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Frank Greenway, M.D. Pennington Center March 3, 2009 Slide 2 Angiogenesis Angiogenesis, growing new blood vessels, is a basic biological process Angiogenesis in adults is used for menses, fetal development and healing wounds. Inhibition of angiogenesis in adults should have minimal side effects or toxicity. Cancer cannot grow past 2mm without angiogenesis and fat needs angiogenesis too. Slide 3 Human Angiogenesis Assay Discs are cut from the veins of placentas (after births). These placentas are left over after the delivery of a baby and would be discarded. The discs are put in a clot-like gel. The discs sprout new blood vessels (initiation) and the new vessels continue to gro over a 2-week period (angiogenic index from 1-16) Slide 4 Human Tissue Predicts Activity CmpdHumanAnimalClinicalUse SteroidYes Psoriasis HeparinYes Tumors NoniYes HerbTumors TaxolYes Tumors Endost. No 10 -5 m Yes Tumors Angiost. No 10 -4 m Yes Tumors Jung SP et al. Angiogenesis. 4(3):175-86, 2001. Hornick CA et al. Angiogenesis. 6(2):143-9, 2003. Slide 5 Sweet Leaf Tea This is a different tea than tea from the plant Camilla, the tea consumed in Britain, the US (black) or in Chinese restaurants (green) Sweet leaf tea is sweet due to a chemical made by the plant called Ruboside that is a non-caloric sweetener. Sweet leaf tea is consumed as part of the diet in an area in China and is related to blackberry, a plant called Rubus. Slide 6 Black Raspberry Slide 7 Inhibition of Angiogenesis by Sweet Leaf Tea in placental vein assay Slide 8 Fat is an Angiogenic Tissue Fat grows and recedes throughout life and is composed basically of fat and vessels. TNP-470 is a fungus-derived angiogenic inhibitor that makes people very sick. TNP-470 and other angiogenic inhibitors have been shown to reverse obesity in rodent models of obesity and it does not make the rodents sick. Slide 9 Intermittent Treatment with TNP-470, 10 mg/kg/d Slide 10 Human Angiogenesis Assay in Fat Tissue Slide 11 Active Ingredient Control 0.0001 M.001 M Slide 12 Sweet Leaf Tea Inhibits Angiogenesis in Human Fat Tissue Slide 13 Crude Extract with 26 Chemicals Slide 14 Partially Purified Extract with 13 Chemicals Slide 15 Purification and Standardization Purification gets rid of the plant chemicals and other plant components that do not inhibit angiogenesis. Purification resulted in 5 chemicals important for effectiveness Standardization is the identification of the important chemicals and being sure that every batch of the purified plant has the full amount of the effective chemicals. Standardization is necessary for a consistent product.