Banxia Xiexin decoction promotes gastric lymphatic pumping by regulating lymphatic smooth muscle cell contraction and energy metabolism in a stress-induced gastric ulceration rat model.

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) formula Banxia Xiexin decoction (BXD) has definite therapeutic effect in treating stress-induced gastric ulceration (SIGU) and many other gastrointestinal diseases, but its effect on gastric lymphatic pumping (GLP) remains unclear. AIM OF THE STUDY: Elucidating the role of GLP in SIGU and BXD treatment, and exploring the molecular mechanisms of GLP regulation. MATERIALS AND METHODS: In vivo GLP imaging were performed on SIGU rat model, and the lymphatic dynamic parameters were evaluated. Gastric antrum tissues and serum were collected for macroscopic, histopathological and ulcerative parameters analysis. Gastric lymphatic vessel (GLV) tissues were collected for RNA-Seq assays. Differentially expressed genes (DEGs) were screened from RNA-Seq result and submitted for transcriptomic analysis. Key DEGs and their derivative proteins were measured by qRT-PCR and WB. RESULTS: GLP was significantly suppressed in SIGU rats. BXD could recover GLP, ameliorate stomach lymphostasis, and alleviate the ulcerative damage. Transcriptome analysis of GLV showed the top up-DEGs were concentrated in smooth muscle contraction signaling pathway, while the top the down-DEGs were concentrated in energy metabolism pathways especially fatty acid degradation pathway, which indicated BXD can promote lymphatic smooth muscle contraction, regulate energy metabolism, and reduce fatty acid degradation. The most possible target of these mechanisms was the lymphatic smooth muscle cells (LSMCs) which drove the GLP. This speculation was further validated by the qRT-PCR and WB assessments for the level of key genes and proteins. CONCLUSIONS: By activating the smooth muscle contraction signaling pathway, restoring energy supply, modulating energy metabolism program and reducing fatty acid degradation, BXD effectively recovered GLP, mitigated the accumulation of inflammatory cytokines and metabolic wastes in the stomach, which importantly contributes to its efficacy in treating SIGU.

Effect of white jade snail secretion on antioxidant capacity and intestinal microbial diversity in mouse model of acute gastric ulcer.

BACKGROUND: In the present work, acute gastric ulcer models were constructed by administering hydrochloric acid/ethanol. The mice ingested white jade snail secretion (WJSS) through gastric infusion. Ulcer areas in gastric tissue were recorded, and malondialdehyde (MDA) and superoxide dismutase (SOD) were also measured. Notably, high-throughput 16S rDNA analysis of intestinal flora and determination of amino acid composition in feces were performed to understand the effect of WJSS on model mice. RESULTS: Compared with the control group, the ulcer area in the WJSS low-, medium- and high-concentration groups declined by 28.02%, 39.57% and 77.85%, respectively. MDA content decreased by 24.71%, 49.58% and 64.25%, and SOD relative enzyme activity fell by 28.19%, 43.37% and 9.60%, respectively. The amounts of amino acids in the low-, medium- and high-concentration groups were slightly lower, and probiotic bacteria such as Bacteroidetes and Lactobacillales increased in different-concentration WJSS groups. Adding WJSS contributes to the establishment of beneficial intestinal flora and the absorption of amino acids. CONCLUSION: Our results showed that WJSS has a beneficial effect on inhibiting hydrochloric acid-ethanolic gastric ulcers, suggesting that WJSS has excellent potential as a novel anti-ulcer agent. Combined with ulcer area, MDA content, SOD content, gut probiotics and other indicators, a high concentration of WJSS had the best protective effect on acute gastric ulcer. © 2023 Society of Chemical Industry.

Licorice flavonoid alleviates gastric ulcers by producing changes in gut microbiota and promoting mucus cell regeneration.

Licorice flavonoid (LF) is the main component of Glycyrrhizae Radix et Rhizoma, a "medicine food homology" herbal medicine, which has anti-digestive ulcer activity, but the mechanism in anti-gastric ulcer (GU) remains to be elucidated. In this study, we manifested that LF increased the viability of human gastric mucosal epithelial (GES-1) cells, attenuated ethanol (EtOH)-induced manifestations, reduced histological injury, suppressed inflammation, and restored gastric mucosal barrier in GU rats. After LF therapy, the EtOH-induced gut dysbiosis was partly modulated, and short-chain fatty acids (SCFAs) like butyric acid, propionic acid, and valeric acid were found in higher concentrations. We discovered that the majority of genera that increased in the GU group had a negative correlation with SCFAs in the intestinal tract. In addition, LF-upregulated SCFAs boosted mucus secretion in the gastric epithelium and the expression of mucoprotein (MUC) 5AC and MUC6, particularly the MUC5AC in the gastric foveola. Moreover, LF triggered the EGFR/ERK signal pathway which promoted gastric mucus cell regeneration. Therefore, the findings indicated that LF could inhibit inflammation, promote mucosal barrier repair and angiogenesis, regulate gut microbiota and SCFA metabolism; more importantly, promote epithelial proliferation via activation of the EGFR/ERK pathway, exerting a protective and regenerative effect on the gastric mucosa.

Gastroprotective Role of Fruit Extracts in Gastric Damage Induced by Non-Steroidal Anti-Inflammatory Drugs: A Systematic Review.

The aim of this study was to systematically review the scientific literature, with Preferred Reporting Items of Systematic Reviews and Meta-analyses (PRISMA) guidelines, of the articles found in the past 11 years on the gastroprotective role of fruit extracts in gastric ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs). Scientific articles published between 2010 and 2020 were included in this systematic review, including in vitro and in vivo models, to define the gastroprotective role of fruit extracts. Studies were selected by Rayyan using PubMed, Web of Science, Scopus, and Science Direct databases. The keywords for the search strategy were: "gastric injury," "gastric ulcer," "fruit," "indomethacin," and "aspirin." Twenty-two articles with animal models of gastric ulcers were included. The NSAIDs used were aspirin and indomethacin. To know the damage caused by these, the ulceration index and biomarkers, such as aggressive/defensive factors involved in the gastric ulceration process, were measured. Most studies have shown that fruit extracts have antiulcer activity, with the most abundant metabolites being flavonoids, followed by terpenes and alkaloids. Possible antiulcer activities such as antioxidant, cytoprotective, gastric acid antisecretory, anti-inflammatory, or angiogenesis stimulant were declared, manifested mainly as a reduction of lipid peroxidation products, an increase in antioxidant enzymes and prostaglandins, and by the formation of a protective film through protein precipitation in the ulcer area. This systematic review demonstrates the importance of fruit extracts as gastric protectors.

Mongolian medicine formulae Ruda-6 alleviates indomethacin-induced gastric ulcer by regulating gut microbiome and serum metabolomics in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ruda-6 (RD-6), a typical traditional Mongolian medicine formulae consisting of 6 herbs, has been traditionally used in treating gastric disorders. Even though it has been shown to protect against gastric ulcers (GU) in animal models, the gut microbiome and serum metabololite-related mechanisms that prevent GU are not well understood. AIM OF THE STUDY: This study was conducted to evaluate the gastroprotective mechanism of RD-6 associated with the alteration of the gut microbiome and serum metabolic profiles in GU rats. MATERIALS AND METHODS: RD-6 (0.27, 1.35 and 2.7 g/kg) or ranitidine (40 mg/kg) were orally administered in rats for three weeks before the induction of gastric ulcer using indomethacin (30 mg/kg, single oral dose). The gastric ulcer index, ulcer area, H&E staining, and the levels of TNF-α, iNOS, MPO and MDA were quantified to evaluate the ulcer inhibitory effects of RD-6. Then, 16S rRNA gene sequencing combined with LC-MS metabolic profiling was performed to investigate the effect of RD-6 on the gut microbiota and serum metabolites in rats. Moreover, a spearman analysis was used to calculate the correlation coefficient between the different microbiota and the metabolites. RESULTS: RD-6 inhibited the gastric lesion damage caused by indomethacin in rats, decreased the ulcer index by 50.29% (p < 0.05), reduced the levels of TNF-α, iNOS, MDA and MPO in gastric tissue. Additionally, RD-6 reshaped the diversity and microbial composition, and reversed the reduced bacteria including [Eubacterium]_xylanophilum group, Sellimonas, Desulfovibrio, and UCG-009, and the increased bacteria Aquamicrobium caused by indomethacin induction. Furthermore, RD-6 regulated the levels of metabolites including amino acids and organic acids, and these affected metabolites were involved in taurine and hypotaurine metabolism and tryptophan metabolism. Spearman analysis revealed that the perturbed gut microbiota were closely related to the changes in differential serum metabolites. CONCLUSION: In view of the 16S rRNA gene sequencing and LC-MS metabolic results, the present study suggests the mechanism of RD-6 ameliorating GU via modulating intestinal microbiota and their metabolites.

Promising effect of Geranium robertianum L. leaves and Aloe vera gel powder on Aspirin®-induced gastric ulcers in Wistar rats: anxiolytic behavioural effect, antioxidant activity, and protective pathways.

BACKGROUND: Many drugs have been restricted in the treatment of gastric ulcers (GU). So, herbal medicines are now in great demand for their better cultural acceptability, compatibility, and minimal side effects. Therefore, our study aimed to assess the protective efficacy of Aloe vera gel and Geranium robertianum extracts against Aspirin®-induced GU in Wistar rats. METHODS: Antioxidant activity and chemical composition of both herbs were analysed. Then, we divided forty female Wistar rats into five groups: a negative control group, a positive control group of Aspirin®-induced GU, and pretreated groups with Aloe Vera, geranium, and Famotidine (reference drug). The locomotor disability, anxiety-like behaviour, and ultrasonography were assessed. Ultimately, scarification of animals to determine gastric juice pH and ulcer index. Then the collection of stomach and liver for histopathological and immunohistochemical examinations, besides tracing the oxidative stress biomarkers and related genes. RESULTS: High content of polyphenols was revealed in both extracts. The pretreatment with Aloe vera gel and geranium showed significant antioxidant activities with free radical scavenging and ferric-reducing power (FRAP). Moreover, they improved the stomach architecture and alleviated anxiety-like behaviour and motor deficits. They significantly reduced the expression of proinflammatory cytokine (TNF-α), inflammatory, and oxidative stress genes (NF-KB, HO-1, Nrf-2) while increasing the Keap-1 in gastric mucosa. CONCLUSION: Data presented a significant protective effect of Aloe vera gel and geranium against Aspirin®-induced GU; they reduced gastric mucosal injury with potential anxiolytic effects through their anti-inflammatory and antioxidant properties. Therefore, they may be considered promising agents for preventing or treating gastric ulceration.

Molecular docking and anti-ulcerative potential of Cucumis (L. Inodorous) on ibuprofen induced gastric ulceration in male wistar animals.

BACKGROUND: The use of NSAIDs have caused stomach injury by inhibiting endogenous mucosal prostaglandin production. Cucumis melo is reported to possess antiulcer potential. This study investigates the mechanism underlying the antiulcer potentials of Cucumis melo (CUM). METHODS: Thirty-five male Wistar rat were randomly assigned to each of seven groups; A(control given water and rat pellets), B(gastric ulcer induced with ibuprofen 400 mg/kg), C (Misoprotol 200 µg/kg), D to G (pretreated with different variation of CUM extract; 25 %, 50 %, 75 % and 100 % at a dose of 1 ml/kg for 3 weeks prior to gastric ulcer induction). Ulcer score, ulcer index and percentage inhibition, total gastric acidity was measured. Antioxidant activities, Malondialdehyde, H+/K+ ATPase, PGE2, TNF-α was done by spectrophotometry. Molecular docking investigation of Cucumis melo compounds against Prostaglandin E2 was carried out. Level of significance was tested at P ≤ 0.05 using Tukey post hoc. RESULT: Total gastric acidity, ulcer score, ulcer index, MDA, TNF-α significantly decreased after CUM treatment when compared to group B. The percentage inhibition, antioxidant activities, PGE2 concentration was significantly increased in all treatment groups compared to group B. Interactions of selected compounds of CUM with Prostaglandin E2 at various docking pockets showed folic acid has highest binding affinity followed by delta7-avenasterol and codisterol to PGE2 receptor. this study shows that one of the mechanisms by which CUM exhibits its antiulcer potential by enhancing Prostaglandin synthesis and antioxidant capacity. Therefore, Cucumis melo can therefore be explored as novel antiulcer agents.

Achillea millefolium Essential Oil Mitigates Peptic Ulcer in Rats through Nrf2/HO-1 Pathway.

Extreme ethanol ingestion is associated with developing gastric ulcers. Achillea millefolium (yarrow) is one of the most commonly used herbs with numerous proven pharmacological actions. The goal of the hereby investigation is to explore the gastroprotective action of yarrow essential oil against ethanol-induced gastric ulcers and to reveal the unexplored mechanisms. Rats were distributed into five groups (n = 6); the control group administered 10% Tween 20, orally, for two weeks; the ethanol group administered absolute ethanol (5 mL/kg) to prompt gastric ulcer on the last day of the experiment. Yarrow essential oil 100 or 200 mg/kg + ethanol groups pretreated with yarrow oil (100 or 200 mg/kg, respectively), orally, for two weeks prior to gastric ulcer induction by absolute ethanol. Lanso + ethanol group administered 20 mg/kg lansoprazole, orally, for two weeks prior to gastric ulcer induction by ethanol. Results of the current study showed that ethanol caused several macroscopic and microscopic alterations, amplified lipid peroxidation, pro-inflammatory cytokines, and apoptotic markers, as well as diminished PGE2, NO, and antioxidant enzyme activities. On the other hand, animals pretreated with yarrow essential oil exhibited fewer macroscopic and microscopic modifications, reduced ulcer surface, and increased Alcian blue binding capacity, pH, and pepsin activity. In addition, yarrow essential oil groups exhibited reduced pro-inflammatory cytokines, apoptotic markers, and MDA, restored the PGE2 and NO levels, and recovered the antioxidant enzyme activities. Ethanol escalated Nrf2 and HO-1 expressions, whereas pretreatment of yarrow essential oil caused further intensification in Nrf2 and HO-1. To conclude, the current study suggested yarrow essential oil as a gastroprotective agent against ethanol-induced gastric lesions. This gastroprotective effect could be related to the antioxidant, anti-inflammatory, and anti-apoptotic actions of the essential oil through the instigation of the Nrf2/HO-1 pathway.

Pharmacodynamic Stance of Phytoconstituents as a Gastric Ulcer Protective Mechanism: An Overview.

Various traditional herbal plants have been associated with unique pharmacological actions. Natural parts as well as processed plant parts are known to possess gastro-protective and gastro- mucosal healing property. Motive of this review analysis is to explain the gastro-protective and gastro-mucosal healing property of different herbal plants and their constituents indigenous to various regions of the globe and elucidate mechanisms of the healing by their metabolic extracts. Moreover, an attempt shall be made to explicate the possible molecular pharmacological targets responsible for healing gastric ulcer activity. A thorough survey of literature has been carried out from various scientific resources and using keywords like peptic ulcer mechanism, gastro-protective agents, gastro-mucosal healing property, natural and processed herbal drugs preventing peptic ulcers. This article will present a running commentary on the prospects and potential of herbal plants exhibiting gastroprotective activity and gastro-mucosal healing property.

Mechanisms of Dendrobium officinale polysaccharides in repairing gastric mucosal injuries based on mitogen-activated protein kinases (MAPK) signaling pathway.

The present study aimed to investigate the protective effects and molecular mechanisms of Dendrobium officinale polysaccharides on gastric mucosal injuries. Following one week of continuous intragastric administration, a gastric mucosal injury model was established using intragastric administration of anhydrous ethanol. The area of gastric ulcer was measured, the contents of interleukin- 6 (IL-6), epidermal growth factor receptor (EGFR), and thyroid transcription factor 1 (TFF-1) in serum were detected by enzyme linked immunosorbent assay (ELISA), and the expressions of EGFR, TFF-1, IL-6, Raf-2, MAP kinase kinase 1 (MEK1), MEK2, and ERK1 in the gastric tissue were determined utilizing qPCR, Western blotting and immunohistochemistry. Simultaneously, Dendrobium officinale polysaccharides and anhydrous ethanol were added to the gastric mucosal cells (GES1) cultured in vitro, and the protective effects of Dendrobium officinale polysaccharides on cell viability was detected using Cell Counting Kit (CCK)-8. The addition of Dendrobium officinale polysaccharides markedly improved the gastric epithelial defect, inflammatory cell infiltration, and redness and swelling stemmed from gastric mucosal injuries and greatly reduced the area of gastric ulcer. The inhibition rates of gastric ulcer were 48.12 ± 2.98, 42.95 ± 1.52, and 27.96 ± 2.05% in the high, medium, and low concentration Dendrobium officinale polysaccharide groups, respectively. Dendrobium officinale polysaccharides could increase the expressions of EGFR and TFF-1 and decrease the expressions of IL-6, Raf-2, MEK1, MEK2, and ERK1. Dendrobium officinale polysaccharides could reduce the level of inflammatory factors and protect gastric mucosa by inhibiting the expression of MAPK pathway genes and proteins.

Gastroprotective effects of extract of Jasminum grandiflorum L. flower in HCl/EtOH-induced gastric mucosal ulceration mice.

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.

Protective effect of standardised fruit extract of Garcinia cowa Roxb. ex Choisy against ethanol induced gastric mucosal lesions in Wistar rats.

BACKGROUND AND AIM: The fruit of Garcinia is a rich and valuable source of bioactive compounds and is traditionally used for treating wounds and ulcers. The present study was carried out to investigate the protective effect of chromatographically standardized fruit extract of Garcinia cowa (GCE) on ethanol-induced gastric lesions in rats and its possible mechanisms. METHODS: The effect of GCE (200 and 400 mg/kg body weight) was evaluated by determining various gastric ulcer parameters like gastric wall mucus, non-protein sulfhydryls (NP-SH) content, microvascular permeability, endogenous antioxidant enzyme, and gastric histopathological study. RESULTS AND CONCLUSIONS: Oral administration of GCE at doses of 200 and 400 mg/kg exhibited significant (p < .01) dose-dependent inhibition of ulcer index by 18.94-44.02%, respectively. Pre-treatment of rats with GCE (400 mg/kg) significantly restored the depleted gastric wall mucus level by 34.09% and NP-SH content by 33.35% induced by ethanol administration. In addition, GCE (400 mg/kg) showed a significant decrease in microvascular permeability of Evans Blue by 47.43%, rationalizing its protective effect. Furthermore, a significant increase in oxidative enzyme levels with reduction in malondialdehyde level and elevation of superoxide dismutase (SOD) activity was observed in the GCE treated group as compared to the ulcer control group. The histopathological assessment also confirmed the protective nature of GCE. HPTLC analysis showed the presence of 0.27%, 0.11% w/w gallic acid, and amentoflavone, respectively in GCE. The content of α-mangostin and xanthochymol in the G. cowa extract sample quantified by HPLC-PDA method was 0.72 and 8.46%, respectively. The results obtained indicate that the protective effect of GCE against gastric ulcers in rats through multiple actions confirmed by the reduction of oxidative stress and restoration of adhered gastric mucus, NP-SH content, and histological architecture.KEY MESSAGESEthanol is the most typical ulcerogenic agent and has been shown to extend the risk of ulcer in humans.Natural products are promising alternative medication for the development of new drugs to regulate gastrointestinal diseases.Garcinia cowa protects the gastric mucosa through multiple actions that include restoration of adhered gastric mucus and inhibition of lipid peroxidation.

Effects of ethanolic extracts of Quercus, Cirsium vulgare, and Falcaria vulgaris on gastric ulcer, antioxidant and inflammatory indices, and gene expression in rats.

INTRODUCTION: Gastric ulcer is a multifaceted process and is usually caused by mucosal damage. Herbal medicines have received much attention considering the side effects of chemical drugs. Nowadays, the use of herbal medicines has received much attention considering the side effects of chemical drugs. Quercus brantii Lindl, Cirsium vulgare (Savi) Ten, and Falcaria vulgaris Bernh are plants used as traditional phytomedicine for gastric ulcer diseases. AIM OF THE STUDY: This study was aimed to investigate the protective effects of hydroalcoholic extracts of these herbs on ethanol-induced gastric ulceration, in addition, to investigate the antioxidant, anti-inflammatory, and gene expression. MATERIALS AND METHODS: Thirty Sprague Dawley rats, (200-250 g), were divided into six groups: Control: intact animals; sham: gavaged with distilled water (14 days); negative control: gavaged with 20 mg/kg of omeprazole (14 days); experimental groups I, II, and III: gavaged with 500 mg/kg of the extract of Falcaria vulgaris, Quercus brantii, and Cirsium vulgare, respectively, (14 days). The number of ulcers and pathological parameters were assessed. The serum superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, total antioxidant capacity, albumin, total protein, haptoglobin, alpha-1-acid glycoprotein, total globulin, alpha-2-macroglobulin, C-fos, C-myc, and Caspase-9 were measured by ELISA and RT-PCR. RESULTS: The extracts significantly reduced gastric ulcer (52.33%). The results showed that the Quercus brantii extract was more effective. There were significant differences between the serum levels of alpha-1-acid glycoprotein and those of alpha-2-macroglobulin. Also, there was a significant difference in the serum level of antioxidant parameters. Changes in the expression of the genes also confirmed the results suggested by other parameters. The expression levels of C-fos, C-myc, and caspase-9 were decreased, but the Bcl-2 expression increased. CONCLUSION: The hydro-alcoholic extracts revealed various protection and noticeable change in the expression of caspase-9, C-myc, C-fos, and Bcl-2 genes in rats.

Gastroprotective Activities of Ethanol Extract of Black Rice Bran (Oryza sativa L.) in Rats.

Black rice is a type of rice in the Oryza sativa L. species. There are numerous reports regarding the pharmacological actions of black rice bran, but scientific evidence on its gastroprotection is limited. This study aimed to evaluate the gastroprotective activities of black rice bran ethanol extract (BRB) from the Thai black rice variety Hom Nil (O. sativa L. indica) as well as its mechanisms of action, acute oral toxicity in rats, and phytochemical screening. Rat models of gastric ulcers induced by acidified ethanol, indomethacin, and restraint water immersion stress were used. After pretreatment with 200, 400, and 800 mg/kg of BRB in test groups, BRB at 800 mg/kg significantly inhibited the formation of gastric ulcers in all gastric ulcer models, and this inhibition seemed to be dose dependent in an indomethacin-induced gastric ulcer model. BRB could not normalize the amount of gastric wall mucus, reduce gastric volume and total acidity, or increase gastric pH. Although BRB could not increase NO levels in gastric tissue, the tissue MDA levels could be normalized with DPPH radical scavenging activity. These results confirm the gastroprotective activities of BRB with a possible mechanism of action via antioxidant activity. The major phytochemical components of BRB comprise carotenoid derivatives with the presence of phenolic compounds. These components may be responsible for the gastroprotective activities of BRB. The 2000 mg/kg dose of oral BRB showed no acute toxicity in rats and confirmed, in part, the safe uses of BRB.

A research on the mechanism of NSAID-related gastric ulcer treated by jia wei wu qi san based on the p38mapk signal pathway.

This study aims to explore the mechanism of NSAID-related gastric ulcer treated by JIA WEI WU QI SAN. Clean-grade SD rats were randomly divided into four groups. Group A was assigned as the control group. Groups B, C and D were intragastrically administered with 2.5mg/kg of indomethacin solution QD after 48 hours. After 15 days of treatment, group B was administered with 0.9% sodium chloride, group C was given rabeprazole (2mg/kg), and group D was administered with JIA WEI WU QI SAN (2g/kg). Abdominal aorta sampling was performed, and gastric tissues were isolated on the 29th day. The protein expression of p-P38MAPK and COX-2 were detected by western blot, while the concentration of PGE2 and IL-1 were determined by ELISA. (1) The expression of IL-1ingroup B dramatically declined in group D (P<0.01). (2)The expression of PGE-2dramatically increased in group D(P<0.01). (3) The expression of COX-2 increased in group D (P<0.05). (4) The expression of p-P38MAPK decreased in group D (P<0.05). JIA WEI WU QI SAN has multiple functions, including the activation of the p-P38MAPK signaling pathway, which promote the activation of COX-2, induce the arachidonic acid to increase the level of PG, and decrease the concentration of IL-1, thereby inducing an inflammatory reaction, and promote gastric mucosa repair.

Gastroprotective Effect of Ethanol Extracts from Bark of Magnolia officinalis on Ethanol-Induced Gastric Mucosal Damage in Rats.

Background. Magnolia officinalis Rehd. and Wils. is widely used in Asian countries because of its multiple pharmacological effects. This study investigated the gastroprotective effect and mechanisms of the ethanol extracts from the bark of Magnolia officinalis (MOE) against ethanol-induced gastric mucosal damage in rats. Methods. MOE was prepared by reflux extraction with 70% ethanol, and its main compounds were analyzed by UPLC-Q-Exactive Orbitrap-MS. DPPH, ABTS, and FRAP methods were used to evaluate the antioxidant capacity of MOE in vitro. The gastroprotective effects of MOE were evaluated by the area of gastric injury, H&E (hematoxylin-eosin), and PAS (periodic acid-Schiff). The mechanism was explored by measuring the levels of cytokines and protein in the NF-κB signaling pathway. Results. 30 compounds were identified from MOE, mainly including lignans and alkaloids. MOE presented a high antioxidant activity in several oxidant in vitro systems. Gastric ulcer index and histological examination showed that MOE reduced ethanol-induced gastric mucosal injury in a dose-dependent manner. MOE pretreatment significantly restored the depleted activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) enzymes, reduced malondialdehyde (MDA), and prostaglandin E2 (PGE2) levels in the gastric tissue in rats. In addition, MOE also inhibited the activation of nuclear factor kappa B (NF-κB) pathway and decreased the production of proinflammatory cytokines. Conclusions. The gastroprotective effect of MOE was attributed to the inhibition of oxidative stress and the NF-κB inflammatory pathway. The results provided substantial evidence that MOE could be a promising phytomedicine for gastric ulcer prevention.

Edible and highly biocompatible nanodots from natural plants for the treatment of stress gastric ulcers.

The incidence rate of stress ulcers has increased in recent years, with an increase in life pressure, unavoidable trauma and other factors. The therapy of acute stress ulcers has always been an important challenge. Carbon dots (CDs) have been reported to show excellent biological activities, but research on the stress ulcer curative effect of CDs is unprecedented. Here, we prepared a series of semi-carbonized nanodots (SCNDs) from natural plants or herbs as precursors and the as prepared SCNDs were later proved to be effective in the treatment and inhibition of stress gastric ulcers in a rat model. One kind of SCND from edible and medicinal plants, charred Atractylodes macrocephala (SCNDs-1), is demonstrated in detail for its strong anti-stress gastric ulcer effect with inhibition up to 90% and shows extremely high biocompatibility and ultra-low toxicity. These SCNDs lead to the reduction of inflammatory factors and oxidative stress, and the protection of the gastric mucosa. The SCNDs also reduce the excessive neuroendocrine response caused by stress, regulate the energy metabolism and the structure of intestinal flora, improve the damage to the body caused by the stress state, thus alleviating the occurrence of stress-induced gastric ulcers. This work provides new insights into the preparation of carbon nanomaterials from natural plants through a semi-carbonization process and opens new ways to apply bio-active and bio-safe SCNDs in the modern pharmaceutical field.

Tablet of Spondias mombin L. Developed from Nebulized Extract Prevents Gastric Ulcers in Mice via Cytoprotective and Antisecretory Effects.

Spondias mombin L. (Anacardiaceae) has a worldwide distribution and is present in all regions of Brazil. Its leaves, flowers and bark are used as teas in folk medicine to treat diseases of the digestive system. This study aimed to evaluate the acute non-clinical toxicity, gastroprotective activity, and the related mechanisms of action of nebulized extract and tablets based on dried Spondias mombin (SmNE). SmNE screening showed the presence of flavonoids (0.65%), polyphenols (25.50%), where the major compound is gallic acid. In the acute oral toxicity assay, a dose of 2000 mg/kg of SmNE administered orally in Swiss mice did not induce any behavioral changes. SmNE (250 or 500 mg/kg p.o) significantly reduced the ulcerative lesion area when compared to the control group in ethanol and non-steroidal anti-inflammatory drug (NSAIDs) models. Results showed that treatment with SmNE (250 mg/kg) reduced acid secretion and gastric content, accompanied with an increase in pH. Previous administration of indomethacin and glibenclamide reversed the protection provided by SmNE, confirming the participation of prostaglandins (PGs) and ATP-sensitive potassium channels (KATP) in its gastroprotective effect. The SmNE tablets met the pharmacopeial quality requirements with gastroprotective activity and similar protection in comparison to the isolated extract administrated. In conclusion, SmNe has a gastroprotective activity related to cytoprotective mechanisms, such as the participation of endogenous prostaglandins and KATP channels, having an anti-secretory effect with systemic action. The formulation obtained presented gastroprotective effects similar to the administration of the extract, the tablets showed favorable compression characteristics by the direct route and met the pharmacopeial quality requirements.

Taxifolin and gastro-adhesive microparticles containing taxifolin promotes gastric healing in vivo, inhibits Helicobacter pylori in vitro and proton pump reversibly in silico.

Taxifolin (3,5,7,3,4-pentahydroxy flavanone or dihydroquercetin, Tax) was identified as a gastroprotective compound and a gastroadhesive formulation was recently developed to prolong its residence time and release in the stomach. So, the gastric healing effectiveness of Tax and gastro-mucoadhesive microparticles containing Tax (MPTax) against the acetic acid induced-gastric ulcer in rats was investigated in this study. Moreover, the interactions between Tax and H+/K+-ATPase were investigated in silico, and its anti- H. pylori activity was determined in vitro. The oral treatment with MPTax (81.37 mg/kg, containing 12.29% of Tax) twice a day for seven days reduced the ulcer area by 63%, compared to vehicle-treated group (Veh: 91.9 ± 10.3 mm2). Tax (10 mg/kg, p.o) reduced the ulcer by 40% but with a p = 0.07 versus Veh group. Histological analysis confirmed these effects. Tax and MPTax increased the gastric mucin amount, reduced the myeloperoxidase activity, and increased the glutathione reduced content at ulcer site. However, only MPTax decreased the lipoperoxide accumulation at ulcer site. Besides, Tax and MPTax normalize the catalase and glutathione S-transferase activity. Tax showed reversible interaction with H+/K+-ATPase in silico and its anti-H. pylori effects was confirmed (MIC = 625 µg/mL). These results suggest that the antiulcer property of Tax involves the strengthening of the gastric protective factors in parallel to its inhibitory interaction with H+/K+-ATPase and H. pylori. Considering that ulcer healing action displayed by Tax was favored by gastroadhesive microparticles, this approach seems to be promising for its oral delivery to treat acid-peptic diseases.

Protective effects of polysaccharides from Panax ginseng on acute gastric ulcers induced by ethanol in rats.

Panax ginseng is a traditional medicine used in China to treat many diseases. Polysaccharides are primary active components and have many pharmacological effects. Gastric ulcer is a serious gastrointestinal disease. However, whether polysaccharides influence gastric ulcers is unclear. In this study, the effective gastroprotective impacts and potential mechanisms of Panax ginseng polysaccharides (GPS) on gastric damage induced by ethanol in rats were investigated by macroscopically evaluating gastric mucosal injuries (improved ulcer index (UI)), histopathological staining (H&E and PAS), increased NO and PGE2 levels, and suppression of oxidative stress (increased superoxide dismutase (SOD) and catalase (CAT) and decreased malondialdehyde (MDA)) and inflammation (reduced tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), and myeloperoxidase (MPO)). Pretreatment with GPS ameliorated the expression of I-κB/NF-κB and JAK/STAT proteins in the rat stomach exposed to ethanol. The results indicated that GPS prevent ethanol-induced gastric injuries in rats by predominantly suppressing gastric inflammation and oxidative stress through NF-κB and STAT inhibition.