Beyond Organoleptic Characteristics: The Pharmacological Potential of Flavonoids and their Role in Leukocyte Migration and in <scp>L</scp>‐Selectin and β2‐Integrin Expression During Inflammation

Suyenaga, Edna Sayuri; Klein‐Júnior, Luiz Carlos; Passos, Carolina dos Santos; Marín, Rafaela; Santin, José Roberto; Machado, Isabel Daufenback; Farsky, Sandra Helena Poliselli; Henriques, Amélia Teresinha

doi:10.1002/ptr.5144

Cited by 14 publications

(5 citation statements)

References 28 publications

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“…The suppressor character of rutin on neutrophil functions were better studied than the compounds cited above. Isolated rutin or the one found in plant extracts decreases in vitro and in vivo neutrophil migration [ 50 ], adhesion [ 51 ], elastase secretion [ 52 ] and NET release [ 27 ]. Quercetin derivatives were commonly found in E.aurata and E.punicifolia extract fractions.…”

Section: Resultsmentioning

confidence: 99%

Eugenia aurata and Eugenia punicifolia HBK inhibit inflammatory response by reducing neutrophil adhesion, degranulation and NET release

Costa

Jesus

Lopes

et al. 2016

BMC Complement Altern Med

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Background Eugenia spp. are used in popular medicine in the treatment of pain, diabetes, intestinal disorders and cough. The aim of the work is to evaluate, ex vivo and in vivo, the anti-inflammatory activity of the hydroethanolic extracts of the leaves of Eugenia aurata (EA) and Eugenia punicifolia HBK (EP) upon neutrophils.MethodsEx vivo, isolated human neutrophils were sensitized by Eugenia extracts (0.1–1000 μg/mL) and stimulated by PMA. In these conditions, different neutrophil activities related to inflammatory process were measured: adhesion, degranulation and NET release. Neutrophil viability and tumor line cells were monitored. In vivo, neutrophil influx was evaluated by peritonitis model performed in mice pretreated with different concentrations of Eugenia extracts. Phytochemical profile was assessed by mass spectrometry.ResultsEx vivo, EA and EP (1000 μg/mL) reduced cell adhesion and degranulation, respectively. NET release was inhibited by EA and EP. Anti-inflammatory activities occurred in the absence of cytotoxicity. In vivo, both EA as EP inhibited neutrophil migration. The phytochemical profile revealed that EA contains myricitrin, rutin, quinic acid and quercetin derivatives. EP presents gallic acid, quercetin derivatives, syringic acid, ellagic acid, monogalloyl-glucose, glycosyringic acid, mudanoside B, HHDP glucose isomer and digalloylglucose isomer. EA and EP inhibit neutrophil migration by different pathways.ConclusionDifferent chemical compositions may explain the anti-inflammatory effects described herein for EA and EP. Both extracts inhibit NET release but only EA reduces cell adhesion whereas EP decreases elastase secretion. This work contributes to the elucidation of cellular mechanisms related to the anti-inflammatory activity for leaves of E. aurata and E. punicifolia HBK.

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Section: Resultsmentioning

confidence: 99%

Eugenia aurata and Eugenia punicifolia HBK inhibit inflammatory response by reducing neutrophil adhesion, degranulation and NET release

Costa

Jesus

Lopes

et al. 2016

BMC Complement Altern Med

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“…Although mice have a lower neutrophil:lymphocyte ratio in blood circulation compared to humans, a mild rise in absolute neutrophil counts in mice, similar to that of human patients, was noticed at 3 h (equivalent to the mean admission time in human patients at the hospital) and at 6 h. [ 4 , 5 , 51 ]. However, rutin per se also induced neutrophilia, which may be explained by its ability to reduce rolling, adhesion and transmigration of WBC [ 52 , 53 ], justifying the increase in the circulating pool of neutrophils in either the presence or absence of BjV. Therefore, rutin could be considered an anti-inflammatory drug, as it prevents neutrophils of committing themselves into the inflammatory reaction, and could be favorably used to diminish the systemic and local lesions resulting from envenomation.…”

Section: Discussionmentioning

confidence: 99%

Rutin (quercetin-3-rutinoside) modulates the hemostatic disturbances and redox imbalance induced by Bothrops jararaca snake venom in mice

2018

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Snakebites are a major Collective Health problem worldwide. In Brazil, Bothrops jararaca snake venom (BjV) evokes hemostatic disturbances, bleeding manifestations, and redox status imbalance. Specific antivenom therapy, although efficacious to revert most snakebite-induced manifestations, is incapable of treating secondary manifestations, such as oxidative/nitrosative stress. Searching for new complementary therapies that could attenuate physiological derangements triggered by envenomation, we elected to test quercetin-3-rutinoside (rutin) by its potential as both a potent antioxidant and a hemostasis modulatory compound. The activity of rutin was evaluated both on the biological activities of crude BjV in vitro, and in vivo by the ability of rutin (14.4 mg/kg b.w.) to modulate hematological, hemostatic and redox status markers altered by BjV injection (1.6 mg/kg b.w., s.c.) in mice. In vitro, rutin failed to inhibit BjV-induced platelet aggregation and biological activities of major BjV enzymes (metalloproteinases, phospholipases A2, serine proteases, and L-amino acid oxidases). On the other hand, rutin attenuated local hemorrhage, and the increase in reactive species, prevented the fall in RBC counts and fibrinogen levels, diminished tail bleeding and shortened prothrombin time (PT) evoked by envenomation. Furthermore, rutin reduced tissue factor (TF) activity and altered the protein expression of TF in liver, lungs, heart and skin. In conclusion, the disturbances in redox status and hemostatic system induced by B. jararaca envenomation were modulated by rutin, suggesting it has a great potential to be used as an ancillary therapeutic agent for snakebites.

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“…Pre-treatment with the extract and ethylacetate fraction significantly (p < 0.05) reduced leucocyte migration. The later phase of acute inflammatory response involves cellular migration to the site of inflammatory stimulus [42]. Inhibition of leucocyte migration by the extract and fraction is suggestive of effect in the later phase of inflammation.…”

Section: Discussionmentioning

confidence: 98%

Eleusine indica Linn, Baertin (Poaceae) Ethanol Leaf Extract and Its Ethyl Acetate Fraction Display Potential Anti-inflammatory Activities

Akah

Ezeugo

2020

JPRI

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Objective: Inflammation is the underlying cause of most of the chronic diseases that occur with aging. Although many drugs are available for the management of inflammatory disorders and their symptoms, most of these drugs possess serious adverse effects that limit their usefulness. This has encouraged the unending search for potent anti-inflammatory drugs from plant sources as alternatives to conventional drug treatment of inflammation. This study investigated the anti-inflammatory activities of the ethanol leaf extract of E. indica and the ethylacetate fraction in rodents. Materials and Methods: The leaves were extracted with ethanol by cold maceration and the extract was fractionated with n-hexane, ethylacetate, butanol and water. The oral acute toxicity (LD50) of the extract and the phytochemical constituents of the extract and the fractions were determined. The anti-inflammatory activities of the ethanol extract (EE) and ethylacetate fraction (ETF) and their possible mechanisms of actions were investigated. Results: The oral LD50 of the extract was above 5000 mg/kg. Both the EE and ETF displayed dose-dependent inhibition of the rat paw edema, with ETF producing between 48-54% edema inhibition. Xylene-induced topical edema was significantly (p < 0.05) reduced by both the EE and ETF, with ETF causing between 48 and 65% inhibition. The EE and ETF preserved the integrity of gastric mucosa. Their average ulcer index (1.37±0.02) was significantly lower than that of indomethacin (5.20±0.23). Pre-treatment with the EE and ETF significantly (p < 0.05) reduced leucocyte migration, especially the neutrophils. Both heat- and hypotonicity-induced hemolysis of RBC membrane were remarkably inhibited. Conclusion: The mechanisms of the anti-inflammatory activity may involve among others inhibition of leukocyte migration and membrane stabilization.

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Beyond Organoleptic Characteristics: The Pharmacological Potential of Flavonoids and their Role in Leukocyte Migration and in L‐Selectin and β2‐Integrin Expression During Inflammation

Cited by 14 publications

References 28 publications

Eugenia aurata and Eugenia punicifolia HBK inhibit inflammatory response by reducing neutrophil adhesion, degranulation and NET release

Eugenia aurata and Eugenia punicifolia HBK inhibit inflammatory response by reducing neutrophil adhesion, degranulation and NET release

Rutin (quercetin-3-rutinoside) modulates the hemostatic disturbances and redox imbalance induced by Bothrops jararaca snake venom in mice

Eleusine indica Linn, Baertin (Poaceae) Ethanol Leaf Extract and Its Ethyl Acetate Fraction Display Potential Anti-inflammatory Activities

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