ABSTRACT
OBJECTIVE: To evaluate synergistic antiulcer activity of ethanolic extracts of Tephrosia purpurea and Bacopa monnieri in ulcer induced rats. METHODS: Ethanolic leaf extracts of both the plants were administered individually and in combination at a dose of 200mg/kg to ulcer induced male albino rats. Omeprazole 10mg/kg was used as standard. Pylorus ligation method, ethanol and indomethacin induced gastric ulcer models were the different gastric ulcer models selected for the induction of ulcer in rats. Ulcer index, ulcer score, total acidity, pH, percentage protection, volume of gastric juice were the parameters evaluated and compared in different groups in all the models. RESULTS: Decrease in the ulcer score, ulcer index, total acidity was observed and percentage protection was significant(*p<0.05 and p<0.01) with the combination extract compared to group received individual plant extracts. CONCLUSION: Our results suggested that combination of two medicinal plants showed synergistic anti ulcer activity and decreased the formation of ulcer lesions in rats.
Subject(s)
Anti-Ulcer Agents , Bacopa , Drug Synergism , Plant Extracts , Plant Leaves , Stomach Ulcer , Tephrosia , Animals , Rats , Male , Plant Extracts/pharmacology , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Bacopa/chemistry , Plant Leaves/chemistry , Tephrosia/chemistry , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Ethanol , Rats, Sprague-DawleyABSTRACT
E. tournefortii has wound healing properties in folk medicine and 5% infusions are used for stomach ulcers. It is also used in colds, abdominal pain, digestive problems, as an appetite enhancer and antispasmodic. For this purpose, in the study biochemical and histopathological evaluation of the ulcer protective effect of the extract obtained from the E. tournefortii in the indomethacin-induced gastric ulcer model in rats was aimed to develop new strategies in the treatment of ulcers. The phytochemical profile of the plant was elucidated for the first time by LC-HRMS in this study. The results indicate that, in terms of TNF-α, IL-1ß, IL-8, IL-6, PGE2, NF-κB, VEGF, NO, COX-1 and COX-2 biochemical parameters, E. tournefortii protects the gastric mucosa to the inflammation, and also modulates the PGE2 pathway, and has a similar effect or even a more positive effect than the reference substance lansoprazole. According to LC-HRMS analysis results, chlorogenic acid, genistein and quinic acid were the main constituents of E. tournefortii extract with 1397.081, 1014.177 and 992.527µg/g extract, respectively. Considering the anti-inflammatory and antioxidant effects of these phenolic components, it is thought that the major components are responsible for the anti-ulcer activity of the E. tournefortii extract.
Subject(s)
Anti-Ulcer Agents , Indomethacin , Phytochemicals , Plant Extracts , Stomach Ulcer , Animals , Rats , Phytochemicals/pharmacology , Phytochemicals/isolation & purification , Stomach Ulcer/chemically induced , Stomach Ulcer/drug therapy , Male , Plant Extracts/pharmacology , Plant Extracts/chemistry , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Rats, Wistar , Gastric Mucosa/drug effects , Dinoprostone/metabolism , Molecular StructureABSTRACT
The present study was designed to assess Tradescantia spathacea's antidiabetic ability, as well as the antiulcer activity of the entire plant extract. The diabetic condition was evaluated using Streptozotocin's oral glucose tolerance test, diabetes-alloxan and diabetes-models. Antiulcer activities were observed in rats where gastric ulcers were either caused by oral administration of ethanol, or pyloric ligation. Standards include ranitidine, glibenclamide and sucralfate. In all models, the blood glucose levels of animals treated with the test extract were found to be significantly lower compared to diabetic care. Similarly, in all models, the ulcer index in the animals treated with the test extract was found to be significantly lower relative to the animals under vehicle supervision. Our findings say T. Spathacea extract has essential anti-diabetic properties, as well as antiulcer properties.
Subject(s)
Anti-Ulcer Agents , Blood Glucose , Diabetes Mellitus, Experimental , Hypoglycemic Agents , Plant Extracts , Rats, Wistar , Stomach Ulcer , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/isolation & purification , Plant Extracts/pharmacology , Plant Extracts/isolation & purification , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Diabetes Mellitus, Experimental/drug therapy , Stomach Ulcer/drug therapy , Stomach Ulcer/prevention & control , Stomach Ulcer/pathology , Stomach Ulcer/chemically induced , Male , Rats , Blood Glucose/drug effects , Blood Glucose/metabolism , Methanol/chemistry , Glucose Tolerance Test , Solvents/chemistry , PhytotherapyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Zingiberis rhizoma recens-/wine-/euodiae fructus-processed Coptidis Rhizoma (CR, zCR/wCR/eCR) are the commonly used processed products of CR in clinic. After being processed with different excipients, the efficacy of CR will change accordingly. I.e., wCR could resolve excessive heat of the upper energizer, zCR could eliminate gastric heat and harmonize the stomach, eCR could smooth the liver and harmonize the stomach. However, the underlying mechanisms were still unclear. AIM OF THE STUDY: To further verify the differential efficacy of the three processed CR products and compare the mechanisms on gastric ulcer. MATERIAL AND METHODS: First, a GU model, whose onset is closely related to the heat in stomach and the disharmony between liver and stomach, was established, and the therapeutic effects of zCR/wCR/eCR/CR were evaluated by pathologic observation and measurement of cytokine levels. Second, metabolomics analysis and network pharmacology were conducted to reveal the differential intervening mechanism of zCR/eCR on GU. Third, the predicted mechanisms from metabolomics analysis and network pharmacology were validated using western blotting, flow cytometry and immunofluorescence. RESULTS: zCR/wCR/eCR/CR could alleviate the pathologic damage to varying degrees. In metabolomics research, fewer metabolic pathways were enriched in serum samples, and most of them were also present in the results of gastric tissue samples. The gastroprotective, anti-inflammatory, antioxidant, and anti-apoptotic effects of zCR/wCR/eCR/CR might be due to their interference on histidine, arachidonic acid, and glycerophospholipids metabolism. Quantitative results indicated that zCR/eCR had a better therapeutic effect than wCR/CR in treating GU. A comprehensive analysis of metabolomics and network pharmacology revealed that zCR and eCR exerted anti-GU effects via intervening in five core targets, including AKT, TNF, IL6, IL1B and PPARG. In the validation experiment, zCR/eCR could significantly reverse the abnormal expression of proteins related to apoptosis, inflammation, oxidative stress, gastric function, as well as the PI3K/AKT signaling pathways. CONCLUSION: zCR and eCR could offer gastroprotective benefits by resisting inflammation and apoptosis, inhibiting gastric-acid secretion, as well as strengthening gastric mucosal defense and antioxidant capacity. Integrating network pharmacology and metabolomics analysis could reveal the acting mechanism of drugs and promote the development of medications to counteract GU.
Subject(s)
Drugs, Chinese Herbal , Metabolomics , Network Pharmacology , Rats, Sprague-Dawley , Stomach Ulcer , Animals , Stomach Ulcer/drug therapy , Stomach Ulcer/pathology , Stomach Ulcer/metabolism , Drugs, Chinese Herbal/pharmacology , Male , Rats , Evodia/chemistry , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Gastric Mucosa/metabolism , Coptis chinensis , Disease Models, Animal , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Cytokines/metabolism , Cytokines/bloodABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional Chinese medicine and a previous literature, many parts of Chinese sumac (Rhus chinensis Mill.), including fruits, are used as traditional herb to prevent or cure many diseases, such as inflammation, diarrhea, malaria, and other acute or chronic gastrointestinal diseases. However, the effects of the fruits on the prevention of gastric ulcer and the underlying mechanisms have not been reported. AIM OF THE STUDY: This experiment aimed to investigate the preventive effect of ethanol extract (RM) from Chinese sumac fruits on indomethacin-induced gastric ulcer in mice and the underlying mechanisms. MATERIALS AND METHODS: A single gavage of indomethacin was used to induce a gastric ulcer model in Kunming male mice. According to the results of histopathological analysis, immunohistochemistry and immunofluorescence analysis, as well as the expression of prostaglandin E-2, antioxidant enzymes and cytokines, the protective effect of RM on indomethacin-induced gastric ulcer was evaluated. The expression levels of several key proteins involved in oxidative stress, inflammation and apoptosis in gastric tissue were detected to illuminate the underlying mechanisms. RESULTS: RM significantly reduced the ulcer index and pepsin activity, improved the microstructure of gastric mucosa and the prostaglandin E-2 content, restored the levels of glutathione and superoxide dismutase, and decreased the contents of malondialdehyde, advanced oxidation protein products, TNF-α, IL-1 ß and IL-6. Further experimental results showed that RM could improve the expression levels of HO-1 and NQO1 by activating the Nrf2 protein pathway to alleviate oxidative stress in gastric tissue. At the same time, RM significantly down-regulated the expressions of p-NF-κB, p-IκBα and iNOS to relieve inflammatory response, and inhibited the cellular apoptosis of gastric tissue by up-regulating Bcl-2 and down-regulating Bax and cleaved Caspase-3. CONCLUSIONS: The current work clarified that the ethanol extract from Chinese sumac fruits can improve the oxidative stress level, inflammatory response and cell apoptosis in gastric tissue by interfering with the expressions of several key regulatory proteins to prevent indomethacin-induced gastric ulcer in mice. This study may provide some insights and scientific evidence on the application of Chinese sumac fruits as a traditional herb to prevent or alleviate gastric ulcer.
Subject(s)
Inflammation/drug therapy , Plant Extracts/pharmacology , Rhus/chemistry , Stomach Ulcer/prevention & control , Animals , Animals, Outbred Strains , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacology , Apoptosis/drug effects , Fruit , Indomethacin/toxicity , Inflammation/pathology , Male , Mice , Oxidative Stress/drug effects , Stomach Ulcer/chemically inducedABSTRACT
Jasminum grandiflorum L. is a medicinal plant used to treat hepatitis and gastritis, but the mechanisms underlying its protective effects against gastrointestinal mucosal damage remain to be elucidated. In this study, we analyzed the effects of four different extracts and two compounds from the flower of J. grandiflorum in a mouse model of HCl/EtOH-induced gastric ulcer. The flower extracts alleviated gastric mucosal ulceration by increasing PGE2 production and the activity of antioxidant enzymes, along with the suppression of reactive oxygen species (ROS) generation, lipid peroxidation, apoptosis-related proteins, pro-inflammatory cytokines and nitric oxide (NO) production.
Subject(s)
Anti-Ulcer Agents/pharmacology , Gastric Mucosa/drug effects , Jasminum , Plant Extracts/pharmacology , Stomach Ulcer/prevention & control , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Antioxidants/pharmacology , Apoptosis Regulatory Proteins/metabolism , Dinoprostone/metabolism , Disease Models, Animal , Ethanol , Flowers , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Hydrochloric Acid , Inflammation Mediators/metabolism , Jasminum/chemistry , Lipid Peroxidation/drug effects , Macrophages/drug effects , Macrophages/metabolism , Male , Mice , Mice, Inbred ICR , NF-kappa B/metabolism , Nitric Oxide/metabolism , Oxidative Stress/drug effects , Plant Extracts/isolation & purification , RAW 264.7 Cells , Stomach Ulcer/metabolism , Stomach Ulcer/pathologyABSTRACT
This study aimed to investigate the antioxidant and protective effect of E. persicus leaf hydroalcoholic extract (EPE) in preventing gastric ulcers induced by ethanol in rats. Wistar rats weighing 180-220 g were randomly divided into five groups. These groups included negative control (normal) group, positive control (ethanolic) group, comparative control (ranitidine recipient) group, group recipient the dose of 250 mg/kg plant extract, and group recipient the dose of 500 mg/kg plant extract. One hour after gavage of the drug and extract, the gastric ulcer was induced by feeding 1 ml of 96% ethanol to each animal except the rats of the negative control group. After one hour, the rats were killed, and their stomachs were separated. Then, the gastric Ulcer index (UI), pH, oxidative stress parameters, and histopathological changes in the stomach of all groups were measured. Pre-treatment of ethanol-induced rats with the EPE reduced (P < 0.05) the ulcer index and gastric juice pH, compared to ethanolic group rats. Furthermore, pre-treatment with EPE at a dose-dependent manner, alleviated the gastric oxidative stress injury in rats through increase the activity of CAT, tissue NO· and GSH levels. EPE also was able to decrease the levels of ROS, MDA, PCO and serum NO·. According to the results, it can be concluded that pre-treatment with EPE prevents the formation of gastric ulcers caused by ethanol, which can be attributed to the antioxidant activity of plant polyphenols compounds.
Subject(s)
Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Asphodelaceae/chemistry , Plant Extracts/pharmacology , Animals , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/isolation & purification , Antioxidants/administration & dosage , Antioxidants/isolation & purification , Dose-Response Relationship, Drug , Ethanol/toxicity , Male , Oxidative Stress/drug effects , Plant Extracts/administration & dosage , Plant Leaves , Polyphenols/isolation & purification , Polyphenols/pharmacology , Ranitidine/pharmacology , Rats , Rats, Wistar , Stomach Ulcer/prevention & controlABSTRACT
The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A.â officinarum (GLJ), C.â rotundus (XF), and HP G-X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8-cineol (22.0 %) and α-terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G-X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G-X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G-X showed the lowest toxicity (TC50 >800â µg/mL) against human gastric mucosal epithelial cells (GES-1) and had the best protective effect against ethanol-induced GES-1â cell damage compared to the individual herbs. In vitro studies demonstrated that HP G-X and the corresponding single herbs significantly reduced IL-6, TNF-α, and COX-2. In addition, inâ vivo investigations indicated that HP G-X can protect the gastric mucosa of mice from ethanol-induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF-κBp65, COX-2, and TRPV1 protein, reduce the concentrations of IL-6 and TNF-α, and relieve heat-induced pain. This study further substantiated the traditional application of HP G-X against gastric ulcers through both inâ vivo and inâ vitro investigations.
Subject(s)
Anti-Ulcer Agents/pharmacology , Cyperaceae/chemistry , Oils, Volatile/pharmacology , Stomach Ulcer/drug therapy , Zingiberaceae/chemistry , Animals , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Cell Survival/drug effects , Cells, Cultured , Ethanol , Female , Gastric Mucosa/drug effects , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Humans , Medicine, Chinese Traditional , Mice , Mice, Inbred BALB C , Oils, Volatile/chemistry , Oils, Volatile/isolation & purification , Stomach Ulcer/chemically induced , Stomach Ulcer/pathologyABSTRACT
Using rat and mouse models of neurogenic, ethanol-induced, and indometacin-induced damage to the gastric mucosa we demonstrated that course preventive treatment with flavonoid complex from aerial parts of Lychnis chalcedonica L. increased the resistance of gastric mucosa to ulcerogenic factors of different etiology. The gastroprotective effect of the phytocomplex in a dose range of 16-1600 µg/kg was comparable with that of the reference drug plantaglucide and was superior to that of the reference drugs eleutherococcus extract and methyluracil in the therapeutic doses. The antiulcerogenic activity of Lychnis chalcedonica flavonoid complex considerably exceeded activity of Lychnis chalcedonica L. extract demonstrated in our previous experiments.
Subject(s)
Anti-Ulcer Agents/therapeutic use , Plant Extracts/therapeutic use , Stomach Ulcer/drug therapy , Animals , Animals, Outbred Strains , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacology , Cytoprotection/drug effects , Disease Models, Animal , Ethanol , Flavonoids/isolation & purification , Flavonoids/pharmacology , Flavonoids/therapeutic use , Gastric Mucosa/drug effects , Gastric Mucosa/pathology , Indomethacin , Lychnis/chemistry , Male , Mice , Neurogenic Inflammation/drug therapy , Neurogenic Inflammation/pathology , Phytotherapy , Plant Extracts/pharmacology , Rats , Rats, Wistar , Silene , Stomach Ulcer/chemically induced , Stomach Ulcer/pathologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Information collected from local traditional healers reported that Eremomastax speciosa (Hochst.) Cufod. has for a long time been used to manage gastric ulcers in many regions of Cameroon and beyond. This traditional use is supported by numerous studies. However, efficacy of this plant has never been tested in case of chronic gastric ulcers associating Helicobacter pylori infection. AIM OF THE STUDY: This study was designed to investigate curative effects of the aqueous extract of E. speciosa leaves (AEESL) against chronic gastric ulcers associated to Helicobacter pylori infection. MATERIALS AND METHODS: Two experimental methods of chronic gastric ulcers, involving H. pylori infection, were performed using Wistar rats, namely: acetic acid-induced ulcers and "unhealed ulcers". E. speciosa extract was tested at three doses (100; 200; 400 mg/kg) and at the end of experiments, some in vivo antioxidant parameters were measured, bacterial load in stomach tissue calculated and histopathological examinations performed. RESULTS: E. speciosa reduced ulcer index at all the doses and significantly increased mucus production as well as antioxidant (mainly SOD and GSH) level. Bacterial load in stomach significantly decreased (p < 0.05) in extract-treated groups (200 and 400 mg/kg) as confirmed by histopathological observations. The extract was found to be non toxic to healthy and cancerous cells (IC50 > 1000 µg/mL). CONCLUSIONS: E. speciosa accelerated healing of gastric ulcers even in presence of indomethacin, while decreasing bacterial loads in rats' stomachs. These results provide supplementary support to the use of E. speciosa in ethnomedicine and open new perspectives regarding development of a herbal-based monotherapy able to efficiently replace/supplement standard antiulcer tri/quadritherapy.
Subject(s)
Acanthaceae/chemistry , Helicobacter Infections/complications , Plant Extracts/pharmacology , Stomach Ulcer/prevention & control , Acetic Acid , Animals , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacology , Antioxidants/metabolism , Disease Models, Animal , Dose-Response Relationship, Drug , Helicobacter Infections/drug therapy , Helicobacter pylori/isolation & purification , Indomethacin/toxicity , Inhibitory Concentration 50 , Male , Plant Extracts/administration & dosage , Plant Leaves , Rats , Rats, Wistar , Wound Healing/drug effectsABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Peptic ulcer is an inflammatory disease that therapeutic options are mainly focused in antisecretory drugs. Sedum dendroideum Moc & Sessé ex DC (Crassulaceae) is employed in folk medicine for the treatment of gastric ulcers. Recently, our group demonstrated that Sedum dendroideum infusion (SDI) is rich in polyphenols (flavonol glycosides, myricetin, quercetin and kaempferol) and promoted gastroprotection against acute ulcer models, without changes gastric acid secretion. AIM OF THE STUDY: Here, we follow the investigation of the healing effects of SDI (ED50 = 191 mg/kg) in the chronic gastric ulcer model induced by 80% acetic acid in rats, elucidating underlying mechanisms. MATERIAL AND METHODS: Rats were orally treated with vehicle (water, 1 mL/kg), SDI (191 mg/kg), omeprazole (40 mg/kg) or sucralfate (100 mg/kg) twice daily for 5 days after ulcer induction. Following treatments, toxicological effects, macroscopic ulcer appearance, microscopic histological (HE, mucin PAS-staining) and immunohistochemical (PCNA and HSP70) analysis, inflammatory (MPO and NAG activity, cytokine levels measurements) and antioxidant (SOD and CAT) parameters were investigated in gastric ulcer tissues. RESULTS: Oral treatment with SDI accelerated gastric ulcer healing, maintained mucin content and promoted epithelial cell proliferation. SDI also reduced neutrophil and mononuclear leukocyte infiltration, TNF-α and IL-1ß levels and the oxidative stress, restoring SOD and CAT activities in the ulcer tissue. CONCLUSIONS: The gastric healing effect of SDI was mediated through endogenous protective events as well as due to the anti-inflammatory and antioxidant actions. Our observations support and reinforce the traditional utilize of Sedum dendroideum as a natural nontoxic therapeutic alternative for the treatment of gastric ulcers.
Subject(s)
Anti-Ulcer Agents/pharmacology , Sedum/chemistry , Stomach Ulcer/prevention & control , Animals , Anti-Inflammatory Agents/isolation & purification , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/isolation & purification , Antioxidants/isolation & purification , Antioxidants/pharmacology , Disease Models, Animal , Female , Omeprazole/pharmacology , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Polyphenols/isolation & purification , Polyphenols/pharmacology , Rats , Rats, Wistar , Sucralfate/pharmacologyABSTRACT
Blumea lacera (Burm.f.) DC. is described as a valuable medicinal plant in various popular systems of medicine. The aim of the experiment reports the in vivo antiulcer activity of methanol extract of Blumea lacera (MEBLL) and in silico studies of bioactive constituents of MEBLL. In this study, fasted Long-Evans rat treated with 80 % ethanol (0.5â¯mL) to induce gastric ulcer, were pretreated orally with MEBLL at different doses (250 and 500â¯mg/kg, p.o., b.w) and omeprazole (20â¯mg/kg, p.o.) and distilled water were used as a reference drug and normal control respectively. In silico activity against gastric H+-K+ATPase enzyme was also studied. The findings demonstrated that the treatment with MEBLL attenuated markedly ulcer and protected the integrity of the gastric mucosa by preventing the mucosal ulceration altered biochemical parameters of gastric juice such total carbohydrate, total protein and pepsin activity. Additionally, the experimental groups significantly (pâ¯<â¯0.001) inhibited gastric lesions and malondealdehyde (MDA) levels and upregulated antioxidant enzymes level. Furthermore, nine compounds were documented as bioactive, displayed good binding affinities to against gastric H+-K+ATPase enzyme while these compounds illustrated inhibitory effect. From these studies, it is established MEBLL has ulcer healing property as unveiled by in vivo and in silico studies.
Subject(s)
Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Asteraceae , Gastric Mucosa/drug effects , Oxidative Stress/drug effects , Plant Extracts/pharmacology , Proton Pump Inhibitors/pharmacology , Stomach Ulcer/prevention & control , Animals , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacokinetics , Antioxidants/isolation & purification , Antioxidants/pharmacokinetics , Asteraceae/chemistry , Disease Models, Animal , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , H(+)-K(+)-Exchanging ATPase/metabolism , Plant Extracts/isolation & purification , Plant Extracts/pharmacokinetics , Plant Leaves , Proton Pump Inhibitors/isolation & purification , Proton Pump Inhibitors/pharmacokinetics , Rats, Long-Evans , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stomach Ulcer/pathologyABSTRACT
Annona coriacea Mart., popularly known as "marolo", "araticum" and "araticum-liso" is a species distributed in Paraguay and Brazil, and easily found in Caatinga, Cerrado, and Pantanal biomes. The araticum has been used in folk medicine to treat stomatitis, neuralgia, rheumatism, headaches, furuncle, ulcers, and dermatitis. This systematic review aimed to provide a comprehensive overview of the ethnomedicinal use, phytochemistry, and pharmacological activity of A. coriacea. A search for scientific articles of electronic databases (Science Direct, PubMed, Lilacs, Scopus, Google Scholar, Scielo, and Web of Science) was performed identifying studies published until November 2020. All papers considering traditional medicinal uses, phytochemistry, and pharmacological properties were included. Forty-six articles (nâ¯=â¯212 subjects) met the inclusion criteria set for this review. Of the 46 articles reviewed, 34 were focused on biological activity investigations, while 12 were limited to phytochemical studies. These studies showed the presence of a diversity of secondary metabolites such as acetogenins, sesquiterpenes, alkaloids, flavonoids, and diterpenes. To date, pharmacological tests have demonstrated significant biological activities of this plant, being the most promising anticancer, anti-inflammatory, antiulcer, and insecticide activities. Additionally, the medicinal utilization of A. coriacea appears to be promising, supporting its possible uses for human health with antioxidant, anxiolytic, antiulcer, insecticide, and antiparasitic activities. Ultimately, comprehensive studies involving clinical trials are required to validate the existing traditional practices and their related health benefits scientifically.
Subject(s)
Annonaceae/chemistry , Anti-Inflammatory Agents/pharmacology , Anti-Ulcer Agents/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Insecticides/pharmacology , Phytochemicals/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/isolation & purification , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Humans , Insecticides/chemistry , Insecticides/isolation & purification , Molecular Conformation , Phytochemicals/chemistry , Phytochemicals/isolation & purificationABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: The subtribe Hyptidinae contains approximately 400 accepted species distributed in 19 genera (Hyptis, Eriope, Condea, Cantinoa, Mesosphaerum, Cyanocephalus, Hypenia, Hyptidendron, Oocephalus, Medusantha, Gymneia, Marsypianthes, Leptohyptis, Martianthus, Asterohyptis, Eplingiella, Physominthe, Eriopidion and Rhaphiodon). This is the Lamiaceae clade with the largest number of species in Brazil and high rates of endemism. Some species have been used in different parts of the world mainly as insecticides/pest repellents, wound healing and pain-relief agents, as well as for the treatment of respiratory and gastrointestinal disorders. AIM OF THE REVIEW: This review aims to discuss the current status concerning the taxonomy, ethnobotanical uses, phytochemistry and biological properties of species which compose the subtribe Hyptidinae. MATERIALS AND METHODS: The available information was collected from scientific databases (ScienceDirect, Pubmed, Web of Science, Scopus, Google Scholar, ChemSpider, SciFinder ACS Publications, Wiley Online Library), as well as other literature sources (e.g. books, theses). RESULTS: The phytochemical investigations of plants of this subtribe have led to the identification of almost 300 chemical constituents of different classes such as diterpenes, triterpenes, lignans, α-pyrones, flavonoids, phenolic acids and monoterpenes and sesquiterpenes, as components of essential oils. Extracts, essential oils and isolated compounds showed a series of biological activities such as insecticide/repellent, antimicrobial and antinociceptive, justifying some of the popular uses of the plants. In addition, a very relevant fact is that several species produce podophyllotoxin and related lignans. CONCLUSION: Several species of Hyptidinae are used in folk medicine for treating many diseases but only a small fraction of the species has been explored and most of the traditional uses have not been validated by current investigations. In addition, the species of the subtribe appear to be very promising as alternative sources of podophyllotoxin-like lignans which are the lead compounds for the semi-synthesis of teniposide and etoposide, important antineoplastic agents. Thus, there is a wide-open door for future studies, both to support the popular uses of the plants and to find new biologically active compounds in this large number of species not yet explored.
Subject(s)
Ethnobotany/methods , Ethnopharmacology/methods , Lamiaceae , Medicine, Traditional/methods , Phytochemicals/therapeutic use , Plant Extracts/therapeutic use , Animals , Anti-Ulcer Agents/isolation & purification , Anti-Ulcer Agents/pharmacology , Anti-Ulcer Agents/therapeutic use , Ethnobotany/trends , Ethnopharmacology/trends , Humans , Hypoglycemic Agents/isolation & purification , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Medicine, Traditional/trends , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Extracts/isolation & purification , Plant Extracts/pharmacologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Propolis has been used in folk medicine to treat gastric disorders for centuries. However, although studies have been conducted to validate the gastroprotective and anti-ulcer activity of some types of propolis, red propolis activity remains unknown. AIM OF THE STUDY: The present study aimed to evaluate the gastroprotective effect of the hydroalcoholic extract of red propolis (HERP), its mode of action, and the main compounds involved in its activity, therefore contributing to validate the chemical and pharmacological potential of this product. MATERIAL AND METHODS: The effect of HERP (30, 100 and 300 mg/kg p.o. and 30 mg/kg i.p.), and the isolated compounds vestitol (VS), neovestitol (NV), methylvestitol (MV), medicarpin (MD), and oblongifolin AB (OB) (10 mg/kg p.o.) were evaluated on gastric ulcers induced by 60% ethanol/0.3 M HCl (5 mL/kg, p.o.) in mice. Histological changes and mucin levels were assessed by HE and PAS, respectively. Moreover, oxidative stress parameters and myeloperoxidase activity were analyzed on ulcerated tissue. The effect of HERP on gastric acid secretion was evaluated by pyloric ligature model and the mechanisms involved in its gastroprotective effect were investigated by pretreating mice with L-NAME (a non-selective nitric oxide synthase inhibitor, 70 mg/kg, i.p.), NEM (a sulfhydryl group chelator, 10 mg/kg, i.p.), yohimbine (an alpha-adrenergic receptor antagonist, 2 mg/kg, i.p.) and indomethacin (a non-selective cyclooxygenase inhibitor, 10 mg/kg, i.p.). RESULTS: HERP (300 mg/kg p.o. or 30 mg/kg i.p.), MV, and MD (10 mg/kg p.o.) protected gastric mucosa against the damage induced by ethanol/HCl. Histological changes were attenuated by the HERP, MV, and MD. Moreover, HERP and MV increased mucin levels. Besides, oxidative stress and MPO activity were reduced by the three treatments. HERP did not display anti-secretory action, but its effect was abolished by indomethacin treatment. CONCLUSIONS: HERP displays gastroprotective property against ethanol/HCl-induced damage. Its effect is dependent on prostaglandins and mucin production. The compounds MV and MD may have an essential role in the activity of HERP. Our data contribute to validate the traditional use of propolis for gastric disorders.
Subject(s)
Anti-Ulcer Agents/pharmacology , Gastric Mucosa/drug effects , Propolis , Stomach Ulcer/prevention & control , Animals , Anti-Ulcer Agents/isolation & purification , Brazil , Disease Models, Animal , Ethanol , Gastric Acid/metabolism , Gastric Mucins/metabolism , Gastric Mucosa/metabolism , Gastric Mucosa/pathology , Hydrochloric Acid , Male , Mice , Oxidative Stress/drug effects , Propolis/chemistry , Prostaglandins/metabolism , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/metabolism , Stomach Ulcer/pathologyABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Sphaeranthus senegalensis DC is a seasonal herb with a spicy smell that grows wild in wet grounds of tropical Africa and Asia. The plant is used in folk medicine for the treatment of various diseases; that includes its use to treat gastric ulcers. AIM OF THE STUDY: This study aimed to investigate the chemical constituents of the hydroethanolic extract of Sphaeranthus senegalensis DC and evaluate its oral safety, gastroprotective activity, and mechanisms of action using laboratory models in rats and mice. MATERIALS AND METHODS: Hydroethanolic extract (70%) of the powdered whole dried material was prepared, and chemical constituents of the resultant extract (denoted HESs) standardized using the high-performance liquid chromatography (HPLC) method. The safety profile of HESs was assessed using 2000 mg/kg, oral (p.o.) for Hippocratic screening in mice, and 800 mg/kg, p.o. for 28 days subchronic toxicity assay in rats. The gastroprotective effect of HESs (25, 100, and 400 mg/kg, p.o.) was investigated using acidified ethanol, piroxicam, water immobilization stress, and acetic acid-induced ulcer models. The gastroprotective mechanisms of HESs were evaluated using its effect on gastric mucus protection, nitric oxide modulation, gastric juice secretory parameters, catalase and myeloperoxidase activities. Histological analysis of the stomach tissues was also carried out. RESULTS: The HPLC analysis indicated the presence of 25.94% phenolics (gallic acid, caffeic acid, and ferulic acid) and 14.53% flavonoids (rutin, morin, luteolin, quercetin, and apigenin). Hippocratic screening and the 28 days subchronic study indicated that HESs is generally safe. Result shows that oral administration of HESs (25, 100 and 400 mg/kg) alleviated the severity of the gastric ulcers induced by acidified ethanol by 35.65% (p < 0.05), 48.70% (p < 0.05) and 78.02% (p < 0.001) respectively; exhibited gastroprotective effect against the gastric lesions induced by piroxicam by 37.97% (p < 0.05), 53.27% (p < 0.05) and 76.23% (p < 0.001) respectively; and decreased the severity of the water immobilization stress-induced gastric ulcers by 32.43% (p < 0.05), 55.26% (p < 0.01) and 74.05% (p < 0.001) respectively, when compared to the vehicle control group. The mechanisms of action assays indicated that the gastroprotective activity was mediated mainly through gastroprotection, antisecretory, and antioxidant activities. Histological analysis showed it inhibited epithelial cell loss, vascular damage, and leucocyte infiltration. CONCLUSION: HESs contains useful phytochemicals, is safe, and exhibited significant gastroprotective action. The results provided justification for its claim in the treatment of gastric ulcers and its evaluation for potential application as a gastroprotective agent.
Subject(s)
Asteraceae , Gastric Mucosa/drug effects , Plant Extracts/administration & dosage , Plant Extracts/chemistry , Stomach Ulcer/prevention & control , Administration, Oral , Animals , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/methods , Ethanol/administration & dosage , Ethanol/chemistry , Ethanol/isolation & purification , Female , Gastric Mucosa/pathology , Male , Mice , Plant Extracts/isolation & purification , Random Allocation , Rats , Rats, Wistar , Stomach Ulcer/chemically induced , Stomach Ulcer/pathology , Toxicity Tests, Subchronic/methods , Water/administration & dosage , Water/chemistryABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Malvaviscus arboreus is traditionally used in Mexico and Central America for culinary and medicinal purposes. Leaves and flowers of this species are commonly used for preparation of salads, herbal teas and herbal dyes. Panamanian, Guatemalan and Mexican healers use this medicinal plant for the management of fever, respiratory complications, dysentery, liver and gallbladder problems, stomachache and gastritis between other health troubles. AIM OF THE STUDY: Considering the traditional use of M. arboreous as well as its content in flavonoids and other polyphenols, the objective of this work was to evaluate the gastroprotective effect of an aqueous extract and identify the potential bio-active principles from flowers of this species. MATERIAL AND METHODS: Fresh flowers of Malvaviscus arboreus were collected, dried, and macerated with water. The aqueous extract (ExAq) was partitioned using an immiscible mixture of water and ethyl acetate, giving an aqueous (MaAq) and organic (MaEA) fractions. The gastroprotective effect was carried out using an ethanol-induced gastric ulcer experimental test in male rats. While tween 20 was used as a negative control, famotidine (10 mg/kg) and L-arginine (300 mg/kg) were used as positive controls. Compounds 1 and 2 were isolated by several chromatographic techniques and the chemical characterization was carried out by means of the analysis of the NMR spectra in one and two dimensions. RESULTS: The integrate extract (ExAq) to 250, 500 and 750 mg/kg showed gastroprotective effect with high levels of 97.8%, 79.5% and 91.1% respectively. The organic fraction (MaEA) displayed a protection of 91.2%, 96.0% and 99.4% when it was evaluated at 125, 250 and 500 mg/kg respectively. Comparison of these results with famotidine at 10 mg/kg (83% of gastroprotection) indicated that ethyl acetate fraction showed a better gastroprotection. The bio-guided separation of this organic mixture, allowed obtaining the most active fraction (C1F4, 60 mg/kg) which was finally purified to obtain two glycosylated flavonols: kaempferol 3-O-D-sophoroside (1) and kaempferol 3-O-D-sambubioside (2). This mixture of flavonoids (40 y 60 mg/kg) showed 93.7 and 92% of gastroprotective activity respectively. CONCLUSION: This study allowed demonstrating that an aqueous extract and its organic fraction (MaEA) from M. arboreous contain glycosylated flavonoids (1 and 2) which are responsible of the gastroprotective properties of M. arboreous. These results will be used in the future development of a standardized treatment useful in the therapeutic management of gastric ulcers.
Subject(s)
Anti-Ulcer Agents/therapeutic use , Glycosides/therapeutic use , Kaempferols/therapeutic use , Malva , Plant Extracts/therapeutic use , Stomach Ulcer/prevention & control , Animals , Anti-Ulcer Agents/isolation & purification , Dose-Response Relationship, Drug , Ethanol/toxicity , Gastrointestinal Agents/isolation & purification , Gastrointestinal Agents/therapeutic use , Glycosides/isolation & purification , Kaempferols/isolation & purification , Male , Plant Extracts/isolation & purification , Random Allocation , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically induced , Stomach Ulcer/pathologyABSTRACT
The root of Lindera reflexa Hemsl. (LR) is a folk Chinses herbal medicine that has been used to treat gastritis and peptic ulcers. In this study, three new stilbenes (1-3) and two known flavonoids (4 and 5) were isolated from the antiulcer purified fractions of LR. The chemical structures of the isolated compounds were characterized comprehensively based on the basis of extensive spectroscopic data. Absolute configurations of compounds 1, 2, and 3 were determined by ECD calculations. The cytotoxic activities of compounds 1-5 were evaluated by MTT assay. Compound 4 showed the strongest inhibitory effect on the proliferation of tumor cells lines MGC803 and SMMC-7721, with IC50 values of 2.65 and 4.13 µM, respectively. The quantitative analysis of 12 compounds of the antiulcer purified fractions of LR were carried out by using the reversed-phase high-performance liquid chromatography (HPLC) method. Within the test range, all calibration curves showed good linearity (R2 > 0.9993). The LOD, LOQ, specificity, precision, and accuracy of the method were verified. Therefore, the present study may provide a valuable method for quality control the antiulcer purified fractions of LR.
Subject(s)
Anti-Ulcer Agents/pharmacology , Flavonoids/pharmacology , Lindera/chemistry , Stilbenes/pharmacology , Anti-Ulcer Agents/isolation & purification , Cell Line, Tumor , China , Flavonoids/isolation & purification , Humans , Molecular Structure , Phytochemicals/isolation & purification , Phytochemicals/pharmacology , Plant Roots/chemistry , Stilbenes/isolation & purificationABSTRACT
AIM AND OBJECTIVE: This study aimed at investigating the gastro-protective effects of Algerian Sahara (Sidr) honey from Apis mellifera intermissa against HCl/Ethanol-induced gastric ulcers in rats. MATERIALS AND METHODS: Total phenolic content, antioxidant activity and phenolic compounds were determined. Then, three groups of rats (control, HCl/ Ethanol-induced ulcer, and orally administered honey) were used for the determination of gastro-protective effect of Sidr honey. RESULTS: Total phenolic content, total flavonoid content, and DPPH activity of the honey sample were determined as 47.35±3.35 mg GAE/ 100 g, 2.13±0.17 mg QE/ 100 g, and 229.24±0.02 mg/mL, respectively. Oral pretreatment of rats with honey (1.2 g/Kg body weight orally at an interval of 2 days) protected gastric mucosa against HCl/Ethanol-induced damage by decreasing ulcer score, the volume and acidity of gastric juice and increasing pH. CONCLUSION: These results were confirmed by the histological assessment, which demonstrated a significant gastro-protective activity of Saharian (Sidr) honey against HCl/Ethanol-induced stomach ulcer. Plasma tumor necrosis factor-α, IL-6 and PGE2 were also measured. Sahara honey significantly decreased the plasma TNF-α, PGE2, and IL-6 concentrations.
Subject(s)
Anti-Ulcer Agents/pharmacology , Antioxidants/pharmacology , Honey/analysis , Plant Extracts/pharmacology , Protective Agents/pharmacology , Stomach Ulcer/drug therapy , Algeria , Animals , Anti-Ulcer Agents/chemistry , Anti-Ulcer Agents/isolation & purification , Antioxidants/chemistry , Antioxidants/isolation & purification , Biphenyl Compounds/antagonists & inhibitors , Ethanol , Flavonoids/chemistry , Flavonoids/isolation & purification , Flavonoids/pharmacology , Gastric Mucosa/drug effects , Hydrochloric Acid , Male , Phenols/chemistry , Phenols/isolation & purification , Phenols/pharmacology , Picrates/antagonists & inhibitors , Plant Extracts/chemistry , Plant Extracts/isolation & purification , Protective Agents/chemistry , Protective Agents/isolation & purification , Rats , Rats, Sprague-Dawley , Stomach Ulcer/chemically inducedABSTRACT
Ziziphus joazeiro Mart., popularly known as 'juazeiro', is a species used in popular medicine for the treatment of bronchitis, gastric ulcers, skin wounds, and in the manufacture of cosmetic and food products. The objective of this study is to evaluate the gastroprotective and cicatrizing activity of the Z. joazeiro Mart. leaf hydroalcoholic extract (EHFZJ). The acute pre-clinical toxicity was determined by the single administration of the EHFZJ (2000 mg/kg/p.o.) and by assessing clinical signs of toxicity, according to established criteria by Malone, or mortality. Gastroprotective activity was identified through classical models of acute gastric lesions induced by indomethacin, absolute and acidified ethanol (100, 200 and 400 mg/kg/per os) and the physical barrier mechanism (400 mg/kg/per os or intraperitoneally). The cicatrizing activity of the EHFZJ was investigated by measuring the speed of wound closure and the percentage of contraction. The acute pre-clinical toxicity of EHFZJ showed no signs of toxicity and mortality. The EHFZJ demonstrated a gastroprotective effect at the 400 mg/kg dose in the classical models of acute gastric injury induced by indomethacin, absolute and acidified ethanol. The EHFZJ administration (orally) demonstrated significant inhibition, suggesting a possible physical barrier mechanism exists. The EHFZJ showed no significant differences in terms of percentage of contraction or the speed of wound closure during the observation times (0, 3, 7, 11 and 14 days). The results obtained in this study provide evidence of a potential gastroprotective activity for the Ziziphus joazeiro Mart. Leaf hydroalcoholic extract.