Human phospholipase A₂group IIa (sPLA₂IIa) is an inflammatory enzyme that plays a significant role in tumorigenesis. Inhibiting the sPLA₂IIa enzyme with an effective molecule can reduce the inflammatory response and halt cancer progression. The present study evaluates quercitrin, a biflavonoid, for sPLA₂IIa inhibition and anticancer activity. Quercitrin inhibited sPLA₂IIa activity to a greater extent—at 86.24% ± 1.41 with an IC₅₀value of 8.77 μM ± 0.9. The nature of sPLA₂IIa inhibition was evaluated by increasing calcium concentration from 2.5 to 15 µM and substrate from 20 to 120 nM, which did not alter the level of inhibition. Intrinsic fluorescence and far UV-CD studies confirmed the direct interaction of quercitrin with the sPLA₂IIa enzyme. This significantly reduced the sPLA₂IIa-induced hemolytic activity and mouse paw edema from 97.32% ± 1.23–16.91% ± 2.03 and 172.87% ± 1.9–118.41% ± 2.53, respectively. As an anticancer activity, quercitrin reduced PC-3 cell viability from 98.66% ± 2.51–18.3% ± 1.52 and significantly decreased the IL-6 level in a dose-dependent manner from 98.35% ± 2.2–37.12% ± 2.4. It increased the mean survival time (MST) of EAC-bearing Swiss albino mice from 30 to 35 days. It obeyed Lipinski’s rule of five, suggesting a druggable property. Thus, all the above experimental results were promising and encouraged further investigation into developing quercitrin as a therapeutic drug for both inflammatory diseases and cancers.

Background: Inflammation is generally connected to tumour progression and development. The secretory phospholipase A2IIa (sPLA2IIa) is an important inflammatory enzyme that catalyse the hydrolysis of membrane phospholipids into arachidonic and lysophosphatidic acid, which are the precursors for production of a lot of pro-inflammatory mediators like prostaglandins, prostacyclins, thromboxanes, leukotrienes and platelet activating factors, which involved in the proliferation, migration, invasion, and metastasis. Therefore, investigating safe and effective sPLA2IIa inhibitors as a therapeutic agent to treat cancer is indeed in need. Methods: Anti-inflammatory function of corosolic acid was evaluated by docking it with sPLA2IIa enzyme, sPLA2IIa inhibition, calcium and substrate concentration-dependent assays; intrinsic fluorescence and UV-CD analysis; neutralisation of sPLA2IIa induced indirect hemolytic and edema. Evaluated the anticancer activity of corosolic acid by MTT assays and caspase-3 expression; the anti-tumour activity by EAC-induced cell line and interleukin 6 expression. Results: The corosolic acid inhibits sPLA2IIa activity to 82.21± 2.82%. The inhibition was evaluated by increasing calcium from 2.5 to 15 μM and substrate from 20 to 120 nM, it did not affect the level of inhibition. Corosolic acid altered the intrinsic fluorescence and UV-CD spectra of sPLA2IIa enzyme, indicating the direct interaction. It neutralised sPLA2IIa induced hemolytic activity from 97± 1.23% to 15.75± 1.44% and edema from 171.51± 2.39% to 119.3± 2.6%. Further, as antiproliferative activity, corosolic acid reduced the PC3 cell viability from 99.66± 0.57% to 23± 2.64% and suppressed LPS-induced IL-6 level from 94.35± 2.2% to 34.36± 2.4%. It increased mean survivability time from 30 to 38 days and displayed the drug-like qualities. Conclusion: All the experimental results have proven the corosolic acid as an anti-inflammatory and anticancer molecule that may further be used to develop it as a drug.

Human group IIA secreted phospholipase A2 (GIIA) is a key enzyme in inflammatory reactions, worsening the condition of several chronic inflammatory diseases. The natural inhibitors of GIIA potentially block the production of inflammatory mediators. In the present study, elemolic acid, a triterpenoid fromBoswellia serratainhibited the GIIA enzyme in a concentration-dependent manner with IC₅₀value of 5.70 ± 0.02 µM. The mode of GIIA inhibition was studied by increasing the concentration of the substrate from 30 to 120 nM, and calcium from 2.5 to 15 mM, the level of inhibition was not changed. 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. 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%. Elemolic acid also reduced the hemorrhagic effect of GIIA along withVipera russeliineurotoxic non-enzymatic peptide -VNTx-II (VR-HC-I). 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.

The bioactive components of Melastoma malabathricum leaves and the chemical compositions of ethanol-based M. malabathricum leaf extract were studied using gas chromatography-mass spectrometry (GC-MS) analysis. Twelve compounds obtained were: phthalic acid hept-4-yl isobutyl ester, oleic acid, n-hexadecanoic acid, melezitose, hexadecanoic acid methyl ester, hexadecanoic acid ethyl ester, D-mannose, 9,10 secocholesta-5,7,10(19) triene-3,24,25, triol, (3β,5Z,7E), 2-myristynoyl pantetheine, propanamide, 3-[3,5di(tetra-butyl)-4hydroxyphenyl]-N-(2hydroxyethyl), cholesta 4,6- dien-3-ol and desulphosinigrin. These compounds were characterized and analyzed for sPLA₂ inhibition by molecular docking using the standard inhibitors. Among these, 2-myristynoyl pantetheine showed better interactions with sPLA₂ lIA enzyme with ‘e’ value of -8.62 (PubChem id: 535560), followed by desulphosinigrin (-7.19) and D-mannose (-4.96). ADME toxicity studies proved that 2-myristynoyl pantetheine is better for in vivo administration. The 2-myristynoyl pantetheine was found to exhibit anti-inflammatory activity.

Inflammation is a normal and necessary prerequisite to healing of the injured tissues. Inflammation contributes to all disease process including immunity, vascular pathology, trauma, sepsis, chemical, and metabolic injuries. The secretory phospholipase A2 (sPLA2) is a key enzyme in the production of pro-inflammatory mediators in chronic inflammatory disorders such as rheumatoid arthritis, coronary heart disease, diabetes, and asthma. The sPLA2 also contribute to neuroinflammatory disorders such as Parkinson's, Alzheimer's, and Crohn's disease. The present study aims to investigate the inhibition of human sPLA2 by a popular medicinal herb Boerhaavia diffusa Linn. as a function of anti-inflammatory activity. The aqueous and different organic solvents extracts of B. diffusa were prepared and evaluated for human synovial fluid, human pleural fluid, as well as Vipera russelli and Naja naja venom sPLA2 enzyme inhibition. Among the extracts, the ethanol extract of B. diffusa (EEBD) showed the highest sPLA2 inhibition and IC50 values ranging from 17.8 to 27.5 μg. Further, antioxidant and lipid peroxidation activities of B. diffusa extract were checked using 2,2-diphenyl-1-picrylhydrazyl radical, thiobarbituric acid, and rat liver homogenate. The antioxidant activity of EEBD was more or less directly proportional to in vitro sPLA2 inhibition. Eventually, the extract was subjected to neutralize sPLA2-induced mouse paw edema and indirect hemolytic activity. The EEBD showed similar potency in both the cases. The findings suggest that the bioactive molecule/s from the EEBD is/are potentially responsible for the observed in vitro and in vivo sPLA2 inhibition and antioxidant activity. The present study aims to investigate the inhibition of human sPLA2 by a popular medicinal herb Boerhaavia diffusa Linn. as a function of anti inflammatory activity. Abbreviation Used: EEBD: Ethanolic extract of boerhaavia diffusa, sPLA2: Secretory phospholipase A2, HSF: Human synovial fluid, HPF: Human pleural fluid, VRV-PLA2-V: Vipera russelli phospholipase A2, NN-PLA2-I: Naja naja phospholipase A2.