Gastroprotective Effect Research Articles

Review of Arnebia euсhroma as a Potential Medicinal Plant Based on Phytochemistry and Pharmacological Activity

Abstract: Arnebia euchroma, commonly known as "Pink Arnebia," is a plant from the Boraginaceae family found in Western and Central Asia. Traditionally, it has been used to treat respiratory, gastrointestinal, and dermatological ailments. Recent studies have highlighted its pharmacological properties and potential health advantages, resulting in increased interest in this plant. Pharmacognostic investigations have revealed the presence of various beneficial phytochemicals. Phytochemical studies have identified several bioactive compounds in A. euсhroma, such as eugormoside A, eugormoside B, scopoletin, and β-sitosterol, which exhibit diverse biological activities like antioxidant, antimicrobial, anticancer, and anti-ulcer effects. The therapeutic potential of these bioactive compounds suggests that A. euсhroma could be beneficial for a wide range of diseases. Pharmacological studies have validated the plant's healing properties, demonstrating its antimicrobial activity against various pathogens. Furthermore, A. euсhroma extracts possess antioxidant and anti-inflammatory properties that can potentially mitigate oxidative stress and inflammation-related diseases. Other pharmacological actions of A. euсhroma include wound healing, gastroprotective, hepatoprotective, and anti-diabetic effects. Overall, A. euсhroma exhibits promise as a medicinal plant with significant health benefits. However, further research is required to identify the active compounds responsible for its pharmacological activity and elucidate their primary mechanisms of action. Additionally, clinical studies are necessary to assess its safety and efficacy when used therapeutically. The primary objective of this review is to showcase the phytochemical composition and traditional ethnopharmacological applications of A. euchroma worldwide. The study examines previous research concerning this plant, laying the foundation for a forward-looking perspective on the potential future of A. euchroma.

Gastroprotective Effect of Aqueous Extract of Unripe Musa Paradisiaca (Banana) Fruit in Rats with Experimentally Induced Gastric Lesions

Background: Unripe banana fruit extract is used to relieve stomach distress in some countries. A few studies in India, China, Sudan, Nigeria and South Africa revealed protection of gastric mucosa after exposed to aggressive agent following administration of unripe banana fruit extract in experimental animals. Objective: To determine the protective effect of aqueous extract of unripe Musa paradisiaca (banana) fruit against ethanol induced gastric lesion in rats. Methodology: This was a prospective experimental study carried out in the department of Pharmacology, Dhaka Medical College, Dhaka within the period from January 2015 to June 2015. Aqueous extract of unripe banana fruit was prepared accordingly. Total 24 rats were randomly divided into 4 groups of 6 in each group. Group-A served as a control group and provided with distilled water (5 ml/kg/body weight) orally by gastric tube. Aqueous extract of Musa paradisiaca was administered orally as Group-B: 0.2 mg/kg/body weight/day, Group-C: 0.4 mg/kg/body weight/day and Group-D: 0.8 mg/kg/body weight/day for 7 days. After 7 days, 1 ml absolute ethanol (a known gastric lesion inducing agent) was orally administered to all groups by gastric tube. After 30 minutes of ethanol administration, all rats were sacrificed and dissected. After separating and opening stomachs, observed lesions were examined and measured with some morphological & histological parameters. Obtained data were subjected to analysis by Student’s unpaired t-test. p-value <0.05 was considered as statistically significant. Results: At the end of experiment, Group-A (control) showed a total of 33 gastric lesions. Group-B, Group-C and Group-D showed 22, 20 and 19 stomach lesions respectively. The difference between control group and experiment groups was statistically significant (p<0.01). Conclusion: The unripe banana fruit extract has dose-dependent gastroprotective effect on rats. So, it may be effective in treating peptic ulcer disease. Eastern Med Coll J. July 2023; 8 (2): 19-23

Gastroprotective Effect of Quercus infectoria Olivier Galls on Ethanol-Induced Gastritis in Rats.

One of the common inflammatory disorders that substantially affects the stomach and its mucosa is gastritis. It can be induced by non-steroidal anti-inflammatory drugs (NSAIDs), antibiotics, alcohol, Helicobacter pylori infection, and stress. These factors affect cellular regeneration, mucus production, and bicarbonate secretion, resulting finally in inflammation and ulceration. Ethanol-induced gastritis is one of the commonly used models for studying the pathology of gastritis and investigating the effect of drugs in managing the disease. Several drugs, such as proton pump inhibitors (PPIs), are available to control and correct the pathological signs of gastritis; however, the side effects of such drugs represent an obstacle to their applications in many cases. Quercus infectoria(QI) Olivier galls are formed as a pathological response to wasp insults to the tree. They are rich in several bioactive molecules, e.g., gallotannins that have been shown to be effective in several inflammatory conditions due to their antioxidant and anti-inflammatory potentials. In this study, we aimed to evaluate the therapeutic potential of QI gall extract (QIGE) in treating ethanol-induced gastritis in rats. To test this, 20 adult male Swiss rats were divided into four groups: healthy control, ethanol-treated (80% in water, 5 ml/kg, per oral gavage), ethanol + omeprazole (20 mg/kg, per oral gavage), and ethanol + QIGE (300 mg/kg, per oral gavage). QIGE was administered for seven days before ethanol administration, which took place three hours after the last QIGE dose. Three hours after ethanol intake, animals were euthanized, gastric content was collected, and stomach tissue was examined for macroscopic changes and then fixed to be further utilized for histological assessment by hematoxylin and eosin (H&E), periodic acid-Schiff (PAS), and Masson's trichrome staining. Ethanol treatment significantly decreased gastric pH and increased gastric acidity compared to healthy control. It also induced clear morphological and histological damage and ulceration, depleted mucus on the gastric epithelium, and induced edema and collagen deposition in gastric submucosa. The QIGE treatment ameliorated the changes in gastric pH and total acidity. It also protected stomach tissue from ethanol-induced ulceration, histopathological changes, edema, and collagen deposition. The protective effects of QIGE were comparable to those of omeprazole. In conclusion, QI gall extract possesses a promising gastroprotective effect against ethanol-induced gastritis.

Effects of the epiphytic patterns on endophytes and metabolites of Dendrobium nobile Lindl.

Dendrobium is an epiphytic herb plant with neuroprotective, gastroprotective, anti-inflammatory, and immunomodulatory effects. It is often found attached to tree trunks or rocks. With the development of the dendrobium industry, numerous epiphytic patterns exist, such as crushed stone, stump, and sawdust. The study of metabolites and endophytes of D. nobile under different epiphytic patterns, which revealed the effects of epiphytic patterns on D. nobile from the perspectives of metabolomics and microbiology, is of great significance for the healthy development of D. nobile. In the study, the D. nobile under five epiphytic patterns grown in the same environment were selected. The metabolites were investigated by widely targeted metabolomics, and the endophytes were sequenced using high-throughput sequencing methods. Then, a correlation analysis between the different metabolites and endophytes was performed. A total of 1,032 metabolites were annotated in D. nobile. There are more flavonoids and phenolic acids accumulated on the epiphytic pattern of Danxia stone, whereas the accumulation of lipids on the other epiphytic patterns and 16 differential metabolites was screened out. The endophyte composition of D. nobile was dominated by Proteobacteria, Actinomycetes, unidentified bacteria, Firmicutes, and Cyanobacteria. For endophytic fungi, Basidiomycota and Ascomycota were the dominant phyla of D. nobile. The relative abundance of Spirosoma, Nocardioides, and Arrhenia in the Danxia stone was significantly higher than that of other epiphytic patterns. According to correlation analysis, we found a significant correlation between differential metabolites and Spirosoma, Nocardioides, and Arrheni. This study confirmed that Dendrobium quality was affected by its epiphytic patterns and revealed its possible causes from a microbiological point of view.

Laurus nobilis Esansiyel Yağının Sıçanlarda İndometasin Kaynaklı Mide Ülserinin Azaltılmasında Potansiyel Rolü

Objective: This study aimed to investigate the gastroprotective effects of Laurus nobilis leaves essential oil (LANO) against indomethacin (INDO)-induced gastric ulcers in rats.
 Materials and Methods: In this study, an indomethacin-induced gastric ulcer model was employed. 30 Sprague-Dawley rats were divided into five groups (n=6): Control, LANO, INDO, INDO with famotidine (FAM), and INDO with LANO. Indomethacin (25 mg/kg) induced ulcers, while LANO and FAM were administered by oral gavage at 200 mg/kg and 40 mg/kg, respectively. Gastric tissues underwent histopathological examination for ulceration, and biochemical assays measured total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), and nitric oxide (NO) levels.
 Results: Compared to the INDO group, treatment with LANO significantly decreased the number of gastric ulcer foci. Biochemically, LANO moderated TOS and OSI levels and preserved TAS, indicating reduced oxidative stress. Additionally, LANO appeared to stabilize NO levels. These biochemical findings were corroborated by histopathological examination.
 Conclusions: The study's results indicate that LANO may be beneficial in protecting against NSAID-induced gastric damage. LANO's observed modulation of oxidative stress markers and NO levels suggests its potential role in managing gastric ulcers.

Enhanced upregulation of SIRT1 via pioglitazone and ligustrazine confers protection against ethanol-induced gastric ulcer in rats

Gastric ulcer is a disturbing disease that impacts many people worldwide. Pioglitazone (Piog), a thiazolidinedione, and ligustrazine (Ligu), a natural component of Ligusticum chuanxiong possess gastroprotective properties. However, the underlying mechanism is not well elucidated. The present study aimed to investigate the gastroprotective effects of Piog (15 mg/kg, p.o.), Ligu (15 mg/kg, p.o.), and their combination against ethanol-induced gastric ulcer in rats. Omeprazole (10 mg/kg) was used as a standard. Pre-treatment for 7 days with Piog, Ligu, and (Piog+Ligu) effectively alleviated ethanol-predisposed oxidative stress and inflammation through restoring HO-1, GSH, and SOD tissue levels and decreasing elevated MDA, TNF-α, ICAM, I-NOS, and IL-1β contents. Moreover, Piog, Ligu, and (Piog+Ligu) markedly inhibited the ethanol-induced increase of gastric NF-KB and BAX. In contrast, this pre-treatment regimen significantly accelerated protein expression of SIRT1, Nrf2, and Bcl-2, along with autophagic proteins, ATG5 and Beclin. Interestingly, macroscopic, histopathological examination and mucin content were in harmony with previous results, where pre-treatment with Piog, Ligu, and (Piog+Ligu) showed a declined mucosal injury as evidenced by the remarkable decrease of the ulcer area percentage by 62.3%, 38.7%, and 91.2%, respectively, compared to the ethanol-ulcerated group. In conclusion, Piog and Ligu exhibited remarkable gastroprotective properties. Our study was the first to show that Piog, Ligu, and (Piog+Ligu) ameliorated oxidative stress, inflammation, and apoptosis and accelerated the autophagic process via the upregulation of the upstream SIRT1 protein. It is worth mentioning that future studies are needed to pave the way for the clinical use of Piog and Ligu as gastro-protective agents.

Gastroprotective Effect of 2,3-Dimethylquinoxaline Against Indomethacin-Induced Gastric Ulcer in Rat.

Gastric ulcers pose a significant health risk due to an imbalance between protective and aggressive factors on the mucous membrane. Nonsteroidal anti-inflammatory drug (NSAID)-induced gastric damage affects 25% of users. Quinoxaline compounds, known for their diverse biological properties, have potential applications in cancer therapy and as antimicrobial agents targeting various pathogens. Our study aimed to investigate the impact of DMQ on gastroprotective mechanisms in an experimental model of indomethacin-induced gastric ulcer. Thirty male Wistar rats were randomly assigned to five groups. Group 1 served as the control, while Group 2 received a single oral dose of IND (30 mg/kg). Groups 3 and 4 received oral DMQ (30 mg/kg and 60 mg/kg, respectively) for three days, with the final dose administered intragastrically one hour before IND administration. Group 5 received esomeprazole (30 mg/kg) orally for three days, with the final dose given one hour before IND administration. Rats were sacrificed four hours after IND induction. Indomethacin-induced ulcers were associated with epithelial damage and blood streaks on the gastric mucosa. However, DMQ significantly decreased levels of inflammatory biomarkers (TNF-α, IL-6, Cox-2, IFN-γ, and IL-β1) while increasing gastroprotective mediator prostaglandin E2 (PGE2) and mucin levels. Histopathological analysis revealed a significant reduction in ulcer-induced pathological alterations and upregulation of tumor suppressor genes (NF-κB levels) following DMQ treatment. Rats treated with Indo+DMQ showed a significant decrease in ulcer index compared to the Indo group, with mild injuries observed. DMQ demonstrated promising gastroprotective effects against IND-induced gastric ulcers, as evidenced by alterations in histopathological data and upregulation of gene expression.

LC-MS-Based Metabolomics Reveals the Mechanism of Protection of Berberine against Indomethacin-Induced Gastric Injury in Rats.

Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders.

Use of Callistemon citrinus as a gastroprotective and anti-inflammatory agent on indomethacin-induced gastric ulcers in obese rats.

Obesity leads to an elevated risk of developing gastrointestinal disease such as gastric ulcers. Callistemon citrinus leaf extract has shown antioxidant, antimicrobial, hepatoprotective, and chemoprotective effects against colon cancer. The aim of this study is to evaluate the gastroprotective effect of C. citrinus leaf extract on indomethacin-induced gastric ulcers in obese rats. Gastric ulcers were induced in female obese Wistar rats using a single oral dose of indomethacin (IND). In the first stage, the rats were fed with a high fat sugar diet (HFSD) for 15 weeks to induce obesity and, at the same time, the diet of the other group of animals included daily administration of ethanolic C. citrinus leaf extract (250 mg/kg) in addition to HFSD. In the second stage, gastric ulcers were induced with IND (30 mg/kg). The gastroprotective activity of C. citrinus, the inflammatory enzyme activities, and cytokines in the stomach were determined. C. citrinus produced a reduction of gastric lesions caused by IND. Myeloperoxidase (MPO), cyclooxygenase-2 (COX-2), and 5-lipoxygenase (5-LOX) activities also decreased. Although inflammatory biomarkers such as TNFα, IL-6, AOPP, and leptin were significantly decreased by C. citrinus, adiponectin levels increased. Moreover, C. citrinus decreased weight gain and morphological and biochemical parameters. The use of indomethacin in rats fed with a high fat-sugar diet increased gastric ulcers. Gastroprotective effect of C. citrinus in obese rats is attributed to the reduction of pro-inflammatory cytokines and the inflammatory enzymes.

Green synthesis of zinc oxide nanoparticles using ethanolic extract of Gliricidia sepium (Jacq.) Kunth. ex. Walp., stem: Characterizations and their gastroprotective effect on ethanol-induced gastritis in rats

The study presents a significant advancement in drug delivery and therapeutic efficacy through the successful synthesis of Gliricidia sepium(Jacq.) Kunth. ex. Walp., stem zinc oxide nanoparticles(GSS ZnONPs). The phenolic compounds present in Gliricidia sepium stem (GSS) particularly vanillic acid, apegnin-7-O-glucoside, syringic acid, and p-coumaric acid which were identified by HPLC. These compounds shown antioxidant and anti-inflammatory properties. GSS ZnONPs demonstrate pronounced gastroprotective effects against ethanol-induced gastritis, evidenced by the reduction in gastric lesions and mucosal injury upon its treatment. Histopathological evaluation and immunohistochemical analysis of nuclear factor erythroid 2-related factor 2 (Nrf2) expression further validate these results, revealing the amelioration of ethanol-induced gastritis and improved gastric tissue condition due to their treatment. Noteworthy is the dose-dependent response of GSS ZnONPs, showcasing their efficacy even at lower doses against ethanol-induced gastritis which is confirmed by different biomarkers. These findings have substantial implications for mitigating dosage-related adverse effects while preserving therapeutic benefits, offering a more favorable treatment approach. This study aims to investigate the potential gastroprotective activity of GSS ZnONPs against gastritis.

Natural xanthones as modulators of the Nrf2/ARE signaling pathway and potential gastroprotective agents.

Oxidative stress is implicated in the initiation, pathogenesis, and progression of various gastric inflammatory diseases (GID). The prevalence of these diseases remains a concern along with the increasing risks of adverse effects in current clinical interventions. Hence, new gastroprotective agents capable of inhibiting oxidative stress by modulating cellular defense systems such as the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway are critically needed to address these issues. A candidate to solve the present issue is xanthone, a natural compound that reportedly exerts gastroprotective effects via antioxidant, anti-inflammatory, and cytoprotective mechanisms. Moreover, xanthone derivatives were shown to modulate the Nrf2/ARE signaling pathway to counter oxidative stress in both in vitro and in vivo models. Thirteen natural xanthones have demonstrated the ability to modulate the Nrf2/ARE signaling pathway and have high potential as lead compounds for GID as indicated by their in vivo gastroprotective action-particularly mangiferin (2), α-mangostin (3), and γ-mangostin (4). Further studies on these compounds are recommended to validate the Nrf2 modulatory ability in relation to their gastroprotective action.

Apium extract alleviates indomethacin-induced gastric ulcers in rats via modulating the VEGF and IK-κB/NF-κB p65 signaling pathway: insights from in silico and in vivo investigations

BackgroundGastric ulcers represent a worldwide health problem, characterized by erosions that affect the mucous membrane of the stomach and may even reach the muscular layer, leading to serious complications. Numerous natural products have been assessed as anti-ulcerogenic agents, and have been considered as new approaches for treatment or prevention of gastric ulcers. The present research investigated the preventive benefits of Apium graveolens L. (Apiaceae), known as celery, seed extract towards indomethacin-induced ulceration of the stomach in rats.MethodsMetabolomic profiling, employing liquid chromatography coupled to high-resolution electrospray ionization mass spectrometry (LC-HR-ESI–MS), was implemented with the aim of investigating the chemical profile of the seeds. Histopathological analysis of gastric tissues, as well as assessment of numerous inflammatory cytokines and oxidative stress indicators, confirmed the in vivo evaluation.ResultsThe prior treatment with A. graveolens seed extract resulted in a substantial reduction in the ulcer index when compared to the indomethacin group, indicating an improvement in stomach mucosal injury. Moreover, the gastroprotective effect was demonstrated through examination of the oxidative stress biomarkers which was significantly attenuated upon pre-treatment with A. graveolens seed extract. Vascular endothelial growth factor (VEGF), a fundamental angiogenic factor that stimulates angiogenesis, was markedly inhibited by indomethacin. A. graveolens seed extract restored this diminished level of VEGF. The dramatic reductions in NF-κB protein levels indicate a considerable attenuation of the indomethacin-induced IKκB/NF-κB p65 signaling cascade. These activities were also correlated to the tentatively featured secondary metabolites including, phenolic acids, coumarins and flavonoids, previously evidenced to exert potent anti-inflammatory and antioxidant activities. According to our network pharmacology study, the identified metabolites annotated 379 unique genes, among which only 17 genes were related to gastric ulcer. The PTGS2, MMP2 and PTGS1 were the top annotated genes related to gastric ulcer. The top biological pathway was the VEGF signaling pathway.ConclusionA. graveolens seed extract possesses significant anti-ulcer activity, similar to famotidine, against gastric lesions induced by indomethacin in rats. It is worth highlighting that the extract overcomes the negative effects of conventional chemical anti-secretory drugs because it does not lower stomach acidity.

Antiulcer activity of Mauritia flexuosa L.f. (Arecaceae) pulp oil: An edible Amazonian species with functional properties

Mauritia flexuosa, known as buriti in Brazil, is a widespread palm tree in Amazonia. It has many ethnobotanical uses, including food, oil, and medicine. The oil obtained from buriti's fruit pulp has high levels of monounsaturated fatty acids, carotenoids, and tocopherols, and is used in the food, cosmetic, and pharmaceutical industries for its antioxidant properties. Many biological activities have been reported for buriti oil, such as antioxidant, antimicrobial, chemopreventive, and immunomodulatory. Due to its high content of bioactive compounds, buriti oil is considered a functional ingredient with possible benefits in preventing oxidative stress and chronic diseases, particularly in the gastrointestinal tract. Peptic ulcer disease is a multifactorial disorder, involving lesions in the stomach and duodenum mucosa, which has a complex healing process. In this context, some nutrients and bioactive compounds help the maintenance of gastrointestinal mucosal integrity and function, such as carotenoids, tocopherols, and unsaturated fatty acids, which makes buriti oil an interesting candidate to be used in the prevention and management of gastrointestinal diseases. This study aimed to evaluate the gastroprotective and antiulcer effects of buriti oil and its possible mechanisms of action. Buriti oil reduced the ulcerative area and lipid peroxidation induced by ethanol. The gastroprotective activity of buriti oil partially depends on nitric oxide and sulfhydryl compounds. In acetic acid-induced gastric ulcers, buriti oil accelerated healing and stimulated the formation of new gastric glands. These results demonstrated the potential of buriti oil as a functional ingredient to promote health benefits in the gastrointestinal tract.

Carvacrol: A Prospective Gold Mine of New Drug Discovery and Development

Carvacrol, a widely extracted monoterpenoid phenol from an abundant number of aromatic plant species including thyme and oregano. At present, carvacrol is being utilized in low concentrations as a preservative and food flavoring agent, in addition to serving as a fragrance element in cosmetic formulations. A great deal of study has been done in recent years as an effort to determine the biological effects of carvacrol for possible therapeutic application. Carvacrol has been identified to have a vast range of biological and pharmacological characteristics which include antidiabetic, antimicrobial, antiinflammatory, anti-obesity, antitumor, hepatoprotective, gastroprotective, and neuroprotective effects based on both in vitro and in vivo experiments. The main objective of this review is to assess current understanding of carvacrol's pharmacological impacts as well as its biosynthesis and plant sources in order to potentially inform the future researchers. It can be postulated that upon extensive research, this noteworthy bioactive phytochemical can be a very promising source of next generation drug development. Bangladesh Pharmaceutical Journal 27(1): 116-125, 2024 (January)

Licorice flavonoid ameliorates ethanol-induced gastric ulcer in rats by suppressing apoptosis via PI3K/AKT signaling pathway

Ethnopharmacological relevanceLicorice is the dry roots and rhizomes of Glycyrrhiza uralensis Fisch., Glycyrrhiza glabra L. and Glycyrrhiza inflata Bat., which was first recorded in Shengnong's herbal classic. Licorice flavonoid (LF) is the main compound isolated from licorice with an indispensable action in treating gastric ulcer (GU). However, the underlying mechanisms need to be further explored. Aim of the studyThis study aimed to investigate and further elucidate the mechanisms of LF against ethanol-induced GU using an integrated approach. Materials and methodsThe anti-GU effects of LF were evaluated in an ethanol-induced gastric injury rat model. Then, the metabolomics approach was applied to explore the specific metabolites and metabolic pathways. Next, the network pharmacology combined with metabolomics strategy was employed to predict the targets and pathways of LF for GU. Finally, these predictions were validated by molecular docking, RT-qPCR, and western blotting. ResultsLF had a positive impact on gastric injury and regulated the expression of GU-related factors. Upon serum metabolomics analysis, 25 metabolic biomarkers of LF in GU treatment were identified, which were primarily involved in amino acid metabolism, carbohydrate metabolism, and other related processes. Subsequently, a “components-targets-metabolites” network was constructed, revealing six key targets (HSP90AA1, AKT1, MAPK1, EGFR, ESR1, PIK3CA) that may be associated with GU treatment. More importantly, KEGG analysis highlighted the importance of the PI3K/AKT pathway including key targets, as a critical route through which LF exerted its anti-GU effects. Molecular docking analyses confirmed that the core components of LF exhibited a strong affinity for key targets. Furthermore, RT-qPCR and western blotting results indicated that LF could reverse the expression of these targets, activate the PI3K/AKT pathway, and ultimately reduce apoptosis. ConclusionLF exerted a gastroprotective effect against gastric ulcer induced by ethanol, and the therapeutic mechanism may involve improving metabolism and suppressing apoptosis through the PI3K-AKT pathway.

Anti H. pylori, anti-secretory and gastroprotective effects of Thymus vulgaris on ethanol-induced gastric ulcer in Sprague Dawley rats.

The objectives of the present study were to evaluate the acute toxicity, gastroprotective, therapeutic, anti-inflammatory and anti H. pylori activities of T. vulgaris total plant extract against ethanol-induced gastric ulcers in Sprague Dawley rats. Animals were divided into five groups i.e G-1 (Normal Control), Group 2 (ulcer control) were administered orally with 0.5% Carboxymethylcellulose (CMC), Group 3 (omeprazole treated) was administered orally with 20 mg/kg of omeprazole and Groups 4 and 5 (Low dose and High dose of the extract) were administered orally with 250, and 500 mg/ kg of Thymus vulgaris extract, respectively. After 1 hour, the normal group was orally administered with 0.5% CMC (5 ml/kg), whereas absolute alcohol (5ml/ kg) was orally administered to the ulcer control group, omeprazole group, and experimental groups. Stomachs were examined macroscopically and microscopically. Grossly, rats pre-treated with T. vulgaris demonstrated significantly decreased ulcer area and an increase in mucus secretion and pH of gastric content compared with the ulcer control group. Microscopy of gastric mucosa in the ulcer control group showed severe damage to gastric mucosa with edema and leukocytes infiltration of the submucosal layer. However, rats pretreated with omeprazole or Thyme vulgaris exhibited a mild to moderate disruption of the surface epithelium and lower level of edema and leukocyte infiltration of the submucosal layer. The T. vulgaris extract caused up-regulation of Hsp70 protein, down-regulation of Bax protein, and intense periodic acid Schiff uptake of the glandular portion of the stomach. Gastric mucosal homogenate of rats pre-treated with T. vulgaris exhibited significantly increased superoxide dismutase (SOD) and catalase (CAT) activities while malondialdehyde (MDA) level was significantly decreased. Based on the results showed in this study, Thymus vulgaris extract can be proposed as the safe medicinal plants for use and it has considerable gastroprotective potential via stomach epithelium protection against gastric ulcers and stomach lesions.

In Vitro and Biological Evaluation of Oral Fast-Disintegrating Films Containing Ranitidine HCl and Syloid® 244FP-Based Ternary Solid Dispersion of Flurbiprofen.

Flurbiprofen (FBP), a nonsteroidal anti-inflammatory drug (NSAID), is commonly used to treat the pain of rheumatoid arthritis, but in prolonged use it causes gastric irritation and ulcer. To avoid these adverse events of NSAIDs, the simultaneous administration of H2 receptor antagonists such as ranitidine hydrochloride (RHCl) is obligatory. Here, we developed composite oral fast-disintegrating films (ODFs) containing FBP along with RHCl to provide a gastroprotective effect as well as to enhance the solubility and bioavailability of FBP. The ternary solid dispersion (TSD) of FBP was fabricated with Syloid® 244FP and poloxamer® 188 using the solvent evaporation technique. The synthesized FBP-TSD (coded as TSD) was loaded alone (S1) and in combination with plain RHCl (S2) in the composite ODFs based on hydroxypropyl methyl cellulose E5 (HPMC E5). The synthesized composite ODFs were evaluated by in vitro (thickness, folding endurance, tensile strength, disintegration, SEM, FTIR, XRD and release study) and in vivo (analgesic, anti-inflammatory activity, pro-inflammatory cytokines and gastroprotective assay) studies. The in vitro characterization revealed that TSD preserved its integrity and was effectively loaded in S1 and S2 with optimal compatibility. The films were durable and flexible with a disintegration time ≈15 s. The release profile at pH 6.8 showed that the solid dispersion of FBP improved the drug solubility and release when compared with pure FBP. After in vitro studies, it was observed that the analgesic and anti-inflammatory activity of S2 was higher than that of pure FBP and other synthesized formulations (TSD and S1). Similarly, the level of cytokines (TNF-α and IL-6) was also markedly reduced by S2. Furthermore, a gastroprotective assay confirmed that S2 has a higher safety profile in comparison to pure FBP and other synthesized formulations (TSD and S1). Thus, composite ODF (S2) can effectively enhance the FBP solubility and its therapeutic efficacy, along with its gastroprotective effect.

Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept.

Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1β, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent.

Gastroprotective effect of rhodanine and 2,4-thiazolidinediones scaffolds in rat stomachs by contribution of anti-apoptotic (BCL-2) and tumor suppressor (P53) proteins

In recent times, the methods used to evaluate gastric ulcer healing worldwide have been based on visual examinations and estimating ulcer dimensions in experimental animals. In this study, the protective effect of rhodanine and 2,4-thiazolidinediones scaffolds compared to esomeprazole was investigated in an ethanol model of stomach ulcers in rats. Pretreatment with experimental treatments or esomeprazole prevented the development of ethanol-induced gastric ulcers. The severity of the lesions and injuries was significantly lower than that of vehicle (10% Tween 80) treated rats. Significant and excellent results were obtained with the compound 6 group, with inhibition percentage and ulcer area values of 97.8% and 12.8 ± 1.1 mm2, respectively. Synthesized compounds 2, 7 and 8 exhibited inhibition percentages and ulcer areas of 94.3% and 31.2 ± 1.1 mm2, 91. 3% and 48.1 ± 0. 8 mm2, 89. 5% and 57. 6 ± 1. 2 mm2, and 89. 1% and 60.3 ± 0. 8 mm2, respectively. These biological outcomes are consistent with the docking studies in which Compounds 7 and 8 showed remarkable binding site affinities toward human H+/K+-ATPase α protein (ID: P20648), rat H+/K+-ATPase α protein (ID: P09626), and Na+/K+-ATPase crystal structure (PDB ID:2ZXE) with binding site energies of − 10.7, − 9.0, and − 10.4 (kcal/mol) and − 8.7, − 8.5, and − 8.0 (kcal/mol), respectively. These results indicate that these test samples were as effective as esomeprazole. Likewise, immunohistochemical staining of antiapoptotic (BCL2) and tumor suppressor (P53) proteins showed strong positive marks in the10% Tween 80- treated group, opposing the mild staining results for the esomeprazole-treated group. Similarly, the staining intensity of the group treated with Compounds 2–8 was variable for both proteins.

ИЗУЧЕНИЕ ЦИТОТОКСИЧНОСТИ ТРИПЕПТИДА LEU-ILE-LYS

Introduction. A comprehensive study of the toxicity of new pharmacologically active substances is a necessary step for their introduction into practical medicine. Earlier, studies of the Leu-Ile-Lys tripeptide, which showed an anti-lithogenic effect in experimental oxalate and urate nephrolithiasis, a nephroprotective effect in experimental type 2 diabetes mellitus, as a well as gastroprotective effect in experimental "indomethacin" gastropathy, were carried out at the Federal State Budgetary Educational Institution of the Ministry of Health of the Russian Federation. Currently, there is an active development of methods for investigating the effectiveness and safety of biologically active substances in vitro, which directly assess the direct effect of the substances under study on the vital activity of cell cultures. Objective. Study of the the cytotoxicity of Leu-Ile-Lys tripeptide in cell culture. Materials and methods. Cytotoxicity was studied on human lung adenocarcinoma cell culture A549. A control group and five experimental groups were identified. Solutions of Leu-Ile-Lys tripeptide were prepared in Dulbecco's Modified Eagle's Medium culture medium with concentrations of 0.5, 1, 2, 5 and 10 mg/ml. A monolayer of cells was prepared, followed by replacement of the culture medium with solutions of the test substance, followed by 24-hour incubation in carbon dioxide at 37° C. As part of the qualitative control, the morphology and density of the monolayer were studied. Quantitative control was carried out by counting the number of cells in the Goryaev chamber. Results. No significant changes in cell morphology, monolayer density, or cell count were detected in comparison to the control in all experimental groups. Conclusion. Thus, the revealed absence of cytotoxicity of the Leu-Ile-Lys tripeptide indicates the prospects for further research of this substance in order to develop new pharmacological agents based on it.