Inhibitory effect of pinostrobin from Renealmia alpinia, on the enzymatic and biological activities of a PLA2.

Abstract Pinostrobin is a flavanone isolated from Renealmia alpinia, a plant used in folk medicine to treat snakebites. We tested the inhibitory ability of pinostrobin on the enzymatic, anticoagulant, myotoxic and edema-inducing activities of a PLA 2 isolated from Crotalus durissus cumanensis venom. The compound displayed IC 50 values of 1.76 mM and 1.85 mM (95% Confidence intervals: 1.34–2.18 and 1.21–2.45) on the PLA 2 enzymatic activity, when either aggregated or monodispersed substrates were used, respectively. When mice were injected with PLA 2 preincubated with 0.4, 2.0 and 4.0 mM of pinostrobin, myotoxic activity induced by the PLA 2 was inhibited up to 87%. Nevertheless, these values decreased up to 56% when the pinostrobin was injected into muscle after PLA 2 . Pinostrobin inhibited edema-forming and anticoagulant activities of the PLA 2 . In order to have insights on the mode of action of pinostrobin, intrinsic fluorescence and ultraviolet studies were performed. Results suggest that pinostrobin interacts directly with the PLA 2 . These findings were supported by molecular docking results, which suggested that pinostrobin forms hydrogen bonds with residues His48 and Asp49 of PLA 2 , besides, a π-π stacking interactions with those of residues Phe5 and Trp31, and rings C of flavanone and Tyr52 of the toxin.