|
1
|
Panchawat S, Pradhan J. Comparative Evaluation of Antiulcer Activity of Ficus religiosa (Stem Bark) Extracts Prepared by Different Methods of Extraction. CURRENT TRADITIONAL MEDICINE 2020. [DOI: 10.2174/2215083805666190328210119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
The stem bark of Ficus religiosa L. (Family-Moraceae) is traditionally
used to treat gonorrhea, diarrhea, dysentery, leucorrhea, menorrhagia, vaginal and other
urogenical disorders, ulcers and gastrohelcosis.
Objective:
The study was aimed at comparing antiulcer activity (ethanol induced gastric ulcer)
for stem bark extracts of Ficus religiosa Linn. prepared by different extraction methods
viz. soxhlet, ultrasonication and microwave assisted extraction.
Methods:
The powdered drug material was extracted by soxhlet (time 48 hours., temperature
60°C and solvent 60% ethanol), Ultrasonic (90 min., 50°C and acetone as solvent)and Microwave
(3 min., 60°C and acetone as solvent) assisted extraction method. The acute toxicity
study was carried out in adult female albino rats by “fix dose” method of OECD guideline
no. 420 for selection of doses. Antiulcerogenic effect of prepared extracts (200mg/kg) was
evaluated by ethanol induced ulcer method using omeprazole (40 mg/kg) as standard drug
and absolute alcohol 99.5% as necrotizing agent.
Result and Conclusion:
Acute toxicity study did not show any significant toxicity signs and
extracts were said to be practically non-toxic at tested dose level of 2000 mg/kg, b.w. The
best antiulcer activity was shown by the hydroalcoholic extract prepared by soxhlet extraction
method. Administration of ethanol produced significant ulcer index (41.00 ± 1.75) in the
control group. Standard drug omeprazole (40 mg/kg) produced percentage protection of
70.31%. Among all three extracts, Ulcer index is significantly (p<0.001) protected by hydroalcoholic
extract (Soxhlet Extraction Method) with percentage protection 52.02%.
Collapse
Affiliation(s)
- Sunita Panchawat
- Department of Pharmaceutical Sciences, Mohanlal Sukhadia University, Udaipur (Rajasthan) 313001, India
| | - Joohee Pradhan
- Department of Pharmaceutical Sciences, Mohanlal Sukhadia University, Udaipur (Rajasthan) 313001, India
| |
Collapse
|
|
2
|
Mostofa R, Ahmed S, Begum MM, Sohanur Rahman M, Begum T, Ahmed SU, Tuhin RH, Das M, Hossain A, Sharma M, Begum R. Evaluation of anti-inflammatory and gastric anti-ulcer activity of Phyllanthus niruri L. (Euphorbiaceae) leaves in experimental rats. BMC COMPLEMENTARY AND ALTERNATIVE MEDICINE 2017; 17:267. [PMID: 28511679 PMCID: PMC5434621 DOI: 10.1186/s12906-017-1771-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/15/2016] [Accepted: 05/08/2017] [Indexed: 01/07/2023]
Abstract
BACKGROUND The medicinal plants signify a massive basin of potential phytoconstituents that could be valuable as a substitute to allopathic drugs or considered as an analogue in drug development. Phyllanthus niruri L. (Euphorbiaceae) is generally used in traditional medicine to treat ulcer and inflammation. In this project we investigated the methanolic extract of leaves of Phyllanthus niruri for anti-inflammatory and anti-ulcer activity. METHODS The anti-inflammatory activity of methanol extract of Phyllanthus niruri leaves was evaluated at the doses of 100, 200 and 400 mg/kg, p.o. while using ibuprofen (20 mg/kg, p.o) as the standard drug. The animals used were Swiss albino rats. Inflammation was induced by injecting 0.1 ml carrageenan (1% w/v) into the left hind paw. Paw tissues from the different groups were examined for inflammatory cell infiltration. On the other hand, antiulcer activity of methanolic extract of P. niruri leaves at the doses of 100, 200 and 400 mg/kg, p.o. were examined against ethanol-acid induced gastric mucosal injury in the Swiss albino rats - keeping omeprazole (20 mg/kg, p.o.) as reference. The rats were dissected and the stomachs were macroscopically examined to identify hemorrhagic lesions in the glandular mucosa. RESULTS P. niruri significantly (p < 0.01) decreased carrageenan-induced paw edema; it exhibited a reduction of 46.80%, 55.32% and 69.14% at doses of 100, 200 and 400 mg/kg, respectively. These findings were further supported by the histological study. The methanolic extract also disclosed good protective effect against ethanol-acid induced gastric mucosal injury in the rats. Administration of the extract's doses (100, 200 and 400 mg/kg) demonstrated a significant (p < 0.01) reduction in the ethanol- acid induced gastric erosion in all the experimental groups when compared to the control. The methanolic extract at the higher dose (400 mg/kg) resulted in better inhibition of ethanol-acid induced gastric ulcer as compare to omeprazole (20 mg/kg). Histological studies of the gastric wall revealed that toxic control rats revealed mucosal degeneration, ulceration and migration of numerous inflammatory cells throughout the section. On the other hand, MEPN treatment groups showed significant regeneration of mucosal layer and significantly prevented the formation of hemorrhage and edema. CONCLUSIONS The investigation suggests that methanolic extract of P. niruri leaf possess anti-inflammatory activity and promotes ulcer protection as ascertained by regeneration of mucosal layer and substantial prevention of the formation of hemorrhage and edema.
Collapse
Affiliation(s)
- Ronia Mostofa
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| | - Shanta Ahmed
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| | - Mst. Marium Begum
- Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh
| | - Md. Sohanur Rahman
- Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi, 6205 Bangladesh
| | - Taslima Begum
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| | - Siraj Uddin Ahmed
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| | | | - Munny Das
- Department of Pharmaceutical Sciences, North South University, Dhaka, 1229 Bangladesh
| | - Amir Hossain
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| | - Manju Sharma
- Department of Pharmacology, Faculty of Pharmacy, Hamdard University, New Delhi, 110062 India
| | - Rayhana Begum
- Department of Pharmacy, Primeasia University, Dhaka, 1213 Bangladesh
| |
Collapse
|
|
3
|
Semipurified Ethyl Acetate Partition of Methanolic Extract of Melastoma malabathricum Leaves Exerts Gastroprotective Activity Partly via Its Antioxidant-Antisecretory-Anti-Inflammatory Action and Synergistic Action of Several Flavonoid-Based Compounds. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2017; 2017:6542631. [PMID: 28168011 PMCID: PMC5267083 DOI: 10.1155/2017/6542631] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/09/2016] [Accepted: 10/26/2016] [Indexed: 12/15/2022]
Abstract
Recent study has demonstrated the gastroprotective activity of crude methanolic extract of M. malabathricum leaves. The present study evaluated the gastroprotective potential of semipurified extracts (partitions): petroleum ether, ethyl acetate (EAMM), and aqueous obtained from the methanolic extract followed by the elucidation of the gastroprotective mechanisms of the most effective partition. Using the ethanol-induced gastric ulcer assay, all partitions exerted significant gastroprotection, with EAMM being the most effective partition. EAMM significantly (i) reduced the volume and acidity (free and total) while increasing the pH of gastric juice and enhanced the gastric wall mucus secretion when assessed using the pylorus ligation assay, (ii) increased the enzymatic and nonenzymatic antioxidant activity of the stomach tissue, (iii) lost its gastroprotective activity following pretreatment with N-omega-nitro-L-arginine methyl ester (L-NAME; NO blocker) or carbenoxolone (CBXN; NP-SH blocker), (iv) exerted antioxidant activity against various in vitro oxidation assays, and (v) showed moderate in vitro anti-inflammatory activity via the LOX-modulated pathway. In conclusion, EAMM exerts a remarkable NO/NP-SH-dependent gastroprotective effect that is attributed to its antisecretory and antioxidant activities, ability to stimulate the gastric mucus production and endogenous antioxidant system, and synergistic action of several gastroprotective-induced flavonoids.
Collapse
|
|
4
|
Motta EV, Lemos M, Costa JC, Banderó-Filho VC, Sasse A, Sheridan H, Bastos JK. Galloylquinic acid derivatives from Copaifera langsdorffii leaves display gastroprotective activity. Chem Biol Interact 2017; 261:145-155. [DOI: 10.1016/j.cbi.2016.11.028] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2016] [Revised: 11/11/2016] [Accepted: 11/24/2016] [Indexed: 02/07/2023]
|
|
5
|
Balan T, Mohd Sani MH, Suppaiah V, Mohtarrudin N, Suhaili Z, Ahmad Z, Zakaria ZA. Antiulcer activity of Muntingia calabura leaves involves the modulation of endogenous nitric oxide and nonprotein sulfhydryl compounds. PHARMACEUTICAL BIOLOGY 2013; 52:410-418. [PMID: 24192248 DOI: 10.3109/13880209.2013.839713] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/02/2023]
Abstract
Abstract Context: Muntingia calabura L. (Muntingiaceae) is a native plant species of the American continent and is widely cultivated in warm areas in Asia, including Malaysia. The plant is traditionally used to relieve pain from gastric ulcers. Objective: This study was designed to determine the antiulcer activity of a methanol extract of M. calabura leaves (MEMC) and the possible mechanisms of action involved. Materials and methods: An acute toxicity study was conducted using a single oral dose of 2000 mg/kg MEMC. The antiulcer activity of MEMC was evaluated in absolute ethanol- and indomethacin-induced gastric ulcer rat models. MEMC was administered orally (dose range 25-500 mg/kg) to rats fasted for 24 h. The animals were pretreated with NG-nitro-l-arginine methyl esters (l-NAME) or N-ethylmaleimide (NEM) prior to MEMC treatment to assess the possible involvement of endogenous nitric oxide (NO) and nonprotein sulfhydryl (NP-SH) compounds in the gastroprotective effect of MEMC. Results: As the administered dose did not cause toxicity in the rats, the oral median lethal dose (LD50) of MEMC was >2000 mg/kg in rats. MEMC exerted significant (p < 0.001) gastroprotective activity in the ethanol- and indomethacin-induced ulcer models dose-dependently. Histological evaluation supported the observed antiulcer activity of MEMC. l-NAME and NEM pretreatment significantly (p < 0.05) reversed and abolished the gastroprotective effect of MEMC, respectively. Discussion and conclusion: The results obtained indicate that MEMC has significant antiulcer activity that might involve the participation of endogenous NO and NP-SH compounds. These findings provide new pharmacological information regarding the potential use of M. calabura.
Collapse
|
|
6
|
Viana AFSC, Fernandes HB, Silva FV, Oliveira IS, Freitas FFBP, Machado FDF, Costa CLS, Arcanjo DDR, Chaves MH, Oliveira FA, Oliveira RCM. Gastroprotective activity of Cenostigma macrophyllum Tul. var. acuminata Teles Freire leaves on experimental ulcer models. JOURNAL OF ETHNOPHARMACOLOGY 2013; 150:316-323. [PMID: 24035848 DOI: 10.1016/j.jep.2013.08.047] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/30/2013] [Revised: 08/23/2013] [Accepted: 08/25/2013] [Indexed: 06/02/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Leguminosae-Caesalpinioideae), popularly known in Brazil as "caneleiro", is widely used in folk medicine against gastrointestinal diseases. In previous studies, the ethanol extract of leaves from Cenostigma macrophyllum Tul. var. acuminata Teles Freire had shown antinociceptive, anti-inflammatory, antibacterial, antioxidant and antiulcerogenic activities. AIM OF THE STUDY The aim of this study was to assess the gastroprotective effect of the hydroalcoholic fraction of leaves of Cenostigma macrophyllum Tul. var. acuminata Teles Freire (Cm-FHA), as well as to elucidate the possible underlying mechanisms of action. MATERIALS AND METHODS Mice were used for the evaluation of the acute toxicity, and mice and rats to study the gastroprotective activity. The potential gastroprotective of Cm-FHA was assessed on different gastric ulcer models in rodents, such as absolute ethanol, HCl/ethanol, ischemia-reperfusion, cold restraint stress and indomethacin. The participation of prostaglandins, NO-synthase pathway and ATP-sensitive potassium channels (KATP) in gastroprotective activity of Cm-FHA were evaluated after treatment with a cyclooxygenase inhibitor (indomethacin), a NO-synthase inhibitor (L-NAME) and a KATP channel blocker (glibenclamide 5mg/kg), respectively. Likewise, the catalase activity was determinated in order to assess the possible participation of antioxidant mechanisms. RESULTS No signs of acute toxicity was observed after oral acute administration of Cm-FHA, considering the analyzed parameters. Likewise, Cm-FHA promoted a protective effect against gastric ulcers induced by absolute ethanol (lesion inhibition by 40% at both 100 and 200mg/kg), HCl/ethanol (lesion inhibition by 50 or 48% at 100 or 200mg/kg, respectively), ischemia-reperfusion (lesion inhibition by 49 or 90% at 100 or 200mg/kg, respectively) and cold restraint stress (lesion inhibition by 63 or 76% at 100 or 200mg/kg, respectively), as well as a increase of catalase activity was observed. Otherwise, Cm-FHA was not able to protect gastric mucosa against indomethacin-induced lesions. Nitric oxide release, the of KATP channels opening and antioxidant activity are the possibly involved in the Cm-FHA-induced gastroprotective activity. CONCLUSION This study corroborates the folk medicine use of Cenostigma macrophyllum for treatment of gastric ulcers, as well as reinforces this species as a valuable source of promising natural drugs with gastroprotective activity.
Collapse
Affiliation(s)
- A F S C Viana
- Medicinal Plants Research Center, Federal University of Piauí, Teresina, Brazil
| | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
7
|
Singh VK, Mishra V, Tiwari S, Khaliq T, Barthwal MK, Pandey HP, Palit G, Narender T. Anti-secretory and cyto-protective effects of peganine hydrochloride isolated from the seeds of Peganum harmala on gastric ulcers. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2013; 20:1180-1185. [PMID: 23880327 DOI: 10.1016/j.phymed.2013.06.017] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/27/2013] [Accepted: 06/18/2013] [Indexed: 06/02/2023]
Abstract
Gastroprotective mechanism of peganine hydrochloride isolated from Peganum harmala seeds was investigated. Peganine hydrochloride was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats. Potential anti-ulcer activity of peganine was observed against CRU (50.0%), AS (58.5%), AL (89.41%) and PL (62.50%) induced ulcer models. The reference drug omeprazole (10mg/kg, p.o.) showed 77.45% protection against CRU, 49.97% against AS and 69.42% against PL model. Sucralfate, another reference drug (500mg/kg, p.o.) showed 62.50% protection in AL induced ulcer model. Peganine significantly reduced free acidity (33.38%), total acidity (38.09%) and upregulated mucin secretion by 67.91%, respectively. Further, peagnine significantly inhibited H(+) K(+)-ATPase activity in vitro with IC50 of 73.47μg/ml as compared to the IC50 value of omeprazole (30.24μg/ml) confirming its anti-secretory activity.
Collapse
Affiliation(s)
- Vinay Kumar Singh
- Medicinal and Process Chemistry Division, CSIR-Central Drug Research Institute, Lucknow 226001, U.P., India
| | | | | | | | | | | | | | | |
Collapse
|
|
8
|
Hwang IY, Jeong CS. Inhibitory Effects of 4-Guanidinobutyric Acid against Gastric Lesions. Biomol Ther (Seoul) 2013; 20:239-44. [PMID: 24116302 PMCID: PMC3792225 DOI: 10.4062/biomolther.2012.20.2.239] [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: 08/24/2011] [Revised: 10/17/2011] [Accepted: 11/23/2011] [Indexed: 11/10/2022] Open
Abstract
This study examined the inhibitory effects of 4-guanidinobutyric acid (4GBA), an alkaloid, against gastric lesions by assessing the inhibition of Helicobacter pylori (H. pylori) and gastric cancer cells. Acute and chronic gastritis were also observed using HCl/ethanol (EtOH) and indomethacin-induced gastric lesion models, respectively. 4GBA inhibited the growth of H. pylori in a dose dependent manner, and showed acid-neutralizing capacity. In the pylorus ligated rats, 4GBA decreased the volume of gastric secretion and gastric acid output slightly, and increased the pH. 4GBA at a dose of 100 mg/kg reduced the size of HCl/EtOH-induced gastric lesions (70.8%) and indomethacin-induced gastric lesions (38.8%). The antigastritic action of 4GBA might be associated with the acid-neutralizing capacity, anti-H. pylori action, and decreased volume of gastric secretion. These results suggest that 4GBA might be useful in the treatment and/or protection of gastritis.
Collapse
Affiliation(s)
- In Young Hwang
- College of Pharmacy, Duksung Womens University, Seoul 132-714, Republic of Korea
| | | |
Collapse
|
|
9
|
α -Mangostin from Cratoxylum arborescens (Vahl) Blume Demonstrates Anti-Ulcerogenic Property: A Mechanistic Study. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2013; 2013:450840. [PMID: 23634169 PMCID: PMC3619625 DOI: 10.1155/2013/450840] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/26/2012] [Accepted: 01/28/2013] [Indexed: 01/17/2023]
Abstract
Cratoxylum arborescens (Vahl) Blume is an Asian herbal medicine with versatile ethnobiological properties including treatment of gastric ulcer. This study evaluated the antiulcerogenic mechanism(s) of α-mangostin (AM) in a rat model of ulcer. AM is a prenylated xanthone derived through biologically guided fractionation of C. arborescens. Rats were orally pretreated with AM and subsequently exposed to acute gastric lesions induced by ethanol. Following treatment, ulcer index, gastric juice acidity, mucus content, histological and immunohistochemical analyses, glutathione (GSH), malondialdehyde (MDA), nitric oxide (NO), and nonprotein sulfhydryl groups (NP-SH) were evaluated. The anti-Helicobacter pylori, cyclooxygenase-2 (COX-2) inhibitory effect, and antioxidant activity of AM were also investigated in vitro. AM (10 and 30 mg/kg) inhibited significantly (P < 0.05) ethanol-induced gastric lesions by 66.04% and 74.39 %, respectively. The compound induces the expression of Hsp70, restores GSH levels, decreases lipid peroxidation, and inhibits COX-2 activity. The minimum inhibitory concentration (MIC) of AM showed an effective in vitro anti-H. pylori activity. The efficacy of the AM was accomplished safely without presenting any toxicological parameters. The results of the present study indicate that the antioxidant properties and the potent anti-H. pylori, in addition to activation of Hsp70 protein, may contribute to the gastroprotective activity of α-mangostin.
Collapse
|
|
10
|
Das SK, Roy C. The protective role of Aegle marmelos on aspirin-induced gastro-duodenal ulceration in albino rat model: a possible involvement of antioxidants. Saudi J Gastroenterol 2012; 18:188-94. [PMID: 22626798 PMCID: PMC3371421 DOI: 10.4103/1319-3767.96452] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2011] [Accepted: 01/08/2012] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/AIM Gastro duodenal ulcer is a common disorder of the gastrointestinal tract. Several Indian medicinal plants have been traditionally and extensively used to prevent different diseases. In the present research studies, Bael fruit (Aegle marmelos (AM), family: Rutaceae) which are also called as Bilva in ancient Sanskrit was used as a herbal drug and its antioxidative role in aspirin- induced gastroduodenal ulceration in albino rat was evaluated using essential biochemical parameters. PATIENTS AND METHODS Mucosal thickness (MT), ulcer index (UI), different biochemical parameters, such as aspartate aminotransferase (AST), alanine aminotransferase (ALT), catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and lipid peroxidation (LPO) were measured in all the groups, to study the possible involvement of antioxidants with gastroduodenal protection. RESULTS A significant decrease in MT, SOD and CAT activities and GSH level and a significant increase in UI, AST, ALT, and ALP activities and LPO level were observed in aspirin treated stomach and duodenum of albino rats. CONCLUSIONS Pretreatment with AM fruit pulp extract for 14 consecutive days showed the reverse effects of aspirin suggesting gastro-duodenal protective and anti- ulcerogenic properties of AM through its antioxidant mechanism.
Collapse
Affiliation(s)
- Shyamal K. Das
- Department of Physiology, Krishnath College, University of Kalyani, Berhampore, Murshidabad, India
| | - Chandan Roy
- Department of Physiology, Katwa College, University of Burdwan, P.O. Katwa, District. Burdwan, West Bengal, India
| |
Collapse
|
|
11
|
Qader SW, Abdulla MA, Chua LS, Sirat HM, Hamdan S. Pharmacological mechanisms underlying gastroprotective activities of the fractions obtained from Polygonum minus in Sprague Dawley rats. Int J Mol Sci 2012; 13:1481-1496. [PMID: 22408403 PMCID: PMC3291972 DOI: 10.3390/ijms13021481] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2011] [Revised: 01/11/2012] [Accepted: 01/18/2012] [Indexed: 11/20/2022] Open
Abstract
The leaves of Polygonum minus were fractionated using an eluting solvent to evaluate the pharmacological mechanisms underlying the anti-ulcerogenic activity of P. minus. Different P. minus fractions were obtained and evaluated for their ulcer preventing capabilities using the ethanol induction method. In this study, Sprague Dawley rats weighing 150–200 g were used. Different parameters were estimated to identify the active fraction underlying the mechanism of the gastroprotective action of P. minus: the gastric mucus barrier, as well as superoxide dismutase, total hexosamine, and prostaglandin synthesis. Amongst the five fractions from the ethanolic extract of P. minus, the ethyl acetate:methanol 1:1 v/v fraction (F2) significantly (p < 0.005) exhibited better inhibition of ulcer lesions in a dose-dependent manner. In addition, rats pre-treated with F2 showed a significant elevation in superoxide dismutase (SOD), hexosamine and PGE2 levels in the stomach wall mucosa in a dose-dependent matter. Based on these results, the ethyl acetate:methanol 1:1 v/v fraction was considered to be the best fraction for mucous protection in the ethanol induction model. The mechanisms underlying this protection were attributed to the synthesis of antioxidants and PGE2.
Collapse
Affiliation(s)
- Suhailah Wasman Qader
- Department of Biological Science, Faculty of Biosciences and Bioengineering, Universiti Teknologi Malaysia, UTM Skudai, Johor 81310, Malaysia; E-Mail:
| | - Mahmood Ameen Abdulla
- Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur 50603, Malaysia; E-Mail:
| | - Lee Suan Chua
- Metabolites Profiling Laboratory, Institute of Bioproduct Development, Universiti Teknologi Malaysia, UTM Skudai, Johor 81310, Malaysia; E-Mail:
| | - Hasnah Mohd Sirat
- Department of Chemistry, Faculty of Science, Universiti Teknologi Malaysia, UTM Skudai, Johor 81310, Malaysia; E-Mail:
| | - Salehhuddin Hamdan
- Department of Biological Science, Faculty of Biosciences and Bioengineering, Universiti Teknologi Malaysia, UTM Skudai, Johor 81310, Malaysia; E-Mail:
- Author to whom correspondence should be addressed; E-Mail: ; Tel.: +60-77229364; Fax: +60-75531112
| |
Collapse
|
|
12
|
Coelho-de-Souza AN, Lahlou S, Barreto JE, Yum ME, Oliveira AC, Oliveira HD, Celedônio NR, Feitosa RG, Duarte GP, Santos CF, de Albuquerque AA, Leal-Cardoso JH. Essential oil ofCroton zehntneriand its major constituent anethole display gastroprotective effect by increasing the surface mucous layer. Fundam Clin Pharmacol 2012; 27:288-98. [DOI: 10.1111/j.1472-8206.2011.01021.x] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
|
|
13
|
Shikama N, Ichikawa T, Iwai T, Yamamoto H, Kida M, Koizumi W, Ishihara K. Different effects of two types of H2-receptor antagonists, famotidine and roxatidine, on the mucus barrier of rat gastric mucosa. Biomed Res 2012; 33:45-51. [DOI: 10.2220/biomedres.33.45] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
|
|
14
|
Abdelwahab SI, Mohan S, Abdulla MA, Sukari MA, Abdul AB, Taha MME, Syam S, Ahmad S, Lee KH. The methanolic extract of Boesenbergia rotunda (L.) Mansf. and its major compound pinostrobin induces anti-ulcerogenic property in vivo: possible involvement of indirect antioxidant action. JOURNAL OF ETHNOPHARMACOLOGY 2011; 137:963-970. [PMID: 21771650 DOI: 10.1016/j.jep.2011.07.010] [Citation(s) in RCA: 73] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/11/2011] [Revised: 07/02/2011] [Accepted: 07/03/2011] [Indexed: 05/31/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Boesenbergia rotunda (L) Mansf. has been used for the treatment of gastrointestinal disorders including peptic ulcer. In the current study we aimed to investiagte the anti-ulcer activities of methanolic extract of B. rotunda (MEBR) and its main active compound, pinostrobin on ethanol-induced ulcer in rats. The possible involevement of lipid peroxidation, nitric oxide, cyclooxygenases and free radical scavenging mechanisms also has been investigated. MATERIALS AND METHODS Pinostrobin was isolated form the rhizomes of B. rotunda. Ulcer index, gastric juice acidity, mucus content, gross and histological gastric lesions and thiobarbituric acid reactive substances (TBARS) were evaluated in ethanol-induced ulcer in vivo. The effect of pinostrobin into lipopolysaccharide/interferon-γ stimulated rodent cells, COX-1 and COX-2 activities were done in vitro. RESULTS Pre-treatment with MEBR, pinostrobin or omeprazole protected the gastric mucosa as seen by reduction in ulcer area and mucosal content, reduced or absence of submucosal edema and leucocytes infiltration. Pinostrobin significantly (p<0.05) lowered the elevated TBARS level into gasteric homogenate. Pinostrobin did not produced significant in vitro inhibition of NO from LPS/IFN-γ activated rodent cells without affecting the viability of these cells. Further, the compound did bot revleaed inhibitory effects on both COX- 1& 2 enzymes. The antioxidant assays also exhibited non significance in vitro. CONCLUSION Thus it can be concluded that MEBR possesses anti-ulcer activity, which could be attributed to indirect anti-oxidant mechanism of pinostrobin but not to the intervention with nitric oxide and COX inflammation pathways.
Collapse
|
|
15
|
Yadav DK, Singh N, Dev K, Sharma R, Sahai M, Palit G, Maurya R. Anti-ulcer constituents of Annona squamosa twigs. Fitoterapia 2011; 82:666-75. [DOI: 10.1016/j.fitote.2011.02.005] [Citation(s) in RCA: 30] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2010] [Revised: 02/09/2011] [Accepted: 02/12/2011] [Indexed: 10/18/2022]
|
|
16
|
Tour N, Talele G. Anti-inflammatory and gastromucosal protective effects of Calotropis procera (Asclepiadaceae) stem bark. J Nat Med 2011; 65:598-605. [PMID: 21400248 DOI: 10.1007/s11418-011-0522-1] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2010] [Accepted: 01/27/2011] [Indexed: 02/05/2023]
Abstract
This study was aimed at evaluating the anti-inflammatory and gastromucosal protective effect of chloroform extract (CH) and hydroalcoholic extract (HE) of the stem bark of Calotropis procera obtained successively by cold maceration. The anti-inflammatory effect of the CH and HE extracts of the stem bark of Calotropis procera against carrageenan-induced paw oedema and also its gastromucosal protective effect has been studied by using two acute models: aspirin (100 mg/kg, p.o.) and ethanol (96%) in albino rats. CH and HE extracts showed significant anti-inflammatory activity at 200 and 400 mg/kg, while CH extract at 400 mg/kg was also found to have a significant gastromucosal protective effect. As part of investigations to obtain compounds with anti-inflammatory and gastromucosal protective effects in this work, a bioassay was carried out with fractions obtained from the CH extract with n-hexane (NF1), 1-butanol (BF1), ethyl acetate (EF1) and chloroform (CF1). The HE extract of the stem bark was fractionated with n-hexane (NF2), 1-butanol (BF2), ethyl acetate (EF2), chloroform (CF2) and water (WF2). The fractions were evaluated for their anti-inflammatory and gastromucosal protective effects. Fractions NF1, CF1, BF2 and EF2 (20 mg/kg) showed significant anti-inflammatory activity, while NF1 and BF2 (20 mg/kg) also showed gastromucosal protective effects. The results obtained for gastromucosal protective effects were also well supported by histopathological examination of the open excised rat stomach.
Collapse
Affiliation(s)
- Nagesh Tour
- R. C. Patel Institute of Pharmaceutical Education and Research, Maharashtra, India.
| | | |
Collapse
|
|
17
|
Santin JR, Lemos M, Klein-Júnior LC, Machado ID, Costa P, de Oliveira AP, Tilia C, de Souza JP, de Sousa JPB, Bastos JK, de Andrade SF. Gastroprotective activity of essential oil of the Syzygium aromaticum and its major component eugenol in different animal models. Naunyn Schmiedebergs Arch Pharmacol 2010; 383:149-58. [PMID: 21140134 DOI: 10.1007/s00210-010-0582-x] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2010] [Accepted: 11/15/2010] [Indexed: 10/18/2022]
|
|
18
|
Verbascoside isolated from Tectona grandis mediates gastric protection in rats via inhibiting proton pump activity. Fitoterapia 2010; 81:755-61. [DOI: 10.1016/j.fitote.2010.03.019] [Citation(s) in RCA: 39] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2010] [Revised: 03/25/2010] [Accepted: 03/26/2010] [Indexed: 11/23/2022]
|
|
19
|
Lakshmi V, Singh N, Shrivastva S, Mishra SK, Dharmani P, Mishra V, Palit G. Gedunin and photogedunin of Xylocarpus granatum show significant anti-secretory effects and protect the gastric mucosa of peptic ulcer in rats. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2010; 17:569-574. [PMID: 19962286 DOI: 10.1016/j.phymed.2009.10.016] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/05/2009] [Revised: 09/18/2009] [Accepted: 10/12/2009] [Indexed: 05/28/2023]
Abstract
In the present study, the gastroprotective mechanism of Xylocarpus granatum fruit and its active constituents gedunin and photogedunin was investigated. Chloroform fraction (Fr-CHCl(3)) of X. granatum fruit was evaluated against cold restraint (CRU), aspirin (AS), alcohol (AL) and pyloric ligation (PL) induced gastric ulcer models in rats and histamine (HA) induced duodenal ulcer model in guinea pigs. Potential anti-ulcer activity of Fr-CHCl(3) was observed against CRU (58.28%), AS (67.81%), AL (84.38%), PL (65.66%) and HA (61.93%) induced ulcer models. The standard drug omeprazole (10mg/kg, p.o.) showed 68.25% protection against CRU, 57.08% against AS and 69.42% against PL model and 70.79% against HA induced duodenal ulcer. Sucralfate, another standard drug (500 mg/kg, p.o.) showed 62.72% protection in AL induced ulcer model. Fr-CHCl(3) significantly reduced free acidity (51.42%), total acidity (30.76%) and upregulated mucin secretion by 58.37% respectively. Phytochemical investigations of Fr-CHCl(3) yielded gedunin (36%), photogedunin (2%). Further, Fr-CHCl(3) and its compounds gedunin and photogedunin significantly inhibited H(+) K(+)-ATPase activity in vitro with IC(50) of 89.37, 56.86 and 66.54 microg/ml respectively as compared to the IC(50) value of omeprazole (30.24 microg/ml) confirming their anti-secretory activity. Conclusively, Fr-CHCl(3) of Xylocarpus granatum was found to possess anti-ulcerogenic activity which might be due to its anti-secretory activity and subsequent strengthening of the defensive mechanism. This study is the first of its kind to show significant anti-secretory effect of gedunin and photogedunin. Therefore it could act as a potent therapeutic agent against peptic ulcer disease.
Collapse
Affiliation(s)
- V Lakshmi
- Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, U.P, India
| | | | | | | | | | | | | |
Collapse
|
|
20
|
Lemos M, de Barros MP, Sousa JPB, da Silva Filho AA, Bastos JK, de Andrade SF. Baccharis dracunculifolia, the main botanical source of Brazilian green propolis, displays antiulcer activity. J Pharm Pharmacol 2010; 59:603-8. [PMID: 17430646 DOI: 10.1211/jpp.59.4.0017] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/31/2022]
Abstract
Abstract
Baccharis dracunculifolia is the most important botanical source of Southeastern Brazilian propolis, known as green propolis for its colour. In a previous study, we described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. We therefore wanted to investigate the possibility of using B. dracunculifolia extract for antiulcer treatment. This study was undertaken to evaluate the anti-ulcerogenic property of hydroalcoholic extract of B. dracunculifolia aerial parts. The HPLC analysis of the chemical composition of B. dracunculifolia extract used in this study revealed the presence mainly of cinnamic acid derivates and flavonoids. Doses of 50, 250 and 500 mg/kg of B. dracunculifolia crude extract and positive controls (omeprazole or cimetidine) significantly diminished the lesion index, the total lesion area and the percentage of lesion compared with negative control groups. The percentage of ulcer inhibition was significantly higher in groups treated with B. dracunculifolia, cimetidine or omeprazole, with all protocols used, compared with negative control groups. Regarding the model of gastric secretion, reductions in the volume of gastric juice and total acidity were observed, as well as an increase in the gastric pH. These results were similar to results from studies carried out with green propolis extract. Although more investigations are required, our results suggest that B. dracunculifolia has potential to be used as a phytotherapic preparation for the treatment of gastric ulcer.
Collapse
Affiliation(s)
- Marivane Lemos
- Núcleo de Ciência e Tecnologia, Area de Ciências Biológicas e da Saúde, Universidade do Oeste de Santa Catarina, Campus de Videira, Rua Paese, 198, Bairro das Torres, Videira-SC, 89560-000, SC, Brazil
| | | | | | | | | | | |
Collapse
|
|
21
|
Antiulcerogenic activity of extract, fractions, and some compounds obtained from Polygala cyparissias St. Hillaire & Moquin (Polygalaceae). Naunyn Schmiedebergs Arch Pharmacol 2010; 381:121-6. [DOI: 10.1007/s00210-009-0485-x] [Citation(s) in RCA: 52] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2009] [Accepted: 12/09/2009] [Indexed: 12/11/2022]
|
|
22
|
Areche C, Schmeda-Hirschmann G, Theoduloz C, Rodríguez JA. Gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean Lamiaceae Sphacele chamaedryoides (Balbis) Briq. J Pharm Pharmacol 2010. [DOI: 10.1211/jpp.61.12.0015] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Abstract
Objectives
The aim of this report was to isolate, identify and assess the gastroprotective effect and cytotoxicity of abietane diterpenes from the Chilean medicinal plant Sphacele chamaedryoides (Balbis) Briq. (Lamiaceae).
Methods
The isolated compounds were identified by spectroscopic means. The gastroprotective effect of the compounds was studied on the HCl/EtOH-induced gastric lesions model in mice. The cytotoxicity of the compounds was assessed on human normal lung fibroblasts (MRC-5) and gastric adenocarcinoma cells (AGS).
Key findings
From the aerial parts of the plant, five phenolic and five p-quinone abietanes, the sesquiterpene spathulenol and two flavonoids were obtained. The main diterpene from the plant was carnosol (7). Lansoprazole at 20 mg/kg reduced gastric lesions by 64.7% (P < 0.01), being statistically similar to carnosol at doses of 10 and 20 mg/kg; the percent lesion reduction with 7 at 5 mg/kg was 49.3%. At a single oral dose of 5 mg/kg, the diterpenes bearing a p-quinone moiety −6,7-dehydroroyleanone (1), royleanone (2), 7,20-epoxyroyleanone (3), taxoquinone (5) and horminone (6) - presented a gastroprotective effect of 54.4, 70.8, 65.0, 35.8 and 52.7%, respectively. Of the C-7 hydroxy derivatives, the activity was much lower for the 7β-OH isomer. The phenolic diterpenes 7 and 7-oxo-11,12,14-trihydroxy-8,11,13-abietatrien-20-al (8) inhibited gastric lesions by 49.3 and 53.0%, respectively. Royleanone (2), 7,20-epoxyroyleanone (3), horminone (6), 8 and spathulenol proved to be cytotoxic with IC50 values in the range of 11–67 μM. The selective cytotoxicity of compounds 1 (IC50: 61 and 366 μM) and 5 (IC50: 310 and 27 μM) against AGS cells and fibroblasts, respectively, merit additional studies.
Conclusions
All the abietanes obtained from S. chamaedryoides present either one or two phenolic OH groups, a quinone system, or both. Several compounds present in the plant showed higher gastroprotective effect than lansoprazole. The cytotoxic effect of most compounds was found at fairly high concentrations and lacked cell specificity. Further studies are required using different tumour cell lines and viability/proliferation assays to assess the specificity of the isolated compounds. The selective cytotoxicity of compounds 1 and 5 against AGS cells and fibroblasts, respectively, merit additional studies.
Collapse
Affiliation(s)
- Carlos Areche
- Laboratorio de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad deTalca, Talca, Chile
| | - Guillermo Schmeda-Hirschmann
- Laboratorio de Productos Naturales, Instituto de Química de Recursos Naturales, Universidad deTalca, Talca, Chile
| | - Cristina Theoduloz
- Depto. de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad deTalca, Talca, Chile
| | - Jaime A Rodríguez
- Depto. de Ciencias Básicas Biomédicas, Facultad de Ciencias de la Salud, Universidad deTalca, Talca, Chile
| |
Collapse
|
|
23
|
Meyre-Silva C, Petry CM, Berté TE, Becker RG, Zanatta F, Delle-Monache F, Cechinel-Filho V, Andrade SF. Phytochemical Analyses and Gastroprotective Effects of Eugenia Umbelliflora (Myrtaceae) on Experimental Gastric Ulcers. Nat Prod Commun 2009. [DOI: 10.1177/1934578x0900400706] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Phytochemical studies of Eugenia umbelliflora Berg. (Myrtaceae) resulted in the isolation of: taraxerol, α-amyrin, β-amyrin, betulin and betulinic acid from the leaves, as well as trimethoxy ellagic acid from the fruits. Given that several triterpenes were found in the extracts, and that these possess gastroprotective activity, the gastroprotective activity of E. umbelliflora leaf extract was evaluated using ethanol, indomethacin, and stress-induced ulcer models in mice. The crude methanol extract was administrated (v.o) in doses of 50, 125 and 250 mg/kg. The results showed that E. umbelliflora leaves display gastroprotective activity, as demonstrated by significant inhibition of ulcer formation in the different models. The results suggest that the gastroprotective activity may be attributed, at least in part, to the triterpenes.
Collapse
Affiliation(s)
- Christiane Meyre-Silva
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Cristiane Maes Petry
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Talita Elisa Berté
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Renan Gandolfi Becker
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Francielle Zanatta
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Franco Delle-Monache
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Valdir Cechinel-Filho
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| | - Sérgio Faloni Andrade
- Núcleo de Investigações Químico-Farmacêuticas (NIQFAR), Universidade do Vale do Itajaí-UNIVALI, 88302-202, Itajaí, Santa Catarina, Brazil
| |
Collapse
|
|
24
|
Lee JH, Lee SH, Kim YS, Jeong CS. Protective effects of neohesperidin and poncirin isolated from the fruits of Poncirus trifoliata
on potential gastric disease. Phytother Res 2009; 23:1748-53. [DOI: 10.1002/ptr.2840] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
|
|
25
|
Ichikawa T, Ito Y, Saegusa Y, Iwai T, Goso Y, Ikezawa T, Ishihara K. Effects of combination treatment with famotidine and methylmethionine sulfonium chloride on the mucus barrier of rat gastric mucosa. J Gastroenterol Hepatol 2009; 24:488-92. [PMID: 19175830 DOI: 10.1111/j.1440-1746.2008.05667.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND AND AIM In Japan, peptic ulcer disease (PUD) is treated clinically with a combination of a mucosal protectant and acid suppressants, but there is scant information regarding the effects of these drugs on normal gastric mucus cells. In the present study, the effects of co-administration of methylmethionine sulfonium chloride (MMSC) and famotidine on rat gastric mucus cells were investigated using both biochemical and histological methods. METHODS Rats were divided into four groups: controls were given carboxymethylcellulose orally once daily for 7 days and the second, third and fourth groups were treated similarly with famotidine (famotidine group), MMSC (MMSC group) or famotidine plus MMSC (combination group). After killing the rats on the 8th day, the stomachs were removed and the biosynthesis and amount of mucin in different areas of the gastric mucosa were compared among groups. Using anti-mucin monoclonal antibodies, the mucin content and immunoreactivity were also compared. RESULTS Both the biosynthesis and accumulation of mucin were significantly decreased in the famotidine group, but increased in the MMSC and combination groups. The amount and immunoreactivity of surface mucus cell-derived mucin were both reduced in the famotidine group, and increased in the MMSC and combination groups. There was no difference among the groups in the content and immunoreactivity of gland mucus cell-derived mucin. CONCLUSION Famotidine-induced suppression of gastric surface mucus cell function is prevented by combined treatment with MMSC, raising the possibility of a more effective cure of PUD.
Collapse
Affiliation(s)
- Takafumi Ichikawa
- Department of Biochemistry, Kitasto University School of Medcine, Sagamihara, Kanagawa, Japan.
| | | | | | | | | | | | | |
Collapse
|
|
26
|
Barros MPD, Lemos M, Maistro EL, Leite MF, Sousa JPB, Bastos JK, Andrade SFD. Evaluation of antiulcer activity of the main phenolic acids found in Brazilian Green Propolis. JOURNAL OF ETHNOPHARMACOLOGY 2008; 120:372-377. [PMID: 18930797 DOI: 10.1016/j.jep.2008.09.015] [Citation(s) in RCA: 91] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/12/2008] [Revised: 08/16/2008] [Accepted: 09/09/2008] [Indexed: 05/26/2023]
Abstract
AIM OF THE STUDY In a previous study, our group described the gastric protective effect of the hydroalcoholic extract of Brazilian green propolis. The main compounds found in Brazilian green propolis include phenolic acids, such as: caffeic, ferulic, p-coumaric and cinnamic acids. This study was therefore carried out to evaluate the antiulcerogenic property of the main phenolic acids found in Brazilian Green Propolis. MATERIAL AND METHODS The anti-ulcer assays were performed using the following protocols: nonsteroidal-antiinflammatory drug (NSAID)-induced ulcer, ethanol-induced ulcer, and stress-induced ulcer. The effects of the phenolic acids on gastric content volume, pH and total acidity, using the pylorus ligated model, were also evaluated. RESULTS It was observed that treatment using doses of 50 and 250 mg/kg of caffeic, ferulic, p-coumaric and cinnamic acids and positive controls (omeprazol or cimetidine) significantly diminished the lesion index, the total area of the lesion and the percentage of lesion in comparison with the negative control groups. In addition, the percentage of ulcer inhibition was significantly higher in the groups treated with the different phenolic acids, cimetidine or omeprazol, in all the protocols used, compared with the negative control groups. In the model to determine gastric secretion, using ligated pylorus, treatment with phenolic acids and cimetidine reduced the volume of gastric juice and total acidity and significantly increased the gastric pH (p<0.05), compared with the control group, with the exception of the group treated with 50mg/kg of p-coumaric acid, in which no significant difference was observed, compared with the control. In relation to the acute toxicity, none sign of toxicity was observed when phenolic acids, used in this study, were administered for rats in dose of 2,000 mg/kg. CONCLUSIONS In conclusion, the results of this study show that caffeic, ferulic, p-coumaric and cinnamic acids display antiulcer activity.
Collapse
Affiliation(s)
- Muriel Primon de Barros
- Núcleo de Ciência e Tecnologia, Area de Ciências Biológicas e da Saúde, Universidade do Oeste de Santa Catarina, Campus de Videira, Videira - SC, 89560-000, SC, Brazil
| | | | | | | | | | | | | |
Collapse
|
|
27
|
Al Mofleh IA, Alhaider AA, Mossa JS, Al-Sohaibani MO, Al-Yahya MA, Rafatullah S, Shaik SA. Gastroprotective effect of an aqueous suspension of black cumin Nigella sativa on necrotizing agents-induced gastric injury in experimental animals. Saudi J Gastroenterol 2008; 14:128-34. [PMID: 19568521 PMCID: PMC2702910 DOI: 10.4103/1319-3767.41731] [Citation(s) in RCA: 60] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2007] [Accepted: 04/26/2008] [Indexed: 12/05/2022] Open
Abstract
BACKGROUND/AIM Previous studies on "Black seed" or "Black Cumin" Nigella sativa (NS) have reported a large number of pharmacological activities including its anti-ulcer potential. These studies employed either fixed oil, volatile oil components or different solvent extracts. In folkloric practices, NS seeds are taken as such, in the form of coarse dry powder or the powdered seeds are mixed with water. This study examines the effect of NS aqueous suspension on experimentally induced gastric ulcers and basal gastric secretion in rats to rationalize its use by herbal and Unani medicine practitioners. MATERIALS AND METHODS The study was conducted at the Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Acute gastric ulceration was produced by various noxious chemicals (80% ethanol, 0.2 M NaOH, 25% NaCl and indomethacin) in Wistar albino rats. Anti-secretory studies were undertaken in a separate group of rats. Gastric wall mucus contents and non-protein sulfhydryl concentration were estimated, and gastric tissue was examined histopathologically. RESULTS An aqueous suspension of Black seed significantly prevented gastric ulcer formation induced by necrotizing agents. It also significantly ameliorated the ulcer severity and basal gastric acid secretion in pylorus-ligated Shay rats. Moreover, the suspension significantly replenished the ethanol-induced depleted gastric wall mucus content levels and gastric mucosal non-protein sulfhydryl concentration. The anti-ulcer effect was further confirmed histopathologically. CONCLUSION These findings validate the use of Black seed in gastropathies induced by necrotizing agents. The anti-ulcer effect of NS is possibly prostaglandin-mediated and/or through its antioxidant and anti-secretory activities.
Collapse
Affiliation(s)
- Ibrahim A Al Mofleh
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
| | - Abdulqader A. Alhaider
- Department of Pharmacology, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | - Jaber S. Mossa
- Department of Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| | | | - Mohammed A Al-Yahya
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Syed Rafatullah
- Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Shaffi A. Shaik
- Department of Family and Community Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
| |
Collapse
|
|
28
|
Antiulcerogenic activity of fractions and 3,15-Dioxo-21α-hydroxy friedelane isolated from Maytenus robusta (Celastraceae). Arch Pharm Res 2008; 31:41-6. [DOI: 10.1007/s12272-008-1118-5] [Citation(s) in RCA: 32] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
|
|
29
|
Zhang D, Du X, Liu M, Li H, Jiang Y, Zhao L, Gu J. Determination of ecabet in human plasma by high-performance liquid chromatography–tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2008; 863:223-8. [PMID: 18258501 DOI: 10.1016/j.jchromb.2008.01.013] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2007] [Revised: 12/29/2007] [Accepted: 01/04/2008] [Indexed: 12/20/2022]
|
|
30
|
de Barros MP, Sousa JPB, Bastos JK, de Andrade SF. Effect of Brazilian green propolis on experimental gastric ulcers in rats. JOURNAL OF ETHNOPHARMACOLOGY 2007; 110:567-71. [PMID: 17126509 DOI: 10.1016/j.jep.2006.10.022] [Citation(s) in RCA: 45] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/07/2006] [Revised: 10/16/2006] [Accepted: 10/19/2006] [Indexed: 05/12/2023]
Abstract
Propolis is a resinous hive product collected by honeybees from plants. The propolis produced in Southeastern of Brazil is known as green propolis because of its color. Modern herbalists recommend its use because it displays antibacterial, antifungal, antiviral, hepatoprotective, anti-inflammatory, immunomodulatory and anti-ulcer properties. The anti-ulcer activity of green propolis hydroalcoholic crude extract was evaluated by using models of acute gastric lesions induced by ethanol, indomethacin and stress in rats. Moreover, the effects of extract on gastric content volume, pH and total acidity, using pylorus ligated model were evaluated. Animals pretreated with propolis hydroalcoholic crude extract (50, 250 and 500 mg/kg) showed a significant reduction in lesion index, total affected area and percentage of lesion in comparison with control group (p<0.05) in the ethanol-induced ulcer model. Green propolis extract, at a higher dose (500 mg/kg), displayed a significant protection by reducing (p<0.05) the evaluated parameters in the gastric ulceration induced by indomethacin. In the stress-induced ulcer model it was observed a significant reduction (p<0.05) in those parameters in animals treated with green propolis extract (250 and 500 mg/kg). Regarding the pylorus ligated model it was observed that green propolis extract (250 and 500 mg/kg) displayed an anti-secretory activity, which lead to a reduction in the gastric juice volume, total acidity and pH. These findings indicate that Brazilian green propolis displays good anti-ulcer activity, corroborating the folk use of propolis preparations, and contributing for its pharmacological validation.
Collapse
Affiliation(s)
- Muriel Primon de Barros
- Núcleo de Ciência e Tecnologia, Area de Ciências Biológicas e da Saúde, Universidade do Oeste de Santa Catarina, Campus de Videira, SC, Brazil
| | | | | | | |
Collapse
|
|
31
|
Lee YS, Kang MH, Cho SY, Jeong CS. Effects of constituents of amomum xanthioides on gastritis in rats and on growth of gastric cancer cells. Arch Pharm Res 2007; 30:436-43. [PMID: 17489359 DOI: 10.1007/bf02980217] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
In this study we investigated the effects of constituents of Amomum xanthioides (AX) on gastritis in rats and on the growth of human gastric cancer cells. The ethanol extract of Amomum xanthioides significantly inhibited HCl ethanol-induced gastric lesions and the growth of Helicobacter pylori (H. pylon). The ethanol extract of AX was further fractionated with hexane, chloroform, butanol and H20. Among these fractions, oral treatment with the butanol fraction at a dose of 350 mg/kg was the most effective at preventing HCl* ethanol-induced gastric lesions. In pylorus ligated rats, the butanol fraction also decreased the volume of gastric secretion and gastric acid output. We isolated six subfractions of the butanol fraction using open column chromatography. Subfraction 4 (150 mg/kg) significantly inhibited HCl* ethanol-induced gastric lesions and gastric secretion in pylorus ligated rats. Using GC-MS we identified the constituents of subfraction 4 to be five aliphatic compounds, 1-hexadecene, 1-nonadecene, cycloeicosane, 1-octadecene and cyclotetracosane. In addition, subfraction 4 reduced cell viability in a dose-dependent manner in human gastric cancer cells (AGS, KATOIII and SNU638). It also increased intracellular Ca2+ concentration in SNU638 cells, an effect that was significantly inhibited by dantrolene, a Ca2+ release blocker. Moreover, dantrolene significantly inhibited subfraction 4-induced cytotoxicity. Taken together, these results suggest that subfraction 4 of the butanol extract of AX has an anti-gastritic effect in rats and is cytotoxic to human gastric cancer cells. The mechanism of its anti-gastritic action may be associated with the inhibition of secretion of gastric acid and anti-H. pylori action. Its cytotoxicity against human gastric cancer cells may be, at least in part, mediated by intracellular Ca2+ dyshomeostasis. From these results, we suggest that AX may be useful for the treatment of gastritis and gastric cancer.
Collapse
Affiliation(s)
- Yong Soo Lee
- College of Pharmacy, Duksung Women's University, Seoul, Korea
| | | | | | | |
Collapse
|
|
32
|
Al Mofleh IA, Alhaider AA, Mossa JS, Al-Soohaibani MO, Rafatullah S. Aqueous suspension of anise “ Pimpinella anisum” protects rats against chemically induced gastric ulcers. World J Gastroenterol 2007; 13:1112-8. [PMID: 17373749 PMCID: PMC4146877 DOI: 10.3748/wjg.v13.i7.1112] [Citation(s) in RCA: 30] [Impact Index Per Article: 1.7] [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 substantiate the claims of Unani and Arabian traditional medicine practitioners on the gastroprotective potential effect of a popular spice anise, “Pimpinella anisum L.” on experimentally-induced gastric ulceration and secretion in rats.
METHODS: Acute gastric ulceration in rats was produced by various noxious chemicals including 80% ethanol, 0.2 mol/L NaOH, 25% NaCl and indomethacin. Anti-secretory studies were undertaken using pylorus-ligated Shay rat technique. Levels of gastric non-protein sulfhydryls (NP-SH) and wall mucus were estimated and gastric tissue was also examined histologically. Anise aqueous suspension was used in two doses (250 and 500 mg/kg body weight) in all experiments.
RESULTS: Anise significantly inhibited gastric mu-cosal damage induced by necrotizing agents and indomethacin. The anti-ulcer effect was further confirmed histologically. In pylorus-ligated Shay rats, anise suspension significantly reduced the basal gastric acid secretion, acidity and completely inhibited the rumenal ulceration. On the other hand, the suspension significantly replenished ethanol-induced depleted levels of gastric mucosal NP-SH and gastric wall mucus concentration.
CONCLUSION: Anise aqueous suspension possesses significant cytoprotective and anti-ulcer activities against experimentally-induced gastric lesions. The anti-ulcer effect of anise is possibly prostaglandin-mediated and/or through its anti-secretory and antioxidative properties.
Collapse
Affiliation(s)
- Ibrahim A Al Mofleh
- Department of Medicine, College of Medicine, King Saud University, PO Box 2925 (59), Riyadh 11461, Saudi Arabia.
| | | | | | | | | |
Collapse
|
|
33
|
Toma W, Hiruma-Lima CA, Guerrero RO, Brito ARMS. Preliminary studies of Mammea americana L. (Guttiferae) bark/latex extract point to an effective antiulcer effect on gastric ulcer models in mice. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2005; 12:345-50. [PMID: 15957368 DOI: 10.1016/j.phymed.2003.06.009] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/03/2023]
Abstract
Plant extracts are some of the most attractive sources of new drugs and have shown promising results for the treatment of gastric ulcers. Several folk medicinal plants and herbs have been used to treat gastrointestinal disorders, including gastric ulcers. Mammea americana L. (Guttiferae) fruit is very common in the diet of the population of northern South America. Our research interest in this plant arose because of its potential medicinal value as a tonic and against stomachache, as used in folk medicine. In this paper we evaluated three different extracts (ethanolic/EtOH, methanolic/MeOH and dichloromethane/DCM) obtained from M. americana L., for their ability to protect the gastric mucosa against injuries caused by necrotizing agents (0.3 M HCl/60% EtOH), hypothermic restraint stress, nonsteroidal anti-inflammatory drugs (NSAID, indomethacin) and pylorus ligation. In the HCl/EtOH-induced gastric-ulcer model, EtOH and DCM extracts demonstrated significant inhibition of the ulcerative lesion index by 54% (12.0 +/- 2.6 mm) and 86% (3.7 +/- 1.8 mm), respectively, in relation to the control value (26.0 +/- 1.4 mm) (p<0.0001). In the NSAID/cholinomimetic-induced lesion model, both EtOH and DCM extracts showed antiulcerogenic effects with significant reduction in the damage to these gastric lesions of 36% (8.3 +/- 2.0 mm) and 42% (7.5 +/- 1.4 mm), respectively, as compared to the control group (13.0 +/- 0.9 mm) (p<0.0001). In the gastric ulcer induced by hypothermic-restraint stress, both extracts also showed significant activity, and inhibited the gastric lesion index by 58% and 75%, respectively. The EtOH and DCM extracts also changed gastric juice parameters as well as those of cimetidine, decreased gastric acid secretion significantly (p<0.0001), increased pH values and promoted reduced acid output (p<0.0001). In all gastric-ulcer-induced models, MeOH extract did not show any significant antiulcerogenic activity, nor did it change gastric-juice parameters (p>0.05). The results suggest that EtOH and DCM extracts obtained from M. americana possess excellent antisecretory and/or gastrotective effect in all gastric ulcer models. These results suggest that the antiulcerogenic compound(s) present in M. americana may be clustered in the apolar fraction, which will be investigated by our group for the probable mechanisms of action.
Collapse
Affiliation(s)
- W Toma
- Department of Pharmacology, Medical School, State University of Campinas, Campinas, São Paulo, Brazil.
| | | | | | | |
Collapse
|
|
34
|
Batista LM, de Almeida ABA, de Pietro Magri L, Toma W, Calvo TR, Vilegas W, Souza Brito ARM. Gastric Antiulcer Activity of Syngonanthus arthrotrichus S ILVEIRA. Biol Pharm Bull 2004; 27:328-32. [PMID: 14993797 DOI: 10.1248/bpb.27.328] [Citation(s) in RCA: 24] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Syngonanthus arthrotrichus SILVEIRA, popularly known as "sempre-vivas mini-saia," is found in mountains of the Espinhaço range in the Brazilian states of Bahia and Minas Gerais. Extracts of this species contain several constituents, including flavonoids which may have antiulcerogenic activity. An ethanolic extract (EEOH), and flavonoid-rich (FRF) and flavonoid-deficient (FDF) fractions obtained from the scapes of S. arthrotrichus were investigated for their ability to prevent ulceration of the gastric mucosa in mice and rats. In the ethanol/HCl-induced ulcer model, lansoprazole (30 mg/kg), EEOH (50, 100, 250 mg/kg) given orally protected the gastric mucosal against injury in mice by 79%, 78%, 73%, and 64% respectively. In the ethanol-induced gastric ulcer model in rats, the lansoprazole (30 mg/kg), FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of rats by 65%, 38% and 25% respectively when compared with the negative control group. In indomethacin/bethanechol-induced gastric ulcers, cimetidine (100 mg/kg) and the EEOH (100, 250 mg/kg) inhibited gastric ulcer formation by 73%, 55% and 32% respectively. In this exactly model other treatments as cimetidine, FRF and FDF (100 mg/kg) each caused 54%, 36% and 45% inhibition, respectively. In the stress-induced gastric ulcer model, cimetidine (100 mg/kg) and the EEOH (50, 100, 250 mg/kg), inhibited gastric ulcer formation by 63%, 73%, 68% and 69% respectively. In the same model, cimetidine, FRF and FDF (100 mg/kg) significantly protected the gastric mucosal of the mice by 60%, 51% and 47% when compared to the control group. In pylorus-ligated mice, cimetidine (positive control) and FRF significantly decreased gastric acid secretion, increased gastric pH and reduced the acid output when compared to the negative control. FDF had no significant effect on these parameters. The protection provided by FRF probably involved an antisecretory mechanism mediated by flavonoids which were absent in FDF. The amount of adherent mucous in the stomach contents was also evaluated with the treatments carbenoxolone (200 mg/kg), FRF and FDF (100 mg/kg) treatment. Each treatments significantly increased the amount of adherent mucous in the gastric juice (8.67+/-1.73, 3.35+/-1.59, 2.1+/-0.41 mg/g of wet tissue, respectively) compared to the control group, indicating a cytoprotective action on the gastric mucosa. Treatment with FRF plus indomethacin and FDF plus indomethacin reduced the prostaglandin biosyntesis (13.6+/-6.5, 27+/-5.5 pg/well) by the mucosa, indicating that the cytoprotective action on the gastric mucosa was not related to the level of prostaglandins. Only FDF (38+/-17 pg/well) maintained the level of prostaglandins and guaranteed the integrity of the mucosa. The results indicate that the EEOH, FRF and FDF have antisecretory and cytoprotective actions, that may be related to the presence of luteoline in the extract and active fractions.
Collapse
Affiliation(s)
- Leônia Maria Batista
- Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, PB, Brazil.
| | | | | | | | | | | | | |
Collapse
|
|
35
|
Murata H, Kawano S, Tsuji S, Kamada T, Matsuzawa Y, Katsu K, Inoue K, Kobayashi K, Mitsufuji S, Bamba T, Kawasaki H, Kajiyama G, Umegaki E, Inoue M, Saito I. Combination therapy of ecabet sodium and cimetidine compared with cimetidine alone for gastric ulcer: prospective randomized multicenter study. J Gastroenterol Hepatol 2003; 18:1029-33. [PMID: 12911658 DOI: 10.1046/j.1440-1746.2003.03093.x] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
BACKGROUND AND AIM Little is known about the clinical efficacy of co-therapy of ecabet sodium, a mucoprotective agent, and a histamine H2-receptor antagonist. The aim of the present study was to assess its additive benefit in combination with cimetidine for gastric ulcer. METHODS In this prospective randomized study, after gastric ulcer was confirmed by endoscopy, 200 patients in 47 hospitals received either ecabet sodium 1 g b.i.d and cimetidine 400 mg b.i.d. (EC), or cimetidine 400 mg b.i.d. alone (C) for 8 weeks. Healing was examined by endoscopy at 4 and 8 weeks. RESULTS Of the intention-to-treat (ITT) population (EC, 103; C, 97), 181 patients comprised the per protocol (PP) analysis (EC, 93; C, 88). At 4 weeks, healing rates were significantly higher in the EC group (60%) than in the C group (36%) ( p < 0.01). At 8 weeks, those by the ITT and PP analyses were 82% (EC) versus 58% (C), and 90% (EC) versus 64% (C), respectively ( p < 0.01 and p < 0.001). Symptom relief rates (EC vs C) at 2, 4 and 8 weeks were 73%versus 47% ( p < 0.01), 89%versus 66% ( p < 0.001), and 97%versus 73% ( p < 0.001), respectively. Significant additive effects of ecabet sodium were observed in patients aged 60 years or older, with solitary and medium to large ulcer, and without smoking or drinking habits. No adverse effects were critical. CONCLUSION Ecabet sodium significantly augmented gastric ulcer healing and symptom relief by cimetidine, especially in the elderly.
Collapse
Affiliation(s)
- Hiroaki Murata
- Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, 1-7 Yamada-Oka, Suita-City, Osaka 565-0871, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Toma W, Gracioso JDS, de Andrade FDP, Hiruma-Lima CA, Vilegas W, Souza Brito ARM. Antiulcerogenic activity of four extracts obtained from the bark wood of Quassia amara L. (Simaroubaceae). Biol Pharm Bull 2002; 25:1151-5. [PMID: 12230107 DOI: 10.1248/bpb.25.1151] [Citation(s) in RCA: 42] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Quassia amara L., a neotropical forest shrub of the Simaroubaceae family, is widely used in Caribbean folk medicine and in some northern states of Brazil for the treatment of gastric ulcers. This plant is a source of numerous compounds including both beta-carbonile and cantin-6 alkaloids as well as, primarily, the bitter compounds known as quassinoids. We analyzed the possible antiulcerogenic activities of four extracts of different polarities: 70% ethanol (70% EtOH), 100% EtOH, 100% dichloromethane (DCM), and 100% hexane (HEX) obtained from Quassia amara bark. All extracts, administered at doses of 5000 mg/kg orally and 1000 mg/kg intraperitoneally, caused neither toxicity or death. In the indomethacin/bethanechol-induced gastric ulcer, 70% EtOH, 100% EtOH, DCM and HEX extracts, 100 mg/kg, p.o., inhibited the gastric ulcer (22.5, 23.4, 50.5, 46.8%, respectively). 70% EtOH, 100% EtOH, DCM, and HEX extracts reduced the gastric injury induced by the hypothermic restraint-stress test in mice (70.7, 80, 60, 82.7%, respectively). In the pylorus ligature of the mouse stomach, following pre-treatment with a single intraduodenal administration of 100 mg/kg of each extract, only 70% EtOH did not change the biochemical parameters of gastric juice. 100% EtOH, DCM and HEX extracts presented decreased gastric juice content, increased pH values and decreased acid output. We also determined the antiulcerogenic activity on HCl-EtOH-induced gastric ulcers in mice at four doses (25, 50, 75, 100 mg/kg, p.o.), then evaluated the possible dose-dependent relation and calculated the ED50 values. Except for 70% EtOH at a dose of 25 mg/kg, the other extracts showed significantly activity (p<0.05). The free mucous amount in the gastric stomach content was also evaluated. All extracts showed significant increases (p<0.05) of free mucous. This effect was abolished when the animals were pre-treated with indomethacin. Prostaglandin synthesis was evaluated by the administration of HEX extracts by the oral route (100 mg/kg). Prostaglandin synthesis was significantly, increased by 52.3% (p<0.05), and this effect was abolished with prior administration of indomethacin. We concluded that Quassia amara is a probable source for a new drug to treat gastric ulcers, and the mechanism of its activity relates to cytoprotective factors, such as mucous and prostaglandins, but there is still the possibility that antisecretory activity is involved in its antiulcerogenic effect.
Collapse
Affiliation(s)
- Walber Toma
- Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, São Paulo, Brazil
| | | | | | | | | | | |
Collapse
|
|
37
|
Al-shabanah OA, Raza M. Effect of ulceration on rat gastric tissue polyamine contents in response to different procedures; inhibition of these effects by cimetidine. Pharmacol Res 1999; 40:75-82. [PMID: 10378994 DOI: 10.1006/phrs.1999.0476] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
The effects of cimetidine an H2 receptor histamine antagonist on aspirin- and cold-restraint-stress-induced gastric lesions have been studied in rats. Cimetidine had a pronounced inhibitory effect on gastric lesions induced by either oral administration of aspirin (400 mg kg-1) or by cold-restraint stress in rats. These inhibitory effects were dose-related in the aspirin treatment group being 47 and 85% (P<0.05 and P<0.001) at 37.5 and 75 mg kg-1 doses, respectively, when compared to the control. Cimetidine was found effective in cold stress but inhibition with the low dose was not significant. However, high dose (75 mg kg-1) showed a significant reduction (P<0.01) in lesion index. In another series of experiments with the same regimen, the effects of different ulcerogenic procedures on the rat gastric tissue polyamine contents (putrescine, spermine and spermidine) and monoacetyl derivatives (N1- and N8-acetylspermidine) have been investigated by using HPLC method. The procedure permits use of n-octane sulphonate as an ion pairing agent on the reversed-phase column. The treatment of rats with aspirin caused a substantial decrease in the concentration of different polyamine contents in the glandular part of stomach tissue. Pretreatment with cimetidine showed a marked protection against this decline in polyamine contents at both the doses tested (37.5 mg kg-1 and 75 mg kg-1) and increased the contents of spermidine and spermine above the control values. In the other part, cold-restraint stress also declined the polyamine contents. Low dose of cimetidine was found ineffective in this model. However, a high dose of cimetidine caused a significant rise in the levels of spermidine and spermine (P<0.001 and P<0.01, respectively) above the control levels. These findings suggest that cimetidine, besides being a H2-receptor antagonist, prevents ulcer formation due to its growth promotional properties, possibly through an increase in tissue polyamine contents that offer a defense barrier against the oxygen-derived free radicals involved in the etiology of ulceration. It is also suggested that the rise in polyamine contents of gastric tissue is a crucial event in cytoprotection against destructive stimuli.
Collapse
Affiliation(s)
- O A Al-shabanah
- Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia
| | | |
Collapse
|