The aim of this study was to investigate the antihyperlipidemic potential of Diosmin (DS) in mice fed with a high-fat diet (HFD). Animals were divided in five groups (n = 6). The total duration of the study was 90 days split into two intervals. During the first 45-day interval, mice were administered with HFD, whereas during the second 45-day interval they were co-administered HFD plus DS or the standard drug atorvastatin. DS was administered at the dose of 100 and 200 mg/kg;p.o. DS treatment to HFD-induced hyperlipidemic mice caused significant decrements in the levels of total cholesterol, triglycerides, LDL-C and VLDL-C. Moreover, DS resulted in significant increase in the levels of HDL-C and improvements in total protein levels, whereas it caused remarkable decreases in SGOT, SGPT and ALP enzymatic activities in hyperlipidemic mice. Histopathological examination of hyperlipidemic mice revealed a disorganized hepatic tissue, fatty changes, and mononuclear cell infiltration, which were all ameliorated by DS administration. The results revealed that DS possesses potential ameliorating benefits again.st hyperlipidemia induced by HFD on lipid profile, liver function enzymes and hepatic histoarchitecture. Further investigations are highly recommended and clinical trials are warranted in order to assess the efficacy and to fully dissect the mode-of-action underpinning the observed antihyperlipidemic effect of DS.
Organic fractions and extracts of willow (Salix safsaf) leaves, produced by sequential solvent extraction as well as infusion and decoction, exhibited anticancer potencies in four cancerous cell lines, including breast (MCF-7), colorectal (HCT-116), cervical (HeLa) and liver (HepG2). Results of the MTT assay revealed that chloroform (CHCl3) and ethyl acetate (EtOAc)-soluble fractions exhibited specific anticancer activities as marginal toxicities were observed against two non-cancerous control cell lines (BJ-1 and MCF-12). Ultra-high-resolution mass spectrometry Q-Exactive™ HF Hybrid Quadrupole-Orbitrap™ coupled with liquid chromatography (UHPLC) indicated that both extracts are enriched in features belonging to major phenolic and purine derivatives. Fluorescence-activated cell sorter analysis (FACS), employing annexin V-FITC/PI double staining indicated that the observed cytotoxic potency was mediated via apoptosis. FACS analysis, monitoring the increase in fluorescence signal, associated with oxidation of DCFH to DCF, indicated that the mechanism of apoptosis is independent of reactive oxygen species (ROS). Results of immunoblotting and RT-qPCR assays showed that treatment with organic fractions under investigation resulted in significant up-regulation of pro-apoptotic protein and mRNA markers for Caspase-3, p53 and Bax, whereas it resulted in a significant reduction in amounts of both protein and mRNA of the anti-apoptotic marker Bcl-2. FACS analysis also indicated that pre-treatment and co-treatment of human amniotic epithelial (WISH) cells exposed to the ROS H2O2 with EtOAc fraction provide a cytoprotective and antioxidant capacity against generated oxidative stress. In conclusion, our findings highlight the importance of natural phenolic and flavonoid compounds with unparalleled and unique antioxidant and anticancer properties.