The current study was aimed at investigating the potential antidepressant activity of Areca catechu nut ethanol extract and its various fractions using behavioral (acute and sub-chronic forced swim tests) and biochemical (monoamines and their metabolite levels using high performance liquid chromatography) tests. The areca nut ethanol extract and its aqueous fraction exhibited antidepressant activity in both acute and sub-chronic forced swim tests (IC₅₀ ~ 50 and 20 mg/kg, respectively), which was further confirmed by unaltered locomotor (horizontal and vertical) activities of rats in the activity cage. Phytochemical analysis revealed that saponins of areca nut may be the active component in its antidepressant action. The rats treated sub-chronically with areca nut extract displayed toxic effects, whereas its active aqueous fraction was non-toxic, indicating the presence of different constituents for antidepressant and toxic effects. In the hippocampus of rats, the areca nut extract (50 mg/kg) and aqueous fraction (20 mg/kg) caused a significant elevation of serotonin (around 35%) and noradrenaline (around 30%) compared with the control (261 ± 25 and 512 ± 29 ng/g, respectively). In conclusion, the areca nut possesses potential antidepressant effect via the elevation of serotonin and noradrenaline.
Nerium oleander leaves extract preparations have been used for centuries against sores, abscesses and solid tumors. The aim of this study was to identify active compound(s) responsible for the antiproliferative activity of N. oleander leaves against MCF-7 breast cancer cell line and to explore their mechanisms of action. The methanolic extract and fractions were screened against four human cancer cell lines: HT-144, MCF-7, NCI-H460 and SF-268 using sulforhodamine B assay. The most active ethyl acetate soluble fraction led to the isolation of eleven pure compounds viz adynerigenin, adynerin, odoroside A, odoroside B, 5-Okaempferobinoside, β-neriursate, oleanderocioic acid, oleandiginoside, oleandrin, 5-Oquercetibinoside and ursolic acid. The methanolic extract and the ethyl acetate soluble fraction exhibited significant growth inhibition (TGI: 0.14 to 3.3 µg/ml) against HT-144, MCF-7, NCI-H460 and SF-268 cell lines. The effects of the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin on the cytoskeleton and nuclei of MCF-7 cells were evaluated using immunofluorescence microscopy. Significant reduction in the mitotic index of MCF-7 cells were exhibited by the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin accompanied by morphological changes such as band-like arrangement of cells, reduction in F-actin processes, disruption of interphase microtubule network and condensation of nuclei. These results support that the N. oleander leaves possess antiproliferative activity against the aforementioned cell lines particularly estrogen receptor positive MCF-7 cells, thereby justifying its traditional use against tumors. Moreover, the antiproliferative effects induced by the methanolic extract, ethyl acetate soluble fraction, odoroside A and oleandrin were possibly related to skeletal and nuclear morphological changes.
Background: Nerium oleander extract preparations have been used in the Arab folkmedicine for the treatment of solid tumors. Objective: In the current investigation, bioassay-guided fractionation of N. oleander stem methanolic extract was performed to identify the active compound(s) responsible for its antiproliferative activity and the mechanism of action of the active compounds was explored. Methods: The methanolic extract, fractions and sub-fractions were screened against four human cancer cell lines: HT-144, MCF-7, NCI-H460 and SF-268 using sulforhodamine B assay. The effects of the active compounds on the cytoskeleton and nuclei of NCI-H460 cells were studied using immunofluorescence microscopy. Results: The more active petroleum ether insoluble sub-fraction led to the isolation of five pure compounds viz adynergenin, adynerin, hemidesmin-2, odoroside A and odoroside B. Odoroside A was the most potent compound with GI50: 0.04 and LC50: 0.74 µM against NCI-H460 cell line, while odoroside B demonstrated moderate growth inhibition and cytotoxicity (GI50: 6.7; LC50: 54 µM). After 24 hours' treatment with odoroside B (50 µM) abnormal mitotic spindles were observed, while > 90% mitotic cells were arrested in the prophase stage. Conclusion: N. oleander stem possesses significant antiproliferative effects against the aforementioned cell lines and the cardenolide odoroside B induces mitotic arrest of NCI-H460 cells in the prophase stage.
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