[vc_row css=”.vc_custom_1530862772427{padding-top: 100px !important;padding-bottom: 60px !important;}”][vc_column][vc_column_text]Van 12 tot 14 maart 2014 werd er een congres gehouden aan de VU Universiteit Amsterdam aangaande angiogenese met wetenschappers uit alle werelddelen. De bedoeling was om van gedachten te wisselen over de huidige kennis en ervaring over het onstaan en behandelen van angiogenese gerelateerde ziekten.[/vc_column_text][/vc_column][/vc_row][vc_row full_width=”stretch_row” css=”.vc_custom_1530862789344{padding-top: 60px !important;padding-bottom: 60px !important;background-color: #fafafa !important;}”][vc_column][vc_column_text]
Simmondsin molecules from Jojoba : in vitro and ex-vivo experiments demonstrating it’s angiogenesis inhibiting properties.
Stefaan T.M. Raes and André D’Oosterlynck
YOEME C.V.B.A., Oudenaarde, Belgium.
Poster presentation (P95) at 5th International meeting on angiogenesis VU University Medical Center, Amsterdam, The Netherlands, March 12–14, 2014
Published in Angiogenesis (2014) 17:762
Jojoba (Simmondsia chinensis (Link) C. K. Schneider), is a shrub belonging to the family of the Simmondsiaceae, commonly known as the Jojoba-family. Jojoba is growing in semi-arid areas and is commercially cultivated for its liquid wax, usually referred to as jojoba oil. Jojoba oil is mainly used in cosmetics to regulate the moisture and as carrier oil for fragrances. The remaining press cake had no further applications until now. It could not serve as livestock feed, because the animals started to emaciate and were arrested in their development. This appetite suppression was solely provoked by a specific molecule i.e. dimethylsimmondsin. It was found that when the press cake is subjected to a specific extraction process a “Total Polar Extract” can be obtained which is very rich in a variety of simmondsin molecules that turned out to be potent inhibitors of the angiogenesis process.
Proliferation of vascular endothelial cells is one of the decisive steps in the angiogenesis process. The Total Polar Extract and some specific simmondsin derivates purified from this extract were evaluated on their ability to inhibit cell proliferation. Human Umbilical Vein Endothelial cells (HUVEC) were stimulated using growth factors such as VEGF (Vascular Endothelial Growth Factor) or b-FGF (basic Fibroblast Growth Factor) and subsequently incubated in the presence or the absence of different simmondsin fractions. Tube formation, another essential feature of the angiogenesis process was also assessed: human Micro Vascular Endothelial Cells (hMVEC) were stimulated with VEGF-A and TNF-α and subsequently incubated with in the presence or the absence of different simmondsin fractions. Furthermore, CAM Assays were also used to score the angiogenesis inhibiting properties of the Total Polar Extract and some of its fractions.
It was found in our experiments that all simmondsins different from dimethylsimmondsin showed much stronger angiogenesis inhibiting activities than the dimethylsimmondsin itself, thus assuming that the food restricting activity of the dimethylsimmondsin should be considered as a side-effect. This means that all earlier described research focused on food restriction simply overlooked the real important biological activities of the simmondsins i.e. their angiogenesis modulating properties. Further research showed that simmondsins are valuable candidates for the development of new angiogenesis inhibiting drugs. Jojoba has been used as a medicinal plant for centuries by the native Indians, but could soon be rediscovered as a valuable source for angiogenesis modulating molecules.
Acknowledgement. In vitro proliferation and tube formation studies were conducted at TNO Prevention and Health, Division of Vascular and Connective Tissue Research, Leiden, The Netherlands. CAM assays were conducted at the State University of Ghent, Fac. of Medicine, Lab. of Experimental Cancerology, Ghent, Belgium.[/vc_column_text][vc_single_image image=”1614″ img_size=”full” alignment=”center”][/vc_column][/vc_row][vc_row css=”.vc_custom_1530862910770{padding-top: 60px !important;padding-bottom: 60px !important;}”][vc_column][vc_column_text]
Angiogenesis inhibiting properties of Simmondsin molecules from Jojoba : ex vivo and in vivo experiments on mice.
André D’Oosterlynck and Stefaan T.M. Raes
YOEME C.V.B.A., Oudenaarde, Belgium.
Poster presentation (P36) at 5th International meeting on angiogenesis VU University Medical Center, Amsterdam, The Netherlands, March 12–14, 2014
Published in Angiogenesis (2014) 17:741
Simmondsins from the Jojoba shrub showed significant angiogenesis modulating properties in a series of in vitro proliferation assays.
Fetal metatarsals of mice were also inhibited in their blood vessel development after addition of simmondsins in the culture medium. A simple test to assess angiogenesis inhibiting features of certain simmondsin fractions purified from the Total Polar Extract from refined Jojoba meal, was a mice fertility experiment. Adult BALB/c mice were divided in 2 groups of 6 couples; one group received standard rodent food whilst the other group received the same food supplemented with desmethyl- and didesmethylsimmondsins in a dose equivalent to 500 mg simmondsins/Kg BW/day from two weeks before mating till the end of the experiment. In order to avoid any side effects, the dimethylsimmondsin was omitted from the diet because of its earlier described suppression of the food intake. Pregnancy was judged by the sudden increase in weight gain of the females. Moment of littering and litter size was recorded. The (dis)ability of mice to reproduce when simmondsins were applied to their diet gave very clear results. All 6 mice couples of the control group gave birth to a litter within 3 or 4 weeks, whilst all 6 simmondsin treated mice couples gave no birth and showed no signs of pregnancy at all and this during the whole duration of the experiment (3 months). When abolishing the simmondsin diet and returning these mice to normal rodent food again, most mice couples started to reproduce again (first litter usually smaller in numbers), demonstrating the reversible fertility suppressive action of the simmondsins. Moreover, pregnant mice that were placed on a simmondsin diet all abrogated their pregnancies.
In another experiment, FVB/N mice were divided in 2 groups; a control group receiving standard rodent food and the simmondsin treated group which received the same food supplemented with Total Polar Extract (equivalent to 600 mg simmondsins/Kg BW/day). Mice were put on their resp. diet 7 days before receiving a bFGF doped matrigel chamber implant, after x weeks control mice were compared to treated mice in their blood vessel score in the chambers. The matrigel chambers were scored on their blood vessel ingrowth 14 days post-implant. The simmondsin treated mice showed a significant smaller amount of blood vessel ingrowths in the matrigel compared to the control Group.
Both experiments clearly demonstrated the angiogenesis inhibitive action upon oral administration of the simmondsins. Quick regain of reproductive capacities shows a temporary and reversible angiogenesis bias induced by the simmondsins.The fact that oral administration of desmethyl- and didesmethylsimmondsins works very well in modulating the angiogenesis process without any visible side-effects offers interesting perspectives for the development of new angiogenesis modulating drugs against angiogenesis related diseases such as rheumatoid arthritis and cancer. Acknowledgement: Mice fertility test were conducted at the mice facility kindly placed at our disposal by the University of Ghent, Fac. of Veterinary Medicine, Lab. of Parasitology, Merelbeke, Belgium. The fetal metatarsal assay and Matrigel Chamber assay was conducted at TNO Prevention and Health, Division of Vascular and Connective Tissue Research, Leiden, The Netherlands.[/vc_column_text][vc_single_image image=”1615″ img_size=”full” alignment=”center”][/vc_column][/vc_row]