Biol. Pharm. Bull. 29(2) 306—314 (2006)

Asian herb known as “Siberian Ginseng” or “Eleutherococcus senticosus” and used for rheumatism and prophylaxis of various diseases including chronic bronchitis, hypertension, and ischemia. The herb has also been known to effectively relieve stress or fatigue, and symptoms associated with diabetes, neuralgia, and cancer. Today this oriental herb is called “adatogen” in the U.S. The major active components of A. senticosus are acanthoside, eleutheroside, chiisanoside, senticoside, triterpenic saponin, syringin, flavone, vitamin, minerals, b-sitosterol, sesamine and savinine. Each chemical compound is known to produce diverse biological activities. In Korea, the extract of the A. senticosus plant is used a component in traditional herbal Korean medicine, and is available as a functional beverage commercially marketed for reducing liver damage and accelerating alcohol detoxification. The efficacy of A. senticosus in animal modes and the mechanisms underlying the aforementioned physiological properties involved in alcohol metabolism is unclear, and is therefore the purpose of this investigation. As much as 80—90% of ingested alcohol is metabolized in the liver, where alcohol is oxidized to acetadehyde. The process is catalyzed by 3 different enzymes: alcohol dehydrogenase (ADH), microsomal ethanol metabolizing system (MEOS), and acetaldehyde dehydrogenase (ALDH). Since acetaldehyde is much more toxic than alcohol, it is associated with a larger number of the metabolic abnormalities in liver disease induced by alcohol. Under normal conditions, acetaldehyde is rapidly converted to acetate by ADH, and therefore very low level of acetaldehyde should remain in the liver tissue or blood. ALDH also plays an important role in the elimination of acetaldehyde through oxidative reactions. Therefore, the severity of liver diseases can be proportional to reductions in ADH or ALDH activities. Development of fatty liver and hyperlipidemia frequently occurs in chronic alcoholics; mainly because ethanol becomes a preferred fuel for the liver and displaces fat as a source of energy, which results in fat accumulation. Furthermore, the redox state secondary to ethanol oxidation is altered, promotings lipogenesis through increasing a-glycerophosphate and acylglycerols. The depressed oxidative capacity of mitochondria caused by chronic alcohol also contributes to fatty liver. Increasing fat accumulations in the liver can also stimulate secretion of lipoproteins into the bloodstream, facilitating the development of hyperlipidemia. Acetyl CoA carboxylase (ACC) is an enzyme that catalyzes the first step in fatty acids biosynthesis and is a rate-limiting enzyme in lipogenesis. Moreover, malic enzyme (ME), glucose-6-phosphate dehydrogenase (G6PDH), and 6-phosphoglucuronic acid dehydrogenase (6-PGDH) are also involved in lipogenesis by supplying NADPH, an essential cofactor for fatty acids and cholesterol biosynthesis. Alcohol has also been suggested to cause fatty liver by altering the NAD /NADH redox potential, which inhibits fatty acid oxidation and the TCA cycle addition to stimulating lipogenesis. Many of alcohol’s toxic effects in the liver have been ascribed to oxidative stress caused by ethanol metabolism. Ethanol, or its metabolites, causes auto oxidation in hepatic cells, which induces marked hepatotoxicity by acting as a pro-oxidative agent or by reducing antioxidant levels. Lipid peroxidation and related membrane damage are key features in alcoholic liver injury. Generally, increased oxidative stress occurs as a consequence of induced MEOS and NADPH oxidation, and ethanol is converted to ethyl and 1-droxyethylradical. Additionally, acetaldehyde binds hepatic glutathione (GSH), depleting the antioxidant reserve. Therefore, the ineffective removal of free radicals can adversely alter the lipid composition of cell membranes via lipid peroxidation and induce depletion of cellular antioxidants, result306 Vol. 29, No. 2 Biol. Pharm. Bull. 29(2) 306—314 (2006)