AUTHOR=Sophiya P. , Urs Deepadarshan , K. Lone Jafar , Giresha A. S. , Krishna Ram H. , Manjunatha J. G. , El-Serehy Hamed A. , Narayanappa M. , Shankar J. , Bhardwaj Ragini , Ahmad Guru Sameer , Dharmappa K. K. 

TITLE=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

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.996285

DOI=10.3389/fphar.2022.996285

ISSN=1663-9812

ABSTRACT=Human phospholipase A2 group IIa (sPLA2IIa) is an inflammatory enzyme that plays a significant role in tumorigenesis. Inhibiting the sPLA2IIa enzyme by an effective molecule can reduce the inflammatory response and halt the cancer progression. In the present study, quercitrin, a biflavonoid evaluated for sPLA2IIa inhibition and anticancer activity. The quercitrin inhibited sPLA2IIa activity to a greater extent, i.e., 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. The intrinsic fluorescence and far UV-CD studies confirmed the direct interaction of quercitrin with the PLA2IIa enzyme. It significantly reduced the sPLA2IIa-induced haemolytic activity and mouse paw edema from 97.32 % ± 1.23 to 16.91 % ± 2.03 and 172.87 % ± 1.9 to 118.41 % ± 2.53, respectively. As an anticancer activity, quercitrin reduced the PC-3 cell viability from 98.66 % ± 2.51 to 18.3 % ± 1.52 and significantly decreased IL-6 level in a dose-dependent manner from 98.35 % ± 2.2 to 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 5, suggesting the druggable property. Thus, all the above experimental results were promising and encouraged further investigation to develop quercitrin into a therapeutic drug for both inflammatory diseases and cancers.