Anti-oncogenic Potential and Inflammation Modulatory Response of Green Synthesized Biocompatible Silver Nanoparticles.

This study presents a novel approach to synthesizing silver nanoparticles (Ag NPs) using a solution combustion synthesis (SCS) method with Catharanthus roseus (C. roseus) leaf extract. The NPs were thoroughly characterized through X-ray diffraction (XRD), Scanning electron microscopy (SEM), Energy dispersive X-ray (EDX), Transmission electron microscopy (TEM), and Selected area electron diffraction (SAED), elucidating their crystal structure. Notably, the synthesized Ag NPs exhibited a significant dose-dependent decline in viability of the MDA-MB 231 breast cancer cell line, with an IC50 value of 13.3 µg/mL, underscoring their potential as potent anticancer agent. Beyond cytotoxicity, the study pioneers an investigation into the biocompatibility of Ag NPs by blood hemolsysis, providing critical insights into their safety and biomedical applicability. Furthermore, this research uncovers a distinctive facet of Ag NPs, revealing their inhibitory effects on the inflammatory enzyme secretory phospholipase A2 (sPLA2), a recognized biomarker for breast cancer. The demonstrated in vitro and in vivo inhibition of sPLA2 highlights the multifaceted potential of Ag NPs in not only targeting cancer cells but also modulating inflammatory responses associated with breast cancer, positioning the study at the forefront of advancements in nanomedicine and cancer therapeutics.

Synthesis of p-CuO/n-ZnO heterostructure by microwave hydrothermal method and evaluation of its photo and bio-catalytic performance.

The use of photocatalysts without noble metals is of great interest in the industrial field for the degradation of organic pollutants. In this study, a CuO/ZnO heterostructure was synthesized using the microwave hydrothermal method and characterized using various analytical techniques. The synthesized CuO/ZnO photocatalyst exhibited a low bandgap energy of 2.4 eV, enabling efficient visible light absorption. The photocatalytic activity of the CuO/ZnO heterostructure was evaluated for the degradation of Methyl Orange (MO) dye and showed a high degradation efficiency of 99 % due to its excellent electron-hole charge separation. The biological activity of the synthesized CuO/ZnO catalyst was further investigated through protein docking studies, which showed promising results. The CuO/ZnO was also evaluated for its anticancer and antibacterial properties. It exhibited effective anticancer activity against prostate cancer cells (PC-3) in a dose-dependent manner, with an IC50 value of 6.87 ± 8. In addition, it demonstrated potent antibacterial activity against Escherichia coli, Staphylococcus aureus, Bacillus cereous and Pseudomonas aeruginola. The results of this study demonstrate the potential of CuO/ZnO heterostructures as promising materials for various applications in the fields of photocatalysis, biomedicine and antimicrobial materials. Future research in this area will focus on further optimizing the properties of the CuO/ZnO heterostructure to enhance its performance in these applications.

Quercitrin neutralizes sPLA2IIa activity, reduces the inflammatory IL-6 level in PC3 cell lines, and exhibits anti-tumor activity in the EAC-bearing mice model.

Human phospholipase A2 group 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 IC50 value 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.

Sinapicacid Inhibits Group IIA Secretory Phospholipase A2 and Its Inflammatory Response in Mice.

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.

Group IIA secreted phospholipase A2 inhibition by elemolic acid as a function of anti-inflammatory activity.

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 from Boswellia serrata inhibited the GIIA enzyme in a concentration-dependent manner with IC50 value 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 with Vipera russelii neurotoxic 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.

Corosolic Acid Inhibits Secretory Phospholipase A2IIa as an Anti-Inflammatory Function and Exhibits Anti-Tumor Activity in Ehrlich Ascites Carcinoma Bearing Mice.

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.