Purification and Structural Characterization of Sulfated Polysaccharides Derived from Brown Algae, Sargassum binderi: Inhibitory Mechanism of iNOS and COX-2 Pathway Interaction

Among the components derived from brown algae, anionic sulfated polysaccharides, which contain sulfated fucose as the major monosaccharide, exert significant biological activities. In this study, we purified and structurally characterized sulfated polysaccharides from brown algae, Sargassum binderi (S. binderi; SBPs), and evaluated their biological activity in vitro and in vivo. The SBPs were separated based on their charges and their biophysical properties were investigated according to their functional groups, structural features, and molecular weights using FTIR, NMR, and MALS. Among all the SBPs, Fraction 4 (SBP-F4), with an average molecular weight of 2.867 × 105 g/mol, had the highest polysaccharide and sulfate contents (75.15 ± 0.25% and 24.08 ± 0.18%, respectively). The biological activities of SBP-F4 were investigated further in vitro and in vivo. Our results showed that SBP-F4 significantly suppressed the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) proteins in LPS-activated macrophages. Moreover, in the LPS-treated zebrafish model, a significant decrease in cell death and NO production was observed. Collectively, these results show that SBPs not only exert protective effects against LPS-induced cytotoxicity but also inhibit the activation and anti-inflammatory activity of macrophages. Therefore, polysaccharides derived from S. binderi are potential anti-inflammatory agents for use in clinical settings.

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Topical Anti-Inflammatory Effects of Isorhamnetin Glycosides Isolated fromOpuntia ficus-indica

BioMed Research International ◽

10.1155/2015/847320 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 28

Author(s):

Marilena Antunes-Ricardo ◽

Janet A. Gutiérrez-Uribe ◽

Carlos Martínez-Vitela ◽

Sergio O. Serna-Saldívar

Keyword(s):

Biological Properties ◽

Skin Aging ◽

Raw 264.7 Cells ◽

Preparative Chromatography ◽

No Production ◽

Ear Edema ◽

Cox 2 ◽

Anti Inflammatory

Opuntia ficus-indica(OFI) has been widely used in Mexico as a food and for the treatment of different health disorders such as inflammation and skin aging. Its biological properties have been attributed to different phytochemicals such as the isorhamnetin glycosides which are the most abundant flavonoids. Moreover, these compounds are considered a chemotaxonomic characteristic of OFI species. The aim of this study was to evaluate the effect of OFI extract and its isorhamnetin glycosides on different inflammatory markersin vitroandin vivo. OFI extract was obtained by alkaline hydrolysis of OFI cladodes powder and pure compounds were obtained by preparative chromatography. Nitric oxide (NO), cyclooxygenase-2 (COX-2), tumor necrosis factor- (TNF-)α, and interleukin- (IL-) 6 production were measured. NO production was tested in lipopolysaccharide-stimulated RAW 264.7 cells whilein vivostudies were carried on croton oil-induced ear edema model. OFI extract and diglycoside isorhamnetin-glucosyl-rhamnoside (IGR) at 125 ng/mL suppressed the NO productionin vitro(73.5 ± 4.8% and68.7±5.0%, resp.) without affecting cell viability. Likewise, IGR inhibited the ear edema (77.4±5.7%) equating the indomethacin effects (69.5±5.3%). Both IGR and OFI extract significantly inhibited the COX-2, TNF-α, and IL-6 production. IGR seems to be a suitable natural compound for development of new anti-inflammatory ingredient.

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Sargassum Horneri (Turner) C. Agardh Regulates Neuroinflammation via Inhibition of LPS-stimulated Microglia Activation in Vitro and in Vivo

10.21203/rs.3.rs-796365/v1 ◽

2021 ◽

Author(s):

Jun Sik Lee ◽

Jun Hwi Cho ◽

Mi Eun Kim

Keyword(s):

Protein Expression ◽

Brown Algae ◽

Microglia Activation ◽

Sargassum Horneri ◽

No Production ◽

Mapk Phosphorylation ◽

Mice Brain ◽

Cox 2

Abstract Previously we reported that Sargassum horneri (Turner) C. Agardh (S. horneri) is a brown algae species that exerts anti-inflammatory activity toward murine macrophages. However, the anti-neuroinflammatory effects and the mechanism of S. horneri on microglia cells are still unknown. We investigated the anti-neuroinflammatory effects of S. horneri extract on microglia in vitro and in vivo. In present study, we found that S. horneri was not cytotoxic to BV-2 microglia cells, and it significantly decreased lipopolysaccharide (LPS)-induced NO production. Moreover, S. horneri also diminished the protein expression of iNOS, COX-2, and cytokines production including IL-1b, TNF-a, and IL-6 on LPS-stimulated microglia activation. S. horneri elicited anti-neuroinflammatory effects by inhibiting phosphorylation of p38 MAPK and NF-kB. In addition, S. horneri inhibited astrocytes and microglia activation in LPS-challenged mice brain. Therefore, these results suggested that S. horneri exerted anti-neuroinflammatory effects on LPS-stimulated microglia cells activation by inhibiting MAPK phosphorylation and NF-kB signaling.

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Anti-Inflammatory Activities of the Ethanol Extract of Prasiola japonica, an Edible Freshwater Green Algae, and Its Various Solvent Fractions in LPS-Induced Macrophages and Carrageenan-Induced Paw Edema via the AP-1 Pathway

Molecules ◽

10.3390/molecules27010194 ◽

2021 ◽

Vol 27 (1) ◽

pp. 194

Author(s):

Laily Rahmawati ◽

Sang Hee Park ◽

Dong Seon Kim ◽

Hwa Pyoung Lee ◽

Nur Aziz ◽

...

Keyword(s):

Molecular Mechanisms ◽

Biological Activities ◽

Ethanol Extract ◽

Raw264.7 Cells ◽

No Production ◽

Paw Edema ◽

Chain Reactions ◽

Anti Inflammatory

Prasiola japonica possesses several biological activities. However, reports on the anti-inflammatory activities and molecular mechanisms of its different solvent fractions remain limited. In this study, we investigated the potential anti-inflammatory activities of P. japonica ethanol extract (Pj-EE) and four solvent fractions of Pj-EE made with hexane (Pj-EE-HF), chloroform (Pj-EE-CF), butanol (Pj-EE-BF), or water (Pj-EE-WF) in both in vitro (LPS-induced macrophage-like RAW264.7 cells) and in vivo (carrageenan-induced acute paw edema mouse models) experiments. The most active solvent fraction was selected for further analysis. Various in vitro and in vivo assessments, including nitric oxide (NO), cytokines, luciferase assays, real-time polymerase chain reactions, and immunoblotting analyses were performed to evaluate the underlying mechanisms. In addition, the phytochemical constituents were characterized by Liquid chromatography-tandem mass spectrometry. In in vitro studies, the highest inhibition of NO production was observed in Pj-EE-CF. Further examination revealed that Pj-EE-CF decreased the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells and suppressed subsequent AP-1-luciferase activity by inhibition of phosphorylation events in the AP-1 signaling pathway. Pj-EE-CF treatment also demonstrated the strongest reduction in thickness and volume of carrageenan-induced paw edema, while Pj-EE-BF showed the lowest activity. Furthermore, Pj-EE-CF also reduced gene expression and cytokines production in tissue lysates of carrageenan-induced paw edema. These findings support and validate the evidence that Pj-EE, and especially Pj-EE-CF, could be a good natural source for an anti-inflammatory agent that targets the AP1 pathway.

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Design, Synthesis, Characterization and in silico molecular docking studies and in vivo anti-inflammatory Activity of Pyrazoline clubbed Thiazolinone Derivatives

Letters in Organic Chemistry ◽

10.2174/1570178617999201106113114 ◽

2020 ◽

Vol 17 ◽

Author(s):

Deepak Kumar Singh ◽

Mayank Kulshreshtha ◽

Yogesh Kumar ◽

Pooja A Chawla ◽

Akash Ved ◽

...

Keyword(s):

Molecular Docking ◽

Biological Activities ◽

Inflammatory Activity ◽

Standard Drug ◽

Docking Score ◽

Chemical Structures ◽

Cox 2 ◽

Anti Inflammatory ◽

Cox 1

Background: The pyrazolines give the reactions of aliphatic derivatives, resembling unsaturated compounds in their behavior towards permanganate and nascent hydrogen. This nucleus has been associated with various biological activities including inflammatory. Thiazolinone is a heterocyclic compound that contains both sulfur and nitrogen atom with a carbonyl group in their structure.Thiazolinone and their derivatives have attracted continuing interest because of their various biological activities, such as anti-inflammatory, antimicrobial, anti-proliferative, antiviral, anticonvulsant etc. The aim of the research was to club pyrazoline nucleus with thiazolinone in order to have significantanti-inflammatory activity. The synthesized compounds were chemically characterized for the establishment of their chemical structures and to evaluate as anti-inflammatory agent. Method: In the present work, eight derivatives of substituted pyrazoline (PT1-PT8) were synthesized by a three step reaction.The compounds were subjected to spectral analysis by Infrared, Mass and Nuclear magnetic resonance spectroscopy and elemental analysis data. All the synthesized were evaluated for their in vivo anti-inflammatory activity. The synthesized derivatives were evaluated for their affinity towards target COX-1 and COX-2, using indomethacin as the reference compound molecular docking visualization through AutoDock Vina. Results: Compounds PT-1, PT-3, PT-4 and PT-8 exhibited significant anti-inflammatory activity at 3rd hour being 50.7%, 54.3%, 52.3% and 57% respectively closer to that of the standard drug indomethacin (61.9%).From selected anti-inflammatory targets, the synthesized derivatives exhibited better interaction with COX-1 and COX-2 receptor, where indomethacin showed docking score of -6.5 kJ/mol, compound PT-1 exhibited highest docking score of -9.1 kJ/mol for COX-1 and compound PT-8 having docking score of 9.4 kJ/mol for COX-2. Conclusion: It was concluded that synthesized derivatives have more interaction with COX-2 receptors in comparison to the COX-1 receptors because the docking score with COX-2 receptors were very good. It is concluded that the synthesized derivatives (PT-1 to PT-8) are potent COX-2 inhibitors.

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In Vitro and In Vivo Anti-Inflammatory Effects of Sulfated Polysaccharides Isolated from the Edible Brown Seaweed, Sargassum fulvellum

Marine Drugs ◽

10.3390/md19050277 ◽

2021 ◽

Vol 19 (5) ◽

pp. 277

Author(s):

Lei Wang ◽

Hye-Won Yang ◽

Ginnae Ahn ◽

Xiaoting Fu ◽

Jiachao Xu ◽

...

Keyword(s):

Nitric Oxide ◽

Brown Seaweed ◽

Sulfated Polysaccharides ◽

Raw 264.7 ◽

Raw 264.7 Macrophages ◽

Sargassum Fulvellum ◽

Pharmaceutical Industries ◽

Anti Inflammatory

In the present study, the in vitro and in vivo anti-inflammatory effects of the sulfated polysaccharides isolated from Sargassum fulvellum (SFPS) were evaluated in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages and zebrafish. The results indicated that SFPS improved the viability of LPS-stimulated RAW 264.7 macrophages from 80.02 to 86.80, 90.09, and 94.62% at the concentration of 25, 50, and 100 µg/mL, respectively. Also, SFPS remarkably and concentration-dependently decreased the production levels of inflammatory molecules including nitric oxide (NO), tumor necrosis factor-alpha, prostaglandin E2, interleukin-1 beta, and interleukin-6 in LPS-treated RAW 264.7 macrophages. In addition, SFPS significantly inhibited the expression levels of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-treated RAW 264.7 macrophages. Furthermore, the in vivo test results indicated that SFPS improved the survival rate of LPS-treated zebrafish from 53.33 to 56.67, 60.00, and 70.00% at the concentration of 25, 50, and 100 µg/mL, respectively. In addition, SFPS effectively reduced cell death, reactive oxygen species, and NO levels in LPS-stimulated zebrafish. Taken together, these results suggested that SFPS possesses strong in vitro and in vivo anti-inflammatory activities, and could be used as an ingredient to develop anti-inflammatory agents in the functional food and pharmaceutical industries.

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In vitro biological activities and in vivo hepatoprotective role of brown algae-isolated fucoidans

Environmental Science and Pollution Research ◽

10.1007/s11356-020-11892-9 ◽

2021 ◽

Author(s):

Marwa E. Atya ◽

Amr El-Hawiet ◽

Mohamed A. Alyeldeen ◽

Doaa A. Ghareeb ◽

Mohamed M. Abdel-Daim ◽

...

Keyword(s):

Brown Algae ◽

Biological Activities

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Sesquiterpene Lactones: Promising Natural Compounds to Fight Inflammation

Pharmaceutics ◽

10.3390/pharmaceutics13070991 ◽

2021 ◽

Vol 13 (7) ◽

pp. 991

Author(s):

Melanie S. Matos ◽

José D. Anastácio ◽

Cláudia Nunes dos Santos

Keyword(s):

Biological Activities ◽

Sesquiterpene Lactones ◽

Physiological State ◽

Plant Secondary Metabolites ◽

Inflammatory Pathways ◽

Inflammatory State ◽

Anti Inflammatory ◽

Inflammatory Molecules

Inflammation is a crucial and complex process that reestablishes the physiological state after a noxious stimulus. In pathological conditions the inflammatory state may persist, leading to chronic inflammation and causing tissue damage. Sesquiterpene lactones (SLs) are composed of a large and diverse group of highly bioactive plant secondary metabolites, characterized by a 15-carbon backbone structure. In recent years, the interest in SLs has risen due to their vast array of biological activities beneficial for human health. The anti-inflammatory potential of these compounds results from their ability to target and inhibit various key pro-inflammatory molecules enrolled in diverse inflammatory pathways, and prevent or reduce the inflammatory damage on tissues. Research on the anti-inflammatory mechanisms of SLs has thrived over the last years, and numerous compounds from diverse plants have been studied, using in silico, in vitro, and in vivo assays. Besides their anti-inflammatory potential, their cytotoxicity, structure–activity relationships, and pharmacokinetics have been investigated. This review aims to gather the most relevant results and insights concerning the anti-inflammatory potential of SL-rich extracts and pure SLs, focusing on their effects in different inflammatory pathways and on different molecular players.

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Effects of prostaglandin lipid mediators on agonist-induced lung endothelial permeability and inflammation

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00519.2016 ◽

2017 ◽

Vol 313 (4) ◽

pp. L710-L721 ◽

Cited By ~ 12

Author(s):

Yunbo Ke ◽

Olga V. Oskolkova ◽

Nicolene Sarich ◽

Yufeng Tian ◽

Albert Sitikov ◽

...

Keyword(s):

Protective Effect ◽

Vascular Endothelial Cells ◽

Biological Activities ◽

Cell Monolayer ◽

Endothelial Permeability ◽

In Vivo Model ◽

Barrier Dysfunction ◽

Anti Inflammatory

Prostaglandins (PG), the products of cyclooxygenase-mediated conversion of arachidonic acid, become upregulated in many situations including allergic response, inflammation, and injury, and exhibit a variety of biological activities. Previous studies described barrier-enhancing and anti-inflammatory effects of PGE2 and PGI2 on vascular endothelial cells (EC). Yet, the effects of other PG members on EC barrier and inflammatory activation have not been systematically analyzed. This study compared effects of PGE2, PGI2, PGF2α, PGA2, PGJ2, and PGD2 on human pulmonary EC. EC permeability was assessed by measurements of transendothelial electrical resistance and cell monolayer permeability for FITC-labeled tracer. Anti-inflammatory effects of PGs were evaluated by analysis of expression of adhesion molecule ICAM1 and secretion of soluble ICAM1 and cytokines by EC. PGE2, PGI2, and PGA2 exhibited the most potent barrier-enhancing effects and most efficient attenuation of thrombin-induced EC permeability and contractile response, whereas PGI2 effectively suppressed thrombin-induced permeability but was less efficient in the attenuation of prolonged EC hyperpermeability caused by interleukin-6 or bacterial wall lipopolysaccharide, LPS. PGD2 showed a modest protective effect on the EC inflammatory response, whereas PGF2α and PGJ2 were without effect on agonist-induced EC barrier dysfunction. In vivo, PGE2, PGI2, and PGA2 attenuated LPS-induced lung inflammation, whereas PGF2α and PGJ2 were without effect. Interestingly, PGD2 exhibited a protective effect in the in vivo model of LPS-induced lung injury. This study provides a comprehensive analysis of barrier-protective and anti-inflammatory effects of different prostaglandins on lung EC in vitro and in vivo and identifies PGE2, PGI2, and PGA2 as prostaglandins with the most potent protective properties.

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2,5-disubstituted-4-thiazolidinones: Synthesis, anti-inflammatory, free radical scavenging potentials and structural insights through molecular docking

Letters in Organic Chemistry ◽

10.2174/1570178618666210706111055 ◽

2021 ◽

Vol 18 ◽

Author(s):

Jagseer Singh ◽

Pooja A Chawla ◽

Rohit Bhatia ◽

Shamsher Singh

Keyword(s):

Free Radicals ◽

Antioxidant Activities ◽

Radical Scavenging ◽

Assay Method ◽

Acidic Group ◽

Active Compounds ◽

Cox 2 ◽

Anti Inflammatory

: The present work reports synthesis and screening of fifteen 2,5-disubstituted-4-thiazolidinones with different substitutions of varied arylidene groups at imino. The structures of the compounds were confirmed by spectral characterization. The compounds were subjected to in vivo anti-inflammatory and in vitro antioxidant activities. The derivatives possessed remarkable activities quite close to standard drugs used. Unlike conventional non-selective NSAIDs, the synthesized compounds did not contain any acidic group, thereby ensuring a complete cure from ulcers. To further substantiate the claim for safer derivatives, the active compounds were docked against the cyclooxygenase (COX)-2 enzyme. It was found that 4-fluorophenylimino substituent at 2- position and 3-nitro moiety on a 5-benzylidene nucleus of the 4-thiazolidinone derivative fitted in the COX-2 binding pocket. The compounds exhibited remarkable activity in scavenging free radicals, as depicted by the DPPH assay method. The structure-activity relationship was also established in the present work with respect to the nature and position of the substituents. The active compounds were evaluated for drug-like nature under Lipinski’s rule of five, and the toxicity behaviour of active compounds was predicted using ADMETlab software. The compounds have the potential to target degenerative disorders associated with inflammation and the generation of free radicals.

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In Vitro and In Vivo Anti-Inflammatory Activity of the Rhizomes of Globba pendula Roxb

Natural Product Communications ◽

10.1177/1934578x211055907 ◽

2021 ◽

Vol 16 (10) ◽

pp. 1934578X2110559

Author(s):

Le Minh Ha ◽

Ngo Thi Phuong ◽

Nguyen Thi Thu Hien ◽

Pham Thi Tam ◽

Do Thi Thao ◽

...

Keyword(s):

Ethyl Acetate ◽

Ethyl Acetate Extract ◽

Inhibitory Effect ◽

Potential Effect ◽

Inflammatory Activity ◽

No Production ◽

Anti Inflammatory ◽

Inflammatory Effect

In this study, we aimed at evaluating in vitro and in vivo anti-inflammatory activity of various extracts of the rhizomes of Globba pendula Roxb. Three extracts ( n-hexane, ethyl acetate, and water) were screened for their inhibitory effect on NO production by lipopolysaccharide-stimulated RAW 264.7 macrophages. The ethyl acetate extract of G. pendula rhizomes (EGP) showed a potential effect with an IC50 value of 32.45 µg/mL. For in vivo study, the ethyl acetate extract was further investigated for its anti-inflammatory effect using collagen antibody-induced arthritic mice (CAIA). The level of arthritis in experimental mice significantly reduced ( P < .05) after treatment with EGP at a dose of 500 mg/kg body weight (b.w.). This study also revealed that EGP is orally non-toxic. Ethyl p-methoxy cinamate was identified as the main constituent of EGP, which may result in its anti-inflammatory effect.

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