Human Group IIA secreted phospholipase A₂ (sPLA₂-IIA) enzyme plays a crucial role in several chronic inflammatory diseases such asasthma, atherosclerosis, gout, bronchitis, etc. Several studies showed that the antioxidants exert an anti-inflammatory function by inhibiting the sPLA₂-IIA enzyme. Hence, the present study evaluated an antioxidant molecule, sinapic acid, for sPLA₂-IIA inhibition as an anti-inflammatory function. Initially, the antioxidant efficacy of sinapic acid was evaluated, and it showed greater antioxidant potency. Further, sinapic acid inhibited 94.4 ± 4.83% of sPLA₂-IIA activity with an IC₅₀ value of 4.16 ± 0.13 µM. The mode of sPLA₂-IIA inhibition was examined by increasing the substrate concentration from 30 to 120nM and the calcium concentration from 2.5 to 15 mM, which did not change the level of inhibition. Further, sinapic acid altered the intrinsic fluorescence and distorted the far UltraViolet Circular Dichroism (UV-CD) spectra of the sPLA₂-IIA, indicating the direct enzyme-inhibitor interaction. Sinapic acid reduced the sPLA₂-IIA mediated hemolytic activity from 94 ± 2.19% to 12.35 ± 2.57% and mouse paw edema from 171.75 ± 2.2% to 114.8 ± 1.98%, demonstrating the anti-inflammatory efficiency of sinapic acid by in situ and in vivo methods, respectively. Finally, sinapic acid reduced the hemorrhagic effect of Vipera russelli venom hemorrhagic complex-I (VR-HC-I) as an anti-hemorrhagic function. Thus, the above experimental results revealed the sinapic acid potency to be an antioxidant, anti-inflammatory and anti-hemorrhagic molecule, and therefore, it appears to be a promising therapeutic agent.

Purpose: In the current study, the evaluation of anti-inflammatory (in vitro) activity of chemically synthesized Urolithin-C was examined. Methods: The synthesis of Urolithin-C (3,8,9-trihydroxy-6H-benzo[c]chromen-6-one) was carried out by chemical method and it was characterized using various techniques. The anti-inflammatory efficacy of synthesized Urolithin-C was studied by membrane stabilization, protein denaturation and protease inhibition assays. In addition, MTT (3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyl tetrazolium bromide) assay was employed to evaluate the cytotoxic effect of Urolithin-C. The anti-inflammatory property of Urolithin-C was further examined using LPS (Lipopolysaccharide) induced RAW 264.7 (Mouse macrophage) cells. Furthermore, the anti-inflammatory properties of Urolithin-C was studied by quantifying pro/anti-inflammatory cytokines using ELISA (enzyme-linked immunosorbent assay). The mechanism of action of Urolithin-C on NF-κB (Nuclear Factor-kappa B) translocation was studied using CLSM (confocal laser scanning microscopy). While gene expression pattern was analyzed using RT-qPCR (Reverse Transcription quantitative Polymerase Chain Reaction). Results: In comparison to the positive control aspirin, Urolithin-C showed a strong anti-inflammatory effect by preventing lysosomal degradation, protein denaturation and inhibition of protease. Furthermore, at the higher dose (200 μg/mL), Urolithin-C was found to be toxic to the mouse macrophages; however, at lower concentration (25 μg/mL) it did not cause toxicity to the said. Thus, 25 μg/mL of Urolithin-C was used to assess the anti-inflammatory activity. Interestingly, Urolithin-C efficiently reduced the expression of pro-inflammatory inducible enzyme (Cox-2), cytokines (IL-2, IL-6, and TNF-alpha) and increased the anti-inflammatory cytokine (TGF-beta1), compared to positive control diclofenac (DFC). Urolithin-C effectively abrogated the NF-κB p65 phosphorylation and its translocation to the nucleus as well. Most importantly, Urolithin-C efficiently suppressed the expression of pro-inflammatory genes and elevated the expression of anti-inflammatory gene. Conclusion: Urolithin-C exhibited anti-inflammatory properties by regulating the expression of pro-inflammatory inducible enzyme, cytokines and the translocation of NF-κB p65 to the nucleus.

Introduction and Aim: Worldwide, mosquitoes are the main vectors of many deadly diseases like malaria, dengue, chikungunya, etc., Anopheles stephensi mosquito which transmits malaria whereas dengue is transmitted mainly by mosquito Aedes aegypti. Current controlling methods such as chemical or microbial pesticides, repellents, biological control agents against mosquito larvae are not so effective. The leading cause of death worldwide is cancer. Nanotechnology can provide alternative effective methods for malaria, dengue and cancer control, diagnosis and treatment. This study investigated the biosynthesis of gold nanoparticles (AuNPs) from Acacia sinuata seed extract and their mosquito larvicidal potential was tested against Aedes aegypti, Anopheles stephensi larvae. The cytotoxic activity of NPs was also analyzed against human cancer cell lines osteosarcoma (MG-63) and colon adenocarcinoma (Caco-2). Materials and Methods: The biosynthesized NPs were confirmed and characterized by conventional techniques UV- visible spectroscopy, FTIR, XRD, HR-TEM, EDX and SAED. Results: The XRD demonstrated the NPs were face-centred, cubic, and crystalline in nature, EDX study confirmed elemental analysis of gold, SAED illustrated the crystalline nature. The HR-TEM studies revealed NPs shape which were mostly spherical and average size of 5.38nm-8.86nm. Third instar larvae of Aedes aegypti, Anopheles stephensi, were susceptible to the larvicidal effects of AuNPs. The synthesized NPs showed a dose-dependent cytotoxic effect against the Caco-2 and MG-63 cell lines, with IC50 (inhibitory concentrations) of 21.31± 0.15 ug/ml and 86.78± 0.23 ug/ml, respectively. Conclusion: These findings reveal that biosynthesized AuNPs have substantial larvicidal and anticancer properties, suggesting they could be used in mosquito control and cancer treatment.

Poultry farm workers are highly susceptible to developing lung inflammatory diseases (asthma, COPD, ARDS, and ALI) due to prolonged exposure to organic dust and other airborne irritants in confined poultry facilities. Secretory phospholipase A2 (sPLA₂-IIA) is a vital proinflammatory enzyme play an important role in the production of inflammatory mediators. Hence, this study examined the regulatory role of secretory phospholipase A2 enzyme in poultry dust induced lung inflammation in in vitro and in vivo models. Lung epithelial A549 cells and BALB/c mice treated with poultry dust increased the sPLA₂-IIA mRNA expression and stimulated the induction of inflammatory symptoms. Inhibition of sPLA₂ enzyme activity by Tricyclic Dipyrido Diazepinone derivative 6 f (sPLA₂ inhibitor) markedly ameliorated ODE-induced lung histopathological conditions, decreased lung edema, cellular infiltration, and protein secretion. Further, downregulated activation of cPLA₂ via decreasing phosphorylation of ERK1/2 and p38. Suppressing cPLA₂ signalling cascade significantly reduced the production of inflammatory cytokines (IL-6, IL-8, and TNF-α) and chemokines (MIP-1, MCP, and RANTES). Consequently, the activation of COX-2 and the production of prostaglandin E2 and thromboxane B2 were significantly decreased. Conclusively, these findings indicated that sPLA₂-IIA could potentially serve as a novel therapeutic target for treating lung inflammation in disease conditions.