem bark are popular remedies for the treatment of chronic ulcers. Since earlier investigations on bark extracts evidenced gastroprotective and gastric acid inhibitory properties, this study evaluated the effects of hydroethanolic extract (HEECb) and the dichloromethanic fraction (DCMF), from Calophyllum brasiliense stem bark, against Helicobacter pylori, in vitro and in vivo. MATERIALS AND METHODS The in vitro assays were performed using the disk diffusion and broth microdilution methods to determine the minimum inhibitory concentration (MIC) values. The test substances were evaluated in vivo taking into account the delay in the gastric ulcer healing in Wistar rats, infected with Helicobacter pylori. RESULTS DCMF appeared the most active and potent in vitro against Helicobacter pylori growth with an MIC of 31 microg/mL. In the in vivo assays, rats ulcerated by acetic acid, and inoculated with Helicobacter pylori showed a marked delay in ulcer healing. Treatment with HEECb (50, 100 and 200 mg/kg) and DCMF (100 and 200 mg/kg) reduced the ulcerated area in a dose-dependent manner. While DCMF, at 200 mg/kg, increased the prostaglandin E2 (PGE2) level, both HEECb and DCMF decreased the number of urease-positive animals, as confirmed by the reduction of Helicobacter pylori presence in histopathological analysis. CONCLUSION The results suggest that the antiulcer activity of Calophyllum brasiliense is due, in part, to its anti-Helicobacter pylori action, validating the popular use of this species.
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Affiliation(s)
- Maria do Carmo Souza
- Department of Basic Science in Health, Faculty of Medical Science, Federal University of Mato Grosso (UFMT), Av. Fernando Correa da Costa s/n, Coxipó, Cuiabá, MT CEP: 78060-900, Brazil.
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Deniz M, Sahin HH, Tekin S, Yeşiller M, Ağaoğlu B, Cetinel S, Yeğen BÇ. Nicotine withdrawal alleviates acetic acid-induced gastric injury in rats. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2009; 27:200-205. [PMID: 21783940 DOI: 10.1016/j.etap.2008.10.006] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/18/2008] [Revised: 10/10/2008] [Accepted: 10/17/2008] [Indexed: 05/31/2023]
Abstract
Epidemiological and experimental studies have demonstrated that cigarette smoking intensifies gastric ulceration. Although nicotine can act as an anxiolytic and antidepressant, its withdrawal may also lead to increased anxiety and depression. In order to associate the toxic actions of nicotine on gastric mucosa with alterations of anxiety level and to evaluate the impact of nicotine withdrawal on the anxiety level and the severity of ulcer, an acetic acid-induced ulcer model was used. Male Sprague-Dawley rats were given either tap water or nicotine bitartarate (50μg/ml in drinking water) for 15 days, while another group of rats had 5 days of withdrawal following 10 days of nicotine treatment. Ulcer was induced by acetic acid on the 15th day of the treatments, and the rats were followed for 3 days until they were decapitated and the gastric tissues were obtained. Using the hole-board test, basal anxiety levels measured on the first day of the treatments were compared with the measurements made at the early and late phases of ulcer induction. Chronic administration of nicotine did not have a potentiating effect on acetic acid-induced gastric ulcer, since the gastric injury, as assessed by both macroscopic and microscopic evaluation and increased gastric myeloperoxidase activity indicating neutrophil recruitment, was not exaggerated or attenuated by nicotine intake. On the other hand, nicotine withdrawal attenuated gastric mucosal injury, despite an increased level of anxiety. Smoking cessation, which triggers the onset of depressive symptoms with nicotine withdrawal, still has a worthwhile positive effect on the gastric mucosa.
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Affiliation(s)
- Mustafa Deniz
- Marmara University, School of Medicine, Department of Physiology, Haydarpaşa 34668, Istanbul, Turkey
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Choi SM, Shin JH, Kang KK, Ahn BO, Yoo M. Gastroprotective effects of DA-6034, a new flavonoid derivative, in various gastric mucosal damage models. Dig Dis Sci 2007; 52:3075-80. [PMID: 17406830 DOI: 10.1007/s10620-006-9657-4] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2006] [Accepted: 10/17/2006] [Indexed: 12/09/2022]
Abstract
This study evaluated the gastroprotective activity of DA-6034 against various ulcerogens including ethanol, aspirin, indomethacin, stress, and acetic acid. The basic mechanisms of DA-6034 as a defensive factor such as mucus secretion and endogenous prostaglandin E(2) synthesis were determined. Rats with gastric lesions induced by ethanol-HCl, aspirin, indomethacin, and stress that had been pretreated with DA-6034 orally showed a statistically significant decrease or decreasing tendency of the gastric lesion. In acetic acid-induced gastric lesions, repeated oral administration of DA-6034 exhibited a U-shape activity in ulcer healing, with the maximum and minimum inhibition being observed at 30 and 10 mg/kg/day, respectively. DA-6034 also increased the mucus content in the gel layer as well as endogenous prostaglandin E(2) synthesis. These results suggest that DA-6034 prevents gastric mucosal injury, and these gastroprotective activities appear to be due to the increase in the gastric defensive systems.
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Affiliation(s)
- Seul Min Choi
- Research Laboratories, Dong-A Pharmaceutical Company, 47-5 Sanggal-dong, Kiheung-gu, Yongin-shi, Kyunggi-do 446-905, Korea
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Amresh G, Zeashan H, Gupta RJ, Kant R, Rao CV, Singh PN. Gastroprotective effects of ethanolic extract from Cissampelos pareira in experimental animals. J Nat Med 2007. [DOI: 10.1007/s11418-007-0141-z] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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Ibrahim M, Khan AA, Tiwari SK, Habeeb MA, Khaja MN, Habibullah CM. Antimicrobial activity of Sapindus mukorossi and Rheum emodi extracts against H pylori: In vitro and in vivo studies. World J Gastroenterol 2006; 12:7136-42. [PMID: 17131475 PMCID: PMC4087774 DOI: 10.3748/wjg.v12.i44.7136] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the antibacterial activity of Sapindus mukorossi (S. mukorossi) and Rheum emodi (R. emodi).
METHODS: Powders of S. mukorossi and R. emodi were extracted successively with petroleum ether, benzene, chloroform and ethanol and were concentrated in vacuum. The disk diffusion method was used for in vitro studies and in vivo studies were performed on male Wister rats. Thirty resistant clinical isolates of H pylori, as determined by their antibiotic sensitivity patterns by E-test, along with two Gram +ve (S. aureus, B. subtilis) and two Gram -ve (E. coli, P. vugaris) organisms were screened for their susceptibility patterns against these extracts.
RESULTS: In our screening, all 30 resistant isolates and the other four organisms (two Gram +ve S. aureus, B. subtilis and two Gram -ve, E. coli, P. vugaris) were sensitive to the test compounds. It was found that ethanol and chloroform extracts of S. mukorossi and ethanol and benzene extracts of R. emodi inhibited H pylori at very low concentrations. In the in vitro study, the isolates showed a considerable zone of inhibition at very low concentrations (10 μg/mL) for both the extracts. In the in vivo study, the H pylori infection was cleared with minimal doses of extracts of S. mukorossi (2.5 mg/mL) and R. emodi (3.0 mg/mL) given orally for seven days.
CONCLUSION: We can conclude from this study that the extracts of S. mukorossi and R. emodi inhibited the growth of pylori in vitro and, in in vivo studies, the H pylori infection cleared within seven days at very low concentrations. We also found that H pylori did not acquire resistance against these herbal extracts even after 10 consecutive passages.
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Affiliation(s)
- Mohammed Ibrahim
- Centre for Liver Research and Diagnostics, Deccan college of Medical Sciences and Allied Hospitals, Kanchanbagh, Hyderabad 500064, India.
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Jainu M, Devi CSS. Antiulcerogenic and ulcer healing effects of Solanum nigrum (L.) on experimental ulcer models: possible mechanism for the inhibition of acid formation. JOURNAL OF ETHNOPHARMACOLOGY 2006; 104:156-63. [PMID: 16202548 DOI: 10.1016/j.jep.2005.08.064] [Citation(s) in RCA: 74] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2005] [Revised: 07/10/2005] [Accepted: 08/27/2005] [Indexed: 05/04/2023]
Abstract
Solanum nigrum, an herbal plant which is recommended in ayurveda for the management of gastric ulcers. Therefore, the purpose of the study was to investigate the antiulcer effect of Solanum nigrum fruits extract (SNE) on cold restraint stress (CRU), indomethacin (IND), pyloric ligation (PL) and ethanol (EtOH) induced gastric ulcer models and ulcer healing activity on acetic acid induced ulcer model in rats. The treatment with SNE at higher dose significantly inhibited the gastric lesions induced by CRU (76.6%), IND (73.8%), PL (80.1%) and EtOH (70.6%), respectively, with equal or higher potency than omeprazole. SNE showed concomitant attenuation of gastric secretory volume, acidity and pepsin secretion in ulcerated rats. In addition, SNE (200 and 400mg/kgb.w.) accelerated the healing of acetic acid induced ulcers after the treatment for 7 days. Further, to ascertain the antisecretory action, the effects of SNE on H(+)K(+)ATPase activity and plasma concentration of gastrin hormone in ulcerated rats were determined. SNE significantly inhibits H(+)K(+)ATPase activity and decreases the gastrin secretion in EtOH-induced ulcer model. The severity of the reaction of ulcerogen and the reduction of ulcer size by SNE was evident by histological findings. Toxicity studies of SNE have also been carried out for its safety evaluation. SNE, thus, offers antiulcer activity by blocking acid secretion through inhibition of H(+)K(+)ATPase and decrease of gastrin secretion. These results further suggest that SNE was found to possess antiulcerogenic as well as ulcer healing properties, which might also be due to its antisecretory activity.
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Affiliation(s)
- Mallika Jainu
- Department of Biochemistry, University of Madras, Guindy Campus, Chennai 600025, Tamil Nadu, India.
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Okabe S, Amagase K. An overview of acetic acid ulcer models--the history and state of the art of peptic ulcer research. Biol Pharm Bull 2005; 28:1321-41. [PMID: 16079471 DOI: 10.1248/bpb.28.1321] [Citation(s) in RCA: 158] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Four types of experimental chronic ulcer models, named acetic acid ulcer models, have been developed to examine the healing process of peptic ulcers, screen anti-ulcer drugs, and better evaluate the adverse effects of various anti-inflammatory drugs on the gastrointestinal mucosa. The model easily and reliably produces round, deep ulcers in the stomach and duodenum, allowing acetic acid ulcer production in mice, rats, Mongolian gerbils, guinea pigs, cats, dogs, miniature pigs, and monkeys. These ulcer models highly resemble human ulcers in terms of both pathological features and healing process. The models have been established over the past 35 years and are now used throughout the world by basic and clinical scientists. One of the characteristic features of acetic acid ulcers in rats is the spontaneous relapse of healed ulcers >100 d after ulceration, an endoscopically confirmed phenomenon. Indomethacin significantly delays the healing of acetic acid ulcers, probably by reducing endogenous prostaglandins and inhibiting angiogenesis in ulcerated tissue. Helicobacter pylori significantly delays healing of acetic acid ulcers and causes relapse of healed ulcers at a high incidence in Mongolian gerbils. Anti-secretory drugs (e.g. omeprazole), prostaglandin analogs, mucosal defense agents (e.g. sucralfate), and various growth factors all significantly enhance healing of acetic acid ulcers. Gene therapy with epidermal growth factor and vascular endothelial growth factor applied to the base of acetic acid ulcers in rats is effective in enhancing ulcer healing. Since an inhibitor of nitric oxide syntase prevents ulcer healing, nitric oxide might be involved in the mechanism underlying ulcer healing. We conclude that acetic acid ulcer models are quite useful for various studies related to peptic ulcers.
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Affiliation(s)
- Susumu Okabe
- Department of Applied Pharmacology, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 602-0897, Japan.
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Gao Y, Tang W, Gao H, Chan E, Lan J, Zhou S. Ganoderma lucidum polysaccharide fractions accelerate healing of acetic acid-induced ulcers in rats. J Med Food 2005; 7:417-21. [PMID: 15671683 DOI: 10.1089/jmf.2004.7.417] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
The polysaccharide (PS) fractions from several medicinal herbs have been reported to have anti-ulcer effects against experimental ulcers in the rat. The water-soluble PS fractions from Ganoderma lucidum (Reishi mushroom) have been shown to inhibit indomethacin-induced gastric mucosal lesions in rats. This study aimed to investigate the effect of the PS fraction from G. lucidum on the healing of gastric ulcers induced by acetic acid in the rat and to elucidate the underlying mechanisms involved. The abdomen of rats was incised, and the stomach was treated with 10 M acetic acid (100 microL) for 1 minute, and then treated with G. lucidum PS (0.1, 0.5, or 1.0 g/kg) intragastrically, once a day for 14 consecutive days. The results indicated that the oral administration of G. lucidum PS at 0.5 and 1.0 g/kg for 2 weeks caused a significant acceleration of ulcer healing by 40.1% and 55.9%, respectively. In the mechanistic studies, additional rats were treated with 10 M acetic acid to induce acute ulcers, and then treated with G. lucidum PS (1.0 g/kg) for 3, 7, 10, or 14 days. Exposure of the rat stomach to acetic acid led to decreased mucus and increased prostaglandin levels. Treatment with G. lucidum PS at 1.0 g/kg significantly (P < .05) suppressed or restored the decreased gastric mucus levels and increased gastric prostaglandin concentrations compared with the control group. These results indicates that G. lucidum PS is an active component with healing efficacy on acetic acid-induced ulcers in the rat, which may represent a useful herbal preparation for the prevention and treatment of peptic ulcers.
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Affiliation(s)
- Yihuai Gao
- Institute of Food, Nutrition and Human Health, Massey University, Auckland, New Zealand
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Koyuturk M, Bolkent S, Ozdil S, Arbak S, Yanardag R. The protective effect of vitamin C, vitamin E and selenium combination therapy on ethanol-induced duodenal mucosal injury. Hum Exp Toxicol 2005; 23:391-8. [PMID: 15346720 DOI: 10.1191/0960327104ht468oa] [Citation(s) in RCA: 14] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
In this study, the effect of a combination of vitamin C, vitamin E and selenium on ethanol-induced duodenal mucosal damage in rats was investigated morphologically and biochemically. The duodenal mucosal injury was produced by oral administration of 1 mL of absolute ethanol to each rat. Animals received vitamin C (250 mg/ kg), vitamin E (250 mg/kg) and selenium (0.5 mg/kg) for 3 days and absolute ethanol 1 hour after last antioxidant administration and were sacrificed 1 hour after absolute ethanol. Extreme degeneration in intestinal mucosa of rats given ethanol was observed morphologically. In addition, an increase in neuronal nitric oxide synthase immunoreactive areas was observed in the rats of the group given ethanol. On the other hand, a normal morphological appearance and a decrease in neuronal nitric oxide synthase immunoreactive areas were detected in the rats given ethanol+vitamin C+vitamin E+ selenium. In the group to which ethanol was administered, an increase in serum cholesterol and a decrease in serum albumin levels were determined. On the other hand, in the group to which ethanol+vitamin C+vitamin E+selenium were administered, serum cholesterol value decreased, and the serum albumin level increased. As a result, we can say that the combination of vitamin C, vitamin E and selenium has a protective effect on ethanol-induced duodenal mucosal injury.
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Affiliation(s)
- M Koyuturk
- Department of Histology and Embryology, Faculty of Medicine, Kadir Has University, 80810 Gayrettepe, Turkey.
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