Inhibitory effects of Mannich bases of heterocyclic chalcones on NO production by activated RAW 264.7 macrophages and superoxide anion generation and elastase release by activated human neutrophils

A series of thirteen triarylpyrazole analogs were investigated as inhibitors of lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) production in RAW 264.7 macrophages. The target compounds 1a–m have first been assessed for cytotoxicity against RAW 264.7 macrophages to determine their non-cytotoxic concentration(s) for anti-inflammatory testing to make sure that the inhibition of PGE2 and NO production would not be caused by cytotoxicity. It was found that compounds 1f and 1m were the most potent PGE2 inhibitors with IC50 values of 7.1 and 1.1 μM, respectively. In addition, these compounds also showed inhibitory effects of 11.6% and 37.19% on LPS-induced NO production, respectively. The western blots analysis of COX-2 and iNOS showed that the PGE2 and NO inhibitory effect of compound 1m are attributed to inhibition of COX-2 and iNOS protein expression through inactivation of p38.

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Bioactive Constituents from the Aerial Parts of Pluchea indica Less

Molecules ◽

10.3390/molecules23092104 ◽

2018 ◽

Vol 23 (9) ◽

pp. 2104 ◽

Cited By ~ 3

Author(s):

Jingya Ruan ◽

Zheng Li ◽

Jiejing Yan ◽

Peijian Huang ◽

Haiyang Yu ◽

...

Keyword(s):

Water Extract ◽

No Production ◽

Raw 264.7 ◽

Inhibitory Effects ◽

Bioactive Constituents ◽

Raw 264.7 Macrophages ◽

Aerial Parts ◽

Inhibitory Activities ◽

First Time ◽

Asteraceae Family

Four new thiophenes, (3′′R)-pluthiophenol (1), (3′′R)-pluthiophenol-4′′-acetate (2), 3′′-ethoxy-(3′′S)-pluthiophenol (3), 3′′-ethoxy-(3′′S)-pluthiophenol-4′′-acetate (4), together with twenty-five known compounds were obtained from the 70% ethanol-water extract of the aerial parts of Pluchea indica Less. Their structures were elucidated by spectroscopic methods. Among the known isolates, compounds 7, 8, 11, 14, 15, 18, 20, 23, 25–27 were isolated from Asteraceae family firstly, while compounds 6, 9, 10, 12, 13, 16, 19, 21, 28 were isolated from Pluchea genus for the first time. Meanwhile, compounds 1, 2, 10, 13, 18, 23 displayed significant inhibitory activities on LPS-induced NO production at 40 µM from RAW 264.7 macrophages, while compounds 3, 4, 26–29 possessed moderate inhibitory effects.

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The Remarkable Antioxidant and Anti-Inflammatory Potential of the Extracts of the Brown Alga Cystoseira amentacea var. stricta

Marine Drugs ◽

10.3390/md19010002 ◽

2020 ◽

Vol 19 (1) ◽

pp. 2

Author(s):

Gina De La Fuente ◽

Marco Fontana ◽

Valentina Asnaghi ◽

Mariachiara Chiantore ◽

Serena Mirata ◽

...

Keyword(s):

Oxidative Stress ◽

No Production ◽

Low Grade ◽

Raw 264.7 ◽

Ros Scavenging ◽

Ligurian Sea ◽

Raw 264.7 Macrophages ◽

Pharmaceutical Industries ◽

Anti Inflammatory ◽

First Time

Inflammation and oxidative stress are part of the complex biological responses of body tissues to harmful stimuli. In recent years, due to the increased understanding that oxidative stress is implicated in several diseases, pharmaceutical industries have invested in the research and development of new antioxidant compounds, especially from marine environment sources. Marine seaweeds have shown the presence of many bioactive secondary metabolites, with great potentialities from both the nutraceutical and the biomedical point of view. In this study, 50%-ethanolic and DMSO extracts from the species C. amentacea var. stricta were obtained for the first time from seaweeds collected in the Ligurian Sea (north-western Mediterranean). The bioactive properties of these extracts were then investigated, in terms of quantification of specific antioxidant activities by relevant ROS scavenging spectrophotometric tests, and of anti-inflammatory properties in LPS-stimulated macrophages by evaluation of inhibition of inflammatory cytokines and mediators. The data obtained in this study demonstrate a strong anti-inflammatory effect of both C. amentacea extracts (DMSO and ethanolic). The extracts showed a very low grade of toxicity on RAW 264.7 macrophages and L929 fibroblasts and a plethora of antioxidant and anti-inflammatory effects that were for the first time thoroughly investigated. The two extracts were able to scavenge OH and NO radicals (OH EC50 between 392 and 454 μg/mL; NO EC50 between 546 and 1293 μg/mL), to partially rescue H2O2-induced RAW 264.7 macrophages cell death, to abate intracellular ROS production in H2O2-stimulated macrophages and fibroblasts and to strongly inhibit LPS-induced inflammatory mediators, such as NO production and IL-1α, IL-6, cyclooxygenase-2 and inducible NO synthase gene expression in RAW 264.7 macrophages. These results pave the way, for the future use of C. amentacea metabolites, as an example, as antioxidant food additives in antiaging formulations as well as in cosmetic lenitive lotions for inflamed and/or damaged skin.

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Inhibitory effects of 16-hydroxycleroda-3,13(14)E-dien-15-oic acid on superoxide anion and elastase release in human neutrophils through multiple mechanisms

European Journal of Pharmacology ◽

10.1016/j.ejphar.2008.02.041 ◽

2008 ◽

Vol 586 (1-3) ◽

pp. 332-339 ◽

Cited By ~ 18

Author(s):

Han-Lin Chang ◽

Fang-Rong Chang ◽

Jin-Shan Chen ◽

Hui-Po Wang ◽

Yi-Hsiu Wu ◽

...

Keyword(s):

Superoxide Anion ◽

Human Neutrophils ◽

Inhibitory Effects

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The roles of extracellular and intracellular calcium in lysosomal enzyme release and superoxide anion generation by human neutrophils

Biochimica et Biophysica Acta (BBA) - General Subjects ◽

10.1016/0304-4165(81)90267-1 ◽

1981 ◽

Vol 677 (3-4) ◽

pp. 512-520 ◽

Cited By ~ 131

Author(s):

James E. Smolen ◽

Helen M. Korchak ◽

Gerald Weissmann

Keyword(s):

Intracellular Calcium ◽

Lysosomal Enzyme ◽

Superoxide Anion ◽

Human Neutrophils ◽

Enzyme Release ◽

Superoxide Anion Generation

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Inhibitory Effects of Methanol Extract of Seeds of Job's Tears (Coix Lachryma-Jobi L Var. Ma-Yuen) On Nitric Oxide and Superoxide Production in Raw 264.7 Macrophages

Immunopharmacology and Immunotoxicology ◽

10.3109/08923970009026011 ◽

2000 ◽

Vol 22 (3) ◽

pp. 545-554 ◽

Cited By ~ 30

Author(s):

Won-Gil Seo ◽

Hyun-Ock Pae ◽

Kyu-Yun Chai ◽

Young-Gab Yun ◽

Tae-Ho Kwon ◽

...

Keyword(s):

Nitric Oxide ◽

Methanol Extract ◽

Superoxide Production ◽

Raw 264.7 ◽

Inhibitory Effects ◽

Raw 264.7 Macrophages ◽

Job’S Tears

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In Vitro Modulator Effect of Total Extract from the Endophytic Paenibacillus polymyxa RNC-D in Leishmania (Leishmania) amazonensis and Macrophages

International Journal of Microbiology ◽

10.1155/2020/8895308 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Débora Meira Neris ◽

Letícia Gonçalves Ortolani ◽

Cynthia Aparecida de Castro ◽

Ricardo de Oliveira Correia ◽

Joice Margareth de Almeida Rodolpho ◽

...

Keyword(s):

Paenibacillus Polymyxa ◽

Leishmania Amazonensis ◽

No Production ◽

Raw 264.7 ◽

Total Extract ◽

Raw 264.7 Macrophages ◽

Promising Target ◽

Mediators Of Inflammation ◽

Infected Cells

Leishmaniases are diseases with high epidemiological relevance and wide geographical distribution. In Brazil, Leishmania (Leishmania) amazonensis is related to the tegumentary form of leishmaniasis. The treatment for those diseases is problematic as the available drugs promote adverse effects in patients. Therefore, it is important to find new therapeutic targets. In this regard, one alternative is the study of biomolecules produced by endophytic microorganisms. In this study, the total extract produced by the endophytic Paenibacillus polymyxa RNC-D was used to evaluate the leishmanicidal, nitric oxide, and cytokines production using RAW 264.7 macrophages. The results showed that, in the leishmanicidal assay with L. amazonensis, EC50 values at the periods of 24 and 48 hours were 0.624 mg/mL and 0.547 mg/mL, respectively. Furthermore, the cells treated with the extract presented approximately 25% of infected cells with an average of 3 amastigotes/cell in the periods of 24 and 48 hours. Regarding the production of cytokines in RAW 264.7 macrophages infected/treated with the extract, a significant increase in TNF-α was observed at the periods of 24 and 48 hours in the treated cells. The concentrations of IFN-γ and IL-12 showed significant increase in 48 hours. A significant decrease in IL-4 was observed in all cells treated with the extract in 24 hours. It was observed in the treated cells that the NO production by RAW 264.7 macrophages increased between 48 and 72 hours. The endophytic Paenibacillus polymyxa RNC-D extract modulates the mediators of inflammation produced by RAW 264.7 macrophages promoting L. amazonensis death. The immunomodulatory effects might be a promising target to develop new immunotherapeutic and antileishmanial drugs.

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