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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Immunomodulating action of the 3-phenylcoumarin derivative 6,7-dihydroxy-3-[3 `,4 `-methylenedioxyphenyl]-coumarin in neutrophils from patients with rheumatoid arthritis and in rats with acute joint inflammation

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Author(s):
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Albiero, Lucineia Reuse [1, 2] ; de Andrade, Micassio Fernandes [2, 3] ; Marchi, Larissa Favaro [4] ; Landi-Librandi, Ana Paula [4] ; Garcia de Figueiredo-Rinhel, Andrea Silva [4] ; Carvalho, Camila Andressa [4] ; Kabeya, Luciana Mariko [4] ; Ribeiro de Oliveira, Rene Donizeti [5] ; Caleiro Seixas Azzolini, Ana Elisa [4] ; Pupo, Monica Tallarico [6] ; Emery, Flavio da Silva [6] ; Lucisano-Valim, Yara Maria [4]
Total Authors: 12
Affiliation:
[1] Univ Fed Mato Grosso, Sinop, MT - Brazil
[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Biochem & Immunol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[3] State Univ Rio Grande Norte, Sch Hlth Sci, Mossoro, RN - Brazil
[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
[5] Univ Sao Paulo, Ribeirao Preto Med Sch, Div Rheumatol, Ave Bandeirantes 3900, BR-14049900 Ribeirao Preto, SP - Brazil
[6] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Pharmaceut Sci, Ave Cafe S-N, BR-14040903 Ribeirao Preto, SP - Brazil
Total Affiliations: 6
Document type: Journal article
Source: Inflammation Research; v. 69, n. 1 NOV 2019.
Web of Science Citations: 0
Abstract

Objective To examine whether free (3-PD-5(free)) and/or liposomal (3-PD-5(lipo)) 6,7-dihydroxy-3-{[}3 `,4 `-methylenedioxyphenyl]-coumarin (3-PD-5) (1) modulate the effector functions of neutrophils from patients with rheumatoid arthritis under remission (i-RA) and with active disease (a-RA), in vitro; and (2) exert anti-inflammatory effect in a rat model of zymosan-induced acute joint inflammation. Methods and results Incorporation of 3-PD-5 into unilamellar liposomes of soya phosphatidylcholine and cholesterol was efficient (57.5 +/- 7.9%) and yielded vesicles with low diameter (133.7 +/- 18.4 nm), polydispersity index (0.39 +/- 0.06), and zeta potential (- 1.22 +/- 0.34 mV). 3-PD-5(free) (1 mu M) and 3-PD-5(lipo) (3 mu M) equally suppressed elastase release and reactive oxygen species generation in neutrophils from healthy subjects and i-RA and a-RA patients, stimulated with immune complexes. 3-PD-5(free) (20 mu M) suppressed the release of neutrophil extracellular traps and chemotaxis in vitro, without clear signs of cytotoxicity. 3-PD-5(lipo) (1.5 mg/kg, i.p.) diminished joint edema and synovial infiltration of total leukocytes and neutrophils, without changing the synovial levels of TNF-alpha, IL-1 beta, and IL-6. Conclusion Altogether, the results reported herein indicate that 3-PD-5 is a promising modulator of the early stages of acute joint inflammation that can help to diminish not only excessive neutrophil infiltration in the synovia but also neutrophil activation and its outcomes in RA patients. (AU)

FAPESP's process: 12/23541-4 - In vitro evaluation of antioxidant and anti-inflammatory derivatives 3-phenylcoumarins in human neutrophils stimulated and in animal models of arthritis.
Grantee:Micássio Fernandes de Andrade
Support Opportunities: Scholarships in Brazil - Doctorate
FAPESP's process: 13/21331-5 - Functional and biochemical study of neutrophils from patients with Rheumatoid Arthritis and its implications in the search for new therapeutic strategies
Grantee:Larissa Fávaro Marchi
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/20810-7 - Systematic study of the molecular mechanisms involved in the inhibition of the oxidative metabolism of the stimulated neutrophils by the Baccharis dracunculifolia, 3-phenylcoumarin derivatives and 3,5,7-triidroxiflavonaimplications on the RA therapeutics
Grantee:Yara Maria Lucisano Valim
Support Opportunities: Regular Research Grants