P.11.2 Naproxcinod, a nitric oxide-donating anti-inflammatory compound, is effective in two mouse models of muscle dystrophy

Background: Lawsonia inermis Linn popularly known as the Henna has played an important role in ayurvedic or natural herbal medicines. The presence of phyto-constituents in henna, that may affect the animal or human health adversely, need to be elucidated for L. inermis Linn species grown in India. Introduction: Introduction: The aim of this research was to perform phytochemical, cytotoxicity and anti-inflammatory studies to understand the potential of leaves of Lawsonia inermis of Indian origin to provide a way forward for therapeutic use in medicine. Methods: We assessed the phytochemical profile for presence of phyto-constituents (alkaloids, carbohydrates, glycosides, steroids, flavonoids, saponins, tannins, proteins/amino acids and gums/mucilage) from various extracts of the plant leaves’. The extracts were further purified by column chromatography for the isolation of plant constituents and monitored by TLC, analyzed by Fourier transform infrared FT-IR spectroscopy, H1NMR, and GC-MS analysis. Fractions were assessed for cytotoxicity and anti-inflammatory properties at various concentrations. We assessed the anti-inflammatory activity by nitric oxide production in various leaf extracts determined by Griess assay. Results: All the spectral results suggest that the compounds from the extract contain aromatic nucleus and OH group along with methoxy group, allyl as well as vinyl group. Fractions of chloroform/methanolic (7:3) leaf extract of Lawsonia inermis confirmed the presence of the two constituents i.e. fraxetin and 1(3H)-isobenzofuranone. We observed significant difference in cytotoxicity at higher concentrations in methanol and chloroform:methanol (8:2) leaf extracts (p>0.05), we could not find any significant differences amongst other leaf extracts at different concentrations. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells. The nitric oxide levels decreased from 1000 µg/ml concentration to lower concentrations with varying degree. Overall the highest nitric oxide production by CHCl3 (70%)/ MeOH (30%) was observed amongst various fractions at different concentrations. Conclusion: The phytochemical, cytotoxicity and anti-inflammatory studies indicating the potential of leaves of the plant to provide a way further for their use in medicine. Fraxetin 1(3H)-isobenzofuranone structures were confirmed in fractions of CHCl3 (70%)/ MeOH (30%) extract as observed as a potent constituents. Some leaf extracts have potential cytotoxic activity on vero cells. Reducing the chloroform concentration during extraction decreases the cytotoxic effect on the cells.The cytotoxicity studies indicates the presence of cytotoxic compounds in some of these extracts, warranting research for fabrication of suitable formulations comprising these constituents to reduce its dose/toxicity for the use of beneficial effects of the plant components.

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Anti-Inflammatory Effect of Simonsinol on Lipopolysaccharide Stimulated RAW264.7 Cells through Inactivation of NF-κB Signaling Pathway

Molecules ◽

10.3390/molecules25163573 ◽

2020 ◽

Vol 25 (16) ◽

pp. 3573

Author(s):

Lian-Chun Li ◽

Zheng-Hong Pan ◽

De-Sheng Ning ◽

Yu-Xia Fu

Keyword(s):

Nitric Oxide ◽

Signaling Pathway ◽

Morphological Changes ◽

Raw264.7 Cells ◽

Enzyme Linked Immunosorbent Assay ◽

Tnf Α ◽

Anti Inflammatory ◽

Factor Α ◽

Oxide Synthase ◽

Necrosis Factor

Simonsinol is a natural sesqui-neolignan firstly isolated from the bark of Illicium simonsii. In this study, the anti-inflammatory activity of simonsinol was investigated with a lipopolysaccharide (LPS)-stimulated murine macrophages RAW264.7 cells model. The results demonstrated that simonsinol could antagonize the effect of LPS on morphological changes of RAW264.7 cells, and decrease the production of nitric oxide (NO), tumor necrosis factor α (TNF-α), and interleukin 6 (IL-6) in LPS-stimulated RAW264.7 cells, as determined by Griess assay and enzyme-linked immunosorbent assay (ELISA). Furthermore, simonsinol could downregulate transcription of inducible nitric oxide synthase (iNOS), TNF-α, and IL-6 as measured by reverse transcription polymerase chain reaction (RT-PCR), and inhibit phosphorylation of the alpha inhibitor of NF-κB (IκBα) as assayed by Western blot. In conclusion, these data demonstrate that simonsinol could inhibit inflammation response in LPS-stimulated RAW264.7 cells through the inactivation of the nuclear transcription factor kappa-B (NF-κB) signaling pathway.

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Ethanesulfohydroxamic Acid Ester Prodrugs of Nonsteroidal Anti-inflammatory Drugs (NSAIDs): Synthesis, Nitric oxide and Nitroxyl Release, Cyclooxygenase Inhibition, Anti-inflammatory, and Ulcerogenicity Index Studies

Journal of Medicinal Chemistry ◽

10.1021/jm101403g ◽

2011 ◽

Vol 54 (5) ◽

pp. 1356-1364 ◽

Cited By ~ 49

Author(s):

Zhangjian Huang ◽

Carlos A. Velázquez ◽

Khaled R. A. Abdellatif ◽

Morshed A. Chowdhury ◽

Julie A. Reisz ◽

...

Keyword(s):

Nitric Oxide ◽

Acid Ester ◽

Cyclooxygenase Inhibition ◽

Inflammatory Drugs ◽

Anti Inflammatory ◽

Ester Prodrugs

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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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Melatonin and Microglia

International Journal of Molecular Sciences ◽

10.3390/ijms22158296 ◽

2021 ◽

Vol 22 (15) ◽

pp. 8296

Author(s):

Rüdiger Hardeland

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Signal Transduction ◽

Endothelial Cells ◽

Bacterial Infections ◽

Melatonin Receptors ◽

Sterile Inflammation ◽

High Complexity ◽

Anti Inflammatory ◽

Multiple Signaling

Melatonin interacts in multiple ways with microglia, both directly and, via routes of crosstalk with astrocytes and neurons, indirectly. These effects of melatonin are of relevance in terms of antioxidative protection, not only concerning free-radical detoxification, but also in prevention of processes that cause, promote, or propagate oxidative stress and neurodegeneration, such as overexcitation, toxicological insults, viral and bacterial infections, and sterile inflammation of different grades. The immunological interplay in the CNS, with microglia playing a central role, is of high complexity and includes signaling toward endothelial cells and other leukocytes by cytokines, chemokines, nitric oxide, and eikosanoids. Melatonin interferes with these processes in multiple signaling routes and steps. In addition to canonical signal transduction by MT1 and MT2 melatonin receptors, secondary and tertiary signaling is of relevance and has to be considered, e.g., via the upregulation of sirtuins and the modulation of pro- and anti-inflammatory microRNAs. Many details concerning the modulation of macrophage functionality by melatonin are obviously also applicable to microglial cells. Of particular interest is the polarization toward M2 subtypes instead of M1, i.e., in favor of being anti-inflammatory at the expense of proinflammatory activities, which is well-documented in macrophages but also applies to microglia.

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A New Flavonol From Saussurea involucrata With Anti-Inflammatory Activity

Natural Product Communications ◽

10.1177/1934578x211007638 ◽

2021 ◽

Vol 16 (5) ◽

pp. 1934578X2110076

Author(s):

Sheng Pan ◽

Zi-Guan Zhu

Keyword(s):

Nitric Oxide ◽

Aerial Part ◽

Raw 264.7 Cells ◽

Raw 264.7 ◽

Spectroscopic Methods ◽

Soluble Extract ◽

Saussurea Involucrata ◽

Tnf Α ◽

Anti Inflammatory

A new flavonol named 6-(2'',3''-epoxy-3''-methylbutyl)-resokaempferol (1), together with five known compounds (2-6) were isolated from the EtOAc-soluble extract of the aerial part of Saussurea involucrata. Their structures were elucidated on the basis of spectroscopic methods. All compounds were evaluated for their anti-inflammatory effects by measuring the production of nitric oxide (NO) and TNF-α in vitro. Among them, compound 1 showed potential inhibitory activity on the production of NO and TNF-α in LPS-induced RAW 264.7 cells with IC50 values of 48.0 ± 1.5 and 41.4 ± 1.7 µM, respectively.

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Dibenzoylthiamine Has Powerful Antioxidant and Anti-Inflammatory Properties in Cultured Cells and in Mouse Models of Stress and Neurodegeneration

Biomedicines ◽

10.3390/biomedicines8090361 ◽

2020 ◽

Vol 8 (9) ◽

pp. 361

Author(s):

Margaux Sambon ◽

Anna Gorlova ◽

Alice Demelenne ◽

Judit Alhama-Riba ◽

Bernard Coumans ◽

...

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Diseases ◽

Cell Line ◽

Mouse Models ◽

Cultured Cells ◽

Therapeutic Potential ◽

Motor Dysfunction ◽

Oxidative Stress Marker ◽

Bv2 Cells ◽

Anti Inflammatory

Thiamine precursors, the most studied being benfotiamine (BFT), have protective effects in mouse models of neurodegenerative diseases. BFT decreased oxidative stress and inflammation, two major characteristics of neurodegenerative diseases, in a neuroblastoma cell line (Neuro2a) and an immortalized brain microglial cell line (BV2). Here, we tested the potential antioxidant and anti-inflammatory effects of the hitherto unexplored derivative O,S-dibenzoylthiamine (DBT) in these two cell lines. We show that DBT protects Neuro2a cells against paraquat (PQ) toxicity by counteracting oxidative stress at low concentrations and increases the synthesis of reduced glutathione and NADPH in a Nrf2-independent manner. In BV2 cells activated by lipopolysaccharides (LPS), DBT significantly decreased inflammation by suppressing translocation of NF-κB to the nucleus. Our results also demonstrate the superiority of DBT over thiamine and other thiamine precursors, including BFT, in all of the in vitro models. Finally, we show that the chronic administration of DBT arrested motor dysfunction in FUS transgenic mice, a model of amyotrophic lateral sclerosis, and it reduced depressive-like behavior in a mouse model of ultrasound-induced stress in which it normalized oxidative stress marker levels in the brain. Together, our data suggest that DBT may have therapeutic potential for brain pathology associated with oxidative stress and inflammation by novel, coenzyme-independent mechanisms.

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