rad natural technologies ltd.

Technical Bulletin 2/2002 Therapeutic Potential of Origanox™ WS

Rad Natural Technologies Ltd. Rad is a biotechnology company, specializing in extraction and purification of active ingredients from plants. Origanox™ WS Origanox™ WS is a natural, completely water soluble antioxidant, extracted from edible herb species, belonging to the Labiatae family of herbs (e.g. Origanum Vulgare and Salvia Officinalis) and considered GRAS by the FDA (21 CFR chapter 21, part 182). No chemicals or solvents are used in the manufacturing process of Origanox™ WS. Origanox™ WS is offered in various standardized grades of antioxidant activity for usage in numerous applications in the food, nutraceutical, feed, cosmetics and pharmaceutical industries. The main active ingredient in Origanox™ WS is Rosmarinic acid, a phenolic acid known for its significant antioxidative abilities and therapeutic properties. Main features of Origanox™ WS: § Powerful antioxidant § Water soluble § Completely natural § Non toxic § Effective in very low dosage § Organoleptic neutral § Stable and active under high frying and baking temperatures (180^oC / 356^oF) Properties for cosmetics and therapeutic applications: § Easy skin penetration § Remarkable anti-inflammatory agent for avoiding and alleviating stinging, itching and redness of the skin § Anti-allergic § Anti-aging agent and strong free radical scavenger § Antimicrobial and antifungal

Origanox™ WS is the commercial name for a natural, water-soluble extract, produced by RAD Natural Technologies Ltd. from edible herbs belonging to the Labiatae family. The main active ingredient of Origanox™ WS is Rosmarinic acid, a hydroxy-cinnamic acid. Origanox™ WS has a strong antioxidant capacity and is applied in the food industry to prolong shelf life and enhance product quality. In this publication we address the potential contribution of Origanox™ WS to human health. Origanox™ WS standard grade contains a minimum of 7% Rosmarinic acid and 16% of phenolic compounds. RAD has the ability to offer also Origanox™ WS with an enriched Rosmarinic acid content of 12-20 % for specialty applications, using a proprietary, patented production technology. Origanox™ WS with a higher Rosmarinic acid content, suitable for medicinal applications, may be offered upon special demand. Rosmarinic acid is considered non-toxic. Toxicity tests carried out in rats show an LD-50 of 560 mg/kg. Rosmarinic acid, a phenolic acid, exhibits significant free radical scavenging, anti-inflammatory, anti-allergic and antimicrobial capabilities^1. It has been reported that oral administration in doses of 1-100 mg/kg in rats inhibited passive cutaneous anaphylaxis. Administered intra-muscular in a dose of 10 mg/kg, Rosmarinic acid impaired, in vivo, the activation of mouse macrophages by heat-killed C. pervum. Rosmarinic acid reduced paw edema, induced in rats by cobra venom factor (CVF), by administering intra-muscular doses of 0.316-3.16 mg/kg. The capacity of Rosmarinic acid to inhibit the activity of lipoxygenase is considerably higher than that of Vitamin C or Vitamin E. Rosmarinic acid is known to be well absorbed through the gastro-intestinal track and it has an excellent dermal permeability. Rosmarinic acid also permeates the blood-brain barrier, which may have important therapeutic implications for certain, brain diseases. Rosmarinic acid increases the production by the human body of prostaglandin E2 and reduces the production of leukotriene B4 in human polymorphonuclear leukocytes. In addition, Rosmarinic acid inhibits the complement C3-convertase. Rosmarinic acid, being an antioxidant, acts also as a free radical scavenger. It suppresses lipid peroxidation and inhibits initiators and promoters of carcinogenesis. Likewise it may be involved in delaying the aging process. The anti-inflammatory activity has been proven both in vitro and in vivo and Rosmarinic acid may therefore be used in the therapy of allergic inflammations and pulmonary edema. In vivo studies have shown excellent skin permeability. There is an indication of binding to the upper skin layers, resulting in a lag time before reaching steady state. After topical administration in the form of a water-oil emulsion, the absolute bio-availability was 60%. Also, after topical administration Rosmarinic acid concentrations in muscle and bone tissue beneath the application site were found comparable to those after systemic administration. The same study indicates that Rosmarinic acid is a substance suitable for trans-dermal applications. Ø ^1 See also Technical Bulletin 1/2002: Origanox™ - Antimicrobial and Antifungal Properties

rad natural technologies ltd.

Ø Therapeutic Potential of Origanox™ WS

Origanox™ Capsules

Origanox™ Capsules are a dietary supplement, containing 500 mg of Origanox™ WS. A daily consumption of 3 capsules provides the body with more then 100 mg of Rosmarinic acid and at least 7,000 ORAC units.

ORAC (Oxygen Radical Absorbance Capacity) is an assay measuring the free radical scavenging capacity of botanical sources for human consumption. The USDA estimates that the average person needs 3,000-5,000 ORAC units per day in order to generate enough free radical scavenging capacity for significantly protecting plasma and tissue. Most Americans have a daily intake of 1,200 ORAC units only.

Origanox™ Cream

Origanox™ Cream is an herbal cream with anti-inflammatory and antimicrobial properties. Origanox™ Cream contains Origanox™ WS and Origanox™ EO (essential oil from Origanum vulgare).

In a recent article “Pharmacology of rosemary (Rosmarinus officinalis Linn.) and its therapeutic potentials” published in the Indian Journal of Experimental Biology. Vol.37, February 1999, pp.124-130, it has been reported that the absorption of Rosmarinic acid has been tested in rats: the terminal half-life t1/2 in oral administration was 1.8 hours. Upon intravenous administration, Rosmarinic acid was detected and measured after 30 minutes in the brain, heart, liver, lung, muscle, spleen and bones. The highest concentration was measured in the lung tissue, where it measured 1.3 times the concentration in the blood; topical administration by means of an ointment revealed a bio-availability of about 60% and a peak time of 4.5 hours.

Below is a partial list of diseases, in which Rosmarinic acid and other hydroxy-cinnamic derivatives may play an important therapeutic role. This list is partly based on the cited article.

Pharmacological Actions	Therapeutic Potential
Inhibition of production of leukotrienes and prostaglandins; inhibition of complement C3-convertase	Bronchial asthma, Allergies, Peptic ulcer, Rheumatoid arthritis, Inflammations
Inhibition of production of lipid peroxides and prostaglandins; scavenging of free radicals released by xanthine oxidase	Hepatoxicity, Atherosclerosis, Ischaemic heart disease
Inhibition of leukotrienes and complement C3-convertase	Psoriasis and other skin diseases
Prevention of the carcinogen-DNA adduct formation	Cancer
Free radical scavenging	Cataract
Free radical scavenging and inhibition of complement C3-convertase	Brain diseases

It may be concluded that Rosmarinic acid possesses a remarkable therapeutic potential. n