Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance

2002 ◽  
Vol 283 (1) ◽  
pp. G187-G195 ◽  
Author(s):  
Jun-Ichi Togawa ◽  
Hajime Nagase ◽  
Katsuaki Tanaka ◽  
Masahiko Inamori ◽  
Tadashi Umezawa ◽  
...  

Natural immunomodulator lactoferrin is known to exert an anti-inflammatory effect. However, there have been no studies that examine the mode of action of lactoferrin in reducing intestinal damage. We investigated the effect of lactoferrin on a trinitrobenzenesulfonic acid (TNBS)-induced colitis model in rats. Bovine lactoferrin was given once daily through gavage, starting 3 days before (preventive mode) or just after TNBS administration (treatment mode) until death. The distal colon was removed to be examined. Colitis was attenuated by lactoferrin via both modes in a dose-dependent manner, as reflected by improvement in macroscopic and histological scores and myeloperoxidase activity. Lactoferrin caused significant induction of the anti-inflammatory cytokines interleukin (IL)-4 and IL-10, significant reductions in the proinflammatory cytokines tumor necrosis factor-α and IL-1β, and downregulation of the nuclear factor-κB pathway. We concluded that lactoferrin exerts a protective effect against colitis in rats via modulation of the immune system and correction of cytokine imbalance. Lactoferrin has potential as a new therapeutic agent for inflammatory bowel disease.

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2631 ◽  
Author(s):  
Zeyuan Wang ◽  
Jianfeng Cai ◽  
Qing Fu ◽  
Lingping Cheng ◽  
Lehao Wu ◽  
...  

Fifteen unreported compounds in Anemarrhena asphodeloides, iriflophene (3), hostaplantagineoside C (7), tuberoside G (8), spicatoside B (9), platycodin D (14), platycoside A (15), platycodin D2 (16), polygalacin D2 (17), platycodin D3 (18), isovitexin (20), vitexin (21), 3,4-dihydroxyallylbenzene-3-O-α-l-rhamnopyranosyl(1→6)-β-d-glucopyranoside (22), iryptophan (24), adenosine (25), α-d-Glucose monoallyl ether (26), together with eleven known compounds (1, 2, 4–6, 10–13, 19 and 23), were isolated from the rhizomes of Anemarrhena asphodeloides. The chemical structures of these compounds were characterized using HRMS and NMR. The anti-inflammatory activities of the compounds were evaluated by investigating their ability to inhibit LPS-induced NO production in N9 microglial cells. Timosaponin BIII (TBIII) and trans-hinokiresinol (t-HL) exhibited significant inhibitory effects on the NO production in a dose-dependent manner with IC50 values of 11.91 and 39.08 μM, respectively. Immunoblotting demonstrated that TBIII and t-HL suppressed NO production by inhibiting the expressions of iNOS in LPS-stimulated N9 microglial cells. Further results revealed that pretreatment of N9 microglial cells with TBIII and t-HL attenuated the LPS-induced expression tumor necrosis factor (TNF)-α and interleukin-6 (IL-6) at mRNAs and protein levels. Moreover, the activation of nuclear factor-κB (NF-κB) and phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways were inhibited by TBIII and t-HL, respectively. Our findings indicate that the therapeutic implication of TBIII and t-HL for neurogenerative disease associated with neuroinflammation.


1997 ◽  
Vol 273 (2) ◽  
pp. R623-R629 ◽  
Author(s):  
N. Vergnolle ◽  
C. Comera ◽  
J. More ◽  
M. Alvinerie ◽  
L. Bueno

Lipocortin 1 is considered a mediator of the anti-inflammatory actions of glucocorticoids. We have shown that this protein is overexpressed and secreted during an experimental colitis induced by intraluminal injection of trinitrobenzenesulfonic acid (TNBS) in rats. We studied here the in vivo regulation of lipocortin 1 expression and secretion in this model, either by glucocorticoids using adrenalectomized or dexamethasone-treated (3 mg/24 h) animals or by pituitary factors using hypophysectomized animals. Inflammation was evaluated by measuring myeloperoxidase activity and by histological scoring of the damage. Lipocortin 1 was detected by immunoblotting, and its secretion was studied by incubating colonic specimens in-culture medium. In the colon of TNBS-injected animals, cumulative histological damage scores were increased in adrenalectomized and decreased in dexamethasone-treated animals compared with control and hypophysectomized animals. The colons of all TNBS-injected animals (controls, adrenalectomized, dexamethasone treated, hypophysectomized) overexpressed and secreted lipocortin 1. In conclusion, the induction of lipocortin 1 overexpression and secretion during this colitis occurs independently of glucocorticoids or pituitary factors.


2020 ◽  
Vol 15 (1) ◽  
pp. 1934578X1989950
Author(s):  
Sungchan Jang ◽  
Min-Seon Kim ◽  
Taejin Park ◽  
Ji H. Sim ◽  
Seung-Young Kim

Ligularia taquetii (H. Lev. & Vaniot) Nakai has traditionally been used to treat inflammation and skin swelling in the Jeju Island, Korea. The objective of this study was to investigate the anti-inflammatory and anti-adipogenic effects of Ligularia taquetii ethanoic extract (LTE), in lipopolysaccharide (LPS)-stimulated RAW264.7 cells and 3T3-L1 adipocytes. Lipopolysaccharide-induced inflammation was reduced by LTE in a concentration-dependent manner, via the nuclear factor-κB signaling pathway. Ligularia taquetii ethanoic extract (100 µg/mL) inhibited the LPS-induced production of nitric oxide (NO) and inducible nitric oxide synthase (iNOS), by 60% and 100%, respectively. In comparison, 200 and 100 µg/mL LTE suppressed the LPS-stimulated production of prostaglandin-2 (PGE2) and cyclooxygenase-2 by 50% and 80%, respectively. Ligularia taquetii ethanoic extract also inhibited the secretion of interleukin-1β and interleukin-6 at 300 and 100 μg/mL by 15% and 30%, respectively. High-performance liquid chromatography-photodiode array analysis, combined with mass analysis, revealed chlorogenic acid (CGA) as the anti-inflammatory constituent of LTE. Conversely, 25, 50, 100, and 200 μg/mL LTE lowered the lipid accumulation by 6%, 8%, 25%, and 60%, respectively, while simultaneously increasing cell viability by 7%, 14%, 34%, and 78%. The anti-adipogenic effect of LTE at 100 µg/mL was equivalent to that of CGA at 50 µg/mL. However, LTE treatment promoted cell proliferation by about 30% compared to its CGA-treated counterpart. These results suggest the potential of LTE as a new resource in the discovery of anti-inflammatory and anti-obesity drugs.


2009 ◽  
Vol 4 (2) ◽  
pp. 204-213 ◽  
Author(s):  
Hadi Esmaily ◽  
Azadeh Hosseini-Tabatabaei ◽  
Reza Rahimian ◽  
Reza Khorasani ◽  
Maryam Baeeri ◽  
...  

AbstractInflammatory bowel disease (IBD) is a multifactorial disease with an unknown etiology characterized by oxidative stress, leucocyte infiltration and a rise in inflammatory cytokines. In this study, we have investigated the effects of silymarin, a mixture of several flavonolignans with established antioxidant and anti-inflammatory properties, on trinitrobenzene sulphonic acid (TNBS)-induced colitis in rats. Experimental colitis was induced in male Wistar-albino rats by delivering TNBS to the distal colon. All the medicines were administered by gavage for seven days. Thirty-six male rats were divided into six groups containing six rats in each one. Control rats received only TNBS. In the treated groups, animals were given different doses of silymarin (40, 80, and 160 mg/kg). Dexamethasone (1 mg/kg) was used as the positive treatment. Colonic status was investigated seven days post induction of colitis through macroscopic, histological, and biochemical analyses. Amelioration of the morphological signs including macroscopic damage, necrotic area, and histology were seen subsequent to treating animals with silymarin. These observations were accompanied by a significant reduction in the degree of both neutrophil infiltration, indicated by decreased myeloperoxidase activity, and lipid peroxidation, as measured by a decline in malodialdehyde content in inflamed colon as well as a decrease in levels of inflammatory cytokines (TNF-α and IL-1β). The results of the present study reveal that the beneficial effect of silymarin in bowel cells is mediated through its anti-oxidant and anti-inflammatory potentials.


2018 ◽  
Vol 38 (5) ◽  
pp. 510-518 ◽  
Author(s):  
HM Hafez ◽  
MA Morsy ◽  
MZ Mohamed ◽  
NM Zenhom

Paeonol, a natural phenolic compound, possesses diverse beneficial effects including antioxidant and anti-inflammatory effects. Gastric ulcer is still the most prevalent irritant illness among the gastrointestinal diseases. The present study explored the protective effect of paeonol at two dose levels in indomethacin (IND)-induced gastric ulcer in rats. Forty-eight male Wistar rats were arranged into six groups: control, paeonol-treated, IND-treated, IND/paeonol (low and high doses)-treated, and ranitidine-treated groups. The oxidative status was evaluated by determining malondialdehyde level, superoxide dismutase activity, reduced glutathione content as well as hemoxygenase-1 (HO-1) gene expressions, and the antioxidant protein; NAD(P)H quinone oxidoreductase 1 (NQO1) immunostaining. The pro-inflammatory genes nuclear factor κB (NF-κB) and interleukin 1β (IL-1β) were estimated together with the proapoptotic gene of caspase 3. IND caused multiple gastric ulcers with evident oxidative damage and elevated pro-inflammatory and proapoptotic markers. Paeonol protected significantly, in a dose-dependent manner, the gastric mucosa from ulcerative lesion of IND similar to the reference drug ranitidine. Paeonol pretreatment diminished gastric oxidative stress and restored the gastric antioxidant capacity by elevating gastric gene expression of HO-1 and protein expression of NQO1. Paeonol also reduced NF-κB, IL-1β, and caspase 3 gene expressions. In conclusion, paeonol offered a gastroprotection dependent on its antioxidant, anti-inflammatory, and antiapoptotic effects.


Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2716
Author(s):  
Maciej Salaga ◽  
Adrian Bartoszek ◽  
Agata Binienda ◽  
Julia B. Krajewska ◽  
Adam Fabisiak ◽  
...  

Diet is considered an important trigger in inflammatory bowel diseases (IBD), as feeding habits can affect intestinal permeability and clearance of bacterial antigens, consequently influencing the immune system. Free fatty acid receptors (FFARs), expressed on the intestinal epithelial cells, belong to the family of luminal-facing receptors that are responsive to nutrients. The objective of this study was to characterize the anti-inflammatory activity and the effect on intestinal barrier function of synthetic FFAR agonists in mouse models of colitis. Therapeutic activity of GW9508 (FFAR1 agonist), 4-CMTB (FFAR2 agonist), AR420626 (FFAR3 agonist), and GSK137647 (FFAR4 agonist) was investigated in two models of semi-chronic colitis: induced by trinitrobenzenesulfonic acid (TNBS), mimicking Crohn’s disease, as well as induced by dextran sulfate sodium (DSS), which recapitulates ulcerative colitis in humans. Moreover, we assessed the influence of FFARs agonists on epithelial ion transport and measured the ion flow stimulated by forskolin and veratridine. Administration of FFAR4 agonist GSK137647 attenuated both TNBS-induced and DSS-induced colitis in mice, as indicated by macroscopic parameters and myeloperoxidase activity. The action of FFAR4 agonist GSK137647 was significantly blocked by pretreatment with selective FFAR4 antagonist AH7614. Moreover, FFAR1 and FFAR4 agonists reversed the increase in the colon permeability caused by inflammation. FFAR4 restored the tight junction genes expression in mouse colon. This is the first evaluation of the anti-inflammatory activity of selective FFAR agonists, showing that pharmacological intervention targeting FFAR4, which is a sensor of medium and long chain fatty acids, attenuates intestinal inflammation.


Author(s):  
Sabrina Hadjira ◽  
Amira Mansour ◽  
Caglar Berke ◽  
Ramdane Seghiri ◽  
Ahmed Menad ◽  
...  

Background: In Algerian traditional medicine, Centaurea species are well known in traditherapy. The Centaurea africana has been used in folk medicine for the treatment of several inflammatory disorders. Objective: This study aims to examine the antioxidant, anti-inflammatory and anti-proliferative potential of both nButanol (BECA) and ethyl acetate (EAECA) extracts of Centaurea africana. Methods: The phytochemical analysis of both BECA and EAECA were explored and the antioxidant activities were investigated by measuring the DPPH° scavenging effect, the reducing power and the inhibition of lipid peroxidation (LPO) induced by Fe2+/ascorbic acid system. The anti-inflammatory properties were determined by measuring the NO° scavenging effect and by using carrageenan-induced rat paw oedema. The antiproliferative activity was studied on HT29 (human colorectal adenocarcinoma), OV2008 (human ovarian cancer) and C6 (Rattus norvegicus brain glioma) cell lines using the Sulforhodamine B assay. Results: The total polyphenol contents (TPC) of EAECA and BECA are recorded at 125.24±10.14 and 53.03±2.50 mgGAE/g extract, respectively. Both extracts revealed the antioxidant activity in a concentration-dependent manner; this effect is more pronounced with EAECA. The BECA exhibited a higher anti-inflammatory activity.This antiinflammatory activity was reflected in a reduction of swelling of carrageenan-evoked edemas (48.45 %), inhibition of nitric oxide (84.7 %), effective decrease in myeloperoxidase activity (58.82 %) and malondialdehyde level (65.58 %). The cytotoxic effect of BECA was found to be more pronounced against C6 cell lines (IC50 value: 131.93 µg/mL) while the cytotoxic activity of EAECA was more effective against HT29 and OV2008 cell lines. Conclusion: The obtained results indicated that EAECA exhibited a high antioxidant activity while BECA has a significant anti-inflammatory activity. Both extracts showed cytotoxic effects against cancer cell lines at certain concentrations in a cell-specific manner.


2016 ◽  
Vol 18 (1) ◽  
pp. 38-47 ◽  
Author(s):  
L.S.S. LEAL ◽  
R.O. SILVA ◽  
T.S.L. ARAUJO ◽  
V.G. SILVA ◽  
A.L.R. BARBOSA ◽  
...  

ABSTRACT Seeds of Acacia farnesiana are commonly sold in the local markets of northeastern Brazil as a therapeutic agent. The present work aimed to evaluate the anti-inflammatory and analgesic activities of proteins obtained from A. farnesiana seeds. Five different protein fractions (albumin, globulin, prolamin, acidic and basic glutelins) were obtained and investigated for the protein pattern, the presence of hemagglutinating and proteolytic activities. The globulin fraction (GLB) was also evaluated for anti-inflammatory and analgesic activities. Globulins reduced the paw edema induced by carrageenan in a dose-dependent manner, which was accompanied by a reduction of myeloperoxidase activity (p < 0.05). Additionally, GLB reduced the neutrophil peritoneal migration induced by carrageenan. However, GLB was not able to inhibit the edema triggered by dextran. Pre-treatment with globulins reduced the abdominal constrictions induced by acetic acid as well as the paw licking time induced by formalin (69.1% at first phase). However, it did not produce a significant antinociceptive effect in the hot plate test (55-56 °C). Treating the GLB with heat (at 100 °C for 30 min) abolished its anti-edematogenic and hemagglutinating activities. Our results showed that seeds from A. farnesiana are a source of proteins with anti-inflammatory and analgesic properties.


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