Ethanol-induced Gastric Injury Research Articles

Targeted quercetin delivery nanoplatform via folic acid-functionalized metal-organic framework for alleviating ethanol-induced gastric ulcer

Gastric ulcers, often caused by factors such as ethanol consumption and Helicobacter pylori infection, present significant treatment challenges due to the limited efficacy and adverse effects of current therapies. This study aimed to develop a nanoscale quercetin (Qu) delivery system using folic acid (FA)-functionalized cyclodextrin-based metal–organic frameworks (CD-MOFs), termed Qu@FA-CMOF nanoplatforms, to enhance therapeutic outcomes for acute gastric ulcers. The FA modification endowed the nanoplatforms with targeted delivery capabilities, improving cellular uptake and facilitating the sustained release of Qu. Comprehensive in vitro and in vivo evaluations demonstrated that Qu@FA-CMOF significantly attenuated gastric tissue injury, reduced oxidative stress, and suppressed inflammation by modulating the Nrf2/HO-1 and COX-2/NF-κB signaling pathways. Furthermore, the nanoplatform exhibited potent anti-apoptotic effects through regulation of the Bax/Bcl-2 pathway, and showed favorable biocompatibility with no significant toxicity observed in major organs. These findings highlight the potential of Qu@FA-CMOF nanoplatforms as a safe and effective therapeutic strategy for ethanol-induced gastric injury, offering a promising avenue for future nanomedicine-based therapies in gastric ulcer treatment.

Potential mechanism of sea cucumber gut peptides in protecting ethanol-induced gastric mucosal injury

Alcoholic gastric injury is a prevalent condition that can result in gastric ulcers. This research delves into the protective effects of sea cucumber gut peptides, Val-Thr-Pro-Tyr (VTPY) and Val-Leu-Leu-Tyr (VLLY), on ethanol-induced gastric injury. These peptides significantly alleviate the pathological symptoms of gastric tissue affected by ethanol, reducing ulcer area and index, epithelial cell loss, submucosal edema, and inflammatory infiltration. High doses of VTPY and VLLY resulted in a significant decrease in ulcer index, with reductions from 5.38 to 2.63 and 1.13, respectively (P < 0.05). Moreover, the levels of P–NF-κB/p65 expression decreased by 33.47% and 54.27%, while myeloperoxidase (MPO) activity decreased by 42.98% and 55.33%, respectively. These treatments also effectively suppressed inflammatory cytokine expression and inhibited macrophage infiltration, ultimately alleviating the inflammatory response in gastric mucosal tissue. They also enhance mitochondrial function by regulating factors associated with mitochondrial dynamics and increasing succinate dehydrogenase (SDH) activity. Furthermore, they alleviate endoplasmic reticulum stress by reducing the immunoglobulin heavy chain-binding protein (Bip), phosphorylated eukaryotic translation initiation factor 2 alpha (P-eIF2α), and activating transcription factor 4 (ATF4) expression levels. Ultimately, high doses of VTPY and VLLY increased the B-cell lymphoma-extra large to B-cell lymphoma-2 associated death promoter ratio (Bcl-XL/Bad ratio) by 138.68% and 247.99%, respectively, while the expression level of cleaved-caspase 3 decreased by 35.26% and 48.22%, thereby preventing the activation of the apoptotic pathway. Sea cucumber gut peptides VTPY and VLLY exhibit effective anti-inflammatory and anti-apoptotic properties, along with anti-endoplasmic reticulum stress effects, by inhibiting the ATF4/Bcl-2 signaling pathway, thus effectively shielding against ethanol-induced gastric damage. VLLY appears to be more potent in this aspect.

Gastroprotective effect of vanillic acid against ethanol-induced gastric injury in rats: involvement of the NF-κB signalling and anti-apoptosis role.

Vanillic acid (VA; 4-hydroxy-3-methoxybenzoic acid) is a flavouring agent found in various natural sources such as olives, fruits, and green tea. While VA exhibits numerous pharmacological effects, its potential protective effects against gastric injury warrants further investigation. Therefore, the primary objective of this study is to elucidate investigate the gastroprotective properties of VA against ethanol-induced gastric injury. Rats were orally administered either saline or VA at different doses (50, 100, and 200mg/kg/day), with omeprazole (20mg/kg) serving as a positive control, for fourteen consecutive days before ethanol administration. Blood and gastric tissue samples were collected one hour after ethanol administration for biochemical, molecular, and histological analyses. Pre-treatment with VA before ulcer induction alleviated both macroscopic and microscopic damage. It also increased antioxidant glutathione levels and decreased malondialdehyde and myeloperoxidase activity, along with reducing inflammatory markers such as tumour necrosis factor (TNF)-α, interleukin (IL)-6, and nuclear factor kappa B (NF-κB). Additionally, VA pre-treatment reversed the elevation of Bax mRNA expression and gastric caspase-3 levels induced by gastric damage. It also mitigated the reduction in Bcl-2 mRNA expression. These findings suggest that VA exerts protective effects against ethanol-induced gastric injury in rats. It achieves this by augmenting gastric antioxidant capacity and mitigating oxidative, inflammatory, and apoptotic damage.

The gastroprotective effect of Yucca filamentosa standardized crude leaves extract versus its nano-cubosomal formulation in ethanol-induced gastric injury

Yucca filamentosa (YF) is widely used in folk medicine for its anti-inflammatory effects. Our study aimed to evaluate the chemical profile of YF extracts. Additionally, the gastroprotective efficacy of its crude leaf extract and nano-cubosomal formulation was assessed in a rat model of ethanol-induced gastric injury by altering the HMGB-1/RAGE/TLR4/NF-κB pathway.The phytochemical composition of YF was investigated using FTIR spectroscopy and LC-MS/MS techniques. Standardization was further accomplished using HPLC. Rats were treated orally with yucca crude extract or its nano-cubosomal formulation at doses of 25, 50, and 100 mg/kg. Famotidine (50 mg/kg, IP) was used as a reference drug. After 1 h, rats were administered ethanol (1 ml, 95 %, orally). One hour later, the rats were sacrificed, and the serum was separated to determine TNF-α and IL-6 levels. Stomachs were excised for the calculation of the ulcer index and histopathological examinations. Stomach tissue homogenate was used to determine MDA and catalase levels. Additionally, the expression levels of HMGB-1/RAGE/TLR4/NF-κB were assessed.Phytochemical analysis confirmed the predominance of steroidal saponins, sucrose, organic and phenolic acids, and kaempferol. The nano-cubosomal formulation demonstrated enhanced gastroprotective, anti-oxidant, and anti-inflammatory efficacy compared to the crude extract at all tested doses. The most prominent effect was observed in rats pretreated with the YF nano-cubosomal formulation at a dose of 100 mg/kg, which was similar to normal control and famotidine-treated rats.Our results highlighted the enhanced gastroprotective impact of the yucca nano-cubosomal formulation in a dose-dependent manner. This suggests its potential use in preventing peptic ulcer recurrence.

Protection effect of Dioscoreae Rhizoma against ethanol-induced gastric injury in vitro and in vivo: A phytochemical and pharmacological study

Ethnopharmacological relevanceDioscoreae Rhizoma, a kind of Chinese yam, is a medicinal and edible plant used in China for strengthening the spleen and stomach. However, there is a lack of modern pharmacology studies regarding its anti-gastric injury activity. Aim of the studyThis study aimed to investigate the phytochemical composition of Chinese yam aqueous extract (CYW) and evaluate its gastroprotective effects against ethanol-induced gastric injury in vitro and in vivo. Materials and methodsThe active components of CYW were identified using HPLC-QTOF-MS/MS in combination with the GNPS molecular networking and network pharmacology. In vitro studies were performed in the RAW264.7/GES-1 cell coculture system. In vivo study, mice were treated with CYW (0.31, 0.63, and 3.14 g/kg BW, orally) for 14 days, followed by a single oral dose of ethanol (10 mL/kg BW) to induce gastric injury. The biochemical, inflammation and oxidative stress markers were analyzed using commercial kits. Histopathology was used to assess the degree of gastric injury. Gene and protein expressions were studied using RT-qPCR and western blotting, respectively. ResultsCYW significantly restored the levels of SOD, GPx and CAT, and reduced the MDA content. Further analyses showed that CYW significantly alleviated the gastric oxidative stress by inhibiting the inflammation via decreasing p-NF-κB and p-IκB-α expression levels and inhibiting the generation of IL-6, TNF-α, and IL-1β. At the same time, the fraction remarkably upregulated Bcl-2, downregulated Bax and increased growth factor secretion, thereby prevented gastric mucous cell. Besides, The combination of HPLC-QTOF-MS/MS, GNPS molecular networking analysis, and network pharmacology demonstrated that linoleic acid, 3-acetyl-11-keto-beta-boswellic acid, adenosine, aminocaproic acid, tyramine, DL-tryptophan, cycloleucine, lactulose, melibiose, alpha-beta-trehalose, and sucrose would be the main active compounds of CYW against ethanol-induced gastric injury. ConclusionThis study showed that CYW is potentially rich source of anti-oxidant and anti-inflammatory bioactive compounds. It showed efficacy against ethanol-induced gastric injury by inhibiting inflammation, oxidative stress, and apoptosis in the stomach. The results of the current work indicate that Dioscoreae Rhizoma could be utilized as a type of natural resource for production of new medicine and functional foods to prevent and/or ameliorate ethanol-induced gastric injury.

The protective effects and potential mechanisms of fulvic acid against ethanol-induced gastric mucosal injury in mice

Fulvic acid (FA) is a kind of natural organic acids extracted from lignite, which is the active ingredient in Wujin oral liquid, a proprietary Chinese medicine used to treat gastric and duodenal ulcers. However, our understanding of the mechanisms of FA remains limited. Currently, the protection of FA and its mechanism were explored using the ethanol-induced gastric mucosal injury mouse model. The histopathological examinations showed FAs at three doses effectively reduced gastric congestion, oedema caused by ethanol, and prevented gastric epithelial cell fall-off. When compared to the model group, FAs reduced IL-1β and IL-6 levels in serum, as well as IL-1β, IL-6, TNF-α, and COX-2 expression levels in tissue. Furthermore, FAs significantly inhibited p65, P38 MAPK, and Erk1/2 phosphorylation in damaged gastric tissue. It was indicated FA has good protection against ethanol-induced gastric mucosa injuries in mice and this effect was related to NF-κB and MAPK signalling pathways.

Aibika Flower Flavonoid Extract Exhibits Antiulcer Activity in a Murine Model of Ethanol-Induced Acute Gastric Injury.

Aibika (Abelmoschus manihot (L.) Medic) is a garden vegetable whose flower has been shown to have various bioactivities. This study investigated the protective effect of aibika flower flavonoid extract (AFF) on ethanol-induced gastric injury in mice. The experimental results showed that pre-feeding 125 and 250 mg AFF/kg BW for 1 week significantly reduced the gastric injury area in the negative control group from 19.2% to 6.7% and 0.6%, respectively. The results of the pathological sections staining also showed that AFF had a protective ability against alcohol-induced injury of gastric tissue and liver tissue. When the mice were exposed to high concentrations of ethanol, AFF pretreatment significantly upregulated the expression of antioxidant enzymes. The pretreatment also promoted the production of the intracellular antioxidant, reduced glutathione, in both gastric tissue and serum. On the contrary, AFF delayed the lipid peroxidation process, which, in turn, reduced the damage to the gastric mucosa. When acute inflammation was induced by ethanol stimulation, AFF significantly downregulated the proinflammatory cytokines and mediators such as TNF-α, IL-1β, IL-6, NF-κB, COX-2, and iNOS. Furthermore, AFF pretreatment greatly promoted the production of healing factors, such as matrix metalloproteinase (MMP)-2, MMP-7, and MMP-9, in the gastric tissue. In addition, AFF significantly reduced gastric cell apoptosis induced by ethanol stimulation. These results demonstrate that AFF has a good protective effect on alcohol-induced gastric ulcer and has the potential to be used in gastrointestinal health care.

Albizzia chinensis (Osbeck) Merr extract YS ameliorates ethanol-induced acute gastric ulcer injury in rats by regulating NRF2 signaling pathway.

Around the world, there is a high incidence of gastric ulcers. YS, an extract from the Chinese herb Albizzia chinensis (Osbeck) Merr, has potential therapeutic applications for gastrointestinal diseases. Here we elucidated the protective effect and underlying mechanism of action of YS on gastric ulcer in rats injured by ethanol. The ethanol-induced gastric ulcer rat model was used to assess the protective effect of YS. A pathological examination of gastric tissue was performed by H&E staining. GES-1 cells damaged by hydrogen peroxide were used to simulate oxidative damage in gastric mucosal epithelial cells. Endogenous NRF2 was knocked down using small interfering RNA. Immunoprecipitation was used to detect ubiquitination of NRF2. Co-immunoprecipitation was used to detect the NRF2-Keap1 interaction. YS (10 and 30 mg/kg, i.g.) significantly reduced the ulcer index, decreased MDA level, and increased SOD and GSH levels in gastric tissues damaged by ethanol. YS promoted NRF2 translocation from cytoplasm to nucleus and enhanced the NQO1 and HO-1 expression levels in injured rat gastric tissue. In addition, YS regulated NQO1 and HO-1 via NRF2 in H2O2-induced oxidative injured GES-1 cells. Further studies on the underlying mechanism indicated that YS reduced the interaction between NRF2 and Keap1 and decreased ubiquitylation of NRF2, thereby increasing its stability and expression of downstream factors. NRF2 knockdown abolished the effect of YS on MDA and SOD in GES-1 cells treated with H2O2. YS reduced the NRF2-Keap1 interaction, promoting NRF2 translocation into the nucleus, which increasing the transcription and translation of NQO1 and HO-1 and improved the antioxidant capacity of rat stomach.

Construction of diallyltrisulfide nanoparticles for alleviation of ethanol-induced acute gastric injury

Gastric ulcer, a significant health issue characterized by the degradation of the gastric mucosa, often arises from excessive gastric acid secretion and poses a challenge in current medical treatments due to the limited efficacy and side effects of first-line drugs. Addressing this, our study develops a novel therapeutic strategy leveraging gas therapy, specifically targeting the release of hydrogen sulfide (H2S) in the treatment of gastric ulcers. We successfully developed a composite nanoparticle, named BSA·SH-DATS, through a two-step process. Initially, bovine serum albumin (BSA) was sulfhydrated to generate BSA·SH nanoparticles via a mercaptosylation method. Subsequently, these nanoparticles were further functionalized by incorporating diallyltrisulfide (DATS) through a precise Michael addition reaction. This sequential modification resulted in the creation of BSA·SH-DATS nanoparticles. Our comprehensive in vitro and in vivo investigations demonstrate that these nanoparticles possess an exceptional ability for site-specific action on gastric mucosal cells under the controlled release of H2S in response to endogenous glutathione (GSH), markedly diminishing the production of pro-inflammatory cytokines, thereby alleviating inflammation and apoptosis. Moreover, the BSA·SH-DATS nanoparticles effectively regulate critical inflammatory proteins, including NF-κB and Caspase-3. Our study underscores their potential as a transformative approach for gastric ulcer treatment.

Protective effect of Enterococcus faecium against ethanol-induced gastric injury via extracellular vesicles.

Recently, Enterococcus has been shown to have gastric protective functions, and the mechanisms by which Enterococcus modulates gastric function are still being investigated. Herein, we investigated how Enterococcus faecium (Efm) and E. faecium-derived extracellular vesicles (EVs) (EfmEVs) exert protective effect against ethanol-induced gastric injury by investigating the effect of EfmEVs on gastric mucosal ulcer scoring, histological lesion, mucosal glycoprotein production, acidity, anti-oxidative function, and inflammatory responses in rat. Pretreatment with Efm showed significant reduction of ethanol-induced gastric injury, as evidenced by the lowering of ulcer index, histological lesion, gastric pH, and inflammatory responses and the enhancement of mucosal glycoprotein production and anti-oxidative function. Further functional studies on three bioactive components [inactivated Efm, EfmEVs (EVs), and EV-free supernatants] of the bacterial culture showed that EVs are mostly responsible for the gastroprotective effect. Moreover, EV secretion is beneficial for the gastroprotective effect of Efm. Hence, EVs mediated the protective effect of Efm against ethanol-induced gastric injury by lowering inflammatory responses and enhancing anti-oxidative function and may be a potent anti-inflammatory and anti-oxidative strategy to alleviate hyperinflammatory gastrointestinal tract conditions.IMPORTANCEThis study indicated that Enterococcus faecium provided a protective effect against rat gastric injury, which involved improvement of the mucosal glycoprotein production, anti-oxidative function, and inflammatory responses. Furthermore, we confirmed that three bioactive components (inactivated Efm, extracellular vesicles, and EV-free supernatants) of E. faecium culture also contributed to the gastroprotective effect. Importantly, E. faecium-derived EVs showed an effective impact for the gastroprotective effect.

Construction of Magnolol Nanoparticles for Alleviation of Ethanol-Induced Acute Gastric Injury.

Ethanol (EtOH) has been identified as a potential pathogenic factor in gastric ulcer development primarily due to its association with gastric injury and excessive production of reactive oxygen species. Magnolol (Mag), the principal active compound in Magnolia officinalis extract, is well studied for its notable anti-inflammatory and antioxidant properties. However, its limited solubility, propensity for agglomeration, and low absorption and utilization rates significantly restrict its therapeutic use. This study aims to overcome these challenges by developing a Mag nanoparticle system targeting the treatment and prevention of EtOH-induced gastric ulcers in mice. Utilizing a click chemistry approach, we successfully synthesized this system by reacting thiolated bovine serum albumin (BSA·SH) with Mag. The in vitro analysis revealed effective uptake of the BSA·SH-Mag nanoparticle system by human gastric epithelial cells (GES-1), showcasing its antioxidant and anti-inflammatory capabilities. Additionally, BSA·SH-Mag exhibited gradual disintegration and release in simulated gastric fluid, resulting in a notable reduction of oxidative stress in gastric tissues and mucosal tissue repair and effectively reducing inflammatory expression. Furthermore, BSA·SH-Mag attenuated EtOH-induced gastric inflammation by decreasing the level of NOX4 protein expression and augmenting the level of Nrf2 protein expression. In conclusion, our findings indicate that BSA·SH-Mag represents a promising candidate as an oral therapeutic for gastric ulcer treatment.

Fish oil ameliorates ethanol-induced gastric injury in rat by modulating gene related to apoptosis

Gastric ulcers are a type of digestive disease that can severely affect a person's quality of life. Our study aimed to investigate the effects of fish oil on ethanol-induced gastric ulcers in rats, with the purpose of providing more comprehensive information on the topic. The study looked at various factors such as gastric ulcer index, and nitric oxide (NO) levels in stomach tissue. To investigate apoptosis, the mRNA levels of Bax, Bcl-2, and Caspase 3 were analyzed. The results showed that fish oil can reduce gastric acidity and the gastric ulcer index in cases of ethanol-induced gastric ulcers. It was found that fish oil can increase NO levels and improve the anti-apoptotic system by increasing the expression of Bcl-2 while decreasing the expression of Bax and Caspase 3. In general, the study demonstrates that fish oil can protect the stomach from ethanol-induced damage by reducing the apoptosis pathway via nitric oxide.

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.

Hinokitiol protects gastric injury from ethanol exposure via its iron sequestration capacity

Hinokitiol is a natural bioactive tropolone derivative isolated from Chamaecyparis obtusa and Thuja plicata, which exhibits promising potential in terms of antioxidant and anti-inflammatory properties and possesses potent iron-binding capacity. In this study, we aimed to investigate the potential role of hinokitiol in protecting against ethanol-induced gastric injury and elucidate the underlying mechanism. Our results demonstrated that hinokitiol effectively attenuated hemorrhagic gastric lesions, epithelial cell loss, and inflammatory response in mice with ethanol-induced gastric injury. Intriguingly, we found that ethanol exposure affects iron levels both in vivo and in vitro. Moreover, the disturbed iron homeostasis was involved in the development of ethanol-induced injury. Iron depletion was found to enhance defense against ethanol-induced damage, while iron repletion showed the opposite effect. To further explore the role of iron sequestration in the protective effects of hinokitiol, we synthesized methylhinokitiol, a compound that shields the iron binding capacity of hinokitiol with a methyl group. Interestingly, this compound significantly diminishes the protective effect against ethanol-induced injury. These findings collectively demonstrated that hinokitiol could potentially be used to prevent or improve gastric injury induced by ethanol through regulating cellular iron homeostasis.

Gastric Mucosal Protective Effects of Cinnamomum cassia in a Rat Model of Ethanol-Induced Gastric Injury.

Cinnamomum cassia (cassia) is a tropical aromatic evergreen tree of the Lauraceae family well known for its fragrance and spicy flavor and widely used in Asian traditional medicine. It has recently garnered attention for its diverse potential health benefits, including anti-inflammatory, anti-cancer, and anti-diabetic properties. However, the gastroprotective effect of C. cassia, particularly against ethanol-induced gastric damage, remains unclear. We investigated the potential gastroprotective property of C. cassia and the underlying mechanisms of action in a rat model of ethanol-induced gastric injury. To assess its effectiveness, rats were fed C. cassia for a 14-day period prior to inducing gastric damage by oral administration of ethanol. Our results indicated that pre-treatment with C. cassia mitigated ethanol-induced gastric mucosal lesions and bleeding. Reduced gastric acid secretion and expression of acid secretion-linked receptors were also observed. Additionally, pretreatment with C. cassia led to decreased levels of inflammatory factors, including TNF-α, p-p65, and IκBα. Notably, C. cassia upregulated the expressions of HO1 and HSP90, with particular emphasis on the enhanced expression of PAS and MUC, the crucial gastric mucosa defense molecules. These findings suggest that C. cassia has protective effects on the gastric mucosa and can effectively reduce oxidative stress and inflammation.

Multifunctional gallic acid self-assembled hydrogel for alleviation of ethanol-induced acute gastric injury

Ethanol-induced acute gastric injury is a prevalent type of digestive tract ulcer, yet conventional treatments strategies frequently encounter several limitations, such as poor bioavailability, degradation of enzymes and adverse side effects. Gallic acid (GA), a natural compound extracted from dogwood, has demonstrated potential protective effects in mitigating acute gastric injury. However, its poor stability and limited bioavailability have restricted applications in vivo. To address these issues, we report a hydrogel constructed only by gallic acid with high bioavailability for alleviation of gastric injury. Molecular dynamic simulation studies revealed that the self-assembly of GA into hydrogel was predominantly attributed to π-π and hydrogen bonds. After assembling, the GA hydrogel exhibits superior anti-oxidative stress, anti-apoptosis and anti-inflammatory properties compared with free GA. As anticipated, in vitro experiments demonstrated that GA hydrogel possessed the remarkable ability to promote the proliferation of GES-1 cells, and alleviates apoptosis and inflammation caused by ethanol. Subsequent in vivo investigation further confirmed that GA hydrogel significantly alleviated ethanol-triggered acute gastric injury. Mechanistically, GA hydrogel treatment enhanced the antioxidant capacity, reduced oxidative stress while simultaneously suppressing the secretion of pro-inflammatory cytokines and reduced the production of pro-apoptotic proteins during the process of gastric injury. Our finding suggest that this multifunctional GA hydrogel is a promising candidate for gastric injury, particularly in cases of ethanol-induced acute gastric injury.

Gastroprotective potential of red onion (Allium cepa L.) peel in ethanol-induced gastric injury in rats: Involvement of Nrf2/HO-1 and HMGB-1/NF-κB trajectories

Ethnopharmacological relevanceThe utilization of plants with therapeutic properties in traditional medicine has a longstanding practice. Among them, the well-known Allium cepa L. commonly known as onion has been valued for its anti-inflammatory and antioxidant potential in the treatment of various ailments, including gastric ulcers. Aim of the studyThis study investigated the gastroprotective potential of red onion peel extract and its fractions in a rat model of ethanol-induced gastric ulcer. Moreover, their phytochemical profiles were compared to identify the active metabolites. Materials and methodsMass spectrometry-based metabolomics and chemometrics were performed for phytochemical analysis. Ethanol-induced gastric ulcer model was used to assess the gastroprotective activity. Nine groups of rats were allocated as follows: Group 1 was the normal control; Group 2 rats were used as a positive control/model and received 1 mL of absolute ethanol; and Group 3 rats were treated with famotidine at a dose of 20 mg/kg orally. Group 4 and 5 rats were treated with total acidified ethanolic extract (T1, T2). Group 6 and 7 rats were treated with anthocyanins-rich fractions (P1, P2). Groups 8 and 9 were the flavonoids-rich fraction (S1, S2) treatment. Prior to scarification, the ulcer index in mm was obtained from gastric tissues photographed beside a ruler with further analysis using ImageJ software. ResultsSeventy key major and discriminatory metabolites were identified including flavonoids, anthocyanins, phenolic acids, and miscellaneous compounds. The examined extract and its fractions significantly reduced the ulcer index and inflammatory cytokines via downregulating HMGB-1/NF-κB. Also, they augmented the expression of Nrf2/HO-1 and reduced NOX1/4 mRNA expression. Moreover, there was a significant reduction in the oxidative stress and apoptotic biomarkers as well as a noticeable enhancement in histopathological changes of the stomach tissues. ConclusionRed onion peels have a promising dose dependent gastroprotective potential in alcohol-induced ulcers via modulating Nrf2/HO-1 and HMGB-1/NF-κB trajectories. This highlights the potential of red onion peels in treating gastric ulcers.

Gastroprotective effect of eupatilin, a polymethoxyflavone from Artemisia argyi H.Lév. & Vaniot, in ethanol-induced gastric mucosal injury via NF-κB signaling pathway

Ethnopharmacological relevanceArtemisia argyi H.Lév. & Vaniot (AA) has been extensively utilized as an important medicine and food homology in China, Japan, Korea, and eastern parts of Russia, owing to its pharmacological effects, which include anti-inflammatory, antibacterial, antitussive, and antiallergic properties. Despite the extract of AA can significantly alleviate gastric mucosal injury, its precise material basis for effectiveness is not yet clear. As one of the polymethoxy flavonoids with high content in AA, the gastroprotective activity and molecular mechanism of eupatilin (EUP) require further investigation. Aim of the studyThis study aims to investigate the gastroprotective effects and possible mechanisms of EUP by using an ethanol-induced gastric mucosal injury model in rats. Materials and methodsEUP was isolated from 95% ethanol extract of AA using a systematic phytochemical method. The gastroprotective activity of EUP was evaluated using a male SD rat model with ethanol-induced gastric mucosa injury. Histopathology evaluation of gastric tissues was performed using hematoxylin and eosin (H&E) staining. The levels of cytokines in the plasma and tissues were tested using the ELISA kits, while western blot analysis was employed to assess the expressions of COX-2, iNOS, and NF-κB pathway proteins. ResultsA sufficient amount of EUP was obtained from AA through chromatographic methods and identified by NMR experiment. In vivo, experimental results proved that EUP could significantly alleviate pathological features, increased SOD, GSH, and IL-10 levels, and decreased the contents of MDA, TNF-α, IL-1β, and IL-6. Further in vitro and in vivo Western blot experimental results showed that EUP significantly down-regulates the expressions of the NF-κB signal pathway to relieve inflammatory responses. ConclusionThis study demonstrated that EUP could exert gastroprotective effects by inhibiting inflammation, enhancing gastric mucosal defense, and ameliorating oxidative stress, which is beneficial for providing scientific data for the development of gastric protection.

Impact of Disease States on the Oral Pharmacokinetics of EIDD-1931 (an Active Form of Molnupiravir) in Rats for Implication in the Dose Adjustment.

The pharmacokinetic alteration of an antimicrobial medication leading to sub-therapeutic plasma level can aid in the emergence of resistance, a global threat nowadays. In this context, molnupiravir (prodrug of EIDD-1931) is the most efficacious orally against corona virus disease (COVID-19). In addition to drug-drug interaction, the pharmacokinetics of a drug can significantly vary during any disease state, leading to disease-drug interaction. However, no information is available for such a recently approved drug. Therefore, we aimed to explore the oral pharmacokinetics of EIDD-1931 in seven chemically induced disease states individually compared to the normal state using various rat models. Induction of any disease situation was confirmed by the disease specific study(s) prior to pharmacokinetic investigations. Compared to the normal state, substantially lowered plasma exposure (0.47- and 0.63-fold) with notably enhanced clearance (2.00- and 1.56-fold) of EIDD-1931 was observed in rats of ethanol-induced gastric injury and carbon tetrachloride-induced liver injury states. Conversely, paclitaxel-induced neuropathic pain and cisplatin-induced kidney injury states exhibited opposite outcomes on oral exposure (1.43- and 1.50-fold) and clearance (0.69- and 0.65-fold) of EIDD-1931. Although the highest plasma concentration (2.26-fold) markedly augmented in the doxorubicin-induced cardiac injury state, streptozocin-induced diabetes and lipopolysaccharide-induced lung injury state did not substantially influence the pharmacokinetics of EIDD-1931. Exploring the possible phenomenon behind the reduced or boosted plasma exposure of EIDD-1931, results suggest the need for dose adjustment in respective diseased conditions in order to achieve desired efficacy during oral therapy of EIDD-1931.

Gastroprotective effects of Polygonatum odoratum in rodents by regulation of apoptotic proteins and inflammatory cytokines

In an increasing interest in natural antiulcer compounds that may have gastric healing effects and possibly prevent ulcer recurrence, Polygonatum odoratum appears as a strong candidate. The gastroprotective potentials of P. odoratum rhizome extract (PORE) were explored on ethanol-induced gastric ulceration in rats. Sprague Dawley rats were caged in 5 groups, normal and ulcer control rats received CMC (1% carboxymethyl cellulose). Omeprazole (20 mg/kg) was given to reference Rats. Experimental rats were treated with 250 mg/kg and 500 mg/kg PORE, respectively. After an hour, the normal control rats received 1% CMC, whereas rat groups 2–5 were given absolute ethanol by oral gavage. After 60 min, rats received anesthesia and were sacrificed. Dissected gastric tissue was analyzed by histopathological and immunohistochemical techniques. PORE treatment significantly lowered the ethanol-induced gastric injury, as shown by up-surging gastric pH and mucus content, reduced leukocyte infiltration, lower ulcerative areas in mucosal layers, and increased antioxidants (SOD and CAT) and (MDA) levels. Furthermore, PORE pre-treated rats showed significantly increased expression of the Periodic acid-Schiff (PAS), HSP-70 protein, and decreased Bax protein in their gastric epithelial layers. PORE treatment showed an important regulation of inflammatory cytokines shown by decreasing the TNF-a, and IL-6 and increasing the IL-10 values. The detected biological activity of PORE is encouraging and presents the scientific evidence for its traditional use as a gastroprotection agent however further studies are required to determine the exact phytochemicals and mechanism pathway responsible for this bioactivity.