Protective Effects of Small-Molecule Oligopeptides Isolated from Tilapia Fish Scale on Ethanol-Induced Gastroduodenal Injury in Rats

Yu L., Li R., Liu W., Zhou Y., Li Y., Qin Y., Chen Y., Xu Y.

Alcohol consumption increases the risk of gastritis and gastric ulcer. Nutritional alternatives are considered for relieving the progression of gastric mucosal lesions instead of conventional drugs that produce side effects. This study was designed to evaluate the gastroprotective effects and investigate the defensive mechanisms of wheat peptides against ethanol-induced acute gastric mucosal injury in rats. Sixty male Sprague–Dawley rats were divided into six groups and orally treated with wheat peptides (0.1, 0.2, 0.4 g/kgbw) and omeprazole (20 mg/kgbw) for 4 weeks, following absolute ethanol administration for 1 h. Pretreatment with wheat peptides obviously enhanced the vasodilation of gastric mucosal blood vessels via improving the gastric mucosal blood flow and elevating the defensive factors nitric oxide (NO) and prostaglandin E2 (PGE2), and lowering the level of vasoconstrictor factor endothelin (ET)-1. Wheat peptides exhibited anti-inflammatory reaction through decreasing inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines tumor necrosis factor α (TNF-α), interleukin (IL)-1β, IL-6, and increasing trefoil factor 1 (TFF1) levels. Moreover, wheat peptides significantly down-regulated the expression of phosphorylated nuclear factor kappa-B (p-NF-κB) p65 proteins in the NF-κB signaling pathway. Altogether, wheat peptides protect gastric mucosa from ethanol-induced lesions in rats via improving the gastric microcirculation and inhibiting inflammation mediated by the NF-κB signaling transduction pathway.

Zhou D., Yang Q., Tian T., Chang Y., Li Y., Duan L., Li H., Wang S.

• Gallic acid (GA) showed protective effects against ethanol-induced gastric ulcer in rats. • The gastroprotective effect of GA could be partly related to the stimulations of gastric nitric oxide and prostaglandin. • Nrf2/HO-1 signaling activation is involved in the protection of GA against ethanol-induced gastric mucosa injury. • Pretreatment with GA could inhibit the apoptosis of gastric mucosal cells. Gallic acid (3,4,5-trihydroxybenzoic acid, GA) is a phenolic compound found in many medicinal plants traditionally used in China or patent medicine such as Feiyangchangweiyan capsule (FY capsule) for the treatment of gastrointestinal diseases for decades. However, the evidence for the gastroprotective effect of GA is deficient and the pharmacological mechanisms remain limited. The present investigation was initiated to demonstrate the gastroprotective effect and to understand potential underlying mechanism of GA on ethanol-induced gastric ulcer in rats. Gastric ulcers were induced by absolute ethanol (5 mL/kg, i.g.) in male Sprague-Dawley rats, GA (10, 30, and 50 mg/kg), FY capsule (0.4 g/kg) and 30 mg/kg Lansoprazole was administered orally. Physiological saline and lansoprazole were used as negative and positive control, respectively. Induction of rats with ethanol resulted in a significant rise in ulcer index, serum levels of inflammatory cytokines markers (IL-1β, IL-6 and TNF-α), TBARS, protein expression of Bax and Caspase-3 and a significant reduction in the activities or levels of endogenous antioxidants (SOD, CAT and GSH), gastric mucosal protective factors (PGE2 and NO) and protein expression of Bcl-2. Pretreatment with GA showed a remarkable decrease in ulcer index, inflammatory cytokines markers, TBARS, protein expression of Bax and Caspase-3 and a significant increase in the activities of endogenous antioxidants, levels of PGE2 and NO, and protein expression of Bcl-2, Nrf2 and HO-1 when compared with ethanol treated groups. This study demonstrated the gastroprotective effect of Gallic acid and FY capsule on ethanol-induced gastric ulcer in rats. The underlying mechanism of GA and FY capsule against gastric ulcer in rats caused by ethanol might be involved in Nrf2/HO-1 anti-oxidative pathway and ultimately played an anti-apoptotic role through regulating Bax, Bcl-2 and Caspase-3.

Liu R., Hao Y., Zhu N., Liu X., Kang J., Mao R., Hou C., Li Y.

The study investigated the protective effect of walnut oligopeptides (WOPs) against ethanol-induced gastric injury using Sprague-Dawley (SD) rats. Rats were randomly divided into seven groups based on body weight (10/group), normal group, ethanol group, whey protein group (220 mg/kg body weight), omeprazole group (20 mg/kg body weight), and three WOPs groups (220, 440, 880 mg/kg body weight). After 30 days of treatment with WOPs, rats were given 5 mL/kg absolute ethanol by gavage to induce gastric mucosal injury. Gastric ulcer index (GUI) were determined and the following measured; gastric content pH, gastric mucin, endogenous pepsinogens (PG), prostaglandin E2 (PGE2), inflammatory cytokines, oxidative stress indicators, and the expression of apoptosis-related proteins were measured to evaluate the gastroprotective effect of WOPs. The results showed that the administration with WOPs markedly mitigated the hemorrhagic gastric lesions caused by ethanol in rats, and decreased the GUI, the gastric content pH, PG1, PG2, and NO levels, enhanced mucin and PGE2. Also, WOPs repressed gastric inflammation through the reduction of TNF-α, IL-6, IL-1β and increase IL-10 levels, and revealed antioxidant properties with the enhancement of superoxide dismutase, glutathione, and catalase activity, while reduction of malondialdehyde. Moreover, WOPs treatment significantly down-regulated Bax, caspase-3 and nuclear factor-κB p65 (NF-κB p65) expression, while up-regulating the expression of Bcl-2 and inhibitor kappa Bα (IκBα) protein. These results indicated that WOPs have protective effects against ethanol-induced gastric mucosal injury in rats through anti-inflammatory, anti-oxidation, and anti-apoptosis mechanisms.

Xiong X., Liang J., Xu Y., Liu J., Liu Y.

The Tilapia collagen peptides mixture TY001 is effective in promoting wound healing in acetic acid-induced skin lesions in zebrafish and in protecting against lipopolysaccharide-induced inflammation and disruption of glucose metabolism in mice. The present study aimed to further examine the wound healing effects of TY001 in streptozotocin-induced diabetic mice.Full-thickness skin excision wounds were created with 8-mm biopsy punches and TY001 was administered via drinking water (15, 30 and 45 g L-1 in emulsion) for 15 days.Wound healing was delayed in diabetic mice but was promoted by TY001 after 5, 10 or 15 days of treatment. Collagen deposition and tissue hydroxyproline contents were increased by TY001. The expressions of insulin growth factor-1, basic fibroblast growth factor, platelet-derived growth factor, transforming growth facts β1, vascular endothelial growth factor and epidermal growth factor were increased by TY001, as indicated by immunobiochemistry and a quantitative polymerase chain reaction. Diabetes-associated serum pro-inflammatory cytokines interleukin (IL)-1β and IL-8 were decreased, whereas anti-inflammatory IL-10 and nitric oxide were increased by TY001, along with increased tissue antioxidant superoxide dismutase and catalase activities. Diabetes-reduced serum protein levels were also recovered by TY001 CONCLUSION: Taken together, Tilapia collagen peptide mixture TY001 was effective with respect to enhancing diabetes-associated wound healing delay, probably via increasing growth factors and collagen deposition in the wound, attenuating diabetes-induced prolonged inflammation, increasing tissue antioxidants and providing nutritional support in diabetic mice. © 2019 Society of Chemical Industry.

Tibbetts S.M., Patelakis S.J., Whitney-Lalonde C.G., Garrison L.L., Wall C.L., MacQuarrie S.P.

Pavlova sp. 459 has been used as a high-quality liquid live-feed for cultivated bivalves, while this is its first evaluation as a low-trophic dry aquafeed ingredient. Pav459 was batch-cultivated in photobioreactors and prepared as an intact-cell meal (direct freeze-drying) and a cell-ruptured meal (freeze-drying following microfluidic high-pressure homogenization) and evaluated for nutritional characteristics relevant for salmonid aquafeeds. Protein quality was based on essential amino acid (EAA) profiles, chemical scores, and in vitro 2-phase gastric/pancreatic digestion (GPD) for salmonids. Nutrients were well-preserved after processing and meals contained 66% protein, 16% lipid, 7% carbohydrate, 24 MJ kg-1 DW energy, and 11% ash. Protein quality of the meals was good as indicated by their high EAA/non-EAA ratios (0.91), high EAA indices of 0.82–1.06 (relative to egg albumin, premium fish meal, and soy protein), high chemical scores (1.4–2.2) for most EAAs (calculated against published salmonid dietary requirements), and high in vitro GPD (82%), irrespective of cell-rupture. Pav459 meals contained health-promoting compounds (fucoxanthin, 358–368 mg (100 g)-1 DW; lutein, 101–162 mg (100 g)-1 DW; total phenolic compounds, 33 mg gallic acid equivalents g−1 DW) with negligible contaminating heavy metals (< 1 ppm) and anti-nutritional factors (ANFs) (1 TUI mg−1 DW trypsin inhibition; < 10 mg g−1DW phytate). Pav459 lipid was highest in PUFA (> 60% of FAME), most of which was nutritionally superior n-3 series (50–52% of FAME) relative to n-6 series (10% of FAME). In addition, the vast majority of n-3 PUFA (81%) was comprised of essential LC-PUFA, eicosapentaenoic acid (EPA, 20:5n-3) at 3% of the meals and docosahexaenoic acid (DHA, 22:6n-3) at 2% of the meals.

Dunlap J.J., Patterson S.

Li D., Li W., Kong S., Li S., Guo J., Guo M., Cai T., Li N., Chen R., Luo R., Tan W.

We wished to investigate the role of a tilapia skin collagen polypeptide (TSCP; molecular weight

Kavitt R.T., Lipowska A.M., Anyane-Yeboa A., Gralnek I.M.

Peptic ulcer disease continues to be a source of significant morbidity and mortality worldwide. Approximately two-thirds of patients found to have peptic ulcer disease are asymptomatic. In symptomatic patients, the most common presenting symptom of peptic ulcer disease is epigastric pain, which may be associated with dyspepsia, bloating, abdominal fullness, nausea, or early satiety. Most cases of peptic ulcer disease are associated with Helicobacter pylori infection or the use of nonsteroidal anti-inflammatory drugs (NSAIDs), or both. In this review, we discuss the role of proton pump inhibitors in the management of peptic ulcer disease, highlight the latest guidelines about the diagnosis and management of H. pylori, and discuss the latest evidence in the management of complications related to peptic ulcer disease, including endoscopic intervention for peptic ulcer-related bleeding. Timely diagnosis and treatment of peptic ulcer disease and its sequelae are crucial in order to minimize associated morbidity and mortality, as is prevention of peptic ulcer disease among patients at high risk, including those infected with H. pylori and users of NSAIDs.

Chakrabarti S., Guha S., Majumder K.

Recent scientific evidence suggests that food proteins not only serve as nutrients, but can also modulate the body’s physiological functions. These physiological functions are primarily regulated by some peptides that are encrypted in the native protein sequences. These bioactive peptides can exert health beneficial properties and thus are considered as a lead compound for the development of nutraceuticals or functional foods. In the past few decades, a wide range of food-derived bioactive peptide sequences have been identified, with multiple health beneficial activities. However, the commercial application of these bioactive peptides has been delayed because of the absence of appropriate and scalable production methods, proper exploration of the mechanisms of action, high gastro-intestinal digestibility, variable absorption rate, and the lack of well-designed clinical trials to provide the substantial evidence for potential health claims. This review article discusses the current techniques, challenges of the current bioactive peptide production techniques, the oral use and gastrointestinal bioavailability of these food-derived bioactive peptides, and the overall regulatory environment.

Yang T., Zhang K., Li B., Hou H.

Protein supplements play an important role in wound healing. The effect of collagen peptide (PCP) and flesh protein peptide (FPP) from Alaska Pollock on wound healing was investigated. The molecular weight distributions of PCP and FPP were in a range of 430–1000 Da and 100–1000 Da, respectively. Compared to vehicle group, the wound healing activities in PCP and FPP were significantly enhanced, which could be corroborated by the increase of wound healing rate, hydroxylproline content, and tensile strength in rat wound model (P

Takeuchi K., Amagase K.

Endogenous prostaglandins (PGs), produced from arachidonic acid by the two isoforms of cyclooxygenase (COX), play a pivotal role in maintaining mucosal integrity by modulating various functions of the gastrointestinal (GI) tract, and PGE2 is most effective in these actions. The PGE2 receptor is classified into 4 specific G-protein coupled subtypes, EP1-EP4, and their distribution accounts for the multiple effects of this prostanoid. PGE2 prevents acid-reflux esophagitis and indomethacin-induced gastric lesions through EP1 receptors, while endogenous PGs protect the stomach against cold restraint stress mediated by mainly PGI2/IP receptors and partly EP4 receptors. PGE2 also exhibits a protective effect against acid-induced duodenal damage and indomethacin-induced small intestinal lesions mediated by EP3/EP4 receptors; these effects in the stomach, duodenum, or small intestine are associated functionally with inhibition of gastric contraction (EP1), stimulation of duodenal HCO3 - secretion (EP3/EP4), or suppression of bacterial invasion due to the inhibition of intestinal motility (EP4) as well as stimulation of mucus secretion (EP3/EP4), respectively. PGE2 also prevents ischemiainduced enteritis and dextran sulfate sodium-induced colitis mediated by EP4 receptors, and the protective mechanisms may be related to the stimulation of mucus secretion and the down-regulation of immune response, respectively. Furthermore, PGE2 shows a healing-promoting effect on gastric ulcers and small intestinal lesions through the up-regulated expression of vascular endothelial growth factor (VEGF) and stimulation of angiogenesis via the activation of EP4 receptors. Finally, COX-1 is mainly responsible for the production of endogenous PGs involved in mucosal protection, while COX-2 is mainly responsible for those involved in the healing of gastric ulcers or small intestinal lesions. These findings contribute to future development of new strategies for the treatment of GI diseases.

Su W., Zhou B., Qin G., Chen Z., Geng X., Chen X., Pan W.

A low pepsinogen (PG) I/II ratio can be used to detect atrophic gastritis (AG). Recent research has found that the PG I/II ratio is associated with several nutritional and metabolic disorders. The aim of this study is to investigate the relationship between the PG I/II ratio and biochemical markers in a Chinese population. In total, 1896 participants in a gastric cancer screening program underwent a health screening test that included assessment of serum pepsinogens. Subjects with PG I/II 

Raish M., Ahmad A., Ansari M.A., Alkharfy K.M., Aljenoobi F.I., Jan B.L., Al-Mohizea A.M., Khan A., Ali N.

This study investigated the therapeutic role of polysaccharides from M. charantia and their mechanism of action against ethanol-induced gastric ulcers in rats. Their effects were determined through macroscopic evaluation of the gastric cavity (gastric ulcer index [GUI]), changes in PGE2, lipid peroxidation (malondialdehyde), antioxidant systems (catalase and reduced glutathione), inflammatory markers (tumor necrosis factor-α [TNF-α], interleukin-6 [IL-6], and myeloperoxidase [MPO]), apoptotic markers (caspase 3, Bax, and Bcl-2), nuclear factor-κB (NF-κB [p65]), and histopathological staining (H&E and PAS). Pretreatment with MCP (300mg/kg p.o.) attenuated the severity of ethanol-induced gastric mucosal damage, reductions in GUI, histopathologic aberrations, and neutrophil invasion, and PGE2 upregulation. These actions were similar to those of omeprazole, a reference anti-ulcer drug. MCP repressed gastric inflammation through the reduction of MPO, TNF-α, and IL-6, and prevented gastric oxidative stress through the inhibition of lipid peroxides with the concomitant enhancement of glutathione and catalase activity. Apoptotic markers indicated that MCP suppressed Bax and caspase-3 activity and enhanced the anti-apoptotic protein Bcl-2, which favored cell survival. MCP downregulated NF-κB and upregulated IκBα. Our study results suggested that the prophylactic administration of MCP reduced ethanol-induced gastric injury in rats through the suppression of gastric inflammation and oxidative stress, predominantly via NF-κB inhibition.

Zhao X., Sun P., Li G., Yi R., Qian Y., Park K.

We conducted the present study to determine the gastric injury preventive effects of polyphenols in Kuding tea (KTPs) in Kunming (KM) mice through the inhibition of gastric-acid secretion and the protection of the gastric mucosa.

Aratani Y.

Myeloperoxidase (MPO) is a heme-containing peroxidase expressed mainly in neutrophils and to a lesser degree in monocytes. In the presence of hydrogen peroxide and halides, MPO catalyzes the formation of reactive oxygen intermediates, including hypochlorous acid (HOCl). The MPO/HOCl system plays an important role in microbial killing by neutrophils. In addition, MPO has been demonstrated to be a local mediator of tissue damage and the resulting inflammation in various inflammatory diseases. These findings have implicated MPO as an important therapeutic target in the treatment of inflammatory conditions. In contrast to its injurious effects at sites of inflammation, recent studies using animal models of various inflammatory diseases have demonstrated that MPO deficiency results in the exaggeration of inflammatory response, and that it affects neutrophil functions including cytokine production. Given these diverse effects, a growing interest has emerged in the role of this well-studied enzyme in health and disease.

Song M., Jia B., Dai D., Xu X., Cao J., Guo J., Wang L., Zhong T., Zhan S., Li L., Zhang H.

BackgroundOptimizing buck semen preservation techniques can significantly advance the goat industry. This study aimed to investigate the effects of chitosan on sperm quality and seminal plasma metabolite profiles in bucks during low-temperature storage at 4°C.ResultsThe results showed that when 0.2 mg/mL chitosan was added to semen dilution, sperm viability and antioxidant capacity were highest and significantly higher than the control group (p &lt; 0.05). Sperm viability decreased progressively with increasing storage time at 4°C. However, on day 5, sperm viability was significantly higher in all groups where chitosan was added to the semen dilutions than in the control group (p &lt; 0.05). A total of 23 classes of metabolites were detected in the non-targeted metabolism group of seminal plasma. The metabolite caused by chitosan mainly included fatty acyls, phospholipids, amino acids and organic acids. Most differential metabolites in fatty acyls and glycerophospholipids in chitosan-treated semen were decreased and enriched in the anabolic pathway of unsaturated fatty acids. Additionally, several oligopeptides showed correlations with sperm quality.ConclusionThese results suggest that adding 0.2 mg/mL chitosan to semen diluent successfully prolongs the low-temperature preservation of semen mainly by altering the anabolism of lipids and amino acids. This provides theoretical support and practical reference for the applying chitosan in the low-temperature preservation of buck semen.

Liu T., Chen Z., Sun L., Xiong L.

ABSTRACT Exploring the link between gut microbiota and chronic gastritis (CG), and assessing the potential mediating influence of blood metabolites. Using aggregated data from genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to explore the genetic links between gut microbiota (412 types) and CG (623,822 cases). Furthermore, we utilized a two-step MR approach to measure the extent to which blood metabolites (1,400 types) mediate the impact of gut microbiota on CG. Through MR, we identified that three genetically predicted gut microbiota increased the risk of CG: the ubiquinol-8 biosynthesis pathway (OR 1.149, 95%CI 1.022–1.291), Odoribacter from the Porphyromonadaceae family (OR 1.260, 95%CI 1.044–1.523), and Coprococcus from the Lachnospiraceae family (OR 1.125, 95%CI 1.010–1.253). Currently, there is no evidence to suggest that genetically predicted CG affects the risk of gut microbiota. Four blood metabolites mediated the proportionate changes in genetically predicted gut microbiota: levels of 4-hydroxyphenylacetate levels by 14.9% (95% CI −0.559%, 30.3%), palmitoleate (16:1n7) levels, and the phosphate to alanine ratio together mediated the same microbiota by 6.97% (95% CI −1.61%, 15.6%) and 7.91% (95% CI −1.67%, 17.5%), while the phosphate to alanine ratio and X-12839 levels together mediated the same microbiota by 8.48% (95% CI −2.87%, 19.8%) and 10.7% (95% CI 0.353%, 21.1%). In conclusion, our research has confirmed a causal link between gut microbiota, blood metabolites, and CG. Metabolites such as 4-hydroxyphenylacetate levels, palmitoleate (16:1n7) levels, the phosphate to alanine ratio, and X-12839 levels have relatively significant mediating roles between gut microbiota and CG. These metabolites may influence the occurrence and development of CG by regulating inflammatory responses, energy metabolism, and gut barrier function. However, the majority of the influence of gut microbiota on CG remains unclear, necessitating further research into other potential mediating risk factors. Clinically, it is crucial to focus on patients suffering from CG who exhibit dysbiosis of gut microbiota. IMPORTANCE The results indicate that interactions between particular gut microbiota and blood metabolites may significantly contribute to the onset and progression of CG. These findings offer new insights and potential targets for early diagnosis, personalized treatment, and prevention of CG.

Shekoohi N., Carson B.P., Fitzgerald R.J.

Liu X., Yuan Z., Luo L., Wang T., Zhao F., Zhang J., Liu D.

Rosa odorata var. gigantea is a popular medicinal plant. Some studies have demonstrated that ethanolic extract of the fruits of R. odorata var. gigantea (FOE) has gastroprotective properties. The aim of this study was to investigate the gastroprotective activity of FOE on water immersion restrained stress (WIRS)-induced gastric mucosal injury in a rat model and elucidate the possible molecular mechanisms involved. A rat stress ulcer model was established in this study using WIRS. After rats were treated with FOE orally for 7 d, the effect of FOE treatment was analyzed by hematoxylin and eosin (H&E) staining, and the changes of inflammatory factors, oxidative stress factors, and gastric-specific regulatory factors and pepsin in the blood and gastric tissues of rats were examined by ELISA assay. Molecular mechanism of FOE was investigated by immunohistochemical assay and Western blot. Compared with the WIRS group, FOE could diminish both the macroscopic and microscopic pathological morphology of gastric mucosa. FOE significantly preserved the antioxidants glutathione peroxidase (GSH-PX), superoxide dismutase (SOD) and catalase (CAT) contents; anti-inflammatory cytokines interleukin-10 (IL-10) and prostaglandin E2 (PGE2) levels as well as regulatory factors tumor necrosis factor-α (TGF-α) and somatostatin (SS) contents, while decreasing malondialdehyde (MDA), nitric oxide synthase (iNOS), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), gastrin (GAS) and endothelin (ET) levels. Moreover, FOE distinctly upregulated the expression of Nrf2, HO-1, Bcl2 and proliferating cell nuclear antigen (PCNA). In addition, FOE activated the expression of p-EGFR and downregulated the expression of NF-κB, Bax, Cleaved-caspase-3, Cyto-C and Cleaved-PARP1, thus promoting gastric mucosal cell survival. The current work demonstrated that FOE exerted a gastroprotective activity against gastric mucosal injury induced by WIRS. The underlying mechanism might be associated with the improvement of anti-inflammatory, anti-oxidation and anti-apoptosis systems.

Mohamed A.O., Abd-Elghaffar S.K., Mousa R.A., Kamel A.A.

Abstract Background Gastric ulcer (GU) is a common gastrointestinal tract illness. Aloe vera has anti-inflammatory, antioxidant, and healing characteristics. This research sought to explore the therapeutic impact of Aloe vera gel on ethanol-provoked GU in rats and to elucidate the underlying mechanisms involved. Methods An ethanol-induced GU rat model was constructed using forty male Wistar rats distributed at random into four groups: control, ulcer, pantoprazole, and Aloe vera. Gross evaluation of the stomach, ulcer index (UI), inhibition index, and gastric pH estimation were analyzed. Gastric malondialdehyde (MDA) and reduced glutathione (GSH) were determined using the spectrophotometric method, and serum gastrin level was measured by an enzyme-linked immunosorbent assay. Gastric nucleotide-binding domain, leucine-rich repeat, and pyrin domain PYD containing protein 3 (NLRP3) and gasdermin D (GSDMD) mRNA expression levels were estimated by quantitative real-time PCR. Finally, the histopathological examination of the glandular part of stomach tissue was done. Results The ulcer group revealed a significant increase in MDA, gastrin, NLRP3, and GSDMD and a decrease in gastric pH and GSH compared to the control group. Gross investigations of the ulcer group revealed a hemorrhagic lesion in the stomach and an increase in UI. Also, histopathological results for this group showed severe epithelial loss, haemorrhage, inflammatory cell infiltration, and blood vessel congestion. However, Aloe vera treatment improved the gross, biochemical, molecular, and histopathological alterations induced by ethanol when compared to the ulcer group. Conclusions Aloe vera exerted antiulcer activities through modulation of oxidant/antioxidant status, anti-secretory properties, and mitigation of pyroptosis.

Zheng H., Liu Y., Lin L., He Y., Zhang K., Chen M., Hong P., Zhou C., Qian Z.

Hepatocellular carcinoma (HCC) is one of the deadliest forms of cancer, but the drugs currently used for its treatment are less than ideal. Tilapia oligopeptides have a wide range of biological activities and are potential sources of new drugs. In this study, the role and mechanism of TBP-1 (Ser-Val-Val-Ala-Ile), an oligopeptide from tilapia, on inflammation and endothelial-mesenchymal transition (EMT) in HCC was investigated using the LPS-induced RAW264.7 inflammation model and the transforming growth factor (TGF)-β1-induced HCC EMT model. The results showed that TBP-1 could effectively inhibit inflammatory response. Moreover, in TGF-β1-induced human hepatocellular carcinoma (HepG2) cells, 100 μM TBP-1 significantly reduced the secretion of N-cadherin (54.2 ± 10.6 %), Vimentin (47.0 ± 9.4 %) and Snail (76.0 ± 9.0 %), increased the secretion of E-cadherin (56.0 ± 16.3 %), inhibited cell metastasis, and participated in the regulatory mechanisms of TGF-β/Smad and non-TGF-β/Smad mediated EMT. TBP-1 may be a potentially valuable inhibitor of HCC.

Xu X., Sui B., Liu X., Sun J.

Due to the lack of an ideal material for TMJ (temporomandibular joint) disc perforation and local inflammation interfering with tissue regeneration, a functional TGI/HA-CS (tilapia type I gelatin/hyaluronic acid-chondroitin sulfate) double network hydrogel was constructed in this paper. It was not only multiply bionic in its composition, structure and mechanical strength, but also endowed with the ability to immunomodulate microenvironment and simultaneously induce in situ repair of defected TMJ discs. On the one hand, it inhibited inflammatory effects of inflammasome in macrophages, reduced the extracellular matrix (ECM)-degrading enzymes secreted by chondrocytes, reversed the local inflammatory state, promoted the proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of synovium-derived mesenchymal stem cells (SMSCs). On the other hand, it gave an impetus to repairing a relatively-large (6 mm-sized) defect in mini pigs’ TMJ discs in a rapid and high-quality manner, which suggested a promising clinical application. • The bionic and functional TGI/HA-CS double network hydrogel had advantages in physical, chemical and mechanical properties. • It inhibited inflammatory effects of inflammasome and reduced secreted ECM-degrading enzymes, thus reversing the local inflammatory state. • It promoted proliferation of TMJ disc cells and induced fibrochondrogenic differentiation of SMSCs via direct and indirect ways.

Ye H., Shang Z., Zhang F., Zha X., Li Q., Luo J.

This study aimed to explore whether Dendrobium huoshanense stem polysaccharide (cDHPS) ameliorates alcohol-induced gastric ulcer (GU) through the strengthening effect of the gastric mucosal barrier in rats and its potential mechanism. In normal rats, the pretreatment of cDHPS effectively strengthened gastric mucosal barrier by increasing mucus secretion and tight junction protein expression. In GU rats, cDHPS supplementation effectively alleviated alcohol-induced gastric mucosal injury and nuclear factor κB (NF-κB)-driven inflammation by strengthening gastric mucosal barrier. Moreover, cDHPS significantly activated nuclear factor E2-related factor 2 (Nrf2) signaling and promoted antioxidant enzymes activities in both normal and GU rats. These results suggested that the pretreatment of cDHPS could strengthen gastric mucosal barrier to inhibit oxidative stress and NF-κB-driven inflammation induced gastric mucosal injury, which was likely related to the activation of Nrf2 signaling.

Salama R.M., Ahmed R.H., Farid A.A., AbdElSattar B.A., AbdelBaset R.M., Youssef M.E., El Wakeel S.A.

Alcohol abuse may lead to the development of gastric mucosal lesions. Dapagliflozin (DAPA), a sodium-glucose cotransporter-2 inhibitor, is clinically used to treat type 2 diabetes mellitus. However, studies showed protective effect of DAPA under various experimental conditions by alleviating oxidative stress and inflammation. The effect of DAPA on experimental gastric ulcer has not been studied yet. Therefore, we attempted to investigate DAPA's protective effect against ethanol (EtOH)-induced gastric lesions. Fifty-six (8-week-old) male Wistar rats were divided into seven groups. DAPA (1, 5, and 10 mg/kg/day; p.o.) was given for seven days, plus a single dose of absolute EtOH (5 ml/kg) on day 8. According to hematoxylin and eosin, and Alcian blue staining of gastric tissue sections, titratable acidity, and macroscopic assessments, DAPA high dose (10 mg/kg) was the most protective, with lesser ulcerations, and higher mucin, relative to the lower two doses and the standard treatment omeprazole (OME). In rats pre-treated with DAPA high dose, colorimetric and ELISA analyses revealed significantly decreased oxidative stress, pro-inflammatory, and apoptosis indices and increased levels of platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF). Western blot analysis revealed reduced pentraxin-3 (PTX3), high-mobility group box 1 (HMGB1), receptor for advanced glycation end products (RAGE), toll-like receptor 4 (TLR4), and myeloid differentiation factor 88 (MyD88) expression. These results were comparable in DAPA (10 mg/kg) and OME pre-treated groups. Overall, DAPA exerted a dose-dependent protective effect against EtOH-induced gastric injury. Gastroprotective effects of DAPA (10 mg/kg) may be associated with influencing HMGB1/RAGE/PTX3 and TLR4/MyD88/VEGF/PDGF pathways.

Alomair M.K., Alabduladheem L.S., Almajed M.A., Alobaid A.A., Alkhalifah E.A., Younis N.S., Mohamed M.E.

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

Liu F., Wang Y., Bello B.K., Fan H., Liu G., Zhang X., Zhang T., Dong Z., Feng X., Chen Y., Teng D., Dong J.

The gastric tissue is often damaged by ingesting large amounts of alcohol. Scutellarin (SCU) is a flavonoid with anti-inflammatory and antioxidant properties. However, its potential effect on alcohol-induced gastric injury has not been investigated. Therefore, the present study investigated its protective effects on gastric injury. Twenty-five male BALB/c mice were divided into five groups, including the control group, alcohol group, SCU (10 mg kg-1, 25 mg kg-1, 50 mg kg-1) combined with alcohol gavage groups. Haematoxylin and eosin (H&E) were used for histopathological observation in gastric tissues. The levels of superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and inducible nitric oxide synthase (iNOS) in gastric tissues were measured by respective biochemical kits. We further investigated the gene expression of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) using real-time quantitative PCR (RT-qPCR). The results demonstrated that alcohol stimulation leads to the production of inflammatory cells. In addition, alcohol stimulation resulted in a significant increase in MDA levels and an obvious decrease in SOD and CAT levels. SCU improves oxidative stress in the gastric by reducing MDA and increasing SOD and CAT levels. It also showed a mitigating effect on the inflammatory response by reducing the transcript levels of Il-1β, Il-6, and Tnf-α, as well as the activity of iNOS. SCU enhances the gastric response to oxidative stress and effectively reduces the inflammatory response. Overall, our data suggest that SCU may be an attractive therapeutic strategy to mitigate the development of gastric tissue injury.

Chakniramol S., Wierschem A., Cho M., Bashir K.M.

Biological molecules in nutraceuticals and functional foods have proven physiological properties to treat human chronic diseases. These molecules contribute to applications in the food and pharmaceutical industries by preventing food spoilage and cellular injury. Technological advancement in the screening and characterization of bioactive peptides has enabled scientists to understand the associated molecules. Consistent collaboration among nutritionists, pharmacists, food scientists, and bioengineers to find new bioactive compounds with higher therapeutic potential against nutrition-related diseases highlights the potential of the bioactive peptides for food and pharmaceutic industries. Among the popular dietary supplements, marine animals have always been considered imperative due to their rich nutritional values and byproduct use in the food and pharmaceutical industries. The bioactive peptides isolated from marine animals are well-known for their higher bioactivities against human diseases. The physiological properties of fish-based hydrolyzed proteins and peptides have been claimed through in vitro, in vivo, and clinical trials. However, systematic study on the physiological and clinical significance of these bioactive peptides is scarce. In this review, we not only discuss the physiological and clinical significance of antioxidant and anticancer peptides derived from marine animals, but we also compare their biological activities through existing in vitro and in vivo studies.