Anti-Angiogenic Activity Of Standardised Methanolic Leaf Extract Of Orthosiphon Stamineus Benth

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Date
2009-03
Authors
Sahib, Hayder
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Abstract
Angiogenesis, a process of new blood vessel development, fonns as a necessary component of nonnal tissue repair, tumour growth and a wide variety of other inflammatory and pathological processes. The inhibition of angiogenesis can play an important role in tumour growth suppression, thereby halting the disease progression. The aim of this study was to investigate the possibility of Orthosiphon stamineus Benth (0. stamineus) as a potential anti-tumour agent via the angiogenesis mechanistic pathway. The specific aim was to use 0. stamineus to target the tumour vasculature by affecting the angiogenesis pathway and identify the mechanisms and compounds involved. The ability of 0. stamineus to perturb cancer cell growth was also investigated and its capability as an adjuvant to enhance the effect of tamoxifen towards breast cancer was also studied. Dry powdered leaves of the plant were serially extracted with petroleum ether, chlorofonn, methanol and water .. A bioactivity-guided extraction was carried out using these samples in a rat aortic ring angiogenesis assay. The methanol extract was found to be the most anti-angiogenic compared to the other extracts (P<O.OS). A unique batch of the sample with defined harvest conditions labelled as MK-OI-07 was found to be the most active compared to other batches. This batch was further fractionated into three fractions, MFl, MF2 and MF3. MFI had high percentage of anti-angiogenesis activity among the other fractions; however, it was lower than the activity of the MK-OI-07 extract. These two samples were found to be non-cytotoxic in the MTT assay against human umbilical vein endothelial cells (HUVEC). In the HUVEC tube fonnation assay, MK-OI-07 inhibited 100% of endothelial tube formation, while MF I inhibited only 47.2% of its growth. Both samples also showed no significant cytotoxic activity towards CCD- 18CO, HCT-116, T-47D and HepG2 cancer cell lines. However, MK-OI-07 and MFI displayed a potent synergistic response when co-administered with tamoxifen against MCF-7 breast cancer cells with a similar level of activity. Due to the importance of anti-oxidants in angiogenesis, both samples were analysed for their free radical scavenging activity by using a DPPH assay that revealed their potent anti-oxidative properties. High performance liquid chromatography (HPLC) analysis on MK-OI-07 and MFI showed high amounts offlavonoids and diterpene with MK-OI-07 having significant amounts of Rosmarinic acid and Orthosiphol A, which were absent in the MFI fraction. In conclusion, 0. stamineus has a potent anti-angiogenic activity by affecting endothelial tube formation. This activity may be due to the presence of flavonoids and diterpene that could inhibit endothelial cell tube formation by inhibiting vascular endothelial growth factor (VEGF) expression.
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Orthosiphon stamineus Benth , as a potential anti-tumour agent
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