The anti-inflammatory activity of standard aqueous stem bark extract of Mangifera indica L. as evident in inhibition of Group IA sPLA2.

Bhadrapura Lakkappa Dhananjaya,Sudharshan Shivalingaiah

doi:10.1590/0001-3765201620140574

Bhadrapura Lakkappa Dhananjaya, Sudharshan Shivalingaiah

Open Access

https://doi.org/10.1590/0001-3765201620140574

Copy DOI

Abstract

The standard aqueous stem bark extract is consumed as herbal drink and used in the pharmaceutical formulations to treat patients suffering from various disease conditions in Cuba. This study was carried out to evaluate the modulatory effect of standard aqueous bark extract of M. indica on Group IA sPLA2. M. indica extract, dose dependently inhibited the GIA sPLA2 (NN-XIa-PLA2) activity with an IC50 value 8.1 µg/ml. M. indica extract effectively inhibited the indirect hemolytic activity up to 98% at ~40 µg/ml concentration and at various concentrations (0-50 µg/ml), it dose dependently inhibited the edema formation. When examined as a function of increased substrate and calcium concentration, there was no relieve of inhibitory effect on the GIA sPLA2. Furthermore, the inhibition was irreversible as evidenced from binding studies. It is observed that the aqueous extract ofM. indica effectively inhibits sPLA2 and it is associated inflammatory activities, which substantiate their anti-inflammatory properties. The mode of inhibition could be due to direct interaction of components present in the extract, with sPLA2 enzyme. Further studies on understanding the principal constituents, responsible for the anti-inflammatory activity would be interesting to develop this into potent anti-inflammatory agent.

Highlights

Phospholipases A (PLA ) (PLA, EC 3.1.1.1.4)are a family of key enzymes, that cleaves fatty acids at the sn-2 position of glycerol phospholipids to liberate free fatty acid and lysophospholipid (Nanda et al 2007, Burke and Dennis 2009).The released free fatty acid i.e., arachidonic acid, is known to liberate potent and short-lived pro-BHADRAPURA LAKKAPPA DHANANJAYA and SUDHARSHAN SHIVALINGAIAH from membrane lipids is the first regulatory and obligatory step in the synthesis of pro-inflammatory mediators in inflammatory
This study provides an insight on the possible biochemical interaction of extract/components to bring about inhibition of sPLA2s and its inflammatory process
Considering the drawbacks and the severe side effects exhibited by current anti-inflammatory therapies that include the non-steroidal antiinflammatory drugs that inhibit either of the LOX or COX-1/2 enzymes (Vane and Botting 1998)

Summary

Introduction

BHADRAPURA LAKKAPPA DHANANJAYA and SUDHARSHAN SHIVALINGAIAH from membrane lipids is the first regulatory and obligatory step in the synthesis of pro-inflammatory mediators in inflammatory. This arachidonic acid metabolic pathway is known to be regulated mainly by secretory phospholipase A , suggesting the importance of enzyme in inflammation related processes (Nanda et al 2007). Group I (GIA) includes the svPLA2s from Elapinae and Hydrophiinae venoms with 115–120 amino acid residues and these svPLA2s are homologous to mammalian pancreatic GIB sPLA2. Group II (GIIA and GIIB) comprises the svPLA s from Crotalinae and Viperinae venoms with 120–125 amino acid residues and homologous to mammalian non-pancreatic Group II-A sPLA (Burke and Dennis 2009). The subgroups described above exhibit a wide variety of physiological and pathological effects including the inflammatory one (Doley et al 2010, Kini 2003)

Methods

Results

Conclusion