Topical Application Luteolin is suitable for topical application; it is not only adsorbed on the skin surface, but penetrates into deeper skin levels. Luteolin is a promising external antiinflammatory agent. Luteolin inhibits the activation of protein kinase C, enzyme involved in the tumor-promoting effect. This makes Luteolin a candidate for preventing skin cancer.78 Other Beneficial Effects Luteolin is an active inhibitor of different hyaluronidases, which modify hyaluronic acid79. Hyaluronic acid, a heteropolysaccharide, is one the polymers that accounts for the toughness and flexibility of cartilage and tendon. Luteolin exhibits spasmolytic effects: Luteolin significantly antagonized acetylcholine- and histamine-induced contraction of smooth muscle in the guinea pig model of modified air overflow80,81 and showed strong anti-histamine properties82,83. Luteolin displays anti-leishmanial activity.84 Luteolin displays strong antinociceptive (against pain originating from peripheral nerves) action in mice.85 This is in accordance with the fact that Luteolin is an active principle of Brazilian plant Wedelia paludosa, traditionally used against the variety of disorders, including painful conditions. Luteolin exhibits estrogenic properties in rats.86,67 While orally administered from day 1 to day 4 of pregnancy it showed dose-dependent anti-implantation activity. A single oral dose prevented 100% implantation. The mean effective dose was found to be 25 mg/kg body weight. Respiratory tract disturbances: Due to its anti-allergic, anti-inflammatory and smooth muscle-relaxing properties, luteolin has potential in the prevention and treatment of many respiratory disorders, including asthmatic conditions, chronic bronchitis, etc.94,96 Opthalmology: Prevention of the neovascular disease of the eye: Luteolin strongly inhibits corneal angiogenesis in vivo.87 Beneficial Effects of Luteolin Glycosides Luteolin-7-glucoside (isolated along with luteolin from Genista rumelica) displayed pronounced capillary strengthening. Luteolin-7- O-glucoside and luteolin-4'-O-glucoside (from Ligustrum vulgare and Phillyrea latifolia, Oleaceae) presented “remarkable” complement inhibiting effect on the classical pathway.88 Luteolin-7-glucoside reportedly protects from ischemic tissue injury (possibly due to its antioxidative and phosphodiesterase-inhibiting properties).89 Luteolin 4'-O-glucopyranoside from Kummerowia striata Thunb. (Leguminosae) was identified as the IL-5 inhibitor.90 Interleukin (IL)-5 is a chemotactic factor of eosinophils; it promotes the growth and survival of eosinophils, which play an important role in the eosinophilia-associated allergic inflammation. Luteolin 7-O-rutinoside (scolymoside) (isolated from Artemisia montana) has strong radical scavenging properties. Its antioxidant activity is comparable to that of L-ascorbic acid. Some luteolin glycosides are reported to have antidiabetic activities. Particularly, luteolin-5-O-ß-rutinoside, isolated from medicinal plant Salvia lavandulifolia and given orally to diabetic rats (2 mg/kg for 20 days) reduced glycemia and increased pancreatic insulin and pancreatic DNA contents. The authors relate the effect to the antioxidative action of the flavonoid, e.g., prevention of oxidative stress that causes the destruction of ß-cells.91 Protective effect of luteolin and its glycosides against tissue injury can be realized through various mechanisms: decrease of capillary fragility, scavenging active oxygen species, inhibition of lipid peroxidation, inhibition of release of leukotrienes and TNF-alpha, suppression of adhesion of leukocytes to endothelium, and so on.92 BIOAVAILABILITY AND PHARMACOKINETICS Preliminary studies in rabbits and rats using [3H]-luteolin and fluorescence spectrophotometry examined the absorption, metabolism and excretion of luteolin.93,94 Metabolism and Absorption In rats orally administered [3H]-luteolin was rapidly absorbed and distributed in various tissues, with highest concentrations in liver and kidney. A comparison of the concentration-time curve of protocatechuic acid (PCA) with that of luteolin indicates that PCA is a product of luteolin.77,79 In order to know whether Luteolin was absorbed by the small intestine, perfusion of the jejunum with Luteolin was performed. The HPLC analysis of the serosal fluid followed by a treatment with -glucoronidase enabled to know if Luteolin was absorbed and in which form (free or as glucoronide conjugates). The comparative absorption of flavonoids and their glycosides across the jejunum and ileum in a rat intestinal model showed that measured levels of luteolin as aglycone were small relative to the amount of total luteolin glucoronides recovered. Treatment with ß-glucuronidase indicated the presence of at least six different glucuronides.95 Excretion Luteolin was rapidly removed from the blood via the kidney and the liver. 12h-urinary excretion in rabbits was 37.7% of the total i. v. dose. In rats the 6h-biliary excretion was about 11.2% of the total i. v. dose.77,79 GENERAL SAFETY Toxicity of Luteolin General Luteolin is considered nontoxic: The determination of LD50 in various animals did not show acute toxicity LD50 of Luteolin Animal Route Dose Reference Mouse Intraperitoneal >180 mg / kg 96,97 Rat Intraperitoneal 411 mg / kg 98 Rat Intramuscular 592 mg / kg 81 Rat Oral >5000 mg/kg SYNORx Mouse Oral 2500 mg / kg 99,100 Table 12: LD50 data of Luteolin Mutagenicity of Luteolin General Luteolin is considered non-mutagenic: Luteolin shows no mutagenicity in the Ames test with or without activation.101 BIBLIOGRAPHY 1 Hoppe, H.A. (1975) Drogenkunde Band 1 Angiospermien, 8th ed., DeGryter, Berlin, New York. 2 Teuscher E. (1989) Pharmakognosie - Biogene Arzneimittel, 3th ed.,Akademie Verlag Berlin. 3 Achterrath-Tuckermann, U.; Kunde, R.; Flaskamp, E.; Isaac, O.; Thiemer, K. (1980) Planta Med. 39, 38-50. 4 Kraft, K. 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Toxicol. 33, 1061-1080. 101 MacGregor, J.T.; Jurd, L. (1978) Mutation Res. 54, 297-309. LUTIMAX - LutiMax Luteolin Formula (100mg) - Free Shipping, Lower Prices for 4 or More Retail Price: $89.95 Sale Price: $69.95 LutiMax - A Natural Bioflavonoid Product Containing Luteolin LutiMax - A Natural Bioflavonoid Product Containing Luteolin, Part 2 FREE AIR MAIL SHIPPING IN THE UNITED STATES! The statements made here have not been evaluated by the FDA. The foregoing statements are based upon sound and reliable studies, and are meant for informational purposes. Consult with your medical practitioner to determine the underlying cause of your symptoms. Copyright 1997-2008 Life Extension Vitamin Supplies and Life Extension Institute, Inc. All rights reserved.