A Novel, Potent, Orally-Active Natural Anti-Angiogenic Preparation

Abstract

In healthy, mature older adults, angiogenesis (growth of new blood vessels) is virtually non-existent. When it occurs in such individuals, it is frequently associated with a pathological condition. Among these are tumour growth and metastasis, age-related macula degeneration, retinopathy and rheumatoid arthritis. Antagonists are beneficial for treating these chronic conditions.

We have previously shown that shark cartilage is anti-angiogenic when administered orally. Subsequent research has demonstrated that this activity could be ascribed to a lipoid fraction. Lipid-rich extracts were isolated from a number of fish species and shark organs and assayed. The ethanolic extract from shark muscle was particularly potent. This preparation, macolipin, which is especially rich in polyunsaturated fatty acids (notably docosahexaenoic acid), produced a 50% inhibition at 5μg/ml. When administered orally macolipin elicited a 50% reduction in angiogenesis at 17mg/kg body weight.

Several plant or vegetable oils including olive oil were shown to have no inhibitory effect in the aortic ring or the in vivo models. However, macolipin, when combined with olive oil (1:9) is twice as potent in the in vitro system. This combination is 6 to 7 times more active when administered orally to rats.

Preliminary experiments suggest that this combination can negate the stimulatory effects of factors such as VEGF, FGF-2 and TGF-β. This suggests that Macolipin/Olive oil (1:9) mixture is a potent orally-active natural product that has significant anti-angiogenic effects.