Antileukemic and therapeutic effects of Naringenin the active principle of Citrus limetta and Citrus sinensis

Abstract

The present study aimed at investigating the phytoconstituents of the citrus fruit extracts, followed newlineby the assessment of their antioxidant and antileukemic activity. The study was divided into four phases. newlineThe results of phase I revealed the presence flavonoids, phenols, alkaloids, tannins, terpenoids and steroids newlinein the citrus fruit peel and pulp. Different chromatographic and spectral analysis indicated the presence newlinenaringenin only in the pulp extracts not in the peel. Hence, further analysis were carried out using the citrus newlinefruit pulp extracts. Phase II results revealed that the citrus fruit pulp extracts and naringenin exhibited good newlinefree radical scavenging activity. Followingly, the anticancer activity of the citrus fruit pulp extracts and newlinenaringenin were determined. The results demonstrated that both the pulp extracts and naringenin were able newlineto induce cell death in Molt-3 cells but were not toxic to normal PBL. newlineThe results also confirmed that the citrus fruit pulp extracts and naringenin induced cell death via newlineapoptosis which was further confirmed by flow cytometric analysis. In phase III, in silico analysis revealed newlinethat naringenin was able to interact with the target proteins, indicating its influence in both apoptotic and newlinecell signaling pathway of leukemia. Phase IV of the present study was to test the efficacy of naringenin newlineagainst CLL patient samples was determined. The results revealed that naringenin downregulated the newlineexpression of Bcl 2, Mcl 1 and Btk proteins, while upregulating cleaved caspase 3 in CLL patient samples, newlinethereby controlling BCR signaling pathway, and also triggers apoptosis by intrinsic pathway. To conclude, newlinethe methanol extract Citrus limetta, Citrus sinensis pulp and naringenin trigger apoptosis by intrinsic newlinepathway in ALL Molt-3 leukemic cells and CLL patient samples under in vitro conditions. Therefore, it newlinemight acts as a potential source for drug development against leukemia.