Inhibition of Neurotoxic Secretory Phospholipases A₂Enzymatic, Edematogenic, and Myotoxic Activities by Harpalycin 2, an Isoflavone Isolated fromHarpalyce brasilianaBenth

Abstract

Secretory phospholipases A2 (sPLA2) exert proinflammatory actions through lipid mediators. These enzymes have been found to be elevated in many inflammatory disorders such as rheumatoid arthritis, sepsis, and atherosclerosis. The aim of this study was to evaluate the effect of harpalycin 2 (Har2), an isoflavone isolated from Harpalyce brasiliana Benth., in the enzymatic, edematogenic, and myotoxic activities of sPLA2 from Bothrops pirajai, Crotalus durissus terrificus, Apis mellifera, and Naja naja venoms. Har2 inhibits all sPLA2 tested. PrTX-III (B. pirajai venom) was inhibited at about 58.7%, Cdt F15 (C. d. terrificus venom) at 78.8%, Apis (from bee venom) at 87.7%, and Naja (N. naja venom) at 88.1%. Edema induced by exogenous sPLA2 administration performed in mice paws showed significant inhibition by Har2 at the initial step. In addition, Har2 also inhibited the myotoxic activity of these sPLA2s. In order to understand how Har2 interacts with these enzymes, docking calculations were made, indicating that the residues His48 and Asp49 in the active site of these enzymes interacted powerfully with Har2 through hydrogen bonds. These data pointed to a possible anti-inflammatory activity of Har2 through sPLA2 inhibition.

Chemical characterization, antioxidant, anti-inflammatory and cytotoxic properties of bee venom collected in Northeast Portugal

“…In fact, the anti-inflammatory properties of BV samples from different origins such as Egypt (Amin and Abdel-Raheem, 2014), Korea (Park et al, 2007;Park et al, 2008;Lee et al, 2009), USA (Chang and Bliven, 1979) and even commercial samples (Jang et al, 2005;Moon et al, 2007;Yoon et al, 2008) have been reported in apitherapy. Furthermore, BV individual compounds have also shown the same properties, as in the case of mast cell degranulating peptide (Banks et al, 1990), MEL (Moon et al, 2006;Park et al, 2007;Srivastava et al, 2012;Rayahin et al, 2014) and PLA2 (Ximenes et al, 2012), which are related with their capacity to reduce pro-inflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukins (IL-In the present work, five bee venom samples obtained from Apis mellifera iberiensis from the Northeast Portugal were chemically characterized and evaluated for their antioxidant, antiinflammatory and cytotoxic properties.…”

Edema Induced by sPLA2 from Crotalus durissus terrificus Involves PLC and PKC Signaling, Activation of cPLA2, and Oxidative Stress

“…Some studies performed with sPLA2 from Crotalus durissus ssp. showed that the calcium binding loop is involved in the pharmacological activity [57], and others performed by [52] showed that regions close to the active site of sPLA2 could also be involved. According to [54], the C-terminal region could also participate in the interaction with pharmacological receptors.…”

“…Subsequently, several works with purified Lys49 basic sPLA2 from snake (Bothrops sp.) were able to induce several pharmacological activities, such as pronounced edema, myonecrosis, oxidative stress, nephrotoxicity, insulin degranulation, and anticoagulant activity [17,[48][49][50][51][52]. In the case of the sPLA2 from Cdt, it was observed that its enzymatic activity can be practically abolished through treatment with certain compounds.…”

“…In the case of the sPLA2 from Cdt, it was observed that its enzymatic activity can be practically abolished through treatment with certain compounds. Numerous natural compounds have the potential to downregulate or modulate the PLA2 activities, as well as other enzymes involved in AA metabolism, including cPLA2 or enzymes involved in prostaglandin metabolization [52][53][54][55][56]. One of the most abundant polyphenols in the human diet, 5-caffeoylquinic acid (5CQA), exerts potent anti-inflammatory, antibacterial, and antioxidant activities.…”

Compounds isolated from Harpalyce brasiliana Benth and their pharmacological properties

“…Two polyphenolic compounds, harpalycin and quercetin, were isolated from the H. brasiliana leaves (Silva et al, 1999). These compounds have numerous biological activities in animal cells, such as free radical scavenging properties and antioxidant and anticholinesterase activities Silva et al (1997) 3-hydroxy-4-isopentenyl-8,9-methylenedioxypterocarpan Silva et al (1999 3β-hydroxy-20(29)-lupen-28-oic acid or betulinic acid Silva et al (1997;1999) Leaves Harpalycin and quercetin 5,7,3′,4′-tetrahydroxyflavonol Silva et al (1999) Roots Leiocarpin, medicarpin, maackiain, cabenegrin A-I and cabenegrin A-II Militão et al (2007) (-)-2-geranyl-3-hydroxy-8,9-methylenedioxypterocarpan Vieira et al (2008) Roots (-)-6aR,11aR-2(4′,5′-dihydroxy-1′-isopentenyl)-3-hydroxy-8,9-methylenedioxypterocarpan and (-)-6aR,11aR-2(4′-hydroxy-1′-isopentenyl)-3-hydroxy-8,9-methylenedioxypterocarpan Araújo et al (2008) 2-Geranyl-2,3′,4,4′-tetrahydroxychalcone Vieira et al (2008) Araújo et al (2008) activities (Djeridane et al, 2006;Katalanić et al, 2010;Ximenes et al, 2012). Although few studies have been performed on this plant to date, the results show that H. brasiliana is a source of several bioactive compounds of medicinal interest.…”