scholarly journals A219 PROTECTIVE EFFECTS OF AKKERMANSIA MUCINIPHILA ON INTESTINAL BARRIER FUNCTION AND INFLAMMATION

2020 ◽  
Vol 3 (Supplement_1) ◽  
pp. 93-94
Author(s):  
J Grondin ◽  
H Wang ◽  
S Haq ◽  
E Y Kwon ◽  
M Surette ◽  
...  
Keyword(s):  
Goblet Cell ◽  
Worm Burden ◽  
Intestinal Inflammation ◽  
Protective Role ◽  
Protective Effects ◽  
Trichuris Muris ◽  
Barrier Integrity ◽  
Akkermansia Muciniphila ◽  
Anti Inflammatory

Abstract Background Akkermansia muciniphila, an anaerobic gram-negative bacteria, accounts for ~3% of human gut microbiota. Despite its mucolytic nature, A. muciniphila has been shown to stimulate mucin production, enhance anti-inflammatory regulatory T cell proliferation and improve gut barrier integrity. Interestingly, an inverse relationship has been established between A. muciniphila and several disease states including inflammatory bowel disease (IBD) suggesting it may have protective and anti-inflammatory effects. However, the precise role and mechanism of A. muciniphila in the pathogenesis of colitis remains unknown. Thus, we hypothesize that A. muciniphila may induce protective effects on intestinal inflammation by influencing host immune response and epithelial barrier integrity. Aims (1) To investigate the protective role of A. muciniphila in intestinal inflammation in a chemically induced model of IBD and (2) to investigate the protective role of A. muciniphila in intestinal inflammation and host defense in a model of enteric parasitic infection. Methods Colitis was induced in germ-free C57BL/6 mice with 2.5% dextran sulphate sodium (DSS) after treatment with either C57BL/6 wild-type (WT) cecal contents or WT cecal contents supplemented with A. muciniphila. Colitis severity was assessed by disease activity index (DAI), macroscopic and histological scores, myeloperoxidase (MPO) assay and cytokine expression. In addition, colitis was induced by Trichuris muris, an intestinal nematode, following treatment with A. muciniphila. Post-infection, the severity of intestinal inflammation was assessed by worm burden, goblet cell staining, cytokines analysis, MPO activity and Muc2 expression. Microbial composition was assessed by 16s rRNA gene sequencing. Results In preliminary studies, mice treated with A. muciniphila and administered DSS for 5 days yielded a significant decrease in DAI, macroscopic scoring, and MPO values compared with controls. IL-10 was also elevated in mice receiving A. muciniphila. Groups receiving A. muciniphila in the T. muris model trended toward decreased worm burden, IL-4, IL-13, as well as increased levels of IL-10, goblet cell expression, and Muc2 and Muc5ac expression. A significant decrease in MPO activity was also observed in the group receiving the A. muciniphila-supplemented gavage. Microbial analysis indicated that 3 weeks post-gavage Akkermansia levels were significantly elevated in groups receiving the A. muciniphila-supplemented WT cecal contents versus WT alone. This significance was maintained post-T. muris infection. Conclusions These findings suggest that A. muciniphila may have a protective role in the context of intestinal inflammation. This research has the potential to fuel the development of novel treatments by utilizing this protective role in IBD. Funding Agencies CIHR

scholarly journals The Protective Role of Feruloylserotonin in LPS-Induced HaCaT Cells

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3064 ◽  
Author(s):  
Yuzhu He ◽  
Byung-gook Kim ◽  
Hye-Eun Kim ◽  
Qiaochu Sun ◽  
Shuhan Shi ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Protective Role ◽  
Related Factor ◽  
Nuclear Factor ◽  
Hacat Cells ◽  
Protective Effects ◽  
Hydroxycinnamic Acid Amides ◽  
Anti Inflammatory ◽  
Underlying Mechanisms

Epidermal inflammation is caused by various bacterial infectious diseases that impair the skin health. Feruloylserotonin (FS) belongs to the hydroxycinnamic acid amides of serotonin, which mainly exists in safflower seeds and has been proven to have anti-inflammatory and antioxidant activities. Human epidermis mainly comprises keratinocytes whose inflammation causes skin problems. This study investigated the protective effects of FS on the keratinocyte with lipopolysaccharides (LPS)-induced human HaCaT cells and elucidated its underlying mechanisms of action. The mechanism was investigated by analyzing cell viability, PGE2 levels, cell apoptosis, nuclear factor erythroid 2-related factor 2 (Nrf2) translocation, and TLR4/NF-κB pathway. The anti-inflammatory effects of FS were assessed by inhibiting the inflammation via down-regulating the TLR4/NF-κB pathway. Additionally, FS promoted Nrf2 translocation to the nucleus, indicating that FS showed anti-oxidative activities. Furthermore, the antioxidative and anti-inflammatory effects of FS were found to benefit each other, but were independent. Thus, FS can be used as a component to manage epidermal inflammation due to its anti-inflammatory and anti-oxidative properties.

scholarly journals Micronized Palmitoylethanolamide Ameliorates Methionine- and Choline-Deficient Diet–Induced Nonalcoholic Steatohepatitis via Inhibiting Inflammation and Restoring Autophagy

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiaji Hu ◽  
Hanglu Ying ◽  
Jie Yao ◽  
Longhe Yang ◽  
Wenhui Jin ◽  
...  
Keyword(s):  
Nonalcoholic Steatohepatitis ◽  
Underlying Mechanism ◽  
Protective Role ◽  
Hepatocellular Injury ◽  
Deficient Diet ◽  
Neuroprotective Effects ◽  
Pathway Activation ◽  
Elevated Expression ◽  
Anti Inflammatory

Nonalcoholic steatohepatitis (NASH) has become one of the serious causes of chronic liver diseases, characterized by hepatic steatosis, hepatocellular injury, inflammation and fibrosis, and lack of efficient therapeutic agents. Palmitoylethanolamide (PEA) is an endogenous bioactive lipid with various pharmacological activities, including anti-inflammatory, analgesic, and neuroprotective effects. However, the effect of PEA on nonalcoholic steatohepatitis is still unknown. Our study aims to explore the potential protective role of PEA on NASH and to reveal the underlying mechanism. In this study, the C57BL/6 mice were used to establish the NASH model through methionine- and choline-deficient (MCD) diet feeding. Here, we found that PEA treatment significantly improved liver function, alleviated hepatic pathological changes, and attenuated the lipid accumulation and hepatic fibrosis in NASH mice induced by MCD diet feeding. Mechanistically, the anti-steatosis effect of PEA may be due to the suppressed expression of ACC1 and CD36, elevated expression of PPAR-α, and the phosphorylation levels of AMPK. In addition, hepatic oxidative stress was greatly inhibited in MCD-fed mice treated with PEA via enhancing the expression and activities of antioxidant enzymes, including GSH-px and SOD. Moreover, PEA exerted a clear anti-inflammatory effect though ameliorating the expression of inflammatory mediators and suppressing the NLRP3 inflammasome pathway activation. Furthermore, the impaired autophagy in MCD-induced mice was reactivated with PEA treatment. Taken together, our research suggested that PEA protects against NASH through the inhibition of inflammation and restoration of autophagy. Thus, PEA may represent an efficient therapeutic agent to treat NASH.

scholarly journals Protective Role of Leptadenia Hastata on the Haematological and Biochemical Alterations in Adrenaline-Induced Hypertensive Rats

2020 ◽  
Vol 14 (1) ◽  
pp. 25-32
Author(s):  
Adewuyi Hassan Abdulsalam ◽  
◽  
Muhammad L. Hadiza ◽  
Onukogu Stella Chiamaka ◽  
Ibrahim Jonathan ◽  
...  
Keyword(s):  
Elevated Serum ◽  
Protective Role ◽  
Protective Effects ◽  
Hypertensive Rats ◽  
Bioactive Constituents ◽  
Once Daily ◽  
Biochemical Alterations ◽  
The Mean ◽  
Normal Controls

Background: Leptadenia hastata (L. Hastata) is a plant used for various diseases in Nigeria. This study evaluated the protective effects of L. hastate on the haematological and biochemical alterations in adrenaline-induced hypertensive rats. Methods: Twenty-five rats were divided equally into five groups (A-E). Groups A-D were given 0.5 mg/kg adrenaline, groups A and B were treated with 100 and 200 mg/kg the extract of L. Hastata, respectively, while groups C and D were treated with 5 mg/kg amlodipine (standard control) and normal saline (untreated control), respectively. Group E were given distilled water (normal controls). The adrenaline was injected intraperitoneally while the extract was given orally once daily for seven days. Results: Treatment with 100 and 200 mg/kg of the extract significantly reduced the elevated serum albumin, ALP, ALT, AST, chloride, sodium and creatinine, cholesterol and LDL concentrations compared with the untreated hypertensive rats. The bicarbonate level, WBC and RBC counts, mean cell hemoglobin and packed cell value were higher in rats treated with the extract compared with the untreated hypertensive rats. The mean cell value, HDL, triglyceride, urea, potassium, total and direct bilirubin concentrations in experimental groups were not significantly different from those in the controls (P<0.05). Conclusion: Our results suggest that treatment of the hypertensive rats with the extract of L. Hastata protects against renal, hepatic and cardiac damages, thus it could be considered as a natural anti-hypertensive agent. Further studies are required to identify the bioactive constituents and the mechanism(s) of action.

scholarly journals Hepato & nephro protective effects of naringenin-loaded tpgs polymeric nanosuspension against cisplatin-induced toxicity

2019 ◽  
Vol 10 (4) ◽  
pp. 2755-2764
Author(s):  
Sumathi Rajamani ◽  
Gobinath Kalyanasundaram ◽  
Tamizharasi Sengodan ◽  
Sivakumar Thangavelu ◽  
Nikhitha K Shanmukhan ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Aqueous Solubility ◽  
Protective Role ◽  
Chemotherapeutic Agents ◽  
Glycol Succinate ◽  
High Pressure Homogenization ◽  
Protective Effects ◽  
Male Wistar Rats ◽  
Nephroprotective Effect

Cisplatin (Cis-Diammineplatinum (II) dichloride/CIS) is one of the most potent chemotherapeutic agents widely used in treatment of various cancers. Naringenin (NAR), a natural flavonoid, protect against CIS-induced injury in rats without hampering CIS beneficial cytotoxic activity. Even though NAR exhibits therapeutic potency, clinical evolution of the molecule is embarrassed because of very less aqueous solubility which corresponds to low availability at the site of the tumor. In our former analysis, nanosuspension of naringenin (NARNS) was developed by the method of high-pressure homogenization. The study had been continued to evaluate the protective role of D-α-Tocopheryl polyethylene glycol succinate (TPGS) coated NARNS, against oxidative stress-induced hepato and nephrotoxicity in male Wistar rats upon CIS treatment. Induction of acute hepato and neprotoxicity was done by intraperitoneal injection (i.p) injection of CIS (7 mg/kg of body weight) and administration of NAR and NARNS. Administration of NARNS virtually suppressed CIS-induced and liver injury evidenced by a reduction of lipid peroxidation level, blood urea nitrogen, serum uric acid, creatinine and elevated enzymatic antioxidant activities of superoxide dismutase, catalase, and glutathione peroxidase in rats liver tissue. Histological studies substantiated the biochemical parameters. The study suggests that NARNS has strong hepato and nephroprotective effect compared to NAR.

Mo1031 PROTECTIVE ROLE OF THE PRO-RESOLVING LIPID MEDIATOR RESOLVIN D1 IN NONSTEROIDAL ANTI-INFLAMMATORY DRUG-INDUCED SMALL INTESTINAL DAMAGE

2020 ◽  
Vol 158 (6) ◽  
pp. S-762
Author(s):  
Takuya Kuzumoto ◽  
Tetsuya Tanigawa ◽  
Hiroyuki Kitamura ◽  
Akira Higashimori ◽  
Yuji Nadatani ◽  
...  
Keyword(s):  
Protective Role ◽  
Lipid Mediator ◽  
Intestinal Damage ◽  
Resolvin D1 ◽  
Drug Induced ◽  
Inflammatory Drug ◽  
Small Intestinal ◽  
Anti Inflammatory

scholarly journals Protective Role of C3aR (C3a Anaphylatoxin Receptor) Against Atherosclerosis in Atherosclerosis-Prone Mice

2020 ◽  
Vol 40 (9) ◽  
pp. 2070-2083
Author(s):  
Lin-Lin Wei ◽  
Ning Ma ◽  
Kun-Yi Wu ◽  
Jia-Xing Wang ◽  
Teng-Yue Diao ◽  
...  
Keyword(s):  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Protective Role ◽  
Plaque Burden ◽  
Aortic Tissue ◽  
M2 Macrophage ◽  
Proinflammatory Mediators ◽  
Anti Inflammatory

Objective: Emerging evidence suggests that C3aR (C3a anaphylatoxin receptor) signaling has protective roles in various inflammatory-related diseases. However, its role in atherosclerosis has been unknown. The purpose of the study was to investigate the possible protective role of C3aR in aortic atherosclerosis and explore molecular and cellular mechanisms involved in the protection. Approach and Results: C3ar −/− /Apoe −/− mice were generated by cross-breeding of atherosclerosis-prone Apoe −/− mice and C3ar −/− mice. C3ar −/− /Apoe −/− mice and Apoe −/− mice (as a control) underwent high-fat diet for 16 weeks were assessed for (1) atherosclerotic plaque burden, (2) aortic tissue inflammation, (3) recruitment of CD11b + leukocytes into atherosclerotic lesions, and (4) systemic inflammatory responses. Compared with Apoe −/− mice, C3ar −/− /Apoe −/− mice developed more severe atherosclerosis. In addition, C3ar −/− /Apoe −/− mice have increased local production of proinflammatory mediators (eg, CCL2 [chemokine (C-C motif) ligand 2], TNF [tumor necrosis factor]-α) and infiltration of monocyte/macrophage in aortic tissue, and their lesional macrophages displayed an M1-like phenotype. Local pathological changes were associated with enhanced systemic inflammatory responses (ie, elevated plasma levels of CCL2 and TNF-α, increased circulating inflammatory cells). In vitro analyses using peritoneal macrophages showed that C3a stimulation resulted in upregulation of M2-associated signaling and molecules, but suppression of M1-associated signaling and molecules, supporting the roles of C3a/C3aR axis in mediating anti-inflammatory response and promoting M2 macrophage polarization. Conclusions: Our findings demonstrate a protective role for C3aR in the development of atherosclerosis and suggest that C3aR confers the protection through C3a/C3aR axis–mediated negative regulation of proinflammatory responses and modulation of macrophage toward the anti-inflammatory phenotype.

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