Endothelium-dependent vasorelaxation and antiproliferation activities of chloroform extract F5 fraction from Crinum amabile Donn ex Ker Gawl. leaves
Medicinal plants are potential sources of bioactive compounds, which due to their multiple pharmacological benefits, could be developed into promising therapeutic drugs. Crinum amabile possesses various biological activities such as antimalaria, anticancer and antihypertension. These encouraging...
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| Format: | Thesis |
| Language: | English |
| Published: |
2019
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| Subjects: | |
| Online Access: | http://psasir.upm.edu.my/id/eprint/83640/1/FPSK%28m%29%202019%202%20ir.pdf http://psasir.upm.edu.my/id/eprint/83640/ |
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| Summary: | Medicinal plants are potential sources of bioactive compounds, which due to their
multiple pharmacological benefits, could be developed into promising therapeutic
drugs. Crinum amabile possesses various biological activities such as antimalaria,
anticancer and antihypertension. These encouraging findings had led to the selection
of this plant species as a viable candidate for developments of anticancer and
antihypertension products. Therefore, this research was undertaken to investigate the
anticancer (cytotoxicity, apoptosis and anti-angiogenesis) and the antihypertensive
properties of this plant. The possible pathways to the underlying mechanism of
respective activities were also elucidated. Firstly, the leaves of C. amabile were
serially extracted using Soxhlet’s apparatus to yield four different extracts:
petroleum ether extract (PE), chloroform extract (CE), methanol extract (ME) and
water extract (WE). Preliminary assays (both anticancer and vasorelaxation) showed
that CE exhibited the highest pharmacological effects. Thus, CE was fractionated
using column chromatography and standardized through thin layer chromatography
to produce six individual fractions. Next, the cytotoxicity of all these extracts and
fractions were tested on various human cancer cell lines using MTS cytotoxicity
assay. Results indicated that F5 fraction exhibited non-cell-specific cytostatic effects
on most of the cancer cell lines, with MCF-7 breast cancer cells being the most
susceptible. However, further studies using two apoptosis assays: annexin-V and
DNA fragmentation assay showed that F5 fraction did not induce cell apoptosis on
MCF-7 cells and no DNA fragmentations were detected. Nonetheless, cell
proliferation assay using MTT assay revealed that F5 fraction was able to inhibit
normal cell proliferation as well as VEGF-induced cell proliferation of normal
endothelial cell: HUVECs. Data from this study illustrated that F5 fraction from leaf
CE of C. amabile was able to exhibit cytostatic effect through anti-proliferation and
anti-angiogenesis activities rather than induction of cell apoptosis. Meanwhile the
vasorelaxation activities of C. amabile extracts and fractions were elucidated on both phenylephrine pre-contracted intact and denuded rat aortic rings. The results
indicated that F5 fraction exhibited the highest vasorelaxation activities and
produced both endothelium-dependent and endothelium-independent vasorelaxation.
In depth studies of its mechanism pathway(s) elucidated that the endotheliumdependent
vasorelaxation induced by F5 fraction was primarily achieved through the
stimulation of PGI2 production and partial association with NO/sGC/cGMP
activation pathway. The study proposed that C. amabile can serve as a promising
lead candidate for both discovery and development of new cytotoxic or vasodilator
drugs. |
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