Intestinal Inflammation In Rats Research Articles

Astragaloside IV ameliorates indomethacin-induced intestinal inflammation in rats through inhibiting the activation of NLRP3 inflammasome

The administration of nonsteroidal anti-inflammatory drugs (NSAIDs) may cause significant intestinal alteration and inflammation and lead to the occurrence of inflammatory diseases resembling duodenal ulcers. Astragaloside IV (AS-IV) is a glycoside of cycloartane-type triterpene isolated from the dried root of Astragalus membranaceus (Fisch.) Bge. (family Fabaceae), and has been used for ameliorating the NSAID-induced inflammation in the small intestine. The present study aimed to investigate the effects of AS-IV on indomethacin (IND)-induced inflammation in the small intestine of rats and its underlying mechanisms. Hematoxylin-eosin (H&E) staining, transmission and scanning electron microscopy were carried out to observe the surface morphology and ultrastructure of the small intestinal mucosa. Immunofluorescence and ELISA tests were employed to detect the expressions of NLRP3, ASC, caspase-1, and NF-κB proteins, as well as inflammatory factors IL-1β and IL-18, to uncover potential molecular mechanisms responsible for mitigating small intestinal inflammation. The results demonstrated that AS-IV significantly decreased the ulcer index, improved the surface morphology and microstructure of the small intestinal mucosa, and increased mucosal blood flow. Molecular docking revealed a strong and stable binding capacity of AS-IV to NLRP3, ASC, caspase-1, and NF-κB proteins. Further experimental validation exhibited that AS-IV markedly decreased levels of IL-1β and IL-18, and inhibited the protein expression of NLRP3, ASC, caspase-1, and NF-κB. Our data demonstrate that AS-IV ameliorates IND-induced intestinal inflammation in rats by inhibiting the activation of NLRP3 inflammasome and reducing the release of IL-1β and IL-18, thereby representing a promising therapy for IND-induced intestinal inflammation.

Moxibustion alleviates intestinal inflammation in ulcerative colitis rats by modulating long non-coding RNA LOC108352929 and inhibiting Phf11 expression

Long noncoding RNA (lncRNAs) are involved in the pathogenesis of ulcerative colitis (UC). Moxibustion, a traditional Chinese medicine, can improve symptoms in patients with UC and reduce intestinal inflammation in rats with UC. However, it remains unclear whether the ameliorative effect of moxibustion on intestinal mucosal inflammation in UC is related to lncRNAs. Thirty-two rats were randomly assigned to four groups: normal control, UC, moxibustion (MOX), and sulfasalazine (SASP). The UC rat model was induced by administering 4% dextran sulfate sodium (DSS) in drinking water. Rats in the moxibustion group underwent bilateral Tianshu (ST25) moxibustion using the herbs-partition moxibustion method. Rats in the sulfasalazine group received SASP solution via gavage twice daily for seven consecutive days. Our results revealed that, compared with the UC group [2.00 (1.00, 2.50)], the DAI score [0.25 (0.00, 0.50)] was significantly lower in the MOX group (P < 0.05). Compared with the UC group [13.00 (11.25, 14.00)], the histopathological score [5.50 (4.00, 7.75)] was significantly lower in the MOX group (P < 0.05). In addition, the CMDI and macroscopic scores were decreased in the MOX group (P < 0.05). Moxibustion significantly decreased the protein expression of inflammatory factors TNF-α, IFN-γ, and IL-1β in the colonic tissues of UC rats (P <0.05), thereby suppressing the inflammatory response. Moreover, moxibustion exerted a regulatory influence on colon lncRNA and mRNA expression profiles, upregulating LOC108352929 and downregulating Phf11 in rats with UC (P <0.05). Moxibustion also led to a reduction in the expression and colocalization of Phf11 and NF-κB in the colons of UC rats. Moreover, knockdown of LOC108352929 in rat enteric glial cells demonstrated a significant upregulation of TNF-α mRNA expression (P <0.05). In summary, these data illustrate that moxibustion effectively ameliorates DSS-induced colonic injury and inflammation while exerting regulatory control over the lncRNA-mRNA co-expression network in UC rats. Collectively, the in vivo and in vitro studies suggested that LOC108352929-Phf11 may serve as a potential biological marker for moxibustion in the treatment of UC.

Total alditols from Cistanche deserticola attenuate functional constipation by regulating bile acid metabolism

Headings ethnopharmacological relevanceFunctional constipation (FC), characterized by chronic constipation, significantly impacts physiological function and induces psychological stress in patients. However, current clinical treatment options for FC are currently limited. Cistanche deserticola, a traditional Chinese medicine that promotes intestinal moisture and bowel relaxation, contains cistanche total alditol extract (CTAE) as its primary active extract. However, the production of CTAE, its overall efficacy, and potential mechanisms for treating FC have yet to been investigated. Aim of the studyThis study aimed to reveal the overall efficacy and potential mechanism of action of CTAE in rats with FC using a combination of stable preparation, pharmacodynamics, non-targeted metabolomics, bile acid metabolomics, and western blotting. Materials and methodsFourteen batches of CTAE underwent quality testing. A rat model of FC was developed using diphenoxylate tablets. The comprehensive pharmacodynamic effects of CTAE on FC were evaluated using fecal characteristics (wet weight, dry weight, and water content), intestinal transmission (colonic EMG amplitude, colonic EMG frequency, propulsion length, and propulsion rate), serum and colon biochemical indicators, distribution of interstitial cells of Cajal (ICC), and pathological examination. Non-targeted metabolomics was performed to assess the changes in endogenous metabolite profiles induced by CTAE. Bile acid metabolomics and western blotting analyses were employed to validate the potential mechanisms of action of CTAE. ResultsCTAE, with a total content of betaine, mannitol, D-fructose, glucose, and sucrose of (75.67 ± 3.73) %, significantly enhanced intestinal transit, regulated neurotransmitters, increased the expression of c-kit in ICC, and alleviated intestinal inflammation in rats with FC. Non-targeted metabolomics revealed that CTAE significantly alleviated FC-induced metabolic disorders, mainly the biosynthesis of primary bile acids. Targeted metabolomic analysis confirmed that CTAE regulated FC-induced bile acid disorders. Western-blotting results confirmed that CTAE increased the expression of CYP8B1, FGF15, TGR5, and FXR, thereby modulating bile acid synthesis and enterohepatic circulation. ConclusionCTAE demonstrates significant therapeutic effects on FC, primarily through the regulation of bile acid synthesis and enterohepatic circulation. These findings provide a promising foundation for the development and clinical application of novel CATE-based drugs.

Effects of intermittent fasting and physical activity on body mass and intestinal inflammation in rats fed a high-fat diet

Obesity has been linked to increased IBD disease activity, lengthened hospital stays, and a higher risk of developing extraintestinal symptoms, according to studies. Therefore, this study aims to evaluate whether intermittent fasting, as well as exercice training on body mass, food intake and intestinal inflammatory in animals feed a high-fat diet. Male wistar rats were used, divided into the following experimental groups: Control Group C (fed with commercial chow), HF group (fed with a high-fat diet), HF + IF Group (fed a high-fat diet associated with Intermittent Fasting), Group C+IF (fed with commercial chow and intermittent fasting) and HF Group +Exercise + IF. The animals were submitted to intermittent fasting protocols of alternate days, in which the animals fasted 24 hours, 3 times a week. A physical activity protocol was applied, where the animals were trained on a programmable treadmill. Body mass and food intake were evaluated weekly and euthanasia and tissue collection were performed at the end of the experiment for morphological evaluation. The results of this study shows that intermittent fasting of alternate days has beneficial effects on adiposity and physiological improvement in the intestine of animals.

Houttuynia cordata Polysaccharide Ameliorates Chronic Inflammation-Induced Intestinal Impairment by Zonula Occludens-1 in Rats

This study aimed to investigate the protective effects of Houttuynia cordata polysaccharide (HCP) against chronic intestinal inflammation in rats that were subjected to low-dose lipopolysaccharide once weekly for 6 weeks. Here, administration of HCP significantly restored morphological changes in the intestine along with enhancement of antioxidant enzymes including superoxide dismutase, catalase, and glutathione peroxidase activities, and reduction of malondialdehyde contents. HCP treatment was also found to attenuate the inflammatory mediators nitric oxide, inducible nitric oxide synthase, total nitric oxide synthase, and interleukin-1beta (IL-lβ) and enhanced the production of short-chain fatty acids. Correspondingly, a significant elevation of zonula occludens-1 (ZO-1) was displayed in the intestine of HCP-treated rats, indicating that the intestinal mechanical barrier could be repaired by HCP treatment. Therefore, these findings suggested that HCP performed protective effects against chronic inflammation-induced intestinal impairment through alleviating inflammation, modifying the redox system, and recovering the intestinal mechanical barrier, mediated by the control of ZO-1 in rats.

Dietary intervention with avocado (Persea americana Mill.) ameliorates intestinal inflammation induced by TNBS in rats.

Nutritional interventions have been shown to be an interesting approach for the treatment of chronic diseases, including inflammatory bowel disease (IBD). Persea americana Mill. (avocado), is a potential food to be used for the prevention or treatment of intestinal inflammation, due to its nutritional value and pharmacological effects. In this study we evaluated if the dietary intervention with avocado fruit pulp could as an intestinal anti-inflammatory diet using a trinitrobenzenesulfonic acid (TNBS) model of intestinal inflammation in rats. For this purpose, 5, 10 or 20% of avocado fruit pulp was incorporated in the diet of rats, for 21days before and 7days after TNBS-induced intestinal inflammation. Dietary intervention with avocado fruit pulp (20%) decreased the extension of colonic lesions (1.38 ± 0.99 vs. 2.67 ± 0.76cm), weight/length colon ratio (151.03 ± 31.45 vs. 197.39 ± 49.48cm), inhibited myeloperoxidase activity (891.2 ± 243.2 vs 1603 ± 158.2 U/g), reduced tumor necrosis factor-α (53.94 ± 6.45 vs. 114.9 ± 6.21pg/mg), interleukin-1β (583.6 ± 106.2 vs. 1259 ± 81.68pg/mg) and interferon gamma (27.95 ± 2.97 vs. 47.79 ± 3.51pg/mg) levels and prevented colonic glutathione depletion (2585 ± 77.2 vs 1778 ± 167.2nmol/g). The consumption of enriched diet with 20% avocado pulp by 28days did not promote any alterations in the biochemical or behavioral parameters evaluated. Avocado showed intestinal anti-inflammatory activity, modulating immune response, and acting as antioxidant. The dietary intervention with avocado was safe, suggesting its potential as a complementary treatment in intestinal inflammation.

Hydrogen-Rich Water Mitigates LPS-Induced Chronic Intestinal Inflammatory Response in Rats via Nrf-2 and NF-κB Signaling Pathways.

Long-term exposure to low-dose lipopolysaccharide can impair intestinal barriers, causing intestinal inflammation and leading to systemic inflammation. Hydrogen-rich water possesses antioxidant and anti-inflammatory functions and exerts inhibitory effects on various inflammatory diseases. In this study, we investigated whether oral hydrogen-rich water could prevent lipopolysaccharide-induced chronic intestinal inflammation. An experimental model was established by feeding hydrogen-rich water, followed by the injection of lipopolysaccharide (200 μg/kg) in the tail vein of rats after seven months. ELISA, Western blot, immunohistochemistry, and other methods were used to detect related cytokines, proteins related to the NF-κB and Nrf-2 signaling pathways, and tight-junction proteins to study the anti-inflammatory and antioxidant effects of hydrogen-rich water. The obtained results show that hydrogen-rich water significantly increased the levels of superoxide dismutase and structural proteins; activated the Nrf-2 signaling pathway; downregulated the expression of inflammatory factors cyclooxygenase-2, myeloperoxidase, and ROS; and decreased the activation of the NF-κB signaling pathway. These results suggest that hydrogen-rich water could protect against chronic intestinal inflammation in rats caused by lipopolysaccharide-induced activation of the NF-κB signaling pathway by regulating the Nrf-2 signaling pathway.

Carvacrol Ameliorates DSS-Induced Intestinal Inflammation in Rats by Suppressing the TLR4/NF-κB Pathway

The present study aimed to explore the therapeutic effects of carvacrol on the ulcerative colitis (UC) inflammation model induced by DSS (dextran sulfate sodium) in rats. Forty rats were randomly divided into the blank, model, low-, middle-, and high-dose carvacrol groups. The rats drank 4.5% DSS for 5 consecutive days to induce the UC model, except for the blank group. Different concentrations of either carvacrol or purified water were supplied by intragastric administration for 7 consecutive days to assess the protective effect of carvacrol on inflammation in UC rats involving the TLR4/NF-κB signaling pathway. In vivo administration of carvacrol was found to ameliorate the symptoms of colitis in rats. Carvacrol significantly improved the pathological symptoms of colitis in the model group and reduced the DAI and pathological scores of rats. At the same time, carvacrol can reduce the expression of IL-6 and TNF-α induced by DSS, inhibit the activation of TLR4, hinder the nuclear translocation of NF-κB (P65), reduce the cleavage of the apoptosis-related protein cleaved-caspase 3, and protect colon cell apoptosis. The results of in vitro experiments showed that carvacrol has a significant inhibitory effect on cell apoptosis caused by the activation of TLR4 induced by LPS and pcDNA3.1tlr4. Research results revealed that carvacrol has a certain protective effect against inflammation-induced injury in ulcerative colitis rats via inhibiting the activation of the TLR4/NF-κB signaling pathway.

Sodium butyrate alleviates intestinal injury and microbial flora disturbance induced by lipopolysaccharides in rats.

Bacterial endotoxin invasion reduces intestinal barrier functions, such as intestinal bacterial translocation and enteric infection. In this study, we investigated whether sodium butyrate (NaB) alleviates lipopolysaccharide (LPS)-induced inflammation by reducing intestinal damage and regulating the microflora. Rats were divided into four groups for the intraperitoneal injection of LPSs and intragastric gavage with NaB: Con, LPS, LPS + NaB, and NaB. The results showed that NaB alleviated intestinal villus injury and inflammatory infiltration caused by LPS. NaB supplementation decreased the mRNA levels of toll-like receptor (TLR)-4, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and the trend was most pronounced in the jejunum. The morphology of the intestinal nucleus and mitochondria was further observed by transmission electron microscopy. The results showed that NaB supplementation alleviated LPS-induced nuclear atrophy, apoptosis, mitochondrial damage, and rupture. Moreover, NaB improved the LPS-induced inflammatory response by regulating the intestinal barrier. Furthermore, 16S rRNA sequencing showed that the LPS increased the abundance of the harmful bacterium Bacteroides, while the abundance of beneficial bacteria decreased. In the LPS + NaB group, the intestinal microbiota destroyed by the LPS was rebalanced, including a decrease in Bacteroides and an increase in Bifidobacterium and Odoribacter. In conclusion, NaB alleviates LPS-induced enteritis by regulating inflammatory cytokines, maintaining the mucosal barrier, and restoring the microbiota changes.

Animal models for inducing inflammatory bowel diseases: integrative review

Objective: To identify and describe comparatively the chemical models of the induction of inflammatory bowel diseases (IBD) in rodents most used and that best mimic the pathogenesis in humans. Methods: Based on an integrative review in the MEDLINE and LILACS databases, it was investigated which experimental induction models were most cited in articles published from 2004 to 2020, with the descriptors "Colitis/CI", "Colitis model ulcerative" and "Intestinal inflammation model." All empirical articles that addressed one or more inflammation models in rats or mice were included. Results: 239 articles were identified; of these, only ten empirical articles were selected. The most used models were colitis induced by TNBS acid, DSS, and colitis induced by acetic acid (AA). Conclusion: It was possible to identify the most used models to promote the induction of intestinal inflammation in rats, and both models proved to be effective according to the limitations observed in the models described, suggesting the need for new works that use more well-defined protocols and that more fully represent the pathophysiological complexity of the disease.

Abdominal paracentesis drainage attenuates intestinal inflammation in rats with severe acute pancreatitis by inhibiting the HMGB1-mediated TLR4 signaling pathway.

BACKGROUNDOur previous studies confirmed that abdominal paracentesis drainage (APD) attenuates intestinal mucosal injury in rats with severe acute pancreatitis (SAP), and improves administration of enteral nutrition in patients with acute pancreatitis (AP). However, the underlying mechanisms of the beneficial effects of APD remain poorly understood.AIMTo evaluate the effect of APD on intestinal inflammation and accompanying apoptosis induced by SAP in rats, and its potential mechanisms.METHODSSAP was induced in male adult Sprague-Dawley rats by 5% sodium taurocholate. Mild AP was induced by intraperitoneal injections of cerulein (20 μg/kg body weight, six consecutive injections). Following SAP induction, a drainage tube connected to a vacuum ball was placed into the lower right abdomen of the rats to build APD. Morphological changes, serum inflammatory mediators, serum and ascites high mobility group box protein 1 (HMGB1), intestinal barrier function indices, apoptosis and associated proteins, and toll-like receptor 4 (TLR4) signaling molecules in intestinal tissue were assessed.RESULTSAPD significantly alleviated intestinal mucosal injury induced by SAP, as demonstrated by decreased pathological scores, serum levels of D-lactate, diamine oxidase and endotoxin. APD reduced intestinal inflammation and accompanying apoptosis of mucosal cells, and normalized the expression of apoptosis-associated proteins in intestinal tissues. APD significantly suppressed activation of the intestinal TLR4 signaling pathway mediated by HMGB1, thus exerting protective effects against SAP-associated intestinal injury.CONCLUSIONAPD improved intestinal barrier function, intestinal inflammatory response and accompanying mucosal cell apoptosis in SAP rats. The beneficial effects are potentially due to inhibition of HMGB1-mediated TLR4 signaling.

β-Carotene attenuates LPS-induced rat intestinal inflammation via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways.

Inflammation is a protective response of the immune defense system and inflammatory response could be regulated by autophagy. β-Carotene has shown anti-inflammatory potential. However, whether β-carotene could alleviate rat intestinal inflammation by modulating autophagy and its anti-inflammation underlying mechanisms remain unknown. In this study, we found that β-carotene significantly reduced (p<.05) the production of nitric oxide (NO), prostaglandin (PG)E2, tumor necrosis factor (TNF)-α, and interleukin-1β (IL-1β) levels by the Griess reaction and enzyme-linked immunosorbent assay (ELISA), and we found that β-carotene significantly suppressed (p<.05) the mRNA expression levels of IL-1β and TNF-α by RT-PCR. In addition, H&E staining revealed that β-carotene could improve intestinal morphology and cell morphology. Furthermore, the levels of signaling proteins of microtubule-associated protein light chain 3 (LC3), AKT, Janus kinase 2/signal transducers and activators of transcription 3 (JAK2/STAT3), nuclear factor-kappa B (NF-κB), and c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) were detected by Western blot analysis. We found that β-carotene significantly attenuated (p<.05) the related signaling proteins activated by lipopolysaccharide (LPS) stimulation in rats. Moreover, this conclusion was also verified in intestinal epithelial cell (IEC)-6. 3-Methyladenine (3-MA) is widely used as inhibitor of autophagy via its inhibitory effect on class III PI3K. Simultaneously, pretreatment of 3-MA suppressed the inhibiting effects of β-carotene on the related signaling proteins. This study demonstrates that β-carotene could attenuate the LPS-induced intestinal inflammation in rats via modulating autophagy and regulating the JAK2/STAT3 and JNK/p38 MAPK signaling pathways. We also found the same phenomenon when we verified the results with the IEC-6 cells. These findings provide new insights into improving the nutritional value of basic diets and enhancing immune performance. PRACTICAL APPLICATIONS: β-Carotene is a generally acknowledged natural carotenoid nutrient that exhibits provitamin A activity, and it is widely found in fruits or vegetables. Our study provide a new insight into the anti-inflammatory mechanism of β-carotene. Treatment with β-carotene can be used for the beneficial effect against LPS-induced inflammation damage. This study not only lays the foundation for the related research on the anti-inflammatory properties of β-carotene in vitro and in rat models, but also holds important significance in the field of food.

L-Glutamine and Physical Exercise Prevent Intestinal Inflammation and Oxidative Stress Without Improving Gastric Dysmotility in Rats with Ulcerative Colitis.

The aim of this study was to evaluate the effects of glutamine supplementation or exercise on gastric emptying and intestinal inflammation in rats with ulcerative colitis (UC). Strength exercise consisted of jump training 4 × 10 repetitions/5 days a week/8 weeks with progressive overload. Endurance exercise consisted of swimming without overload for a period of 1 h a day/5 days a week/8 weeks. Another group (sedentary) of animals was supplemented with L-glutamine (1 g/kg of body weight) orally for 8 weeks before induction of UC. Colitis was induced by intra-colonic administration of 1 mL of 4% acetic acid. We assessed gastric emptying, macroscopic and microscopic scoring, oxidative stress markers, and IL-1β, IL-6, and (TNF-α) levels. The UC significantly increased (p < 0.05) the gastric emptying compared with the saline control group. We observed a significantly decrease (p < 0.05) in body weight gain in UC rats compared with the control groups. Both exercise interventions and L-glutamine supplementation significantly prevented (p < 0.05) weight loss compared with the UC group. Strength and endurance exercises significantly prevented (p < 0.05) the increase of microscopic scores and oxidative stress (p < 0.05). L-glutamine supplementation in UC rats prevented hemorrhagic damage and improved oxidative stress markers (p < 0.05). Strength and endurance exercises and glutamine decreased the concentrations of inflammatory cytokines IL-1β, IL-6, and TNF-α compared with the UC group (p < 0.05). Strength and endurance exercises and L-glutamine supplementation prevented intestinal inflammation and improved cytokines and oxidative stress levels without altering gastric dysmotility in rats with UC.

Rosiglitazone ameliorates radiation-induced intestinal inflammation in rats by inhibiting NLRP3 inflammasome and TNF-α production.

Radiation-induced acute intestinal injury is a common and serious occurrence following abdominal and pelvic irradiation. The Nod-like receptor protein 3 (NLRP3)-dependant inflammasome and inflammation activation is crucial in this process. In a pre-experimental design of radiation-induced intestinal injury, we found that rosiglitazone inhibited caspase-1 which is a key marker of inflammasome activation. The purpose of the present study was to clarify the inhibitory effect of rosiglitazone on the NLRP3 inflammasome both in vivo and in vitro. Radiation-induced intestinal injury after rosiglitazone treatment, and the expression of interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), caspase-1 and NLRP3 in a radiation-induced intestinal injury model in a rat and macrophages were observed. We found that rosiglitazone ameliorated radiation-induced intestinal injury in rats by suppressing the expression of caspase-1, NLRP3, IL-1β and TNF-α. Treatment with rosiglitazone in vitro reduced the expression of NLRP3, and the NLRP3 activator monosodium urate (MSU) reversed the inhibition of IL-1β and TNF-α by rosiglitazone in macrophages. MSU reversed the protective effect of rosiglitazone on radiation-induced intestinal injury in rats by reversing the rosiglitazone-induced inhibition of IL-1β and TNF-α. Taken together, these findings indicate that the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone, ameliorates radiation-induced intestine inflammation in rats via inhibiting the induction of the NLRP3-dependent inflammasome in macrophages.

Sulfated Polysaccharide from Digenea simplex Decreases Intestinal Inflammation in Rats

Sulfated polysaccharides derived from seaweeds have important biological activities. The aim of this work was to demonstrate the anti-inflammatory effect of a sulfated polysaccharide extracted from the seaweed Digenea simplex (Wulfen) C. Agardh 1822 on 2,4,6-trinitrobenzene sulfonic acid–induced colitis in rats. After inducing colitis, rats were euthanized, and the colon was excised to determine macroscopic lesion scores and wet weight and to histologically evaluate and quantify glutathione, malondialdehyde, myeloperoxidase, nitrate/nitrite, and cytokines. The polysaccharide, composed of β-d-galactose and 3,6-α-l-anhydrogalactose residues, reduced wet weight as well as macroscopic and microscopic lesion scores. It also reduced myeloperoxidase activity; reduced proinflammatory cytokines, malondialdehyde, and nitrate/nitrite levels; and preserved glutathione consumption in the colon. According to these results, we can infer that the sulfated polysaccharide derived from D. simplex has an anti-inflammatory effect on induced colitis in vivo.

Bidens pilosa (Black Jack) Standardized Extract Ameliorates Acute TNBS-induced Intestinal Inflammation in Rats.

Bidens pilosa is an herb popularly used to treat inflammation, hemorrhoids, fever, and gastric ulcers with reported pharmacological activities and chemical composition that sustain its selection as a potential intestinal anti-inflammatory product. Based on this, we examined the effects of a B. pilosa fatty acid-standardized supercritical preparation on the intestinal inflammatory process induced by trinitrobenzenesulphonic acid in rats, using either preventative or curative treatments. We also investigated the safety of plant extract by acute and sub-chronic toxicological analysis. The intestinal anti-inflammatory activity was related to modulation of the immune response, increasing IL-10 production and reducing IL-1β, IL-6, and TNF-α level, the oxidative stress, and the MUC production in the inflamed colon. Optic, scanning, and transmission electron microscopy (TEM) analysis supported the beneficial effects promoted by B. pilosa, which were closely related to downregulation of heparanase, Hsp70, Mapk 3, and NF-κB signaling and with the presence of long-chain fatty acids in extract. Our data suggest that B. pilosa supercritical preparation is a chemically standardized preparation potentially useful as complementary intestinal anti-inflammatory agent to treat inflammatory bowel disease.

Fatty Acid Profile of Synbiotic Cheese and its Effect on Intestinal Inflammation in Rats

Porang (Amorphophallus oncophyllus) is a local perennial plant rich in glucomannan. The objective of this study was to determine the effect of porang glucomannan addition during cheese processing on fatty acid profile, organic acid and vitamin B6 of goat milk cheese ripened with Lactobacillus rhamnosus. In addition, the effect of cheese consumption on short-chain fatty acid profile in the caecum digesta of inflammatory rats was evaluated. We found that the addition of glucomannan to the cheese during its ripening increased the levels of myristic, pentadecanoic acid, and cis-oleic acids. Rats consuming this cheese had elevated cecal levels of propionic, butyric, total short-chain fatty acids, and lactic acid bacteria. Consumption of synbiotic cheese also decreased the intestinal inflammation via increasing the total lactic acid bacteria, propionic, butyric, and total short-chain fatty acids.

Sacral nerve stimulation improves colonic inflammation mediated by autonomic-inflammatory cytokine mechanism in rats.

Vagal nerve stimulation (VNS) was reported to have a therapeutic potential for inflammatory bowel disease (IBD). This study was designed to determine effects and mechanisms of SNS on colonic inflammation of in rodent models of IBD and compare the difference among SNS, VNS, and SNS plus VNS. Intestinal inflammation in rats was induced by intrarectal administration of TNBS (2,4,6-Trinitrobenzenesulfonic acid) on the first day. Five days after intrarectal TNBS, the rats were treated with sham-VNS, VNS, Sham-SNS, SNS, and SNS+VNS for 10days. In another experiment, after 10days of 4% DSS (dextran sodium sulfate) in drinking water, rats were treated with 10-day sham-SNS and SNS. Various inflammatory responses were assessed; mechanisms involving autonomic functions and inflammatory cytokines were investigated. (a) VNS, SNS, and VNS+SNS significantly and equally decreased the disease activity index and macroscopic scores, and normalized colon length; (b) IL-10 was decreased by TNBS but increased with SNS, VNS, and SNS+VNS; pro-inflammatory cytokines, IL-6, IL-17A, MCP-1 and TNF-α, were increased by TNBS but decreased with SNS, VNS, and SNS+VNS (P<.05); MPO activity was decreased by SNS, VNS, and SNS+VNS; (c) SNS, VNS, and SNS+VNS remarkably increased vagal activity that was suppressed by TNBS (P<.05); (d) smilar SNS effects were noted in rats with DSS-induced colitis. SNS presents similar anti-inflammatory effects as VNS by inhibiting pro-inflammatory cytokines and increasing anti-inflammatory cytokines via the autonomic pathway. Similar to VNS, SNS may also have a therapeutic potential for colonic inflammation.

Anti-inflammatory Effects of Abdominal Vagus Nerve Stimulation on Experimental Intestinal Inflammation.

Electrical stimulation of the cervical vagus nerve is an emerging treatment for inflammatory bowel disease (IBD). However, side effects from cervical vagal nerve stimulation (VNS) are often reported by patients. Here we hypothesized that stimulating the vagus nerve closer to the end organ will have fewer off-target effects and will effectively reduce intestinal inflammation. Specifically, we aimed to: (i) compare off-target effects during abdominal and cervical VNS; (ii) verify that VNS levels were suprathreshold; and (iii) determine whether abdominal VNS reduces chemically-induced intestinal inflammation in rats. An electrode array was developed in-house to stimulate and record vagal neural responses. In a non-recovery experiment, stimulation-induced off-target effects were measured by implanting the cervical and abdominal vagus nerves of anaesthetized rats (n = 5) and recording changes to heart rate, respiration and blood pressure during stimulation (10 Hz; symmetric biphasic current pulse; 320 nC per phase). In a chronic experiment, the efficacy of VNS treatment was assessed by implanting an electrode array onto the abdominal vagus nerve and recording in vivo electrically-evoked neural responses during the implantation period. After 14 days, the intestine was inflamed with TNBS (2.5% 2,4,6-trinitrobenzene sulphonic acid) and rats received therapeutic VNS (n = 7; 10 Hz; 320 nC per phase; 3 h/day) or no stimulation (n = 8) for 4.5 days. Stool quality, plasma C-reactive protein and histology of the inflamed intestine were assessed. Data show that abdominal VNS had no effect (two-way RM-ANOVA: P ≥ 0.05) on cardiac, respiratory and blood pressure parameters. However, during cervical VNS heart rate decreased by 31 ± 9 beats/minute (P ≥ 0.05), respiration was inhibited and blood pressure decreased. Data addressing efficacy of VNS treatment show that electrically-evoked neural response thresholds remained stable (one-way RM ANOVA: P ≥ 0.05) and therapeutic stimulation remained above threshold. Chronically stimulated rats, compared to unstimulated rats, had improved stool quality (two-way RM ANOVA: P < 0.0001), no blood in feces (P < 0.0001), reduced plasma C-reactive protein (two-way RM ANOVA: P < 0.05) and a reduction in resident inflammatory cell populations within the intestine (Kruskal–Wallis: P < 0.05). In conclusion, abdominal VNS did not evoke off-target effects, is an effective treatment of TNBS-induced inflammation, and may be an effective treatment of IBD in humans.

Pulmonary Aspergillus fumigatus infection in rats affects gastrointestinal homeostasis

Microbiota inhabiting mucosal tissues is involved in maintenance of their immune homeostasis. Growing body of evidence indicate that dysbiosis in gut influence immune responses at distal sites including lungs. There are also reports concerning gut involvement with pulmonary injury/inflammation in settings of respiratory viral and bacterial infections. The impact of infections with other microorganisms on gut homeostasis is not explored. In this study, the rat model of sublethal pulmonary infection with Aspergillus fumigatus was used to investigate the effect of fungal respiratory infection on gut immune-mediated homeostasis. Signs of intestinal damage, intestinal and gut-draining lymphoid tissue cytokine responses and gut bacterial microbiota diversity were examined. Intestinal injury, inflammatory cell infiltration, as well as increased levels of intestinal interferon-γ (IFN-γ) and interleukin-17 (IL-17) (as opposed to unchanged levels of anti-inflammatory cytokine IL-10) during the two-week period depict intestinal inflammation in rats with pulmonary A. fumigatus infection. It could not be ascribed to the fungus as it was not detected in the intestine of infected rats. Increased production of pro-inflammatory cytokines by major gut-draining mesenteric lymph nodes point to these lymphoid organs as places of generation of cytokine-producing cells. No changes in spleen or systemic cytokine responses was observed, showing lack of the effects of pulmonary A. fumigatus infection outside mucosal immune system. Drop of intestinal bacterial microbiota diversity (disappearance of several bacterial bands) was noted early in infection with normalization starting from day seven. From day three, appearance of new bacterial bands (unique to infected individuals, not present in controls) was seen, and some of them are pathogens. Alterations in intestinal bacterial community might have affected intestinal immune tolerance contributing to inflammation. Disruption of gut homeostasis during pulmonary infection might render gastrointestinal tract more susceptible to variety of physiological and pathological stimuli. Data which showed for the first time gut involvement with pulmonary infection with A. fumigatus provide the baseline for future studies of the impact of fungal lung infections to gut homeostasis, particularly in individuals susceptible to these infections.