METHODS: In the present study, a prenylated flavone (isoglabratephrin) was isolated from aerial parts of Tephrosia apollinea using a bioassay-guided technique. Chemical structure of the isolated compound was elucidated using spectroscopic techniques (NMR, IR, and LC-MC), elemental analysis and confirmed by using single crystal X-ray analysis. The antiproliferative effect of isoglabratephrin was tested using three human cancer cell lines (prostate (PC3), pancreatic (PANC-1), and colon (HCT-116) and one normal cell line (human fibroblast).
RESULTS: Isoglabratephrin displayed selective inhibitory activity against proliferation of PC3 and PANC-1 cells with median inhibitory concentration values of 20.4 and 26.6 μg/ml, respectively. Isoglabratephrin demonstrated proapoptotic features, as it induced chromatin dissolution, nuclear condensation, and fragmentation. It also disrupted the mitochondrial membrane potential in the treated cancer cells.
CONCLUSION: Isoglabratephrin could be a new lead to treat human prostate (PC3) and pancreatic (PANC-1) malignancies.
METHODS: Different parts of the plants were subjected to sequential extraction method. Cytotoxicity of the extracts was determined by dimethylthiazol-2-yl)- 2,5diphenyl tetrazolium bromide (MTT) assay on 2 human cancer (colon and breast) and normal (endothelial and colon fibroblast) cells. Anti-angiogenic potential was tested using ex vivo rat aortic ring assay. DPPH (1,1-diphenyl-2-picrylhydrazyl) assay was conducted to screen the antioxidant capabilities of the extracts. Finally, total phenolic and flavonoid contents were estimated in the extracts using colorimetric assays.
RESULTS: The results indicated that out of 6 plants tested, 4 plants (Nicotiana glauca, Tephrosia apollinea, Combretum hartmannianum and Tamarix nilotica) exhibited remarkable anti-angiogenic activity by inhibiting the sprouting of microvessels more than 60%. However, the most potent antiangiogenic effect was recorded by ethanol extract of T. apollinea (94.62%). In addition, the plants exhibited significant antiproliferative effects against human breast (MCF-7) and colon (HCT 116) cancer cells while being non-cytotoxic to the tested normal cells. The IC50 values determined for C. hartmannianum, N. gluaca and T. apollinea against MCF-7 cells were 8.48, 10.78 and 29.36 μg/ml, respectively. Whereas, the IC50 values estimated for N. gluaca, T. apollinea and C. hartmannianum against HCT 116 cells were 5.4, 20.2 and 27.2 μg/ml, respectively. These results were more or less equal to the standard reference drugs, tamoxifen (IC50 = 6.67 μg/ml) and 5-fluorouracil (IC50 = 3.9 μg/ml) tested against MCF-7 and HCT 116, respectively. Extracts of C. hartmannianum bark and N. glauca leaves demonstrated potent antioxidant effect with IC50s range from 9.4-22.4 and 13.4-30 μg/ml, respectively. Extracts of N. glauca leaves and T apollinea aerial parts demonstrated high amount of flavonoids range from 57.6-88.1 and 10.7-78 mg quercetin equivalent/g, respectively.
CONCLUSIONS: These results are in good agreement with the ethnobotanical uses of the plants (N. glauca, T. apollinea, C. hartmannianum and T. nilotica) to cure the oxidative stress and paraneoplastic symptoms caused by the cancer. These findings endorse further investigations on these plants to determine the active principles and their mode of action.
Methods: Antioxidant properties were assessed through various radical (DPPH, ABTS, and nitric oxide) scavenging assays and determination of total phenolic content and ferric reducing antioxidant power level. ARPE-19 cells were preincubated with samples before the addition of GO (to generate H2O2). Cell viability, change in intracellular reactive oxygen species (ROS), H2O2 levels in cell culture supernatant, and gene expression were assessed.
Results: F2 showed higher antioxidant levels than the extract when assessed for radical scavenging activities and ferric reducing antioxidant power. F2 protected the ARPE-19 cells against GO-H2O2-induced oxidative stress by reducing the production of H2O2 and intracellular reactive oxygen species. This was achieved by the activation of nuclear factor erythroid 2-related factor 2 (Nrf2/NFE2L2) and superoxide dismutase (SOD2), as well as downregulation of nitric oxide producer (NOS2) at the transcriptional level.
Conclusions: The results showed that myricetin derivatives from S. malaccense have the capacity to exert considerable exogenous antioxidant activities and stimulate endogenous antioxidant activities. Therefore, these derivatives have excellent potential to be developed as therapeutic agents for managing DR.
MATERIALS AND METHODS: Total phenolic content, antioxidant activity and phenolic compounds were determined. Then, three groups of rats (control, HCl/ Ethanol-induced ulcer, and orally administered honey) were used for the determination of gastro-protective effect of Sidr honey.
RESULTS: Total phenolic content, total flavonoid content, and DPPH activity of the honey sample were determined as 47.35±3.35 mg GAE/ 100 g, 2.13±0.17 mg QE/ 100 g, and 229.24±0.02 mg/mL, respectively. Oral pretreatment of rats with honey (1.2 g/Kg body weight orally at an interval of 2 days) protected gastric mucosa against HCl/Ethanol-induced damage by decreasing ulcer score, the volume and acidity of gastric juice and increasing pH.
CONCLUSION: These results were confirmed by the histological assessment, which demonstrated a significant gastro-protective activity of Saharian (Sidr) honey against HCl/Ethanol-induced stomach ulcer. Plasma tumor necrosis factor-α, IL-6 and PGE2 were also measured. Sahara honey significantly decreased the plasma TNF-α, PGE2, and IL-6 concentrations.
RESULTS: The mRNA expression of PPARα was significantly induced in HCT116 cells following treatment with chrysin for 36 h, but the mRNA expression of PPARα was inhibited, when the cells were treated with a combination of chrysin and MK886 (PPARα inhibitor). This phenomenon proved that the incorporation of MK886 lowers the expression levels of PPARα, thus enabling us to study the function of PPARα. The cell population of the G0/G1 phase significantly increased in chrysin-treated cells, which was accompanied by a decrease in the percentage of S phase cell population after 12 h of treatment. However, treatments of HCT116 cells with chrysin only or a combination of chrysin and MK886 did not show the opposite situation in the G0/G1 and S phase cell populations, indicating that the expression of PPARα may not be associated with the cell cycle in the treated cells. The migration rate in chrysin-treated HCT116 cells was reduced significantly after 24 and 36 h of treatments. However, the activity was revived, when the expression of PPARα was inhibited, indicating that the migration activity of chrysin-treated cells is likely correlated with the expression of PPARα. Comparison of the CYP2S1 and CYP1B1 mRNA expression in chrysin only treated, and a combination of chrysin and MK886-treated HCT116 cells for 24 and 36 h showed a significant difference in the expression levels, indicating that PPARα inhibitor could also modify the expression of CYP2S1 and CYP1B1.
CONCLUSION: The study indicates that PPARα may play an essential role in regulating the migration activity, and the expression of CYP2S1 and CYP1B1 in chrysin-treated colorectal cancer cells.