Structure characteristics, protective effect and mechanisms of ethanol-fractional polysaccharides from Dendrobium officinale on acute ethanol-induced gastritis.

Gastritis is a common disease characterized by gastric ulcers and severe bleeding. Excessive daily alcohol consumption can cause acute gastritis, impacting individuals' quality of life. This study aims to explore the protective effects of different ethanol-fractional polysaccharides of Dendrobium officinale (EPDO) on acute alcohol-induced gastric injury in vivo. Results showed that EPDO-80, identified as a ß-glucan, exhibited significant anti-inflammatory properties in pathology. It could reduce the area of gastric mucosal injury and cell infiltration. EPDO-80 had a dose-effect relationship in reducing the levels of malondialdehyde and cyclooxygenase-2 and decreasing the levels of inflammation mediators such as tumor necrosis factor α. More extensively, EPDO-80 could inhibit the activation of the TNFR/IκB/NF-κB signaling pathway, reducing the production of TNF-α mRNA and cell apoptosis in organs. Conversely, EPDO-80 could promote changes in the gut microbiota structure. These findings suggest that EPDO-80 could have great potential in limiting oxidative stress and inflammation mediated by inhibiting the NF-κB signaling pathway, which is highly related to its ß-glucan structure and functions in gut microbiota.

Protective Effect of Mormodica balsamina Leaf Extract on the Gastric Morphology of Experimental Rats Against Ethanol Induced Gastric Ulcers / Efecto Protector de los Extractos de Hojas de Mormodica balsamina en la Morfología Gástrica de Ratas Experimentales Contra Úlceras Gástricas Inducidas por Etanol

SUMMARY: Mormodica balsamina is a valuable medicinal plant that is used to treat wounds and inflammation; its leaves are also used as an antibiotic and in the treatment of stomach pain. This study was conducted to determine the anti-ulcer activity of methanolic leaf extract of Mormodica balsamina on ethanol-induced ulcer in albino rats. A total of 32 rats were used for the study. Groups I and II served as the baseline and negative controls respectively, while groups III-VII served as the test groups. Group I was untreated, while group II received 1ml/kg body weight of the vehicle (2 % DMSO). Three test groups (III - V) received methanol extracts (75 mg, 150 mg, 300 mg/kg body weight respectively) while the other three test groups (VI - VIII) received aqueous extracts (75 mg, 150mg, 300 mg/kg body weight respectively) via oral gavage for seven days prior to ulcer induction. The rats were sacrificed, stomachs excised and ulcers scored. Histological sections were produced and examined. Findings revealed that M. balsamina extracts protected the rats' gastric epithelia from ethanol induced ulceration to varying degree with the high dose (150 and 300 mg/kg) of both extracts offering the best preservation (42 % and 50 % ulcer protective index respectively) when compared to untreated animals. Histological findings correlated with calculated ulcer indices, with treated animals having less severe gastric mucosal lesions. In conclusion, extracts of M. balsamina may possess reasonable antiulcer activities in rats against ethanol induced gastric ulcer.

Mormodica balsamina es una valiosa planta medicinal que se utiliza para tratar heridas e inflamaciones; sus hojas también se utilizan como antibiótico y en el tratamiento del dolor de estómago. Este estudio se realizó para determinar la actividad antiulcerosa del extracto metanólico de hojas de Mormodica balsamina sobre la úlcera inducida por etanol en ratas albinas. Se utilizaron un total de 32 ratas para el estudio. Los grupos I y II sirvieron como referencia y controles negativos respectivamente, mientras que los grupos III-VII sirvieron como grupos de prueba. El grupo I no se trató, mientras que el grupo II recibió 1 ml/kg de peso corporal del vehículo (2% de DMSO). Tres grupos de prueba (III - V) recibieron extractos de metanol (75 mg, 150 mg, 300 mg/ kg de peso corporal respectivamente) mientras que los otros tres grupos de prueba (VI - VIII) recibieron extractos acuosos (75 mg, 150 mg, 300 mg/kg de peso corporal respectivamente) por sonda oral durante siete días antes de la inducción de la úlcera. Se sacrificaron las ratas, se extirparon los estómagos y se puntuaron las úlceras. Se realizaron y examinaron secciones histológicas. Los resultados revelaron que los extractos de M. balsamina protegieron el epitelio gástrico de las ratas de la ulceración inducida por etanol en diversos grados, y la dosis alta (150 y 300 mg/kg) de ambos extractos ofreció la mejor conservación (42 % y 50 % de índice de protección contra úlceras, respectivamente) en comparación con los animales no tratados. Los hallazgos histológicos se correlacionaron con los índices de úlcera calculados, y los animales tratados tenían lesiones de la mucosa gástrica menos graves. En extractos de M. balsamina puede poseer actividades antiulcerosas razonables en ratas contra la úlcera gástrica inducida por etanol.

Xiaojianzhong decoction attenuates aspirin-induced gastric mucosal injury via the PI3K/AKT/mTOR/ULK1 and AMPK/ULK1 pathways.

CONTEXT: Xiaojianzhong decoction (XJZD), classically prescribed in Chinese medicine, has protective and healing effects on gastric mucosal injury. However, the exact mechanism behind this effect remains unclear. OBJECTIVE: To investigate the effect of XJZD on gastric mucosal injury and explore its underlying mechanisms. MATERIALS AND METHODS: C57BL/6 mice were randomized into six groups (n = 10): the control group receiving sterile water, the model (aspirin 300 mg/kg), the XJZD high-dose (12 g/kg), XJZD medium-dose (6 g/kg), XJZD low-dose (3 g/kg) and omeprazole (20 mg/kg) groups, by gavage daily for 14 days. The area of gastric mucosal injury, mucosal injury index and degree of histopathological damage were analysed. Gastric mucosal epithelial cell apoptosis was detected. Epithelial cell autophagy was observed. The expression levels of tight junction proteins and proteins related to apoptosis, autophagy and the pentose phosphate pathway were analysed. RESULTS: The results showed that after treatment with XJZD (12, 6 and 3 g/kg), the mucosal injury area was reduced (83.4%, 22.6% and 11.3%), the expression level of ZO-1 and occludin was up-regulated, the apoptosis rate of epithelial cells was reduced (40.8%, 25.4% and 8.7%), the expression of autophagy-related proteins LC3 and Beclin1 was decreased and the expression of p62 was increased, the PI3K/AKT/mTOR/ULK1(ser757) signalling pathway was activated, and the AMPK/ULK1(ser317) signalling pathway was inhibited. In addition, XJZD can antagonize the imbalance of redox homeostasis caused by aspirin and protect the gastric mucosa. DISCUSSION AND CONCLUSIONS: XJZD protects against aspirin-induced gastric mucosal injury, implying it to be a potential therapeutic agent.

Molecular Mechanism of Cinnamomum cassia against Gastric Damage and Identification of Active Compounds.

Cinnamomum cassia is a natural product found in plants that has been used as a folk remedy for inflammation. In this study, we investigated the mechanism underlying the anti-inflammatory and antioxidant properties of C. cassia extract (ECC) in lipopolysaccharide (LPS)-induced murine RAW 264.7 cells, in comparison with 4-hydroxycinnamaldehyde, a C. cassia extract component. ECC and 4-hydroxycinnamaldehyde inhibited the production of nitrite oxide in a dose-dependent manner and did not show any change in cellular toxicity when treated with the same dose as that used in the nitrite assay. Moreover, they attenuated ROS accumulation after lipopolysaccharide (LPS) stimulation. ECC and 4-hydroxycinnamaldehyde decreased the mRNA and protein expression levels of inflammatory mediators (iNOS and COX-2) and cytokines such as TNF and IL-6. We also found that ECC and 4-hydroxycinnamaldehyde mitigated the phosphorylation of ERK, JNK, and transcription factors, such as NF-κB and STAT3, suppressing NF-κB nuclear translocation in LPS-activated macrophages. In addition, administration of ECC in a Sprague Dawley rat model of acute gastric injury caused by indomethacin significantly increased the gastric mucus volume. Analysis of serum and tissue levels of inflammatory mediators revealed a significant decrease in serum PGE2 and myeloperoxidase levels and a reduction in gastric iNOS, COX-2, and p65 protein levels. Collectively, these results suggest that ECC has antioxidant and anti-inflammatory effects and is a potential candidate for curing gastritis.

Korean Red Ginseng Extract Inhibits IL-8 Expression via Nrf2 Activation in Helicobacter pylori-Infected Gastric Epithelial Cells.

Helicobacter pylori (H. pylori) causes gastric diseases by increasing reactive oxygen species (ROS) and interleukin (IL)-8 expression in gastric epithelial cells. ROS and inflammatory responses are regulated by the activation of nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of Nrf2 target genes, superoxide dismutase (SOD) and heme oxygenase-1 (HO-1). We previously demonstrated that Korean red ginseng extract (RGE) decreases H. pylori-induced increases in ROS and monocyte chemoattractant protein 1 in gastric epithelial cells. We determined whether RGE suppresses the expression of IL-8 via Nrf2 activation and the expression of SOD and HO-1 in H. pylori-infected gastric epithelial AGS cells. H. pylori-infected cells were treated with RGE with or without ML385, an Nrf2 inhibitor, or zinc protoporphyrin (ZnPP), a HO-1 inhibitor. Levels of ROS and IL-8 expression; abundance of Keap1, HO-1, and SOD; levels of total, nuclear, and phosphorylated Nrf2; indices of mitochondrial dysfunction (reduction in mitochondrial membrane potential and ATP level); and SOD activity were determined. As a result, RGE disturbed Nrf2-Keap1 interactions and increased nuclear Nrf2 levels in uninfected cells. H. pylori infection decreased the protein levels of SOD-1 and HO-1, as well as SOD activity, which was reversed by RGE treatment. RGE reduced H. pylori-induced increases in ROS and IL-8 levels as well as mitochondrial dysfunction. ML385 or ZnPP reversed the inhibitory effect of RGE on the alterations caused by H. pylori. In conclusion, RGE suppressed IL-8 expression and mitochondrial dysfunction via Nrf2 activation, induction of SOD-1 and HO-1, and reduction of ROS in H. pylori-infected cells.

The therapeutic effect of Huazhuojiedu decoction on precancerous lesions in a gastric cancer model via the regulation of lnc 517368.

ETHNOPHARMACOLOGICAL RELEVANCE: Huazhuojiedu decoction, a Chinese herbal preparation, has been proven to be clinically effective in treating precancerous lesions in gastric cancer (PLGC). This formula is optimized from a classic formula called "Ganluxiaodu Dan." Although some experiments have shown that Huazhuojiedu decoction is effective against PLGC, the mechanism remains unclear. AIM OF THE STUDY: To investigate the treatment of PLGC with Huazhuojiedu decoction from the perspective of lncRNA in vitro and in vivo. MATERIALS AND METHODS: A PLGC rat model was prepared and randomly divided into a Huazhuojiedu decoction group (HG), a vitacoenzyme group (VG), a model group (MG), and a normal group (CG). Each group was given a corresponding concentration of medicine and distilled water for 10 weeks. The pathological changes in the gastric mucosa were observed by hematoxylin-eosin staining (HE). High-throughput sequencing was performed to detect the differentially expressed lncRNAs in the HG, MG, and CG. Quantitative real-time reverse transcription-polymerase chain reaction (RT-qPCR) was used to verify differentially expressed lncRNAs, and rat-human homology information was obtained from the University of California, Santa Cruz (UCSC) Genome Database. Human gastric mucosal epithelial cells (GES-1) were used to prepare precancerous lesions of gastric cancer cells (MC). A Huazhuojiedu decoction drug-containing serum was prepared to treat the MC cells. The effects of the Huazhuojiedu decoction and the lncRNA ENST00000517368 (lnc 517368) knockdown or overexpression on PLGC cell proliferation and apoptosis were evaluated in vitro using CCK-8, flow cytometry, and RT-qPCR. RESULTS: The HE results showed that gastric mucosal pathology was significantly improved in the HG. High-throughput sequencing results showed that compared with the CG, 91 lncRNAs upregulated in the MG were restored and downregulated in the HG (P < 0.05), and 115 lncRNAs downregulated in the MG were restored and upregulated in the HG (P < 0.05). The results of RT-qPCR were consistent with the sequencing results. The differentially expressed genomic rat lncRNA ENSRNOT00000079699 is homologous to human lnc 517368. In cell experiments, high expression of lnc 517368 promoted proliferation and reduced apoptosis in PLGC cells, while the Huazhuojiedu decoction reduced the expression of lnc 517368 and improved cell morphology. CONCLUSIONS: Huazhuojiedu decoction inhibited cell proliferation and promoted apoptosis in PLGC cells, and its effect may be partially dependent on the downregulation of lnc 517368.

Protection against indomethacin-induced loss of intestinal epithelial barrier function by a quercetin oxidation metabolite present in onion peel: In vitro and in vivo studies.

Oxidative stress is directly implicated in the loss of intestinal epithelial barrier function (IEBF) induced by non-steroidal anti-inflammatory drugs (NSAIDs). Previous studies by our research team demonstrated that 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxy-3(2H)-benzofuranone (BZF), a quercetin oxidation metabolite that naturally occurs in onion peels, exhibits an antioxidant potency notably higher than quercetin. Thus, we assessed the potential of BZF and a BZF-rich onion peel aqueous extract (OAE) to protect against the loss of IEBF in Caco-2 cell monolayers and in rats exposed to indomethacin. In vitro, pure BZF and OAE standardized in BZF (100 nM), protected against the drop in transepithelial electrical resistance by 70 - 73%. Likewise, it prevented the increase in fluorescein-isothiocyanate labelled dextran (FITC-dextran) paracellular transport by 74% and oxidative stress by 84 - 86%. In vivo, BZF, given orally at a dose 80 µg/Kg bw as OAE, totally abolished a 30-fold increase in FITC-dextran serum concentration induced by indomethacin. This effect was dose-dependent and largely conserved (85%) when OAE was given 180-min prior to indomethacin. The IEBF-protective effect of OAE was accompanied by a full prevention of the NF-ĸB activation, and the increases in interleukine-8 secretion and myeloperoxidase activity induced by indomethacin. The protection was also associated with a 21-fold increase in Nrf2, and a 7-fold and 9-fold increase in heme oxygenase-1 and NAD(P)H-quinone oxidoreductase 1, respectively. The IEBF-protecting effect of OAE involves, most likely, its dual capacity to activate Nrf2 while inhibiting NF-ĸB activation. The extremely low doses of BZF needed to promote such actions warrants extending its IEBF-protective effects to other NSAIDs.

Effectiveness of the fruit of Rosa odorata sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils in the protection and the healing of ethanol-induced rat gastric mucosa ulcer based on Nrf2/NF-κB pathway regulation.

ETHNOPHARMACOLOGICAL RELEVANCE: Rosa odorata Sweet var. gigantea (Coll. et Hemsl.) Rehd. et Wils (Rosaceae), is also known as "GU-GONG-GUO", the root of which has been recognized as common ethnodrug from the Yi nationality for treating inflammatory bowel disease. The aim of the present study was to investigate the preventive and curative effects of extract from the fruits of Rosa odorata Sweet var. gigantea (Coll.et Hemsl.) Rehd. et Wils (FOE) in vitro and in vivo as well as elucidate the potential mechanisms of the action involved. MATERIALS AND METHODS: Male Wistar rats were applied to ethanol-induced gastric ulcer model. They were divided into six groups: control, model (GU), positive (Magnesium aluminate chewable tablets, 125 mg/kg), FOE low (125 mg/kg), middle (250 mg/kg) and high (500 mg/kg) doses groups. Histopathology observation of gastric tissues was detected by hematoxylin and eosin (H&E) staining. The expression of Nrf2, HO-1, Keap1, NF-κB p65 and IKKα/ß in gastric tissues were evaluated by immunohistochemistry (IHC). The levels of cytokines in serum and tissues were measured by Enzyme-linked immunosorbent assay (ELISA). The expression of Nrf2, HO-1, Keap1, NF-κB p65, IKKα/ß, PCNA and COX2 proteins were ulteriorly assessed by Western blotting to elucidate the molecular mechanism of FOE's protective effect on gastric ulcer. RESULTS: MTT detection showed that LPS reduced RAW264.7 cell survival, and FOE blocked the inhibition of RAW264.7 cell growth induced by LPS. When RAW264.7 cells were treated with both FOE (100 µg mL-1) and LPS (5 µg mL-1) for 24 h, compared with the model group, the level of NO, TNF-α, IL-6, IL-1ß and MDA significantly decreased, and the activity of SOD was significantly reduced. Obvious pathological injuries in the GU model group were observed, which was improved after treatments with FOE. The contents of pro-inflammatory factors in serum and tissues were decreased by 25% whereas prostaglandin E2 (PGE2) and epidermal growth factor (EGF) were increased by 30% in a dose-dependent manner after FOE (500 mg/kg) treatments. In addition to the promotion effects of superoxide dismutase (SOD), FOE (500 mg/kg) also attenuated the levels of nitric oxide (NO) and malondialdehyde (MDA) by 20%. Likewise, the expression of NF-κB p65, IKKα/ß and Keap1 were suppressed after treatments with FOE whereas Nrf2 and HO-1 showed the opposite trend, which mechanisms were found to be associated with Nrf2/NF-κB signaling pathways. CONCLUSION: The study demonstrated that FOE is able to protect against GU via inhibiting NF-κB signaling pathway and activating Nrf2 signaling pathway, which might provide a stronger theoretical basis for the treatment of GU.

An aqueous extract from Artemisia capillaris inhibits acute gastric injury through mucosal stabilization.

BACKGROUND: Artemisia capillaris is among the most abundantly used traditional medicines, utilized in East Asia to treat diverse illnesses, including gastrointestinal tract diseases. We previously reported that an aqueous extract of A. capillaris (AEAC) inhibited gastric inflammation induced by HCl/ethanol via reactive oxygen species scavenging and NF-κB downregulation. To date, the pharmacological potential of AEAC for promoting mucosal integrity has not been studied. RESULTS: Here, we report that a single treatment with AEAC increased mucus production, and repeated administration of AEAC abolished HCl/ethanol-induced mucosal injury in vivo. Single- and multiple-dose AEAC treatments measurably increased the expression of mucosal stabilizing factors in vivo, including mucin (MUC) 5 AC, MUC6, and trefoil factor (TFF) 1 and TFF2 (but not TFF3). AEAC also induced mucosal stabilizing factors in both SNU-601 cells and RGM cells through phosphorylation of extracellular signal-regulated kinases. CONCLUSION: Taken together, our results suggest that AEAC protects against HCl/ethanol-induced gastritis by upregulating MUCs and TFFs and stabilizing the mucosal epithelium. © 2021 Society of Chemical Industry.

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.

Mechanism exploration of ancient pharmaceutic processing (Paozhi) improving the gastroprotective efficacy of Aucklandiae Radix.

ETHNOPHARMACOLOGICAL RELEVANCE: Processing, also called Paozhi in Chinese, is an ancient Chinese pharmaceutic processing technique developed along with the Chinese herbal medicines (CHMs). The understanding of the mechanism of Paozhi has been investigated for several decades. Aucklandiae Radix (CAR) and its roasted processed products are all used in indigestion as a kind of CHMs. Processed Aucklandiae Radix (PAR) had a stronger effect to protect gastric mucosa than CAR, while the main compounds in CAR were reduced sharply after being processed. The underlying mechanism of this phenomenon is still unclear. AIM OF THE STUDY: This study was aimed to evaluate whether PAR have a stronger gastroprotective effect than CAR and the underlying mechanisms of such circumstance. MATERIALS AND METHODS: Ultra-fast liquid chromatography coupled with quadrupole time of flight mass spectrometry (UFLC-QTOF-MS/MS) coupled with multivariate statistical analyses was employed to explore chemical compounds which had a relatively stable content in PAR. Based on the compounds selected as the research object, network pharmacology was applied to visualize the relationships between the selected components and the gastroprotective-related targets from disease database, at the same time the possible intervention path of CAR/PAR which might be responsible for the effect of CAR/PAR on gastritis-induced rats was also built. Then, the key proteins were detected by western blotting to verify and compare the pharmacological effects of CAR/PAR. RESULTS: Through UFLC-QTOF-MS/MS and orthogonal partial least squares discriminant analysis (OPLS-DA), sixteen compounds stable in PAR were discovered, of which saussureamine C and saussureamine B were estimated as the core compounds to exert gastroprotective in PAR predicted by network pharmacology analysis. Under the guide of KEGG pathway enrichment analysis, PI3K/AKT, p38 MAPK (Mitogen-activated protein kinase) and nuclear factor-kappa B (NF-κB) signaling pathways were forecasted as the possible healing mechanisms of CAR/PAR, and that result was verified by the experiments in vivo. PAR performed a stronger ability to reduce the level of p38 MAPK and NF-κB p65 than CAR, which may partially explain the different ability of CAR/PAR against gastric mucosa damage. CONCLUSION: This study clarified that although Paozhi entailed a sharp decrease on the main compounds of CAR, there were some compounds which were not sensitive to high temperature and preserved in PAR and had a relative higher content in PAR than in CAR. PAR has stronger influence on MAPKs/NF-κB signaling pathway than CAR, which may reveal that the stronger gastroprotective effect of PAR perhaps rely on the constitutions with a higher relative abundance after Paozhi. The present research combined UFLC-QTOF-MS/MS and network pharmacology deeply investigated the impact of the roasted processing on the chemical constitutions and gastroprotective effect of CAR and offered reference for the clinical application of CAR/PAR.

Protective effect of sterols extracted from Lotus plumule on ethanol-induced injury in GES-1 cells in vitro.

In this study, sterols were isolated from Lotus plumule by Soxhlet extraction and saponification and were further characterized by GC-MS analysis. The results showed that the sterols extracted from Lotus plumule mainly contained ß-sitosterol, fucosterol, and campesterol. Models were established in vitro to investigate the protective effects of Lotus plumule sterols (LPSs) on ethanol-induced injury in human gastric epithelium (GES-1) cells. The results showed that appropriate concentrations of LPSs and ß-sitosterol could protect GES-1 cells from ethanol-induced injury by reducing ROS levels, reducing calcium ion release, increasing antioxidant enzyme activity and maintaining mitochondrial membrane potential. Western blot experiment results also showed that appropriate concentrations of LPSs and ß-sitosterol could up-regulate the expression of the anti-apoptotic protein Bcl-2 and down-regulate the pro-apoptotic proteins Bax and caspase-3 in GES-1 cells. Meanwhile, sterol pretreatment groups down-regulated the protein expression levels of p-P38 and p-JNK in ethanol-damaged GES-1 cells and up-regulated the expression level of p-ERK, suggesting that sterols protect GES-1 cells from ethanol-induced damage by regulating the MAPK signaling pathway. Taken together, Lotus plumule sterols could effectively prevent gastric cell damage in vitro and suggest the potential application of LPSs as bioactive ingredients for healthy foods.

Gastroprotective effect and mechanisms of Chinese sumac fruits (Rhus chinensis Mill.) on ethanol-induced gastric ulcers in mice.

This paper aimed to study the effect of the phenol-rich fraction from Chinese sumac fruits on ethanol-induced gastric ulcers in mice and to further elucidate the potential mechanisms. The results showed that the phenol-rich fraction of the fruits significantly decreased the ulcer index, restored the levels of prostaglandin E-2, heat shock protein 70, glutathione and superoxide dismutase, and reduced the malondialdehyde content. Further analyses revealed that the fraction significantly alleviated the gastric oxidative stress by upregulating the Nrf2 protein pathway to increase the HO-1 and NQO1 expression levels, suppressed the inflammation by reducing the expression levels of p-NF-κB and p-IκBα and inhibited the secretion of tumor necrosis factor-α, interleukin-1ß, and interleukin-6. In addition, the fraction remarkably prevented gastric mucous cell apoptosis by upregulating Bcl-2 and downregulating Bax and cleaved caspase3. This experiment clarified for the first time that the phenol-rich fraction from Chinese sumac fruits can prevent ethanol-induced gastric ulcers in mice by inhibiting the oxidative stress, inflammatory response and cell apoptosis. The results obtained from the current work indicated that the phenol-rich fraction from Chinese sumac fruits could be applied as a kind of natural resource for producing new functional foods to prevent and/or improve gastric ulcers induced by ethanol.

Gastroprotective Effects of Spirulina platensis, Golden Kiwifruit Flesh, and Golden Kiwifruit Peel Extracts Individually or in Combination against Indomethacin-Induced Gastric Ulcer in Rats.

This study was conducted to investigate the therapeutic effect of hydro-alcoholic extract of Spirulina platensis (SP), golden kiwifruit (Actinidia chinensis) flesh (KF), and golden kiwifruit peel (KP) individually or in combination (SFP) on indomethacin-induced gastric ulcer in rats. Negative control rats (GI) were orally administered distilled water in parallel with other treatments. The positive control rat group (GII) was administered 30 mg kg-1 indomethacin to induce gastric ulcers. The KF and KF extracts were used individually or together with SP in treating indomethacin-induced gastric ulcerated rat groups. Gastric ulcerated rat's groups GIII, GIV, GV, GVI, and GVII were orally administered at 30 mg kg-1 rat body weight as total phenolic content (TPC) equivalent from SP, KF, KP, SPF extracts, and Lansoprazole (30 mg kg-1, as reference drug) daily up to 14 days, respectively. The relevant biochemical parameters, antioxidant biomarkers, and histopathological examination were examined. Remarkably, treating rats with SP, KF, KP, and SFP extracts markedly reduced gastric juice and stomach volume expansion induced by indomethacin. The SP significantly retrieved the pH of gastric juice to a regular rate compared to GI. The ulcer index (UI) was significantly attenuated by SP, KF, KP, and SFP administration. The protection index percentage (PI %) was 80.79, 54.51, 66.08, 75.74, and 74.86% in GIII, GIV, GV, GVI, and GVII, respectively. The gastric mucin content was significantly better attenuated by 95.7 in GIII compared to its content in GI. Lansoprazole increased mucin content by 80.3%, which was considerably lower than SP and SFP. SP, KF, KP, SFP, and Lansoprazole improved the reform of gastric mucosal-increased secreted mucus by 95.6, 61.3, 64.8, 103.1, and 80.2% in GIII, GIV, GV, GVI, and GVII, respectively. Interestingly, SFP efficiently increased vit. B12 level by 46.0% compared to other treatments. While Lansoprazole administrating did not significantly attenuate vit. B12 level. The SP and SFP improved iron and Hemoglobin (HB) levels depending on treatment. SP, KF, KP, and SFP significantly decreased the malondialdehyde (MDA) and increased reduced glutathione (GSH) as well as superoxide dismutase (SOD) levels in blood and stomach tissues. The most potent effect was observed with SP, and SFP was even better than Lansoprazole. Histopathologically, treating rats with SP extract showed a marked reduction of gastric damage and severity changes induced by indomethacin. KP was much better than KF in lessening gastric histopathological damages caused by indomethacin. SFP significantly alleviates gastric histopathological alterations. The lansoprazole-treated group (GVII) greatly relieved the gastric histopathological changes and recorded mild focal necrosis and desquamation of the mucosa in addition to mild oedema in the serosal layer. In conclusion, the presented results proved the antiulcer potential of SP and A. chinensis extracts against an indomethacin-induced gastric ulcer in rats, which may be due to their antioxidant and anti-inflammation efficiency. Thus, these data suggested that SP, KF, KP, and SFP extracts as natural and safe alternatives have a gastroprotective potential against indomethacin-induced gastric ulceration. The antioxidative and anti-inflammatory properties are probable mechanisms.

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.

Propolis and Its Gastroprotective Effects on NSAID-Induced Gastric Ulcer Disease: A Systematic Review.

Gastric ulcer disease induced by the consumption of NSAIDs is a major public health problem. The therapy used for its treatment causes adverse effects in the patient. Propolis is a natural product that has been used for the treatments of different diseases around the world. Nevertheless, there is little information about the activity of propolis in gastric ulcers caused by treatment with NSAIDs. Therefore, this review evaluates and compares the gastroprotective potential of propolis and its function against NSAID-induced gastric ulcers, for which a systematic search was carried out in the PubMed and ScienceDirect databases. The main criteria were articles that report the gastroprotective activity of propolis against the damage produced by NSAIDs in the gastric mucosa. Gastroprotection was related to the antioxidant, antisecretory, and cytoprotective effects, as well as the phenolic compounds present in the chemical composition of propolis. However, most of the studies used different doses of NSAIDs and propolis and evaluated different parameters. Propolis has proven to be a good alternative for the treatment of gastric ulcer disease. However, future studies should be carried out to identify the compounds responsible for these effects and to determine their potential use in people.

Chemical Constituents and Anti-Gastric Ulcer Activity of Essential Oils of Alpinia officinarum (Zingiberaceae), Cyperus rotundus (Cyperaceae), and Their Herbal Pair.

The essential oil (EO) of the herbal pair (HP), Alpinia officinarum-Cyperus rotundus (HP G-X) has been conventionally used in traditional Chinese medicine (TCM) for 'warming the stomach' and relieving pain. However, its pharmacologically active compounds, as well as the mechanism of its anti-gastric ulcer properties remain unclear. In this study, the EOs obtained from HP G-X and its corresponding single herbs were analyzed using GC/MS. A total of 74, 56, and 85 compounds were detected in A. officinarum (GLJ), C. rotundus (XF), and HP G-X, accounting for 93.2 %, 89.5 %, and 92.0 % of the total content, respectively. GLJ mainly contains 1,8-cineol (22.0 %) and α-terpineol (11.8 %), whereas cyperenone (22.4 %) and cyperene (12.3 %) were the major constituents in XF. These four compounds were also detected in the HP G-X with relatively high composition as 11.8 %, 5.5 %, 11.8 %, and 10.6 %, respectively. Although no new compounds were detected in HP G-X, the relative concentration of some compounds increased, while others decreased or even disappeared. HP G-X showed the lowest toxicity (TC50 >800 µg/mL) against human gastric mucosal epithelial cells (GES-1) and had the best protective effect against ethanol-induced GES-1 cell damage compared to the individual herbs. In vitro studies demonstrated that HP G-X and the corresponding single herbs significantly reduced IL-6, TNF-α, and COX-2. In addition, in vivo investigations indicated that HP G-X can protect the gastric mucosa of mice from ethanol-induced damage by inhibiting the inflammatory reaction and providing analgesia. It can also inhibit the expression of NF-κBp65, COX-2, and TRPV1 protein, reduce the concentrations of IL-6 and TNF-α, and relieve heat-induced pain. This study further substantiated the traditional application of HP G-X against gastric ulcers through both in vivo and in vitro investigations.

Preparation and preliminary quality evaluation of aspirin/L-glutamate compound pellets.

L-glutamate is an important component of protein. It can prevent gastrointestinal damage caused by NSAIDs. We constructed two-phase enteric-coated granules of aspirin and L-glutamate compound by extrusion spheronization method and fluidized bed coating. The subliminal effective dose of L-glutamate is 100 mg/kg tested by model of gastric ulcer of rats induced by aspirin and drug administration. HPLC-UV and UV-Vis methods were adopted to determine content and cumulative release of aspirin and L-glutamate as quality analysis method indexes. The prescription and process optimization were carried out with yield, sphericity and dissolution. The two-phase compound granules have good sphericity of 0.93 ± 0.05 (aspirin pellets) and 0.94 ± 0.02 (L-glutamate pellets), content of salicylic acid (0.24 ± 0.03)%, dissolution of aspirin (2.36 ± 0.11)%. Quality evaluation and preliminary stability meet the commercial requirements. The stored environment of compound preparation should be sealed in a cool and dark place.

Effects of orally administered Euglena gracilis and its reserve polysaccharide, paramylon, on gastric dysplasia in A4gnt knockout mice.

Euglena gracilis is widely utilized as food or supplement to promote human and animal health, as it contains rich nutrients. In this study, we administered spray-dried powder of E. gracilis and paramylon, ß-glucan stored in E. gracilis cells, to A4gnt knockout (KO) mice. A4gnt KO mice are a mutant mouse model that spontaneously develops gastric cancer through hyperplasia-dysplasia-adenocarcinoma sequence in the antrum of the stomach, and we observed the effects of E. gracilis and paramylon on the early involvements of A4gnt KO mice. Male and female 10-week-old A4gnt KO mice and their age-matched wildtype C57BL/6J mice were orally administered with 50 mg of E. gracilis or paramylon suspended in saline or saline as a control. After 3-week administration, animals were euthanatized and the stomach was examined histopathologically and immunohistochemically. Gene expression patterns of the stomach, which have been reported to be altered with A4gnt KO, and IgA concentration in small intestine were also analyzed with real-time PCR and ELISA, respectively. Administration of Euglena significantly reduced the number of stimulated CD3-positive T-lymphocytes in pyloric mucosa of A4gnt KO mice and tend to reduce polymorphonuclear leukocytes infiltration. Euglena administration further downregulated the expression of Il11 and Cxcl1 of A4gnt KO mice. Euglena administration also affected IgA concentration in small intestinal contents of A4gnt KO mice. Paramylon administration reduced the number of CD3-positive lymphocytes in pyloric mucosa of A4gnt KO mice, and downregulated the expressions of Il11 and Ccl2 of A4gnt KO mice. Although we found no significant effects on gross and microscopic signs of gastric dysplasia and cell proliferation, the present study suggests that the administration of Euglena and paramylon may ameliorate the early involvements of A4gnt mice through the effects on inflammatory reactions in the gastric mucosa. The cancer-preventing effects should be studied with long-term experiments until actual gastric cancer formation.

Isolation and characterization of flavonoid compounds from Stachytarpheta jamaicensis (L.) Vahl and its role as anti-gastro ulcerative agent in rats.

CONTEXT: Stomach ulcer is one of the most common gastrointestinal problems in the world. OBJECTIVE: This study aimed to isolate flavonoid compounds from methanol extract of the aerial parts of Stachytarpheta jamaicensis (L.) Vahl. and evaluate its protective and therapeutic effects against gastric ulcer. MATERIALS AND METHODS: Chromatographic techniques were used for the identification of the isolated compounds. To explore the effects of the plant extract, it was administrated by oral gavage for one week either before or post-ethanol ulcer induction. Ranitidine was also evaluated as a reference drug. Stomach pH, gastric juice volume, lesions number, glutathione, superoxide dismutase, malondialdehyde, succinate dehydrogenase, lactate dehydrogenase, acid phosphatase, Interleukin-10, intracellular adhesion molecule-1, prostaglandin E2, and total protein levels were estimated in gastric tissue. Stomach histopathological features were also monitored. RESULTS: Six flavonoid compounds were isolated, where five of them were isolated for the first time (vitexin, isovitexin, apigenin 7,4'-dimethyl ether, 5,7,2'-trimethoxyflavone, and scutellarein), while apigenin was previously reported. Treatment with plant extract recorded amelioration in all the biochemical parameters. CONCLUSION: The methanol extract of plant aerial parts had prophylactic and treatment effects against gastric ulcer in rats, where its treatment effect exceeded its protective role. The extract recorded anti-inflammatory, and antioxidant effects due to the presence of flavonoid compounds.