Molecular modeling and inhibition of phospholipase A2 by polyhydroxy phenolic compounds

Silva, Saulo L. da; Calgarotto, Andrana K.; Maso, Victor; D’Amico, Daniela; Baldasso, Paulo A.; Veber, C.; Villar, José Augusto Ferreira Perez; Oliveira, Alfredo R. M. de; Comar, Moacyr; Oliveira, Kélson Mota Teixeira de; Marangoni, Sérgio

doi:10.1016/j.ejmech.2008.02.043

Cited by 57 publications

(30 citation statements)

References 32 publications

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“…In this direction, it was also suggested that vitamin E has the ability to bind to the hydrophobic pocket of PLA 2 , inhibiting free access of substrate to the catalytic site (Takeda et al, 2004). In relation to the mode of action, several studies have concluded that the inhibition of polyphenolic compounds on PLA 2 , is due to the interactions between the enzyme and the hydroxyl groups present in this type of metabolites, through hydrogen bonds that results in the formation of a stable complex (Chandra et al, 2002;Da Silva et al, 2009;Lindahl et al, 1997;Toyama et al, 2009). However, the activity of polyphenolic compounds may involve varying degrees of interactions such as hydrophobic connections mediated by aromatic rings, which should also be considered.…”

Section: Discussionmentioning

confidence: 99%

Correlation of the inhibitory activity of phospholipase A2 snake venom and the antioxidant activity of Colombian plant extracts

Pereañez¹,

Lobo-Echeverri²,

Rojano³

et al. 2010

Rev. bras. farmacogn.

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RESUMO:Veneno de cobra continua a ser um problema importante de saúde em muitos países da América Latina. Apesar dos avanços na terapia antiveneno, os efeitos locais causados por fosfolipases A 2 miotóxica (PLA 2 ) presentes no veneno, ainda persistem. Em busca de alternativas para antagonizar a atividade da PLA 2 do veneno de Bothrops asper, foram selecionados 36 extratos pertencentes a dezessete famílias de plantas vasculares e briófitas. Uma inibição significativa da atividade enzimática de PLA 2 presente no veneno de B. asper foi observada em onze extratos. Além disso, a atividade antioxidante dos extratos foi avaliada. Os resultados evidenciaram uma correlação estatisticamente significativa entre os extratos com ação inibitória contra a PLA 2 e aqueles com atividade antioxidante. Também, a quantidade de fenóis foi avaliada e foi encontrada uma relação entre a atividade biológica e a presença dessas substâncias. Nove extratos foram testados contra uma fração do veneno rico em PLA 2 básica (Fx-V B. asper), resultando em um efeito inibitório na atividade desta fração da PLA 2 na faixa de 30-80%. Esta atividade foi apoiada pela inibição que esses extratos apresentaram na citotoxicidade causada pelo Fx-V B. asper sobre mioblastos C2C12 de músculo esquelético de murino. Os resultados podem indicar a minimização dos esforços na busca de inibidores da PLA 2 , com foco nas amostras com propriedades antioxidantes conhecidas.Unitermos: fosfolipase A 2 , veneno de cobra, Bothrops asper, extratos de plantas, antioxidantes, DPPH.ABSTRACT: Snakebite continues to be a significant health problem in many countries of Latin America. Even though, there has been an improvement in the antivenom therapy, the local effects caused by myotoxic phospholipases A 2 (PLA 2 ) present in the venoms, still persist. In search for alternatives to antagonize the PLA 2 activity of Bothrops asper's venom, 36 extracts belonging to seventeen families of vascular plants and bryophytes were screened. A significant inhibition of the enzymatic activity of PLA 2 present in B. asper's whole venom was seen in eleven of these extracts. In addition, the antioxidant activity of all the extracts was evaluated. The results evidenced a significant statistical correlation between extracts with an inhibitory effect against PLA 2 and those with an antioxidant activity. Moreover, the amount of phenols was quantified finding a relationship between the bioactivity and the presence of these compounds. Nine extracts were screened against a fraction of the venom rich in basic PLA 2 (Fx-V B. asper), exhibiting an inhibitory effect on PLA 2 activity of this fraction in a range of 30-80%. This activity was supported by the inhibition that these extracts presented on the cytotoxicity caused by Fx-V B. asper on murine skeletal muscle C2C12 myoblasts. The results obtained, could point to minimize efforts in the search of PLA 2 inhibitors by focusing in samples with known antioxidant properties.

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Section: Discussionmentioning

confidence: 99%

Correlation of the inhibitory activity of phospholipase A2 snake venom and the antioxidant activity of Colombian plant extracts

Pereañez¹,

Lobo-Echeverri²,

Rojano³

et al. 2010

Rev. bras. farmacogn.

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“…The PLA2 inhibition could be explained by the richness of the studied extracts in phenolic compounds, since it was previously reported that phenolic compounds present an important capacity of inhibiting the enzymatic activity of PLA2 (Kammoun et al 2011). Molecular-modelling studies suggested that phenolic hydroxyls are linked to the amino acid Asp 49 of PLA2 and influence the capacity of this residue to participate in the coordination of the calcium atom, that is, essential to the catalytic activity (Da Silva et al 2009). …”

Section: Inhibition Of Phospholipase A2 Activitymentioning

confidence: 94%

Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous:Diplotaxis simplex

Jdir

Khemakham

Najjaa

et al. 2016

Pharmaceutical Biology

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Context The present study deals with new biological properties of the wild edible Diplotaxis simplex (Viv.) Spreng (Brassicaceae). Objectives The current study evaluates the antioxidant, the anti-inflammatory and the anti-cancer properties of ethyl acetate and ethanol extracts from D. simplex flowers. Materials and methods The anti-proliferative activity of the extracts (10-70 mg/mL) was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) against human colon cancer cell line Caco-2. The anti-inflammatory potential was evaluated by the inhibitory effect of the extracts (1.5-7.5 mg/mL) on phospholipase A2 activity as well as on carrageenan-induced paw oedema in mice. Extracts (200 mg/kg) or indomethacin (50 mg/kg) as positive control were injected intraperitoneally for albino mice prior to the induction of the oedema by carrageenan. Antioxidant activities were investigated using various complementary methods.Results Flower extracts contained a high level of polyphenolics (17.10-52.70 mg GAE/g) and flavonoids (74.20-100.60 mg QE/g), which correlate with its appreciable antioxidant potential in b-carotene peroxidation (IC 50 value: 12.50-27.10 mg/mL), DPPH radical-scavenging (IC 50 value: 0.20-0.40 mg/mL), Fe 3+ reducing (EC 50 value: 0.10-0.14 mg/mL) and Fe 2+ chelating (IC 50 value: 0.20-0.60 mg/mL) assays. These extracts were effective in inhibiting cancer cell growth (IC 50 value: 62.0-63.25 mg/mL). Besides, the ethyl acetate extract inhibited phospholipase A2 activity (IC 50 value: 2.97 mg/mL) and reduced the paw oedema in mice (from 0.38 ± 0.01 to 0.24 ± 0.01 cm), 4 h postcarrageenan challenge. Conclusion These data suggest that D. simplex may be useful as a candidate in the treatment of inflammation and the colon cancer.ARTICLE HISTORY

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“…The inflammatory enzyme phospholipase A2 is well known for its capability of formation of mediators of inflammation such as prostaglandins and leukotrienes. Phospholipase A2 catalyses the conversion of phospholipid to arachidonic acid which is effectively converted to prostaglandins by cyclooxygenase, the formed prostaglandins cause inflammation [38][39][40]. PLA2 inhibitory activity of ethyl acetate and methanol leaf extracts were evaluated, among the two extracts ethyl acetate leaf extract shown promising PLA2 inhibitory activity when compared to methanol leaf extract.…”

Section: Discussionmentioning

confidence: 99%

Anti-Inflammatory Activity of Manilkara Zapota Leaf Extract

Konuku

Karri

Gopalakrishnan

et al. 2017

Int J Curr Pharm Sci

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Objective: Manilkara zapota is a medicinal plant which is native to Mexico and Central America, and widely distributed in India. Various parts of this plant are traditionally used for treatment of several diseases, including inflammation-associated ailments. The main aim of the present study is to evaluate the anti-inflammatory potential of ethyl acetate and methanolic extracts of M. zapota leaf. Methods:In vitro secretary phospholipase A2 (PLA2) and 5-Lipoxygenase (5-LOX) assays and In vivo studies using carrageenan induced rat paw edema model were performed to assess the anti-inflammatory activity of M. zapota leaf extracts. Results:In vitro studies suggest that M. zapota leaf extracts exhibited significant SPLA2 and 5-LOX inhibitory activities. In in vivo studies M. zapota leaf extracts showed dose dependent inhibition of carrageenan induced paw edema in rats. The anti-inflammatory activity of ethyl acetate leaf extract was superior to methanolic extract. Conclusion:This study concluded that ethyl acetate leaf extract of M. zapota exhibited significant anti-inflammatory activity and warranted further investigation to isolate and identify the components.

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Molecular modeling and inhibition of phospholipase A2 by polyhydroxy phenolic compounds

Cited by 57 publications

References 32 publications

Correlation of the inhibitory activity of phospholipase A2 snake venom and the antioxidant activity of Colombian plant extracts

Correlation of the inhibitory activity of phospholipase A2 snake venom and the antioxidant activity of Colombian plant extracts

Anti-inflammatory and anti-proliferative activities of the wild edible cruciferous:Diplotaxis simplex

Anti-Inflammatory Activity of Manilkara Zapota Leaf Extract

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