scholarly journals The Anti-Inflammatory Role of Mannich Curcuminoids; Special Focus on Colitis

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1546 ◽  
Author(s):  
Gábor J. Szebeni ◽  
Lajos I. Nagy ◽  
Anikó Berkó ◽  
Alexandra Hoffmann ◽  
Liliána Z. Fehér ◽  
...  

The incidence of inflammatory bowel disease (IBD) increases gradually in Western countries with high need for novel therapeutic interventions. Mannich curcuminoids, C142 or C150 synthetized in our laboratory, have been tested for anti-inflammatory activity in a rat model of TNBS (2,4,6-trinitrobenzenesulphonic acid) induced colitis. Treatment with C142 or C150 reduced leukocyte infiltration to the submucosa and muscular propria of the inflamed gut. C142 or C150 rescued the loss of body weight and C150 decreased the weight of standard colon preparations proportional with 20% less tissue oedema. Both C142 and C150 curcumin analogues caused 25% decrease in the severity of colonic inflammation and haemorrhagic lesion size. Colonic MPO (myeloperoxidase) enzyme activity as an indicator of intense neutrophil infiltration was 50% decreased either by C142 or C150 Mannich curcuminoids. Lipopolysaccharide (LPS) co-treatment with Mannich curcuminoids inhibited NF-κB (nuclear factor kappa B) activity on a concentration-dependent manner in an NF-κB-driven luciferase expressing reporter cell line. Co-treatment with LPS and curcuminoids, C142 or C150, resulted in NF-κB inhibition with 3.57 μM or 1.6 μM half maximal effective concentration (EC50) values, respectively. C150 exerted a profound inhibition of the expression of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-4 (IL-4) in human PBMCs (peripheral blood mononuclear cells) upon LPS stimulus. Mannich curcuminoids reported herein possess a powerful anti-inflammatory activity.

Author(s):  
Sangeeta Mohanty ◽  
Abhisek Pal ◽  
V Badireenath Konkimalla ◽  
Sudam Chandra Si

Objective: The objective of this study was to establish the anti-inflammatory activity of sulforaphane (SFN) in different acute and subchronic models of inflammation. Methods: The anti-inflammatory activity of SFN was evaluated by the secretion of proinflammatory cytokines in rat peripheral blood mononuclear cells (interleukin-6 [IL-6] and tumor necrosis factor alpha [TNF-α]) which are important mediators of inflammation as determined by enzyme-linked immunosorbent assay. Furthermore, paw volume was determined in various acute models of inflammation, and percentage inhibition of granuloma tissue was assessed by cotton pellet-induced granuloma model. From serum, serum glutamic pyruvic transaminase, serum glutamic oxaloacetic transaminase, and alkaline phosphatase levels were determined which is followed by assay for estimation of antioxidants such as superoxide dismutase (SOD), catalase, and glutathione (GSH). Results: SFN showed significant anti-inflammatory activity against paw edema induced by carrageenin/histamine/egg-albumin. A remarkable control in inflammation was observed most notably at the highest test dose of 5 mg/kg in the subchronic granuloma model. In addition, the release of inflammatory cytokines such as IL-6 and TNF-α which is responsible for inflammatory activity gets attenuated by SFN (∗p<0.05; ∗∗p< 0.01). Moreover, toxic control rats showed significant decreased levels of GSH, catalase, and SOD and increased the level of serum hepatic enzymes which gets reversed by SFN in dose-dependent manner. Conclusions: The present findings demonstrated that SFN can recover inflammation by inhibiting TNF-α and IL-6 in inflammation process.


2020 ◽  
Vol 2020 ◽  
pp. 1-19
Author(s):  
Madhuvanthi Chandrakanthan ◽  
Shiroma M. Handunnetti ◽  
Galbada Sirimal Arachchige Premakumara ◽  
Selvaluxmy Kathirgamanathar

This study aimed at investigating the anti-inflammatory potential of essential oil from rhizome and leaf of Alpinia calcarata Rosc. (ACEO) with the focus of its topical anti-inflammatory activity along with its dominant compounds 1,8-cineole and α-terpineol using mouse ear edema model. ACEOs were analyzed by GC-MS. The anti-inflammatory activity was determined by studying the inhibition of overproduction of proinflammatory mediators—nitric oxide, reactive oxygen species, prostaglandins, cyclooxygenases, and cytokines induced by lipopolysaccharides in murine macrophages. Topical anti-inflammatory and antinociceptive activity was studied by 12-O-tetradecanoylphorbol-13-acetate (TPA) induced skin inflammation and formalin-induced pain model in mice, respectively. Rhizome oil has 1,8-cineole (31.08%), α-terpineol (10.31%), and fenchyl acetate (10.73%) as major compounds whereas the ACEO from leaves has 1,8-cineole (38.45%), a-terpineol (11.62%), and camphor (10%). ACEOs reduced the production of inflammatory mediators in vitro in a concentration-dependent manner. Further, ACEO and its major compounds reduced ear thickness, weight, myeloperoxidase, and cytokines significantly (p<0.01) in mouse ear. Dose-dependent reduction in flinching and licking in both the phases of pain sensation concludes the topical analgesic effect. Our findings suggest the potency of topical use of ACEOs for inflammatory disease conditions.


Blood ◽  
2000 ◽  
Vol 96 (5) ◽  
pp. 1879-1888
Author(s):  
Shahram Salek-Ardakani ◽  
John R. Arrand ◽  
David Shaw ◽  
Mike Mackett

Glycosaminoglycans (GAG) are a group of negatively charged molecules that have been shown to bind and directly regulate the bioactivity of growth factors and cytokines such as basic fibroblast growth factor, transforming growth factor-β, IL-7, and interferon-γ. The ability of GAG to interact with human IL-10 (hIL-10) and the effect of these interactions on its biologic activity were analyzed. It was demonstrated by affinity chromatography that hIL-10 binds strongly to heparin–agarose at physiological pH. Biosensor-based binding kinetic analysis indicated an equilibrium dissociation constant, Kd, of 54 nmol/L for this interaction. Human IL-10 stimulated CD16 and CD64 expression on the monocyte/macrophage population within peripheral blood mononuclear cells, with optimal concentrations between 1 and 10 ng/mL. Soluble heparin, heparan sulfate, chondroitin sulfate, and dermatan sulfate were shown to inhibit the hIL-10–induced expression of CD16 and CD64 in a concentration-dependent manner. Heparin and heparan sulfate were most effective with IC50 values of 100 to 500 μg/mL. Considerably higher concentrations of dermatan sulfate and chondroitin 4-sulfate were required with an IC50 of 2000 to 5000 μg/mL, whereas chondroitin 6-sulfate was essentially inactive. The antagonistic effect of heparin on hIL-10 activity was shown to be dependent on N-sulfation, inasmuch as de-N-sulfated heparin had little or no inhibitory effect on the IL-10– induced expression of CD16, whereas the effect of de-O-sulfated heparin was comparable to that of unmodified heparin. Furthermore, the inhibition of cell-bound proteoglycan sulfation reduced the hIL-10–mediated expression of CD16 molecules on monocytes/macrophages. Taken together, these findings support the hypothesis that soluble and cell-surface GAG and, in particular, their sulfate groups are important in binding and modulation of hIL-10 activity.


Author(s):  
Pankaj Lohumi ◽  
Tirath Kumar ◽  
Lipi Nogai

Objective: The work is aimed to draw out the health beneficial properties of a weed (Parthenium hysterophorus Linn). The present work is organized to evaluate the antioxidant and anti-inflammatory activity of the ethanolic root extract of Parthenium hysterophorus Linn.Methods: In the present work the ethanolic extract was determined by using soxhlet apparatus. The antioxidant scavenging activity of this extract was determined by applying three different assay methods: (1) DPPH (1, 1-diphenyl-2-picryl hydrazyl) free radical method. (2) Nitric oxide scavenging assay and (3) Reducing power method. The anti-inflammatory activity was determined by in vivo method i.e. Carrageenan induced rat paw edema.Results: DPPH radical scavenging activities of the standard antioxidant and extracts were found to be increased in dose dependent manner. The percentage inhibition increases from 4.19% to 97.09% within the concentration range of 10µg/ml to 160µg/ml. Parthenium hysterophorus Linn effectively reduced the generation of nitric oxide radicals from sodium nitroprusside solution in a concentration dependent manner and percentage inhibition increases from 3.53% to 55.21% within the concentration range 10µg/ml to 160µg/ml. All the concentrations of extract significantly showed higher absorbance than the absorbance of control reaction (0.9705) in reducing power assay. A Higher absorbance indicates high reducing power due to the formation of reduced intermediates. Parthenium hysterophorus Linn showed highly significant anti-inflammatory activity at a dose of 200 mg/kg and the lesser effect was observed at 100 mg/kg with the percentage change in paw volume at 0 min, 30 min, 60 min, 90 min and 120 min.Conclusion: Thus, from above experimental observations, it can be stated that Parthenium is a natural antioxidant and bearing anti-inflammatory activity. 


Biomedicines ◽  
2019 ◽  
Vol 7 (4) ◽  
pp. 73 ◽  
Author(s):  
Paolo Governa ◽  
Maria Grazia Cusi ◽  
Vittoria Borgonetti ◽  
José Mauricio Sforcin ◽  
Chiara Terrosi ◽  
...  

Bee propolis, especially Euro-Asian poplar propolis, is among the most well-known natural products traditionally used to treat pharyngitis and minor wounds. The aim of this research was to investigate the pharmacological properties responsible for poplar propolis effectiveness using, for the first time, different in vitro approaches applied to a chemically characterized sample. The anti-inflammatory activity was compared with flurbiprofen by determining pro-inflammatory cytokines released by lipopolysaccharide-stimulated human peripheral blood mononuclear cells (PBMC). The antibacterial activity against Gram+ and Gram- bacteria was assessed, as well as antiviral effects on H1N1 influenza a virus. Poplar propolis (5 and 25 µg/mL) exerted a concentration-dependent anti-inflammatory activity. In this range of concentrations, propolis effect was not inferior to flurbiprofen on cytokines released by lipopolysaccharide (LPS)-stimulated human PBMC. Poplar propolis was found to upregulate IL-6 and IL-1β in non-stimulated PBMC. S. aureus, S. pyogenes, and S. pneumoniae were the most susceptible bacterial strains with inhibitory concentrations ranging from 156 to 625 µg/mL. A direct anti-influenza activity was not clearly seen. Effective anti-inflammatory concentrations of propolis were significantly lower than the antibacterial and antiviral ones and results suggested that the anti-inflammatory activity was the most important feature of poplar propolis linked to its rationale use in medicine.


2007 ◽  
Vol 12 (6) ◽  
pp. 800-808 ◽  
Author(s):  
He Xiao ◽  
Jian-Nan Feng ◽  
Zu-Yin Yu ◽  
Lei Zhang ◽  
Ming Yu ◽  
...  

In this study, the authors apply a computer-based strategy to screen thousands of small-molecule, nonpeptidic organic compounds in the Available Chemicals Directory database and to select a series of potential candidates as ligands of the proposed CD4 D1 surface pocket. Then, several cell-based models are used to determine the actual biological functions of these compounds. A small molecule designated A5 ( N-((pyridine-4-yl)methylene)thiophene-2-carbohydrazide) was obtained by a virtual screening followed by 3 cell-based functional assays. The results show that A5 could specifically block the CD4—major histocompatibility complex II binding in a rosetting assay, inhibit the mixed lymphocyte reaction—induced T-cell proliferation in a concentration-dependent manner, and reduce the PMA plus ionomycin—stimulated interleukin-2 secretion from peripheral blood mononuclear cells. ( Journal of Biomolecular Screening 2007:800-808)


2003 ◽  
Vol 47 (12) ◽  
pp. 3704-3707 ◽  
Author(s):  
Jung-Hyun Choi ◽  
Min-Jin Song ◽  
Seung-Han Kim ◽  
Su-Mi Choi ◽  
Dong-Gun Lee ◽  
...  

ABSTRACT The effects of moxifloxacin, a new methoxyfluoroquinolone, on the production of proinflammatory cytokines from human peripheral blood mononuclear cells (PBMCs) were evaluated. Moxifloxacin inhibited the production of tumor necrosis factor alpha (TNF-α) and/or interleukin-6 (IL-6) by PBMCs stimulated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), and heat-killed bacteria in a concentration-dependent manner without cytotoxic effects. The addition of moxifloxacin reduced the population of cells positive for CD-14 and TNF-α and for CD-14 and IL-6 among the LPS- or LTA-stimulated PBMCs. By Western blot analysis, moxifloxacin pretreatment reduced the degradation of IκBα in LPS-stimulated PBMCs. In conclusion, moxifloxacin could interfere with NF-κB activation by inhibiting the degradation of IκBα and reduce the levels of production of proinflammatory cytokines.


2021 ◽  
Vol 12 ◽  
pp. 204062232110486
Author(s):  
Youxia Liu ◽  
Huyan Yu ◽  
Sijing Wu ◽  
Xia Yang ◽  
Congcong Cao ◽  
...  

Background: Our previous study revealed that plasma levels of a-2,6-sialyltransferase 1 (ST6GAL1) were increased in patients with IgA nephropathy (IgAN). ST6GAL1 catalyzes terminal sialylation of IgG to shift the antibody effector function to the anti-inflammatory pattern. However, the role of plasma ST6GAL1 in the progression of IgAN and underlying mechanisms are still unknown. Methods: A total of 180 IgAN patients were included. The kidney outcomes were defined as the eGFR decline or proteinuria remission. Peripheral blood mononuclear cells (PBMCs) were either stimulated with purified sialylated IgG (SA-IgG) or with non-sialylated IgG (NSA-IgG) from IgAN patients to detect the levels of interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) in supernatant. Results: Compared with the lower ST6GAL1 (reference), the risk of eGFR decline decreased for the higher ST6GAL1 group after adjustment for baseline eGFR, systolic blood pressure (SBP), and proteinuria. The results showed that patients with higher ST6GAL1 levels had a higher rate of proteinuria remission. ST6GAL1, expressed as a continuous variable, was a protective factor for eGFR decline and proteinuria remission. An in vitro study showed that the administration of recombinant ST6GAL1 (rST6GAL1) decreased the levels of IL-6 and TNF-α in PBMCs. Furthermore, the administration of rST6GAL1 resulted in the enrichment of SA-IgG in a concentration-dependent manner. In addition, as compared to control, purified SA-IgG-treated PBMCs showed a significant decrease in the expression of IL-6 and TNF-α. Conclusion: Our study indicated that elevated ST6GAL1 was associated with a slower progression of IgAN, which may play a protective effect by increasing IgG sialylation to inhibit the production of proinflammatory cytokines in PBMCs.


2012 ◽  
Vol 141 (1) ◽  
pp. 542-546 ◽  
Author(s):  
Damodharan Vijayalakshmi ◽  
Ramamurthy Dhandapani ◽  
Sivalingam Jayaveni ◽  
Panneer Selvam Jithendra ◽  
Chellan Rose ◽  
...  

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