Indomethacin-induced Gastric Ulcer In Rats Research Articles

Protective Effects of Infliximab on Indomethacin-Induced Gastric Ulcer in Rats: The Role of MAPK/NF-KB p65 Signaling Pathway

Protective Effects of Infliximab on Indomethacin-Induced Gastric Ulcer in Rats: The Role of MAPK/NF-KB p65 Signaling Pathway

Mitigation of Indomethacin-Induced Gastric Ulcer in Rats by 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline: Modulation of Inflammatory Mechanisms

Objective: To investigate the gastroprotective influence of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in a rat model of indomethacininducedgastric ulcers. Methods: Thirty male Wistar rats were randomly divided into five groups (n = 6) as follows: Group 1 (control), Group 2 (indomethacin only, 30 mg/kg), Group 3 (indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 30 mg/kg), Group 4 (indomethacin with 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline, 60 mg/kg), and Group 5 (indomethacin with esomeprazole, 30 mg/kg). The efficacy of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline in mitigating gastric ulcers induced by indomethacin in rats was evaluated based on gastric morphology, histopathology, and inflammatory biomarkers. Results: Indomethacin-induced stomach ulcers resulted in epithelial damage and blood streaks on the gastric mucosa. However, treatmentwith indomethacin and 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline (60 mg/kg) significantly (P < 0.05) reduced ulcers compared to the indomethacin-only group. Inflammatory cells were observed in the indomethacin group, while the 60 mg/kg 2,3-Dichloro-6- (trifluoromethoxy) quinoxaline-treated group exhibited the restoration of normal epithelial tissue and minimal inflammatory cells, similar to the control and esomeprazole-treated groups. Furthermore, 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline significantly decreased inflammatory biomarkers (TNF-α, IL-6, INF-γ, and IL-β1) and increased gastroprotective mediator levels (PGE2 and mucin), both with P-values below 0.05, in contrast to the effects of indomethacin. Conclusion: This study provides clinical evidence highlighting the gastroprotective properties of 2,3-Dichloro-6-(trifluoromethoxy) quinoxaline. Its initial application reveals, for the first time, its efficacy in treating gastric ulcers induced by indomethacin. However, further tests are warranted to validate these findings.

Concomitant Effects of Metformin and Vitamin C on Indomethacin-Induced Gastric Ulcer in Rats: Biochemical and Histopathological Approach.

Gastric ulcer is one of the most common and serious conditions in the gastrointestinal tract. One of the main causes of gastric ulcers is using of non-steroidal anti-inflammatory drugs (NSAIDs) which have limited their use in clinical practice. Several studies have revealed that metformin and Vitamin C (Vit C) exhibit protective effects against gastric mucosal damage in different animal models. However, no studies indicate their combination's effect on gastric ulcer models. Therefore, this study aims to investigate the protective effects of metformin and Vit C combination on indomethacin-induced gastric ulcers. In total, thirty rats were divided into six groups, including the control group, rats received indomethacin (50 mg/kg, i.p.), rats received indomethacin and pretreated with ranitidine (100 mg/kg), metformin (100 mg/kg, i.p.), Vit C (100 mg/kg), or metformin combined with Vit C. Four hours after indomethacin administration, rats were euthanized, and gastric tissues were removed for macroscopic, histopathologic, and biochemical examinations. All therapeutics used in this study were found to alleviate gastric mucosal injury caused by indomethacin, as observed in histopathologic and macroscopic evaluations. Both Vit C and metformin were observed to significantly decrease lipid peroxidation and enhance the activity of anti-oxidative enzymes, SOD, GPx, and catalase. However, a more significant effectiveness was observed in catalase and GPx activities when Vit C was co-administered with metformin. In conclusion, the present study revealed that metformin and Vit C combination therapy could potentially treat gastric ulcers associated with indomethacin.

Atractylenolide I Alleviates Indomethacin-Induced Gastric Ulcers in Rats by Inhibiting NLRP3 Inflammasome Activation.

Atractylodes macrocephala Koidz, a traditional Chinese medicine, contains atractylenolide I (ATR-I), which has potential anticancer, anti-inflammatory, and immune-modulating properties. This study evaluated the therapeutic potential of ATR-I for indomethacin (IND)-induced gastric mucosal lesions and its underlying mechanisms. Noticeable improvements were observed in the histological morphology and ultrastructures of the rat gastric mucosa after ATR-I treatment. There was improved blood flow, a significant decrease in the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, and IL-18, and a marked increase in prostaglandin E2 (PGE2) expression in ATR-I-treated rats. Furthermore, there was a significant decrease in the mRNA and protein expression levels of NOD-like receptor thermal protein domain associated protein 3 (NLRP3), apoptosis-associated speck-like protein (ASC), cysteinyl aspartate specific proteinase-1 (caspase-1), and nuclear factor-κB (NF-κB) in rats treated with ATR-I. The results show that ATR-I inhibits the NLRP3 inflammasome signaling pathway and effectively alleviates local inflammation, thereby improving the therapeutic outcomes against IND-induced gastric ulcers in rats.

Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-β1 enhancing activities.

Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-β1). On the other hand, pretreatment with apigenin (10 and 20mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-β1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.

Tamarix aphylla derived metabolites ameliorate indomethacin-induced gastric ulcers in rats by modulating the MAPK signaling pathway, alleviating oxidative stress and inflammation: In vivo study supported by pharmacological network analysis.

Nature has proven to be a treasure resource of bioactive metabolites. In this regard, Tamarix aphylla (F. Tamaricaceae) leaves crude extract was investigated for its gastroprotective effect against indomethacin-induced damage to the gastric mucosa. Additionally, phytochemical investigation of the methanolic extract afforded eight flavonoids' derivatives (1-8). On pharmacology networking study, the isolated compounds identified 123 unique targets where only 45 targets were related to peptic ulcer conditions, these 45 targets include 11 targets specifically correlate to gastric ulcer. The protein-protein interaction defined the PTGS2 gene as one of the highly interacted genes and the complete pharmacology network defined the PTGS2 gene as the most represented gene. The top KEGG signaling pathways according to fold enrichment analysis was the EGFR tyrosine kinase inhibitor resistance pathway. As a result, these findings highlighted the significance of using T. aphylla leaves crude extract as an anti-gastric ulcer candidate, which provides a safer option to chemical antisecretory medicines, which are infamous for their negative side effects. Our findings have illuminated the potent anti-inflammatory and antioxidant effects of T. aphylla, which are likely mediated by suppressing IL-1β, IL-6, TNF-α, and MAPK signaling pathways, without compromising gastric acidity.

Parthenolide alleviates indomethacin-induced gastric ulcer in rats via antioxidant, anti-inflammatory, and antiapoptotic activities.

Parthenolide (PTL) is a sesquiterpene lactone that occurs naturally. It demonstrates a variety of beneficial effects, such as antioxidant, anti-inflammatory, and antiapoptotic properties. The study investigated the potential protective impact of PTL on indomethacin (INDO) induced stomach ulcers in rats. The rats were classified into 5 distinct categories. Group 1 served as the "control" group. Rats in the second group received a single oral dosage of INDO (50 mg kg-1). Rats inGroups three and four received 20 and 40 mg kg-1 oral PTL 1 h before INDO. Omeprazole (30mgkg-1) was given orally to Group 5 rats 1h before INDO. Pretreatment with PTL increased stomach pH and decreased gastric volume as well as reduced the morphological and histological changes induced by INDO. Analysis of probable pathways showed that pre-treatment with PTL successfully reduced oxidative, inflammatory, and apoptotic consequences caused by INDO. The ingestion of PTL leads to a notable increase in the levels of glutathione reduced (GSH) and the activities of superoxide dismutase (SOD) and catalase (CAT). Furthermore, PTL decreased the concentration of malondialdehyde (MDA). In contrast, it was shown that PTL increased both cyclooxygenase-1 (COX-1) and prostaglandin E2 (PGE2). PTL shows a significant decrease in the expression of interleukin-1 beta (IL-1β), tumor necrosis factor-alpha (TNF-α), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB). PTL therapy resulted in a decrease in Bcl-2-associated X protein (Bax) levels and an increase in B-cell lymphoma 2 (Bcl2) levels. In conclusion, PTL offers gastroprotection by its antioxidant, anti-inflammatory, and anti-apoptotic qualities.

The protective effects of Gamma-linolenic acid against indomethacin-induced gastric ulcer in rats.

The primary goal of the investigation was to analyse the anti-inflammatory and antioxidant properties of Gamma-linolenic acid (GLA) on rats with indomethacin (IND)-induced gastric ulcers. Thirty rats were divided into five groups: Control, IND (50 mg/kg, p.o.), IND pretreated with GLA 100 mg/kg (p.o. for 14 d), IND pretreated with GLA 150 mg/kg (p.o. for 14 d) and IND pretreated with omeprazole (20 mg/kg, p.o. for 14 d). The stomach tissues were examined to calculate the ulcer index and pH and analyse biochemical markers (prostaglandin E2 (PGE2), cyclooxygenase 1 (COX1), TNF-1, IL-6 and intercellular adhesion molecule-1 (ICAM1)) and oxidative stress parameters (malondialdehyde: (MDA), superoxide dismutase (SOD), glutathione (GSH) and CAT (catalase)) as well as undergo histopathological assessment. GLA 100 and 150 mg/kg showed a protective effect against IND-induced gastric damage. It reduced levels of COX1, TNF-1, IL-6 and ICAM and increased PGE2 levels. GLA also normalised antioxidant function by modulating MDA, SOD, GSH and CAT. GLA intervention protects against IND-induced gastric ulcers by restoring oxidant/antioxidant balance and reducing inflammation.

Gastro-Protective, Antioxidant, and Anti-Inflammatory Potential of Three Vegetable Oils Against Indomethacin-Induced Gastric Ulceration in Rats: in Vivo and in Vitro Study

Gastro-Protective, Antioxidant, and Anti-Inflammatory Potential of Three Vegetable Oils Against Indomethacin-Induced Gastric Ulceration in Rats: in Vivo and in Vitro Study

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

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

Luteolin ameliorates Indomethacin-Induced Gastric Ulcer in Rats via Activation of Nrf2/HO-1 Pathway

Luteolin ameliorates Indomethacin-Induced Gastric Ulcer in Rats via Activation of Nrf2/HO-1 Pathway

Gastroprotective effect of Vien Khoi Tim capsules on indomethacin-induced gastric ulcers in rats

Available anti-ulcer drugs unveil partial effectiveness and numerous adverse reactions. Plants offer an alternative strategy in the search for new drugs in the therapy and prevention of peptic ulceration. The present study investigated the possible protective effect of the herbal formulation Vien Khoi Tim (VKT) on indomethacin-induced gastric mucosal damage in rats. VKT was tested at two doses (1.44 & 0.48 capsules/kg/d po) ten days before the indomethacin single-dose challenge (40 mg/kg po). Animals were sacrificed six hours after indomethacin administration, and gastric tissues were collected for gross observation and histopathological analyses. The results revealed that the administration of indomethacin caused evident gastric mucosal damage with morphological and histological manifestations. VKT pretreatment tended to avert the rise in lesion numbers, reduce the ulcer index, and improve the severity of bleeding streaks and epithelial sloughing in gastric mucosa on the macroscopic examination compared to the model group. It is worth noting that no ulcerative lesions were observed in the gastric tissues of rats receiving VKT upon microscopic examination. Our results indicated that Vien Khoi Tim capsules might possess a protective role against indomethacin-induced gastric ulcers. Additional research is needed to better understand the mechanism by which Vien Khoi Tim capsules exert their gastroprotective effect.

Apple extract protects against indomethacin-induced gastric ulcers in rats by suppressing oxidative stress – The implication of Nrf-2/HO-1 signaling pathway: In silico and in vivo studies

Gastric ulcers represent a worldwide health problem, characterized by erosions with different degrees in the gastrointestinal mucosa. In the current study, we explore the protective effects of the extract of apple seeds (Malus domestica, family: Rosaceae), regarded as environmental wastes, against indomethacin-induced gastric ulcers in rats. The chemical composition of the seeds extract was investigated through liquid chromatography high-resolution electrospray ionization mass spectrometry (LC-HR-ESI-MS). The metabolomics profiling resulted in identification of 17 compounds (1–17) of different chemical classes. The gene ontology analysis demonstrated that the total extract of M. domestica seeds possess an antiulcer activity through PI3K-Akt signaling pathway as the top identified signaling pathway. The present research work evidenced the reuse of apple seeds waste as an effective therapy to treat NSAIDs-induced gastric ulcer, attributed to its anti-inflammatory and antioxidant properties. It is important to note that the extract does not cause the undesirable effects of traditional antisecretory drugs.

Assessing the hypolipidemic and gastro-liver protective activity of herbal combination with emphasis on PPI amid selected multiple antihypertensive drug combination in experimental animal models.

Peptic ulcer (PU) and hypertension are chronic diseases affecting up to 10% and 30% of the adult population worldwide. Most of these patients will require treatment with a combination of antihypertensive medicines, which have adverse effects on the body's different organs. This study specifically focused on antihypertensive multi-drug induced PU disease and disturbance of liver function. During a 14-day oral administration of antihypertensive drugs, Cilnidipine (1 mg/kg), Rosuvastatin (1 mg/kg), Bisoprolol (0.52 mg/kg), and Clopidogrel (7.81 mg/kg) were observed for their effects on the stomach lining and liver function in Wister albino rats. This study aimed to assess the potential of an herbal combination of (BO) + (BA) + (ZO) 0.26 mg/kg body weight (b.w.) Powder and water mixture on the ulcer, lipid profile, and liver function for 14 days in the treatment of the indomethacin-induced gastric ulcers in rats at doses of 30 mg/kg b.w. for three days. Esomeprazole (20 mg/kg b.w.) is used as a standard reference to evaluate antiulcer activity in rat models. The experiment suggests that the gastroprotective effect of the herbal combination can be attributed to its reducing effect on the peptic and the Serum Glutamic Pyruvic Transaminase (SGPT) levels and within the normal range of 34.67 ± 0.88 IU/L. The results for Total Cholesterol (TC), Triglyceride (TG), High-density lipoprotein (HDL) and Low-density lipoprotein (LDL) of the herbal combination were 52 ± 9.81495 (mg/dl), 70 ± 12.12435 (mg/dl), 23.33 ± 6.06446 (mg/dl), 14.5 ± 1.32790 (mg/dl), respectively, where the standard group (atorvastatin) 5 mg/kg TC, TG, HDL and LDL were 69.77 ± 9.92 (mg/dl), 47.7 ± 10.35 (mg/dl), 33.43 ± 5.70 (mg/dl), 26.8 ± 3.70 (mg/dl), and control group total cholesterol, triglyceride, HDL and LDL were 68.67 ± 2.20 (mg/dl), 124.07 ± 2.94 (mg/dl), 49.14 ± 1.05 (mg/dl), 54.11 ± 1.15 (mg/dl). CThis investigation reported that antihypertensive drugs did not produce gastrointestinal (GI) toxicity, and the morphological structure of the organ was not changed. So, it could be concluded that the herbal combination used in this experiment has a promising role in controlling lipid profile, liver function, and antiulcer effects. Moreover, multiple drug therapy for hypertension does not cause any harm to the stomach. Further investigations might be carried out on a larger scale to make these statements more valid.

Protective Effects of Ethanol Extract from Hippophae rhamnoides L. Leaves against Indomethacin-Induced Gastric Ulcer in Rats

We aimed to determine the effects of ethanol extract of Hippophae rhamnoides L. leaves on indomethacin-induced gastric ulcer in rats. 35 male Sprague Dawley rats were divided into 7 groups (n=5) at random: healthy; Hippophae rhamnoides L. leaves ethanol extract (HR) III; indomethacin; indomethacin+famotidine; indomethacin+HRI (100 mg/kg); indomethacin +HRII (250 mg/kg) and indomethacin +HRIII (500 mg/kg). All rats except the healthy group fasted for 24 hours. At the end of this period, HR and famotidine (20 mg/kg) were administered by oral gavage to the corresponding rat groups. Five minutes after the HR treatments, 25 mg/kg of indomethacin was applied by oral gavage to all groups except the Healthy and HR III groups. Six hours after indomethacin administration, stomach tissues were removed for investigation macroscopic and biochemically (Superoxide dismutase activity, Glutathione, and Malondialdehyde levels). HR administration improved ulcerative injury in stomach tissues caused by the indomethacin-induced gastric ulcer. HR administration reduced indomethacin-induced ulcer areas. Moreover, HR treatment significantly decreased malondialdehyde levels, increased glutathione levels, and elevated superoxide dismutase activity. HR significantly improved gastric ulcer by alleviating oxidative stress that could be important in ulcer. HR may be a new potential treatment option for ulcer treatment with an antioxidant effect. These findings may provide a mechanistic basis for using HR leaves to treat gastric ulcer.

Huang-Qi-Jian-Zhong-Tang accelerates healing of indomethacin-induced gastric ulceration in rats via anti-inflammatory and antioxidant mechanisms

Ethnopharmacological relevanceHuang-Qi-Jian-Zhong-Tang (HQJZT) is a canonical traditional Chinese medicine (TCM) formula that has been widely used in both the prevention and treatment of gastrointestinal diseases, including gastric ulcer, duodenal ulcer, and chronic atrophic gastritis, in China. Aim of the studyIn the present study, we investigated the gastroprotective potential of HQJZT in a rat model of indomethacin (IND)-induced gastric ulcer and explained the biochemical, cellular, and molecular mechanisms involved. Materials and methodsObservations were conducted at the macroscopic level to ascertain the ulcer index (UI) and the curative index (CI). Histopathological examinations were conducted, and a microscopic score (MS) was computed. The gastric juice volume, total acidity, pH value, and pepsin activity were quantified. Antioxidant and oxidative parameters were assessed, namely GSH, CAT, SOD, and MDA content. The RFLSI Pro instrument was employed to measure the blood flow within the gastric mucosa continuously. The mRNA levels of the inflammatory cytokines were assessed using droplet digital PCR (ddPCR). Molecular docking was employed to examine the interaction between representative active components of HQJZT and the binding sites associated with the NF-κB and STAT signaling pathways. The protein expression and localization of p-JAK, p-STAT, p-IκBβ, and p–NF–κB were evaluated through immunofluorescence analysis. ResultsThe administration of HQJZT treatment demonstrated a significant reduction in gastric lesions induced by IND, leading to a notable decrease in the UI. Additionally, HQJZT treatment significantly decreased gastric juice volume, acidity, and pepsin activity, accompanied by increased pH value. IND-treated stomachs exhibited severe hemorrhagic necrosis, submucosal edema, and epithelial cell destruction. However, the administration of HQJZT effectively counteracted these pathological changes. Furthermore, HQJZT administration significantly increased blood flow to the gastric mucosa. HQJZT enhanced antioxidant defenses and modulated oxidative stress by increasing SOD, CAT, and GSH activities while reducing MDA levels. Moreover, HQJZT reversed IND-induced increases in mRNA expression levels of inflammatory cytokines. Molecular docking analysis revealed that the representative active components of HQJZT could bind to the NF-κB and STAT signaling pathways. In addition, immunofluorescence microscopy revealed that HQJZT markedly attenuated the phosphorylation of IκΒβ, NF-κB, JAK, and STAT. ConclusionsThe therapeutic and protective effect of HQJZT on gastric ulcers is attributed to its ability to suppress gastric acid secretion, enhance antioxidative defenses and blood flow, mitigate proinflammatory cytokines, and inhibit the activation of NF-κB and STAT signaling pathways.

Caffeic acid phenethyl ester attenuates indomethacin-induced gastric ulcer in rats.

Gastric ulcer is one of the most frequent gastrointestinal ailments worldwide. Indomethacin, one of the most potent NSAIDs, suffers undesirable ulcerogenic activity. Caffeic acid phenethyl ester (CAPE) has known health benefits. The current study examined the potential of CAPE to combat indomethacin-induced gastric ulcers in rats. Animals were randomized into 5 groups: control, Indomethacin (50 mg/kg) mg/kg), Indomethacin + CAPE (5 mg/kg/day), Indomethacin + CAPE (10 mg/kg), and Indomethacin + Omeprazole (30 mg/kg). CAPE prevented the rise in ulcer index, attenuated histopathological changes and preserved gastric mucin concentration. CAPE efficiently significantly prevented accumulation of malondialdehude (MDA) and prevented exhaustion of the enzymatic activities of catalase (CAT) and superoxide dismutase (SOD). Further, CAPE prevented the rise in the expression of tumor necrosis factor-α (TNF-α), cyclo-oxygenase-2 (COX-2) and nuclear factor kapp-B (NFκB). This was associated with down-regulation of Bax and up-regulation of Bcl-2 mRNA. Finally, CAPE prevented induced indomethacin-induced decrease in heat shock protein 70 (HSP70) in gastric tissues. In conclusion, CAPE possesses the ability to prevent indomethacin-induced gastric ulcer in rats. This involves, at least partially, antioxidation, anti-inflammation, anti-apoptosis and enhancement of HSP70 expression.

An integrated network analysis, RNA-seq and in vivo validation approaches to explore the protective mechanism of Mongolian medicine formulae Ruda-6 against indomethacin-induced gastric ulcer in rats.

Gastric ulcer (GU) is one of the most prevalent digestive diseases that seriously affects people's health. Previous studies have demonstrated the anti-GU effect of Ruda-6 (RD-6), a classic formulae of traditional Mongolian medicine. However, the underlying mechanism of RD-6 against GU remains elusive. Thus, we conducted an integrative approach of network analysis, RNA-seq, and in vivo validation experiment to elucidate the therapeutic mechanisms of RD-6 in preventing GU. A network analysis was performed to predict the potential targets of RD-6. Rats were pretreated with RD-6 at different doses for 21days, followed by GU induction with indomethacin injection. The ulcer index and inhibition rates were calculated, and the levels of inflammatory related factors were determined by ELISA. The gastroprotective mechanism of RD-6 against ulceration was verified by RNA-seq and the key pathway was detected by in vivo validation. As the network analysis predicted, RD-6 exerts anti-GU effects by regulating 75 targets and 160 signaling pathways. Animal experiment results suggested that pretreatment with RD-6 significantly ameliorated the gastric mucosal injury and inflammatory response, as evidenced by a reduced ulcer index, decreased interleukin (IL)-1β, IL-6, and IL-17 levels, and increased prostaglandin E2 (PGE2) levels in the GU model rats induced by indomethacin. RNA-seq data identified four potential hub genes that were primarily involved in the IL-17 signaling pathway. Furthermore, in vivo validation experiment showed that RD-6 inhibited the IL-17 signaling pathway by down-regulating the expression of IL17RA, proto-oncogene C-Fos (FOS), IL1B and prostaglandin-endoperoxide synthase 2 (PTGS2). Taken together, the present study provides evidence that RD-6 could effectively protect against indomethacin-induced GU, which might be attributed to suppressed inflammation. The IL-17 signaling pathway may be one of the crucial mechanisms that mediates the effect of RD-6.

Gastroprotective Effect of Bidens pilosa L. Leaves against Indomethacin-Induced Gastric Ulceration in Rats

Gastroprotective Effect of Bidens pilosa L. Leaves against Indomethacin-Induced Gastric Ulceration in Rats

Andrographis paniculata as Promising Novel Protective Therapy of Oxidative Stress in Indomethacin-Induced Gastric Ulcer in Rats

This research investigated the effect of Andrographis paniculata (AP) on oxidative stress following indomethacin-induced gastric ulcer in rats. A total of 20 male albino Wistar rats (150-180g) used for this study were grouped into four (n=5): 1, Negative Control; 2, Positive Control and 3, test group treated with normal chow, 20mg/kg indomethacin, 20 mg/kg indomethacin plus omeprazole at 20mg/kg and 20mg/kg indomethacin plus AP at 16.7 mg/kg respectively. After treatment period, estimation of oxidative stress parameters was carried out on the animals. The LD50 of aqueous extract of AP was 50mg/kg bw. Body weight change was significantly reduced in omeprazole treated group compared to all other groups while extract treated group had significantly increased body weight change. There was a significant increase in malondialdehyde (MDA) level of ulcer untreated group compared to other groups. The two treated groups had significantly reduced MDA compared to ulcer untreated group. There was a significant decrease in the levels of GPx and SOD of ulcer untreated group compared to control. Meanwhile, these were significantly increased in extract and omeprazole treated groups compared to ulcer untreated group. Catalase was significantly increased in all three groups when compared to control but its level was significantly increased in extract treated group compared to ulcer untreated and omeprazole treated groups. From this study, AP has proved to protect against oxidative stress implicated in the pathogenesis of ulcer. If this result is applicable to humans, further research and use of AP in ameliorating debilitating consequences of peptic ulcer should be encouraged.