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GIIA is also a biomarker for cardiovascular diseases 10, 11, sepsis 12 and chronic graft failure 13. Supporting that, the raised GIIA concentration is evident in most of the inflammatory exudates and plasma of arthritis patients 5, inflammatory bowel diseases, acute coronary syndrome 6, asthma 7, atherosclerosis 8, acute respiratory distress syndrome (ARDS) 6 and recently, elevated levels of GIIA was found in samples of COVID-19 patients and it is parallel to disease severity 9. The GIIA concentration is usually meagre in healthy conditions (~вЂ‰3В ng/mL) but considerably increases during infections and inflammatory reactions (250вЂ“500В ng/mL) 4. Among the nine catalytically active human secreted sPLA 2 enzymes, Group II secreted phospholipase A 2 (GIIA) generally plays a significant role in causing chronic inflammatory diseases 3.

Several scientific studies showed that human secreted phospholipase A 2 enzymes play a role in many oxidative and inflammatory reactions 2. Inflammation is a necessary prerequisite for lifesaving, but when it is prolonged results in detrimental implications like sepsis, systemic shock, and tissue injury 1.

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Inflammation is a pathophysiological process that involves a series of complex cascades of cellular and biochemical events that occur during tissue injury. Thus, the elemolic acid has been proven as a potent inhibitor of GIIA enzyme and modulated the GIIA induced inflammatory response by in situ and in vivo methods. Elemolic acid also reduced the hemorrhagic effect of GIIA along with Vipera russelii neurotoxic non-enzymatic peptide -VNTx-II (VR-HC-I). Elemolic acid neutralized the GIIA mediated indirect hemolytic activity from 94.5 to 9.8% and reduced GIIA induced mouse paw edema from 171.75 to 113.68%. The inhibitor-enzyme interaction was examined by fluorimetry and Circular Dichroism (CD) studies elemolic acid altered intrinsic fluorescence intensity and shifted far UV- CD spectra of GIIA enzyme, suggesting the direct interaction with GIIA. The mode of GIIA inhibition was studied by increasing the concentration of the substrate from 30 to 120В nM, and calcium from 2.5 to 15В mM, the level of inhibition was not changed. In the present study, elemolic acid, a triterpenoid from Boswellia serrata inhibited the GIIA enzyme in a concentration-dependent manner with IC 50 value of 5.70вЂ‰В±вЂ‰0.02В ВµM. The natural inhibitors of GIIA potentially block the production of inflammatory mediators.

Human group IIA secreted phospholipase A2 (GIIA) is a key enzyme in inflammatory reactions, worsening the condition of several chronic inflammatory diseases.