Ethanol-induced Injury Research Articles

Menstrual blood-derived mesenchymal stem cells combining with platelet-rich plasma infusion in endometrium repair.

Thin endometrium caused by various factors affects the conception rate of females worldwide; however, current medications are still insufficient. Therefore, a novel approach is needed. We previously reported the effect of menstrual blood-derived mesenchymal stem cells (MenSCs) in ameliorating ethanol-induced endometrial injuries. In the present study, we aimed to investigate whether the effect of MenSCs is enhanced by a combination of platelet-rich plasma (PRP) infusion. An endometrial injury mouse model was established by infiltrating 95% ethanol for 15 s into the uterus, followed by MenSCs, PRP, or MenSCs + PRP treatment. Pathological changes were observed by HE staining. The expression of CK18, vimentin, ItgαVβ3, and VEGF was determined using IHC staining and WB blotting. Compared with the model, MenSCs, PRP, and MenSCs + PRP treatments significantly improved endometrial damage and thickness, with the combined therapy displaying the most pronounced efficacy. The density of CK18-, vimentin-, and ItgαVβ3 positive cells increased most significantly in the MenSCs + PRP group of mice. In addition, the protein expression of CK18, vimentin, and VEGF was significantly upregulated after MenSCs + PRP, MenSCs, and PRP treatment, with MenSCs + PRP therapy showing the best efficacy. MenSCs + PRP therapy is more beneficial for ameliorating ethanol-induced endometrial damage than MenSCs or PRP alone, providing a basis for the investigation of novel approaches for treating thin endometria.

Protective Effect of Enterococcus faecium and Its Extracellular Vesicles Against Ethanol-Induced Intestinal Injury.

In this study, we examined the impact of Enterococcus faecium (E. faecium, Efm) and its extracellular vesicles (EVs) on intestinal morphological structure, antioxidant function, inflammatory response, and permeability in rats. In a 5-day feeding experiment, a total of 72 female Sprague Dawley (SD) rats were randomly allotted into nine groups with eight rats per group. The study was conducted in three parts. First, we examined the impact of Efm on ethanol-induced intestinal injury. Second, we investigated the protective effects of various active components of bacterial culture on intestinal function invivo. Third, we explored the impact of Efm with elevated EV secretion on intestinal function. The rats were treated by gavage administration (5 mL/kg body weight [BW]) every other day for a total of three times. After the last treatment at 2 h, the phosphate buffered saline (PBS)group received 5 mL/kg BW of PBS orally, whereas the other groups were orally administered 5 mL/kg BW of absolute ethanol to induce intestinal injury. After the feeding trial, eight rats per treatment were collected for intestinal samples. Our findings demonstrate that pretreatment with Efm can reverse morphological alterations in intestinal tissues, enhance superoxide dismutase/malondialdehyde levels, increase intestinal permeability, and reduce the inflammation levels, thereby regulating intestinal damage. Pretreatment with EfmEVs reversed the detrimental effects of ethanol-induced intestinal damage, displaying a discernible decline in inflammation, augmented permeability, and bolstered antioxidant capacity. Moreover, the release of EVs contributes to the intestinal safeguarding mechanism of Efm. EVs act as mediators in Efm's protective response against ethanol-induced intestinal injury by mitigating inflammation and enhancing antioxidant activity. The Clinical Trial Registration Number: FOSU210403.

Selenium Attenuates Ethanol-induced Hepatocellular Injury by Regulating Ferroptosis and Apoptosis.

Ferroptosis is a newly identified type of cell death which is strongly linked to the development of several diseases. Whereas, the role of ferroptosis in the improvement of ethanol-induced hepatocytes injury by selenium has not been confirmed. In this study, an in vitro cell damage model was established using half inhibition concentration of ethanol to induce NCTC clone 1469. Cell activity, lipid peroxidation, apoptosis and the expression of markers related to ferroptosis pathway was determined. A mouse model of alcoholic liver disease (ALD) was constructed and the effectiveness of selenium and ferrostatin-1 in treating ALD in vivo was assessed by serum liver function tests, tissue staining and immunohistochemistry for ferroptosis related proteins. Pretreatment with selenomethionine and ebselen significantly improved ethanol-induced reduction in hepatocyte viability, elevated GSH levels and SOD enzyme activity, reduced MDA and iron content, while improving ethanol-induced changes in apoptosis levels and ferroptosis markers GPX4, SLC7A11, and ACSL4, with the effect of Selenomethionine being more significant. In vivo results also indicated that intervention with selenium or ferroptosis inhibitors significantly improved ethanol-induced liver tissue damage, significantly reduced serum ALT and AST levels, upregulated GPX4 and SLC7A11, but reduced ACSL4 protein levels in liver tissue. The process of ethanol damage to hepatocytes is regulated by the ferroptosis pathway. Selenium may exert a beneficial role in ethanol-induced hepatocyte injury by antagonizing oxidative stress and regulating apoptosis and ferroptosis pathways.

Neuroinflammatory responses and blood–brain barrier injury in chronic alcohol exposure: role of purinergic P2 × 7 Receptor signaling

Alcohol consumption leads to neuroinflammation and blood‒brain barrier (BBB) damage, resulting in neurological impairment. We previously demonstrated that ethanol-induced disruption of barrier function in human brain endothelial cells was associated with mitochondrial injury, increased ATP and extracellular vesicle (EV) release, and purinergic receptor P2 × 7R activation. Therefore, we aimed to evaluate the effect of P2 × 7R blockade on peripheral and neuro-inflammation in ethanol-exposed mice. In a chronic intermittent ethanol (CIE)-exposed mouse model, P2 × 7R was inhibited by two different methods: Brilliant Blue G (BBG) or gene knockout. We assessed blood ethanol concentration (BEC), brain microvessel gene expression by using RT2 PCR array, plasma P2 × 7R and P-gp, serum ATP, EV-ATP, number of EVs, and EV mtDNA copy numbers. An RT2 PCR array of brain microvessels revealed significant upregulation of proinflammatory genes involved in apoptosis, vasodilation, and platelet activation in CIE-exposed wild-type animals, which were decreased 15–50-fold in BBG-treated–CIE-exposed animals. Plasma P-gp levels and serum P2 × 7R shedding were significantly increased in CIE-exposed animals. Pharmacological or genetic suppression of P2 × 7R decreased receptor shedding to levels equivalent to those in control group. The increase in EV number and EV-ATP content in the CIE-exposed mice was significantly reduced by P2 × 7R inhibition. CIE mice showed augmented EV-mtDNA copy numbers which were reduced in EVs after P2 × 7R inhibition or receptor knockout. These observations suggested that P2 × 7R signaling plays a critical role in ethanol-induced brain injury. Increased extracellular ATP, EV-ATP, EV numbers, and EV-mtDNA copy numbers highlight a new mechanism of brain injury during alcohol exposure via P2 × 7R and biomarkers of such damage. In this study, for the first time, we report the in vivo involvement of P2 × 7R signaling in CIE-induced brain injury.

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.

Trilobatin, a Novel Naturally Occurring Food Additive, Ameliorates Alcoholic Liver Disease in Mice: Involvement of Microbiota-Gut-Liver Axis and Yap/Nrf2 Signaling Pathway.

Trilobatin, a novel natural food additive, exerts a protective effect on acute liver injury. However, whether Trilobatin can protect against alcoholic liver disease (ALD) has not been elucidated. This research is intended to ascertain the impact of Trilobatin on ALD in mice and decipher the potential underlying mechanisms. Lieber-DeCarli liquid alcohol diet was used to induce ALD in mice, followed by administration of Trilobatin (10, 20, 40 mg·kg-1·d-1) for 15 days. The results suggested that Trilobatin significantly alleviated ethanol-induced hepatic injury in mice. Furthermore, RNA-Seq analysis revealed that yes-associated protein (YAP) downregulation occurred in the liver after Trilobatin treatment. Mechanistically, Trilobatin directly bound to YAP and hindered its nuclear translocation, which activated the Nrf2 pathway to reduce pro-inflammatory cytokines and oxidative stress. Intriguingly, 16S rDNA analysis results revealed that Trilobatin reshaped the gut microbiota, reducing harmful bacteria and increasing beneficial bacteria. It also enhanced tight junction proteins, defending against damage to the intestinal barrier. These findings not only highlight the microbiota-gut-liver axis and YAP/Nrf2 pathway as crucial potential targets to treat ALD but also reveal that Trilobatin effectively protects against ALD, at least partly, through modulating the microbiota-gut-liver axis and YAP/Nrf2 pathway.

Elucidating hydroxysafflor yellow A's multi-target mechanisms against alcoholic liver disease through integrative pharmacology

BackgroundAlcoholic liver disease (ALD) significantly contributes to global liver-related morbidity and mortality. Natural products play a crucial role in the prevention and treatment of ALD. Hydroxysafflor yellow A (HSYA), a unique and primary component of Safflower (Carthamus tinctorius l.), exhibits diverse pharmacological activities. However, the impact and mechanism of HSYA on ALD have not been fully elucidated. PurposeThe purpose of this study was to employ an integrative pharmacology approach to assess the multi-targeted mechanism of HSYA against ALD. MethodsNetwork pharmacology and molecular docking techniques were used to analyze the potential therapeutic signaling pathways and targets of HSYA against ALD. An ALD model in zebrafish larvae was established. Larvae were pretreated with HSYA and then exposed to ethanol. Liver injury was measured by fluorescence expression analysis in the liver-specific transgenic zebrafish line Tg (fabp10a:DsRed) and liver tissue H&E staining. Liver steatosis was determined by whole-mount oil red O staining and TG level. Additionally, an ethanol-induced hepatocyte injury model was established in vitro to observe hepatocyte damage (cell viability, ALT level), lipid accumulation (oil red O staining, TC and TG), and oxidative stress (ROS, MDA, GPx and SOD) in HepG2 cells treated with or without HSYA. Finally, qRT-PCR combined with network pharmacology and molecular docking was employed to validate the effects of HSYA on targets. ResultsHSYA exhibited a significant, dose-dependent improvement in ethanol-induced liver injury in zebrafish larvae and HepG2 cells. Network pharmacology analysis revealed that HSYA may exert pharmacological effects against ALD through 341 potential targets. These targets are involved in various signaling pathways, including lipid metabolism and atherosclerosis, PI3K-Akt signaling pathway, MAPK signaling pathway, and ALD itself. Molecular docking studies displayed that HSYA had a strong binding affinity toward the domains of IL1B, IL6, TNF, PPARA, PPARG, HMGCR and ADH5. qRT-PCR assays demonstrated that HSYA effectively reversed the ethanol-induced aberrant gene expression of SREBF1, FASN, ACACA, CPT1A, PPARA, IL1B, IL6, TNFα, ADH5, and ALDH2 in vivo and in vitro. ConclusionThis study offers a comprehensive investigation into the anti-ALD mechanisms of HSYA using an integrative pharmacology approach. The potential targets of HSYA may be implicated in enhancing ethanol catabolism, reducing lipid accumulation, mitigating oxidative stress, and inhibiting inflammatory response.

Revealing the exceptional antioxidant activity of phosphorylated polysaccharides from medicinal Abrus cantoniensis Hance

Abrus cantoniensis Polysaccharides (ACP) exhibit antioxidant activity and immune-regulatory functions. Abrus cantoniensis Hance widely distributed in the Guangdong and Guangxi regions of China. In this study, this research investigated the impact of phosphorylation modification on the biological activity of ACP, aiming to provide theoretical insights for its development. This research modified ACP through phosphorylation and evaluated changes in its in vitro antioxidant capacity, including free radical scavenging and resistance to cellular oxidative damage. Additionally, this research administered both native ACP and phosphorylated ACP (P-ACP) to mice to assess their protective effects against acute ethanol-induced oxidative injury. This research explored whether these effects were mediated through the Keap1-Nrf2 signaling pathway and their influence on gut microbiota. Results revealed that phosphorylation significantly enhanced ACP's antioxidant capacity and protective effects (p < 0.05). P-ACP improved mice resistance to acute oxidative injury, mitigating the adverse effects of 50 % ethanol (p < 0.05). Moreover, both ACP and P-ACP are involved in modulating the expression of the Keap1-Nrf2 signaling pathway and, to some extent, alter the composition of the gut microbiota in mice. In summary, phosphorylation modification effectively enhances ACP's antioxidant capacity and provides better protection against acute oxidative injury in mice.

Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.

Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.

Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20mg/kg, and the remaining two groups received 250 and 500mg/kg CMEE for 2 weeks. After that, food was taken away for 24h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

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.

Galangin Prevents Against Ethanol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation via NF-κB/MAPK Signaling Pathways in Mice and Caco-2 Cells.

The potential of natural phytochemicals in addressing ethanol-related public safety concerns has been garnering attention. Galangin, a potent flavonoid renowned for its antioxidative and anti-inflammatory characteristics, is derived from the galanga plant, and propolis is derived from bees. Here, we documented the effects of galangin on ethanol-stimulated intestinal tight junction damage and investigated its potential protective mechanism in both in vivo and in vitro models, which has not been extensively investigated. Our results revealed that galangin efficaciously mitigated ethanol-induced intestine injury and dysfunction of the intestinal barrier. Concurrently, galangin significantly counteracted the ethanol-induced upregulation of NLRP3 inflammasome-associated proteins and activated the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) signaling pathways in both the mouse colon and Caco-2 cells. Interestingly, similar to galangin, inhibitors of MAPKs and the NF-κB p65 reduced ethanol-induced NLRP3 inflammasome activation and intestinal tight junction damage. To sum up, our results showed that galangin blocks the ethanol-induced perturbation of the intestinal barrier and activation of the NLRP3 inflammasome via the NF-κB/MAPK signaling pathways.

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.