Inhibitory effect of pinostrobin from Renealmia alpinia, on the enzymatic and biological activities of a PLA2.
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 PLA2 isolated from Crotalus durissus cumanensis venom. The compound displayed IC50 values of 1.76mM and 1.85mM (95% Confidence intervals: 1.34-2.18 and 1.21-2.45) on the PLA2 enzymatic activity, when either aggregated or monodispersed substrates were used, respectively. When mice were injected with PLA2 preincubated with 0.4, 2.0 and 4.0mM of pinostrobin, myotoxic activity induced by the PLA2 was inhibited up to 87%. Nevertheless, these values decreased up to 56% when the pinostrobin was injected into muscle after PLA2. Pinostrobin inhibited edema-forming and anticoagulant activities of the PLA2. 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 PLA2. These findings were supported by molecular docking results, which suggested that pinostrobin forms hydrogen bonds with residues His48 and Asp49 of PLA2, besides, a π-π stacking interactions with those of residues Phe5 and Trp31, and rings C of flavanone and Tyr52 of the toxin.
Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia. Electronic address: isabel.gomez@udea.edu.co.
Isabel
I
Gómez-Betancur
Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Jaime Andrés
JA
Pereañez
Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Arley Camilo
AC
Patiño
Programa de Ofidismo/Escorpionismo, Facultad de Ciencias Farmacéuticas y Alimentarias, Universidad de Antioquia UdeA, Calle 70 No. 52-21, Medellín, Colombia.
Dora
D
Benjumea
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D020134:Catalytic Domain; D004487:Edema / Q000473:pathology; D044950:Flavanones / Q000737:chemistry / Q000494:pharmacology*; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D064801:Phospholipase A2 Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D054467:Phospholipases A2 / Q000737:chemistry / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D030521:Zingiberaceae / Q000737:chemistry*
D000925:Anticoagulants; D044950:Flavanones; D064801:Phospholipase A2 Inhibitors; D054467:Phospholipases A2; C411294:pinostrobin
Myotoxic activity; Phospholipase A(2); Pinostrobin; Renealmia alpinia; Snakebite