Quercetin as an inhibitor of snake venom secretory phospholipase A2

Abstract

As polyphenolic compounds isolated from plants extracts, flavonoids have been applied to various pharmaceutical uses in recent decades due to their anti-inflammatory, cancer preventive, and cardiovascular protective activities. In this study, we evaluated the effects of the flavonoid quercetin on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), an important protein involved in the release of arachidonic acid from phospholipid membranes. The protein was chemically modified by treatment with quercetin, which resulted in modifications in the secondary structure as evidenced through circular dichroism. In addition, quercetin was able to inhibit the enzymatic activity and some pharmacological activities of sPLA2, including its antibacterial activity, its ability to induce platelet aggregation, and its myotoxicity by approximately 40%, but was not able to reduce the inflammatory and neurotoxic activities of sPLA2. These results suggest the existence of two pharmacological sites in the protein, one that is correlated with the enzymatic site and another that is distinct from it. We also performed molecular docking to better understand the possible interactions between quercetin and sPLA2. Our docking data showed the existence of hydrogen-bonded, polar interactions and hydrophobic interactions, suggesting that other flavonoids with similar structures could bind to sPLA2. Further research is warranted to investigate the potential use of flavonoids as sPLA2 inhibitors.

Anti-inflammatory medicinal plants and the molecular mechanisms underlying their activities

“…In a study to evaluate the effects of the flavonoid, quercetin, on Crotalus durissus terrificus secretory phospholipase A2 (sPLA2), it was reported that the protein was chemically modified by treatment with quercetin, which resulted in modifications in the secondary structure as evidenced through circular dichroism (Kim et al, 2004). In addition, quercetin was able to inhibit the enzymatic activity and some pharmacological activities of sPLA2, including its antibacterial activity, its ability to induce platelet aggregation, and its myotoxicity by approximately 40% (Cotrim et al, 2011). Cochinchina momordica seed extract (SKMS10) was also shown to exhibit anti-inflammatory activities by down-regulating cPLA2 among other molecular mechanisms of action (Kang et al, 2009).…”

Phospholipases A2 Protein Structure and Natural Products Interactions in Development of New Pharmaceuticals

“…Herein, sPLA2 and specific substrate 4-nitro-3-octanoyloxy-benzoic acid (4NOB3A) were used to screening samples with inhibitory properties (Cotrim, De Oliveira, Diz Filho et al, 2010). Briefly, crude extract is tested and if it inhibited the substrate cleavage by the enzyme, this extract is subjected to different extractions with increasing polarity solvents.…”

“…Recently, such method has been used for the evaluation of the sPLA2 treatment with different NC, mainly flavonoids. (Cotrim, De Oliveira, Diz Filho et al, 2010;De Oliveira et al, 2009;Iglesias, Aparicio, Rodrigues-Simioni et al, 2005;Santos et al, 2011;Toyama, Diz Filho, Cavada et al, 2011). In these studies native and modified PLA2 with different flavonoids (naringin, quercetin and morin) were prepared in 10 mM sodium phosphate buffer pH 7.4.…”

“…Mass Spectrometry (MS) can also be used for the evaluation of sPLA2 modifications induced by NC treatment, as was previously done to naringin and quercetin (Cotrim, De Oliveira, Diz Filho et al, 2010;Santos, Toyama, Oliveira et al, 2011). This technique can be applied to measure the mass-to-charge ratio of native and NC-treated PLA2.…”

“…3. Analysis of the interaction of a natural compound with phospholipase A2 by docking technique (Cotrim, De Oliveira, Diz Filho et al, 2010).…”