L-Carnosine

• Carnosine is a beta-alanylhistidine dipeptide found in skeletal muscle and nervous tissue that has been reported to possess antioxidant activity.
  **Inhibition of low-density lipoprotein oxidation by carnosine histidine. J Agric Food Chem 2001 Jan;49(1):511-6
• Carnosine (beta-alanyl-L-histidine) is a physiological dipeptide which can delay aging and rejuvenate senescent cultured human fibroblasts.
  **Carnosine, the anti-ageing, anti-oxidant dipeptide, may react with protein carbonyl groups. Mech Ageing Dev 2001 Sep 15;122(13):1431-45
• Carnosine is a potential dietary antioxidant because it is absorbed into plasma intact.
  **Ibid.
• In a laboratory test, carnosine inhibited LDL oxidation.
  **Ibid.
• Carnosine protects the brain against oxidative injury and thereby increases the survival of the animals subjected to ischemia.  Carnosine protects rats under global ischemia. Brain Res Bull 2000 Nov 1;53(4):445-8
  **The role of phenolics, conjugated linoleic acid, carnosine, and pyrroloquinoline quinone as nonessential dietary antioxidants. Nutr. Rev. 53: 49-58. Di Mascio, P., Kaiser, S., and Sies, H. 1989.
• The N-acetylated form of natural dipeptide L-carnosine appears to be potent nonsurgical treatment for senile cataracts.
  **N-Acetylcarnosine, a natural histidine-containing dipeptide, as a potent ophthalmic drug in treatment of human cataracts. Peptides 2001 Jun;22(6):979-94

Bromelain

• Bromelain's actions include inhibition of platelet aggregation, and the modulation of cytokines, the clotting cascade, and prostaglandins. Clinically, bromelain is primarily utilized to reduce inflammation and enhance the healing time in instances of musculoskeletal injuries, including surgical wounds. Other therapeutic applications of bromelain have included administration as a synergistic drug to potentiate the action of antibiotics, as a mucolytic to assist with the clearing of sputum from the respiratory tract, as a proteolytic digestive enzyme, and as a nutraceutical to prevent the symptoms of angina.
  **Monograph:Bromelain. Altern Med Rev 1998 Aug;3(4):302-5

• Bromelain's properties include: (1) interference with growth of malignant cells; (2) inhibition of platelet aggregation; (3) fibrinolytic activity; (4) anti-inflammatory action; (5) skin debridement properties. These biological functions of bromelain, a non-toxic compound, have therapeutic values in modulating: (a) tumor growth; (b) blood coagulation; (c) inflammatory changes; (d) debridement of third degree burns; (e) enhancement of absorption of drugs.
  **Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinicalapplication. An update. J Ethnopharmacol 1988 Feb-Mar;22(2):191-203

•  Data from a study of the immunological effects of an orally applied bromelain drug on 16 breast cancer patients in comparison with healthy donors suggest that orally applied bromelain stimulates the deficient monocytic cytotoxicity of mammary tumor patients, which may partially explain its proposed antitumor activity.
  **Effects of oral bromelain administration on the impaired immunocytotoxicity of mononuclear cells from mammary tumor patients. Oncol Rep 1999 Nov-Dec;6(6):1191-9

• Bromelain, a pineapple-derived plant product, added to C57Bl/6 mice laboratory chow decreased lung metastasis of Lewis lung cancer cells implanted subcutaneously. This antimetastatic potential was demonstrated by both the active and inactive bromelain with or without proteolytic, anticoagulant properties.
  **Antimetastatic effect of bromelain with or without its proteolytic and anticoagulant activity. J Cancer Res Clin Oncol 1988;114(5):507-8

• Proteolytic enzymes including bromelain extracted from pineapple stems may have significant kidney protective effects -- Recently, it has emerged that extracellular proteases have specific regulatory roles in modulating immune responses. The results of this study indicate that bromelain is a novel inhibitor of T cell signal transduction and suggests a novel role for extracellular proteases as inhibitors of intracellular signal transduction pathways.
  **Bromelain, from pineapple stems, proteolytically blocks activation of extracellular regulated kinase-2 in T cells. J Immunol 1999 Sep 1;163(5):2568-75

• Proteolytic enzymes including bromelain extracted from pineapple stems may have significant kidney protective effects. This study investigated the possible beneficial effect of proteolytic enzymes the development of renal hypertension following surgically-induced kidney injury in the rats. Results indicate that systemic treatment with these enzymes slowed degeneration of the undamaged kidney and prevented proteinuria without affecting high blood pressure.
  **Effect of chronic therapy with proteolytic enzymes on hypertension-induced renal injury in the rat model of Goldblatt hypertension. Am J Nephrol 1998;18(6):570-6

• Bromelain may be clinically useful as an antidiarrhea drug.
  **Bromelain prevents secretion caused by Vibrio cholerae and Escherichia coli enterotoxins in rabbit ileum in vitro. Gastroenterology 1997 Jul;113(1):175-84

• Bromelain can temporarily inactivate enterotoxigenic Escherichia coli (ETEC) receptors in vivo and protect against ETEC induced diarrhoea. Bromelain may therefore be an effective prophylaxis against ETEC infection.
  **Bromelain protects piglets from diarrhoea caused by oral challenge with K88 positive enterotoxigenic Escherichia coli. Gut 1998 Aug;43(2):196-202

•  The thiol protease, bromelain, an extract from pineapple stem, has antithrombotic and anticoagulant activities in vivo.
  **Bromelain proteases reduce human platelet aggregation in vitro, adhesion to bovine endothelial cells and thrombus formation in rat vessels in vivo. In Vivo 1999 Jan-Feb;13(1):7-12

• Bromelain, quercetin, N-acetylcysteine, and vitamin C are safe, natural therapies that may be used as primary therapy for perennial allergic rhinitis or in conjunction with conventional methods.
  **Natural treatment Of perennial allergic rhinitis. Altern Med Rev 2000 Oct;5(5):448-54

• ---

• Quercetin

• The flavonoids quercetin and rutin protected living cells against DNA strand breaks by way of their metal ion chelating mechanism. Quercetin also protected against menadione-induced DNA single strand breaks by acting as both a metal chelator and radical scavenger.
  **Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000 Sep 15;29(6):507-14

• It is now clear that levels of endogenous anti-oxidants such as GSH decrease with age. This study suggests that dietary antioxidants, particularly quercetin, could play a significant role in the reduction of inflammatory responses associated with the aging process.
  **Antioxidants may contribute in the fight against ageing: an in vitro model. Mech Ageing Dev 2000 Dec 20;121(1-3):217-30

• Therapy with the bioflavonoid quercetin is well tolerated and provides significant symptomatic improvement in most men with chronic pelvic pain syndrome.
  **Quercetin in men with category III chronic prostatitis: a preliminary prospective, double-blind, placebo-controlled trial. Urology 1999 Dec;54(6):960-3

• Alcohol-free red wine extract and one of its components, quercetin can inhibit LDL oxidation after in vivo supplementation.
  **Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affection plasma antioxidant vitamin and carotenoid concentrations.  Clin. Chem 2000 Aug;46 (8 Pt 1):1162-1170.

• Quercetin is a botanical compounds with anti-ulcer activity.
  **The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000 Dec;14(8):581-591

• Diabetic cataracts are caused by an elevation of polyols within the lens of the eye catalyzed by the enzyme aldose reductase. Flavonoids, particularly quercetin and its derivatives, are potent inhibitors of aldose reductase.
  **Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001 Apr;6(2):141-66

• Escalating concentration of flavonoid quercitin (0-10 microM) in culture cell medium enhanced the rate of cell growth and diminished levels of lipid peroxidation breakdown products.
  **East Afr Med J 1996 Nov;73(11):752-7 Effects of beta-carotene, flavonoid quercitin and quinacrine on cell proliferation and lipid peroxidation breakdown products in BHK-21 cells.

• Bromelain, quercetin, N-acetylcysteine, and vitamin C are safe, natural therapies that may be used as primary therapy for perennial allergic rhinitis or in conjunction with conventional methods.
  **Natural treatment Of perennial allergic rhinitis. Altern Med Rev 2000 Oct;5(5):448-54

• Quercetin is a naturally occurring plant compounds with antioxidant properties. Its consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis.  Results of a study of the influence of flavonoids on lipid peroxidation show that quercetin could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and the flavonoid.
  **Flavonoids and urate antioxidant interplay in plasma oxidative stress. Mol Cell Biochem 2001 May;221(1-2):79-87

• In a study comparing the effects of selected bioflavonoids on the proliferation of androgen-independent human prostatic tumor cells (PC-3),complete growth retardation was observed in cells treated with 100 microM quercetin.
  **Flavonoids suppress androgen-independent human prostate tumor proliferation. Nutr Cancer 2000;38(1):116-122

• Protection by the flavonoid quercetin against tert-butylhydroperoxide (tert-BOOH)- and menadione-induced DNA single strand breaks was investigated in Caco-2 cells. Rutin protected against tert-BOOH-induced DNA strand breaks by way of its metal ion chelating mechanism. Quercetin also protected against menadione-induced DNA single strand breaks by acting as both a metal chelator and radical scavenger.
  **Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000 Sep 15;29(6):507-514

• A study investigated the chemopreventive effects of quercetin and rutin when added to standard diet and fed to normal and azoxymethane (AOM)-treated mice. Both the number of mice exhibiting focal areas of dysplasia (FAD) and the total number of FAD observed were significantly reduced in AOM-treated animals fed flavonoids compared with mice maintained on the standard diet.
  **Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis 2000 Sep;21(9):1655-1660

Rutin

• Rutin is an efficient suppressors of oxygen radical overproduction by rheumatoid arthritis neutrophils.
  **Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators(1). Biochem Pharmacol 2001 Sep 15;62(6):743-746

• Rutin exhibited a powerful protective effect against ethanol-induced lesions of the gastric mucosa in an experimental model of ulcer formation. The gastroprotective effect of rutin appears through an anti-lipoperoxidant effect, and also by enhancement of the anti-oxidant enzymatic (glutathione peroxidase) activity.
  **Evidence for protective and antioxidant properties of rutin, a natural flavone, against ethanol induced gastric lesions. J Ethnopharmacol 2000 Jul;71(1-2):45-53

• Proteolytic enzymes including rutin may have significant kidney protective effects.
  **Effect of chronic therapy with proteolytic enzymes on hypertension-induced renal injury in the rat model of Goldblatt hypertension. Am J Nephrol 1998;18(6):570-6

• The flavonoid rutin protected living cells against DNA strand breaks by way of their metal ion chelating mechanism.
  **Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000 Sep 15;29(6):507-14

• Natural non-toxic bioflavonoid rutin (vitamin P) inhibited oxygen radical overproduction in both rheumatoid arthritis and Fanconi anemia in an equally efficient manner and therefore may be considered as a useful supporting pharmaceutical agent for the treatment of "free radical" pathologies.
  **Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators(1). Biochem Pharmacol 2001 Sep 15;62(6):743-746 treatment. Free Radic Biol Med 2001 Sep 15;31(6):754-762

• Rutin is a naturally occurring plant compounds with antioxidant properties. Its consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis. Results of a study of the influence of flavonoids on lipid peroxidation show that rutin could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and the flavonoid.
  **Flavonoids and urate antioxidant interplay in plasma oxidative stress. Mol Cell Biochem 2001 May;221(1-2):79-87

• Heterocyclic amines (HCA's) are promutagens produced by high temperature cooking of meat products and are activated by cytochrome P450 (CYP) lA2. Data suggest a chemopreventive potential for the citrus bioflavonoid rutin towards CYPlA2 mediated mutagenesis of HCA's.
  **Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome P450 1A2 activity. Anticancer Res 2000 Sep;20(5B):3609-3614

• Rutin (and/or its metabolites) inhibits ovariectomy-induced trabecular bone loss in rats, both by slowing down resorption and increasing osteoblastic activity.
  **Rutin inhibits ovariectomy-induced osteopenia in rats. J Bone Miner Res 2000 Nov;15(11):2251-2258

•  Protection by the flavonoid rutin against tert-butylhydroperoxide (tert-BOOH)- and menadione-induced DNA single strand breaks was investigated in Caco-2 cells. Rutin protected against tert-BOOH-induced DNA strand breaks by way of itsmetal ion chelating mechanism.
  **Mechanism of protection by the flavonoids, quercetin and rutin, against tert-butylhydroperoxide- and menadione-induced DNA single strand breaks in Caco-2 cells. Free Radic Biol Med 2000 Sep 15;29(6):507-514

• A study investigated the chemopreventive effects of quercetin and rutin when added to standard diet and fed to normal and azoxymethane (AOM)-treated mice. Both the number of mice exhibiting focal areas of dysplasia (FAD) and the total number of FAD observed were significantly reduced in AOM-treated animals fed flavonoids compared with mice maintained on the standard diet.
  **Chemoprevention studies of the flavonoids quercetin and rutin in normal and azoxymethane-treated mouse colon. Carcinogenesis 2000 Sep;21(9):1655-1660

L-Cysteine

• N-acetylcysteine (NAC) can increase levels of glutathione which is necessary for detoxification and is depleted by toxic metals.
  **Effects of Toxic Metals on Learning Ability and Behavior. www.talkinternational.com

• Decreased risks of neural tube defects were associated with increased intakes of cysteine and zinc for women who used supplements.
  **Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies. Epidemiology 1999 Nov;10(6):711-6

• In laboratory studies, sulphur-containing amino acids (SCAAs) including L-cysteine enhance synaptic glutamate release from rat brain cells. These central actions of the SCAAs may have wide-ranging implications for a range of neurological and neuropsychiatric disease states and their treatment.
  **Endogenous sulphur-containing amino acids: potent agonists at presynaptic metabotropic glutamate autoreceptors in the rat central nervous system. Br J Pharmacol 2001 Jul;133(6):815-24

• Nitric oxide is a powerful weapon used by macrophages to kill tumor cells and pathogenic bacteria. L-cysteine enhances the repair activity of nitric oxide in disrupted cells.
  **L-cysteine-mediated destabilization of dinitrosyl iron complexes in proteins. Biol Chem 2001 Jun 21 [epub ahead of print]

• L-cysteine exerts direct anti-aggregating effects on human platelets and whole blood through an increased bioavailability of platelet nitric oxide.
  **N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets. Eur J Clin Invest 2001 May;31(5):452-61

• Supplementation with antioxidants such as alpha-tocopherol, N-acetyl cysteine, ascorbic acid, beta-carotene, and selenium can offer an achievable and inexpensive adjunct therapy to help inhibit the development of retinopathy in diabetes.
  **Abnormalities of retinal metabolism in diabetes and experimental galactosemia: vii. effect of long-term administration of antioxidants on the development of retinopathy. Diabetes 2001 Aug;50(8):1938-42

• Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, **N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These agents may have antioxidant effects at the biochemical level but are also known to influence redox-sensitive cell signaling.
  Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000 Aug;72(2 Suppl):653S-69S

• In a study of neurotoxic processes associated with Parkinson’s disease, N-acetyl-L-cysteine was effective in providing protection against L-glutamate-induced cell death and neurotoxicity induced by N-methyl-4-phenylpyridinium ion (MMP+) in murine pheochromocytoma cells.
  **Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells. Neurotoxicology 2001 Apr;22(2):283-288

• Amino acid L-cyst(e)ine was found to prevent serum-induced cell death of TIG-1 human fetal lung fibroblasts and other cell types.
  **Apoptotic cell death induced by serum and its prevention by thiols. J Cell Physiol 1994 Oct;161(1):63-70

• Antioxidant treatment is neuroprotective in experimental bacterial meningitis. Treatment with N-acetylcysteine significantly inhibited the increase in cortical malondialdehyde, and attenuated the loss of endogenous antioxidants in the cortex of infant rats infected with Streptococcus pneumoniae.
  **Oxidative stress in brain during experimental bacterial meningitis: differential effects of alpha-phenyl-tert-butyl nitrone and N-acetylcysteine treatment. Free Radic Biol Med 2001 Sep 15;31(6):754-762

Green Tea

• Chlorophyll a and b from green tea (Camellia sinensis) possess potent suppressive activities against tumor promotion.
  Potent suppressive activity of chlorophyll a and b from green tea (Camellia sinensis) against tumor promotion in mouse skin. J UOEH 1998 Sep 1;20(3):181-8

• Green tea contains polyphenolic compounds also known as epicatechins, which are antioxidant in nature. The major and most chemopreventive constituent in green tea responsible for these biochemical or pharmacological effects is (-)-epigallocatechin-3-gallate (EGCG).
  Green tea polyphenolic antioxidants and skin photoprotection (Review). Int J Oncol 2001 Jun;18(6):1307-13

• The catechins are believed to be active constituents of green tea accounting for the reported chemoprevention of certain cancers. The results of a 2001 study support an antioxidant role for catechins in their direct interaction with DNA radicals.
  Green tea catechins partially protect DNA from (.)OH radical-induced strand breaks and base damage through fast chemical repair of DNA radicals. Carcinogenesis 2001 Aug;22(8):1189-93

• Epidemiological studies have shown that tea catechin intake is associated with lower risk of cardiovascular disease.
  Absorption, metabolism and antioxidative effects of tea catechin in humans. Biofactors 2000;13(1-4):55-9

• In vitro biochemical studies have reported that catechins help to prevent oxidation of plasma low-density lipoprotein (LDL). LDL oxidation has been recognized to be an important step in the formation of atherosclerotic plaques and subsequent cardiovascular disease.
  Ibid.

• Treatment of green tea polyphenols to skin has been shown to modulate the biochemical pathways involved in inflammatory responses, cell proliferation and responses of chemical tumor promoters as well as ultraviolet light-induced inflammatory markers of skin inflammation. Topical treatment with EGCG on mouse skin also results in prevention of UVB-induced immunosuppression and oxidative stress.
  Green tea polyphenolic antioxidants and skin photoprotection (Review). Int J Oncol 2001 Jun;18(6):1307-13

• Catechin is a naturally occurring plant compounds with antioxidant properties. Its consumption has been associated with the protective effects of certain diets against some of the complications of atherosclerosis.
  Results of a study of the influence of flavonoids on lipid peroxidation show that catechin could protect endogenous urate from oxidative degradation, and demonstrate an antioxidant synergy between urate and the flavonoid.
  **Flavonoids and urate antioxidant interplay in plasma oxidative stress. Mol Cell Biochem 2001 May;221(1-2):79-87

Alpha lipoic acid

• Oxidative stress has been implicated as a causal factor in the aging process of the heart and other tissues. Data from a 2001 animal study indicate that the aging heart is under increased mitochondrial-induced oxidative stress, which is significantly attenuated by lipoic acid supplementation.
  **Oxidative stress in the aging rat heart is reversed by dietary supplementation with (R)-(alpha)-lipoic acid. FASEB J 2001 Mar;15(3):700-6

• Oxidative stress contributes to endothelial dysfunction. Alpha-lipoic acid has therapeutic potential, particularly in patients with imbalance between increased oxidative stress and depleted antioxidant defense.
  **Beneficial effects of alpha-lipoic acid and ascorbic acid on endothelium-dependent, nitric oxide-mediated vasodilation in diabetic patients: relation to parameters of oxidative stress. Free Radic Biol Med 2001 Jul 1;31(1):53-61

• Pathophysiological mechanisms of cataract formation include deficient glutathione levels contributing to a faulty antioxidant defense system within the lens of the eye. Nutrients to increase glutathione levels and activity include lipoic acid, vitamins E and C, and selenium.
  **Natural therapies for ocular disorders, part two: cataracts and glaucoma. Altern Med Rev 2001 Apr;6(2):141-66

• Lipoic acid synergistically enhances the tumoricidal action of Vitamin C.
  **Cytotoxicity of ascorbate, lipoic acid, and other antioxidants in hollow fibre in vitro tumours. Br J Cancer 2001 Jun 1;84(11):1544-50

• Potent antioxidant alpha-lipoic acid in conjunction with mitochondrial dehydrogenase complexes has been shown to lower blood glucose in diabetic animals. Alpha-lipoic acid mimics insulin action.
  **The antihyperglycemic drug alpha-lipoic acid stimulates glucose uptake via both GLUT4 translocation and GLUT4 activation: potential role of p38 mitogen-activated protein kinase in GLUT4 activation. Diabetes 2001 Jun;50(6):1464-71

• Experimental studies show that glutathione metabolism in several tissues sensitively responds to an exhaustive bout of exercise. Study of glutathione-deficient animals clearly indicates the central importance of having adequate tissue glutathione to protect against exercise-induced oxidative stress. Among the various thiol supplements studied, N-acetyl-L-cysteine and alpha-lipoic acid hold the most promise. These agents may have antioxidant effects at the biochemical level but are also known to influence redox-sensitive cell signaling.
  **Thiol homeostasis and supplements in physical exercise. Am J Clin Nutr 2000 Aug;72(2 Suppl):653S-69S.

Taurine

• Taurine, or 2-aminoethane sulfonic acid, is an intracellular amino acid and has been suggested to have a function in protecting biological systems from oxidative tissue damage. We would conclude that taurine has beneficial effects in cerulein-induced acute pancreatitis and lung injuries by preventing the production of oxygen free radicals.
  **Effects of taurine on cerulein-induced acute pancreatitis in the rat. Pharmacology 2001 Jul;63(1):1-7

• In pre-term and term infants, taurine insufficiency results in impaired fat absorption, bile acid secretion, retinal function, and hepatic function, all of which can be reversed by taurine supplementation. Therefore, this small beta-amino acid, taurine, is indeed conditionally essential.
  **The role of taurine in infant nutrition. Adv Exp Med Biol 1998;442:463-76

• Taurine supplementation of the transplant donor may be useful to protect transplanted organs.
  Taurine attenuates cold ischemia-reoxygenation injury in rat liver. Transplantation 2000 Jun 15;69(11):2290-6

• This animal study demonstrates beneficial effects of taurine on early changes in diabetic kidneys and suggest that diabetic nephropathy associated with hyperglycemia is largely mediated by oxidative stress.
  **Melatonin and taurine reduce early glomerulopathy in diabetic rats. Free Radic Biol Med 1999 Apr;26(7-8):944-50

• Taurine treatment has a protective effect against Thioacetamide-induced liver cirrhosis by decreasing oxidative stress.
  **Taurine has a protective effect against thioacetamide-induced liver cirrhosis by decreasing oxidative stress. Hum Exp Toxicol 2001 May;20(5):251-4

• There is considerable evidence that taurine promotes the bioavailability of the lipid soluble vitamins A, D, E, K, and F, probably by forming different types of water soluble, easily hydrolyzable complexes. This form of delivery may be an additional, secondary mechanism for the transport of lipid soluble vitamins, which is extremely important for mammals and humans directly after birth for a variety of physiological functions such as: vision in normal and in emergency situations, rapid blood clotting, sperm eruption, and situations requiring a prompt consumption of lipid soluble vitamins characteristic of excitable systems.
  **Taurine as a universal carrier of lipid soluble vitamins: a hypothesis. Amino Acids 2000;19(2):409-421

Licorice

• Consuming a diet rich in plant foods will provide a milieu of phytochemicals, non-nutritive substances in plants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer. Licorice root is among the foods and herbs with the highest anticancer activity.
  **Phytochemicals: Health Protective Effects. Can J Diet Pract Res 1999;60(2):78-84

• Glabridin from licorice is a phytoestrogen, binding to the human estrogen receptor. Glabridin and its derivatives inhibit the growth of breast cancer cells.
  **Estrogenic and antiproliferative properties of glabridin from licorice in human breast cancer cells. Cancer Res 2000 Oct 15;60(20):5704-9

• Licorice extract showed a significant protective effect against cytotoxic N-nitrosamines NDMA, NYPR, NDBA, and NPIP. N-nitrosamines are common environmental carcinogens.
  **Protective Effect of Broccoli, Onion, Carrot, and Licorice Extracts against Cytotoxicity of N-Nitrosamines Evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide Assay. J Agric Food Chem. 1998 Feb 16;46(2):585-589.

• In a study of a 100-day experimental intoxication with lead and chromium, licorice diminished the manifestations of adverse effects of lead and chromium on the functional status of digestive organs.
  **[Untitled}. Gig Sanit 2001 Mar;2:46-49

• In an animal experiment, glycyrrhizin (GR), a component of licorice root extract, stimulated the immune system defense against herpes simplex infection. Mice suffering from herpes simplex encephalitis increased their survival rate by 2.5 times.
  **Glycyrrhizin increases survival of mice with herpes simplex encephalitis. Acta Virol 2001 Feb;45(1):51-4

• The flavonoid glabridin (derived from licorice) acts synergistically with lycopene, as an effective antioxidant against LDL oxidation. These observations suggest a superior antiatherogenic characteristic to a combination of different natural antioxidants over that of an individual one.
  **Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Antioxid Redox Signal 2000 Fall;2(3):491-506
• Dibenzoylmethane (DBM), a constituent of licorice, exerts a strong inhibitory action on mammary carcinogenesis in mice. Feeding 1% DBM to laboratory mice inhibited formation of DMBA-DNA adducts in mammary glands and lowered the proliferation rate of the mammary gland in vivo.
  **Inhibition by dietary dibenzoylmethane of mammary gland proliferation, formation of DMBA-DNA adducts in mammary glands, and mammary tumorigenesis in Sencar mice. Cancer Lett 2001 Jul 26;168(2):125-132
• A constituent of licorice has powerful cancer fighting properties. Glycyrrhetinic acid, a strong 11beta-HSD inhibitor isolated from licorice, induces apoptosis (cell suicide) of murine thymocytes via accumulation of corticosterone.
  **Magnolol from Magnolia officinalis inhibits 11beta-hydroxysteroid dehydrogenase without increases of corticosterone and thymocyte apoptosis in mice. Planta Med 2001 Feb;67(1):33-37
• In atherosclerotic apolipoprotein E-deficient mice, consumption of flavonoids from licorice decreased LDL oxidation, LDL retention, and LDL aggregation and attenuated macrophage foam cell formation and atherosclerosis.
  **Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxid Redox Signal 1999;1(4):585-594
• Licorice is an herbal drug that has been used extensively and its clinical efficacy documented.
  **The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000 Dec;14(8):581-591

• Lycopene acts synergistically, as an effective antioxidant against LDL oxidation, with several natural antioxidants including the flavonoid glabridin (derived from licorice). These observations suggest a superior antiatherogenic characteristic to a combination of different natural antioxidants over that of an individual one.
  **Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Antioxid Redox Signal 2000 Fall;2(3):491-506

Rosemary leaf

• Extracts of rosemary modulate cytochrome P450 (CYP) and detoxication enzymes in animal studies, suggesting that these compounds may have significant chemopreventive potency.
  **Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns. Food Chem Toxicol 2001 Sep;39(9):907-918
• Water-soluble extract of rosemary leaves containing rosmarinic acid, flavones and monoterpenes enhanced the action of xenobiotic metabolizing enzymes CYP 1A1, 2B1/2, 2E1 and GST, QR and UGT in rat liver after dietary administration. The induction of these enzymes could be attributed to flavones, monoterpenes or an additive effect of all components.
  **Effects of a water-soluble extract of rosemary and its purified component rosmarinic acid on xenobiotic-metabolizing enzymes in rat liver. Food Chem Toxicol 2001 Feb;39(2):109-117
• A search of cancer for chemopreventive agents from spices revealed that the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids.
  **Chemistry and antioxidative factors in rosemary and sage. Biofactors 2000;13(1-4):161-166
• In a test involving foodborne microorganisms, rosemary extract exhibited potent antibacterial activity against a variety of pathogenic bacteria.
  **Antimicrobial effect of rosemary extracts. J Food Prot 2000 Oct;63(10):1359-1368

• Rosemary exhibits superoxide dismutase-like activity, indicating its effectiveness as an antioxidant.
  **Measurement of superoxide dismutase-like activity of natural antioxidants. Biosci Biotechnol Biochem 1995 May;59(5):822-6

• Carnosol, a phenolic compound extracted from the herb rosemary has been reported to have anti-cancer activity. This study suggests that carnosol may be useful as a novel chemotherapeutic agent against B-lineage leukemias, and possibly other types of cancers.
  **Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells. Cancer Lett 2001 Sep 10;170(1):33-9

• Supplementation with an antioxidant derived from rosemary could have cosmetic benefits and may represent an efficient tool to minimize free radical-induced skin damage.
  **Induction of heat shock protein synthesis in human skin fibroblasts in response to oxidative stress: regulation by a natural antioxidant from rosemary extract. Int J Tissue React 2001;23(2):51-8

• Lycopene, rosemary and licorice -- The polyphenols glabridin (derived from licorice), rosmarinic acid or carnosic acid (derived from rosemary) inhibit LDL oxidation in a dose-dependent manner. When lycopene was added to LDL in combination with glabridin, rosmarinic acid, or carnosic acid, synergistic antioxidative effects were obtained against LDL oxidation.
  **Lycopene synergistically inhibits LDL oxidation in combination with vitamin E, glabridin, rosmarinic acid, carnosic acid, or garlic. Antioxid Redox Signal 2000 Fall;2(3):491-506

Zinc

• Zinc, a trace element that influences cell metabolism through a variety of mechanisms, appears to play an integral role in maintaining normal ocular function. This element is present in high concentrations in ocular tissue, particularly in retina and choroid. Zinc deficiency has been shown in a number of species to result in a variety of gross, ultrastructural and electrophysiologic ocular manifestations. The physiological functions for zinc have been studied predominantly in retina and retinal pigment epithelium where zinc is believed to interact with taurine and vitamin A.
  **Zinc and the eye. J Am Coll Nutr 2001 Apr;20(2Suppl):106-118

• Increased intake of zinc around the time of conception is associated with decreased risk of neural tube defects for women who used supplements.
  **Periconceptional nutrient intake and risk for neural tube defect-affected pregnancies. Epidemiology 1999 Nov;10(6):711-6

• Combined therapy with Coenzyme Q 10 (CoQ 10), L-carnitine, Zn, Mg, N-acetyl cysteine, vitamin C, vitamin E and selenium were effective in reducing damage to liver cells in mice treated with Ochratoxin A, a potent liver toxin. The combined antioxidants enhanced the liver’s antioxidant/detoxification system, as evidenced by an increase in the level of reduced glutathione in that organ.
  **Significance Of Apoptosis And Its Relationship To Antioxidants After Ochratoxin A Administration In Mice. J Pharm Pharmaceut Sci 3(3):281-291, 2000

• Zinc has a role in retinal metabolism and may be beneficial in macular degeneration.
  **Nutrition supplements and the eye. Eye 1998;12 ( Pt 1):127-33

• Exercise increases zinc loss from the body, and dietary intake for some athletes, especially females, may be inadequate.
  **Trace mineral requirements for athletes. Int J Sport Nutr 1994 Jun;4(2):104-19

• Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn.
  **Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly. J Am Coll Nutr 1990 Jun;9(3):214-25

• Zinc is a pivotal component of the antioxidant defense network that protects membranes from oxidation.
  **The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001 Jul 15;31(2):266-74
  
• Zinc supplementation has potentially beneficial antioxidant effects in people with type 2 diabetes mellitus. These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes.
  **Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr 2001 Jun;20(3):212-8

Copper and Zinc

• Zinc and copper are involved in cell and tissue growth. Zinc plays an important role in DNA and protein synthesis and is intimately involved with copper as cofactors in several important enzyme systems.
  **Zinc and copper status in children with bronchial asthma and atopic dermatitis. J Egypt Public Health Assoc 1990;65(5-6):657-68

• Zinc is a pivotal component of the antioxidant defense network that protects membranes from oxidation.
  **The antioxidant properties of zinc: interactions with iron and antioxidants. Free Radic Biol Med 2001 Jul 15;31(2):266-74

• Greater than 60% of a group of triathletes had low zinc and copper intakes.
  **Dietary patterns, gastrointestinal complaints, and nutrition knowledge of recreational triathletes. Am J Clin Nutr 1990 Apr;51(4):690-7

• Supplemental Zn blocks exercise-induced increases in reactive oxygen species in competitive runners given a twice-daily supplement of 25mg of zinc and 1.5 mg of copper.
  **Exercise-induced changes in immune function: effects of zinc supplementation. J Appl Physiol 1994 Jun;76(6):2298-303

• After four weeks of treatment, supplementation with 2 mg copper per day produced an increase in LDL cholesterol and the percentage of cholesterol as LDL compared to the placebo group, and a concomitant decline in VLDL-cholesterol levels and the percentage of cholesterol as VLDL. At wk 6, the percentage of cholesterol as LDL increased and that of cholesterol as VLDL decreased compared to baseline values in the supplemented group.
  **Copper supplementation effects on indicators of copper status and serum cholesterol in adult males. Biol Trace Elem Res 1991 Jul;30(1):19-35

• Zinc supplementation has potentially beneficial antioxidant effects in people with type 2 diabetes mellitus. These results are particularly important in light of the deleterious consequences of oxidative stress in people with diabetes.
  **Potential antioxidant effects of zinc and chromium supplementation in people with type 2 diabetes mellitus. J Am Coll Nutr 2001 Jun;20(3):212-8

Red wine and grape skin

• Phenolics from grapes and wines can play a role against oxidation and development of atherosclerosis. The highest antioxidant capacity was obtained with red wines. Red wine contributes to a very significant catechin dietary intake.
  **Antioxidant capacities and phenolics levels of French wines from different varieties and vintages. J Agric Food Chem 2001 Jul;49(7):3341-8

• Moderate red wine consumption is inversely associated with coronary ischemia, and both red wine and purple grape juice (PGJ) contain flavonoids with antioxidant and antiplatelet properties believed to be protective against cardiovascular events.
  **Select flavonoids and whole juice from purple grapes inhibit platelet function and enhance nitric oxide release. Circulation 2001 Jun 12;103(23):2792-8

• The suppression of platelet-mediated thrombosis represents a potential mechanism for the beneficial effects of purple grape products, independent of alcohol consumption, in cardiovascular disease.
  **Ibid.

• Resveratrol, a phytoalexin found in grapes, nuts, fruits, and red wine, is a potent antioxidant with cancer-preventive properties. In human epidermoid carcinoma cells resveratrol induces a G(1)-phase arrest of the cell cycle followed by apoptosis, or programmed cell suicide.
  **Resveratrol causes WAF-1/p21-mediated G(1)-phase arrest of cell cycle and induction of apoptosis in human epidermoid carcinoma A431 cells. Clin Cancer Res 2001 May;7(5):1466-73

• Red wine significantly preserves plasma antioxidant defences and reduces both LDL oxidation and thrombotic activation.
  **Red wine protects diabetic patients from meal-induced oxidative stress and thrombosis activation: a pleasant approach to the prevention of cardiovascular disease in diabetes. Eur J Clin Invest 2001 Apr;31(4):322-8

• Red wine have a beneficial effect in the prevention of cardiovascular disease in diabetic patients.
  **Ibid.

• The anthocyanin profile of red wines clearly differs from that presented by grapes employed in making it, because red wine contains a higher relative amount of malvidin-3-O-glucoside than grapes, and the relative amount of other anthocyanins in wines is usually lower than in grapes.
  **Value of high-performance liquid chromatographic analysis of anthocyanins in the differentiation of red grape cultivars and red wines made from them. J Chromatogr A 2001 Apr 27;915(1-2):53-60

• Anthocyanins obtained from red wine substantially decreased sugar concentration in urine and blood serum in rats with diabetes experimentally induced via streptozotocin. The anthocyanins also inhibited loss of body mass caused by the streptozotocin. Simultaneously antocyan pigment was shown to considerably prevent generation of free oxygen radicals. Also observed was the decrease of peroxidation of lipids, as shown by lowering of the concentration of unsaturated fatty acids oxidation products in urine and blood serum.
  **[The effect of anthocyanin dye from grapes on experimental diabetes]. Folia Med Cracov 2000;41(3-4):5-15

• Three different phenolic (anthocyanin, other flavonoid, and phenolic acid) fractions from wine were tested for their effects on melanogenesis of normal cells and growth of human melanoma cells. The results suggest that all of these phenolic fractions have potential as therapeutic agents in the treatments of human melanoma.
  **Effects of wine phenolics and sorghum tannins on tyrosinase activity and growth of melanoma cells. J Agric Food Chem 2001 Mar;49(3):1620-1624

• Phenolic acids and quercetin-3-glucuronide, catechins and quercetin-3-glucoside, and anthocyanins were obtained from Italian red wine. The anthocyanin fraction was the most effective both in scavenging reactive oxygen species and in inhibiting lipoprotein oxidation and platelet aggregation.
  **Antioxidant Activity of Different Phenolic Fractions Separated from an Italian Red Wine. J Agric Food Chem 1998 Feb 16;46(2):361-367

• In atherosclerotic apolipoprotein E-deficient mice, consumption of flavonoids from red wine decreased LDL oxidation, LDL retention, and LDL aggregation and attenuated macrophage foam cell formation and atherosclerosis.
  Macrophage foam cell formation during early atherogenesis is determined by the balance between pro-oxidants and anti-oxidants in arterial cells and blood lipoproteins. Antioxid Redox Signal 1999;1(4):585-594

• A mixed antioxidant containing alpha-tocopherol (Vitamin E), ascorbic acid (Vitamin C), beta-carotene (Vitamin A) and grape seed catechins and milk thistle derived silybin suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture. Life Sci 2001 May 25;69(1):75-86

• Alcohol-free red wine extract and one of its components, quercetin, can inhibit LDL oxidation after in vivo supplementation.
  **Nonalcoholic red wine extract and quercetin inhibit LDL oxidation without affecting plasma antioxidant vitamin and carotenoid concentrations. Clin Chem 2000 Aug;46(8 Pt 1):1162-1170

Pycnogenol

• Pycnogenol may be useful for the prevention and/or treatment of Alzheimer’s Disease and other vascular or neurodegenerative diseases associated with Beta-amyloid toxicity.
  **Pycnogenol protects vascular endothelial cells from beta-amyloid-induced injury. Biol Pharm Bull 2000 Jun;23(6):735-737

• Pycnogenol selectively induced death in human mammary cancer cells (MCF-7) and not in normal human mammary MCF-10 cells.
  **Selective induction of apoptosis in human mammary cancer cells (MCF-7) by pycnogenol. Anticancer Res 2000 Jul-Aug;20(4):2417-20

• Results of a study done at UC Berkeley indicate the therapeutic potential of the French maritime pine bark extract Pycnogenol in patients with inflammatory skin disorders.
  **Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression. Free Radic Biol Med 2000 Jan 15;28(2):219-27

• Pycnogenol has a beneficial effect on the progression of vascular retinopathy. Without any treatment the retinopathy progressively worsened during a clinical trial and the visual acuity significantly decreased; on the contrary, the Pycnogenol-treated patients showed no deterioration of retinal function and a significant recovery of visual acuity was also obtained.
  **Treatment of vascular retinopathies with Pycnogenol((R)). Phytother Res 2001 May;15(3):219-23

• Pycnogenol can be recommended both for prevention and treatment of chronic venous insufficiency and related veno-capillary disturbances.
  **PYCNOGENOL in chronic venous insufficiency. Phytomedicine 2000 Oct;7(5):383-8

• Pycnogenol(R) supplementation reduces a risk factor for cardiovascular diseases, that is, platelet aggregation in smokers. The bioflavonoids in Pycnogenol(R) reduced platelet aggregation stimulated by tobacco smoke.
  **Pine bark extract reduces platelet aggregation. 2000 Mar 21;2(2):73-77

• In a study of genetic effects, French maritime pine bark extract (Pycnogenol) was shown to downregulate both calgranulin A and B genes which are known to be upregulated in psoriasis and various dermatoses. Thus, the authors conclude, PBE could be therapeutic human dermatoses.
  **From ancient remedies to modern therapeutics: pine bark uses in skin disorders revisited. Phytother Res 2001 Feb;15(1):76-78

• Pycnogenol, an extract from French maritime pine bark (PBE), is a complex mixture of bioflavonoids and an effective scavenger of reactive oxygen species including xanthine oxidase, xanthine dehydrogenase, horseradish peroxidase, and lipoxygenase.
  **Enzyme inhibition and protein-binding action of the procyanidin-rich french maritime pine bark extract, pycnogenol: effect on xanthine oxidase. J Agric Food Chem 2000 Nov;48(11):5630-5639

• Pycnogenol may inhibit the accumulation of fat droplets in adipose tissue.
  **Inhibition of lipogenesis by pycnogenol. Phytother Res 2000 Sep;14(6):472-473

• In a laboratory study of human cells, pycnogenol inhibited activation of the transcriptional regulatory protein nuclear factor NF-kappa B and expression of cell adhesion molecules VCAM-1 and ICAM-1. This suggests that this phytochemical may play an important role in halting or preventing the atherogenic process and may have a therapeutic rolein atherosclerosis, inflammation, ischemic vascular disorders, diabetes, and cancer metastasis..
  **Pycnogenol inhibits tumor necrosis factor-alpha-induced nuclear factor kappa B activation and adhesion molecule expression in human vascular endothelial cells. Cell Mol Life Sci 2000 May;57(5):834-841

Citrus Bioflavonoid

• Naringenin, a citrus bioflavonoid, lowers the plasma and hepatic cholesterol concentrations in rats fed a high-cholesterol diet.
  **Cholesterol-lowering activity of naringenin via inhibition of 3-hydroxy-3-methylglutaryl coenzyme A reductase and acyl coenzyme A:cholesterol acyltransferase in rats. Ann Nutr Metab 1999;43(3):173-80

• Naringen is a botanical compounds with anti-ulcer activity.
  **The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000 Dec;14(8):581-591

• Heterocyclic amines (HCA's) are promutagens produced by high temperature cooking of meat products and are activated by cytochrome P450 (CYP) lA2. Data suggest a chemopreventive potential for the citrus bioflavonoid naringin towards CYPlA2 mediated mutagenesis of HCA's.
  **Effects of citrus flavonoids on the mutagenicity of heterocyclic amines and on cytochrome P450 1A2 activity. Anticancer Res 2000 Sep;20(5B):3609-3614

• Hesperidin bioflavonoid obtained from citrus cultures may present a potential therapeutical use as a mild anti-inflammatory agent.
  **Pharmacological evaluation of the anti-inflammatory activity of a citrus bioflavonoid, hesperidin, and the isoflavonoids, duartin and claussequinone, in rats and mice. J Pharm Pharmacol 1994 Feb;46(2):118-22

• Certain bioflavonoids are potent antioxidants and have pharmacologic effects similar to those of vitamin E. Citrus-derived bioflavonoid hesperidin lowers the concentration of plasma cholesterol and the hepatic triglyceride content regardless of the dietary vitamin E level.
  **Interactive effect of hesperidin and vitamin E supplements on cholesterol metabolism in high cholesterol-fed rats. Int J Vitam Nutr Res 2001 Jan;71(1):36-44

• Plant flavonoids attenuate inflammation and the immune response through their inhibition of important regulatory enzymes.
  **Biological properties of flavonoids pertaining to inflammation. Microcirculation 2000;7(6 Pt 2):S29-34

• Chronic venous insufficiency (CVI) is accompanied by a marked inflammatory response. Recent studies suggest that treatment with flavonoids may be beneficial.
  **Biological properties of flavonoids pertaining to inflammation. Microcirculation 2000;7(6 Pt 2):S29-34

• Citrus, in addition to providing an ample supply of vitamin C, folic acid, potassium, and soluble fibre, contains a host of active phytochemicals. Consuming a diet rich in plant foods will provide a milieu of phytochemicals, non-nutritive substances in plants that have been associated with protection from and/or treatment of conditions such as cardiovascular disease and cancer.
  **Phytochemicals: Health Protective Effects. Can J Diet Pract Res 1999;60(2):78-84g

Milk Thistle

• Silymarin is a polyphenolic flavonoid derived from milk thistle (Silybum marianum) that has anti-inflammatory, cytoprotective, and anticarcinogenic effects.
  **Silymarin suppresses TNF-induced activation of NF-kappa B, c-Jun N-terminal kinase, and apoptosis. J Immunol 1999 Dec 15;163(12):6800-9

• Sylmarin derived from milk thistle has a powerful suppressive effect on human prostate carcinoma DU145 cells.
  **Cell signaling and regulators of cell cycle as molecular targets for prostate cancer prevention by dietary agents. Biochem Pharmacol 2000 Oct 15;60(8):1051-9

• Recent studies have identified and defined the cancer preventive and anticarcinogenic potential of a polyphenolic flavonoid antioxidant, silymarin (isolated from milk thistle) and found that these effects of silymarin are due to the major active constituent, silibinin, present therein.
  **Tissue distribution of silibinin, the major active constituent of silymarin, in mice and its association with enhancement of phase II enzymes: implications in cancer chemoprevention. Carcinogenesis 1999 Nov;20(11):2101-8

• Experimental results suggest that silibinin derived from milk thistle could be a useful agent for the intervention of hormone-refractory human prostate cancer. Silibinin treatment of cells grown in serum resulted in a significant decrease in both intracellular and secreted forms of PSA concomitant with a highly significant to complete inhibition of cell growth via a G1 arrest in cell cycle progression.
  **Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci U S A 1999 Jun 22;96(13):7490-5

• Sylmarin derived from milk thistle citrus bioflavonoid is a botanical compounds with anti-ulcer activity.
  **The plant kingdom as a source of anti-ulcer remedies. Phytother Res 2000 Dec;14(8):581-591

• A mixed antioxidant containing milk thistle derived silybin, alpha-tocopherol (Vitamin E), ascorbic acid (Vitamin C), beta-carotene (Vitamin A) and grape seed catechins suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture. Life Sci 2001 May 25;69(1):75-86

• Treatment with milk thistle extracts silymarin and silibinin alone or, more effectively in combination with cysteine donors, provide a benefit for peritoneal macrophages of continuous ambulatory peritoneal dialysis-patients due to a normalization and activation of the cellular thiol status followed by a restoration of specific functional capabilities.
  **Restoration of the cellular thiol status of peritoneal macrophages from CAPD patients by the flavonoids silibinin and silymarin. Free Radic Res 2001 Feb;34(2):137-151

• The enrichment of a diet of rats by flavonoids of milk thistle, Silybum marianum, reduced toxicity of T-2 toxin and was accompanied by reduction of a degree of change of total and nonsedimentable activity of lysosomal enzymes and microsomal xenobiotic metabolizing enzymes.
  **[Effects of bioflavonoids on the toxicity of T-toxin in rats. A biochemical study]. Vopr Pitan 2000;69(5):20-23

• Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has potent antiproliferative effects against various malignant cell lines. In a study of the compound's effect on androgen-independent prostate cancer PC-3 cells, silibinin reduced insulin receptor substrate 1 tyrosine phosphorylation, indicating an inhibitory effect on the insulin-like growth factor I receptor-mediated signaling pathway. These results suggest a novel mechanism by which silibinin acts as an antiproliferative agent and justify further work to investigate potential use of this compound or its derivatives in prostate cancer treatment and prevention.
  **Silibinin up-regulates insulin-like growth factor-binding protein 3 expression and inhibits proliferation of androgen-independent prostate cancer cells. Cancer Res 2000 Oct 15;60(20):5617-5620

Coenzyme Q-10

• In a study of neurotoxic processes associated with Parkinson's disease, N-acetyl-L-cysteine was effective in providing protection against L-glutamate-induced cell death and neurotoxicity induced by N-methyl-4-phenylpyridinium ion (MMP+) in murine pheochromocytoma cells.
  **Effect of antioxidants on L-glutamate and N-methyl-4-phenylpyridinium ion induced-neurotoxicity in PC12 cells. Neurotoxicology 2001 Apr;22(2):283-8

• Intimal oxidation of LDL is considered an important early event in atherogenesis, and certain antioxidants are antiatherogenic. Dietary coenrichment with vitamin E (VitE) plus ubiquinone-10 (coenzyme Q-10) protects against atherogenesis, whereas enrichment with VitE alone can increase oxidizability of LDL lipid against ex vivo oxidation.
  **Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol 2001 Apr;21(4):585-93

• In mice, supplementation with Vitamin E plus coenzyme Q-10 are more antiatherogenic than Q-10 or Vitamin E supplements alone and disease inhibition is associated with a decrease in aortic lipid hydroperoxides.
  **Dietary cosupplementation with vitamin E and coenzyme Q(10) inhibits atherosclerosis in apolipoprotein E gene knockout mice. Arterioscler Thromb Vasc Biol 2001 Apr;21(4):585-93

• The mean plasma levels of coenzyme Q(10) (CoQ(10)) and alpha-tocopherol were significantly lower in patients with cervical intraepithelial neoplasia (CIN) and cervical cancer compared with controls. The findings suggest that CoQ(10) and alpha-tocopherol antioxidants may play a role in the pathogenesis of CIN. The decrease in CoQ(10) and alpha-tocopherol levels may be caused by deficient dietary intake in women with CIN. Alternatively, low antioxidant levels may reflect increased utilization to counteract oxidative stress.
  **Coenzyme Q(10) and alpha-tocopherol concentrations in cervical intraepithelial neoplasia and cervix cancer. Obstet Gynecol 2001 Apr;97(4 Suppl 1):S3

• Animal studies indicate a neuroprotective effect of CoQ(10) as a potent antioxidant and oxygen derived free radicals scavenger in the cerebral ischemia.
  **Effect of coenzyme Q(10) on biochemical and morphological changes in experimental ischemia in the rat brain. Brain Res Bull 2000 Nov 1;53(4):399-407

• Combined therapy with Coenzyme Q 10 (CoQ 10), L-carnitine, Zn, Mg, N-acetyl cysteine, vitamin C, vitamin E and selenium were effective in reducing damage to liver cells in mice treated with Ochratoxin A, a potent liver toxin. The combined antioxidants enhanced the liver's antioxidant/detoxification system, as evidenced by an increase in the level of reduced glutathione in that organ.
  **Significance Of Apoptosis And Its Relationship To Antioxidants After Ochratoxin A Administration In Mice. J Pharm Pharmaceut Sci 3(3):281-291, 2000

• Coenzyme Q10 belongs to important antioxidants and it has a key role in the synthesis of adenosinetriphosphate. Its beneficial effect was proved in several diseases, e.g. in mitochondrial encephalopathy, mitochondrial myopathy, mitochondrial cardiomyopathy.
  **[Effect of coenzyme Q10 in patients with kidney diseases]. Cas Lek Cesk 2001 May 24;140(10):307-310

• A group of patients with kidney disease received antioxidative therapy for three months (E vitamin, C vitamin, riboflavin) and for the last two months coenzyme Q10 was added. Levels of antioxidant CoQ10 were lower in patients with nephropathy who underwent conservative treatment. Such deficit can be amended by CoQ10 administration, which could be therefore taken as complementary treatment of nephrology.
  **Ibid.

Raspberry leaf

• Of four fruits tested, red raspberries had the highest oxygen radical absorbance capacity (ORAC) at the ripe stage. Compared with fruits, leaves were found to have higher ORAC values. Jewel black raspberry and blackberries may be the richest source for antioxidants.
  **Antioxidant activity in fruits and leaves of blackberry, raspberry, and strawberry varies with cultivar and developmental stage. J Agric Food Chem 2000 Feb;48(2):140-6

• Water-soluble extract of rosemary leaves containing rosmarinic acid, flavones and monoterpenes enhanced the action of xenobiotic metabolizing enzymes CYP 1A1, 2B1/2, 2E1 and GST, QR and UGT in rat liver after dietary administration. The induction of these enzymes could be attributed to flavones, monoterpenes or an additive effect of all components.
  **Effects of a water-soluble extract of rosemary and its purified component rosmarinic acid on xenobiotic-metabolizing enzymes in rat liver. Food Chem Toxicol 2001 Feb;39(2):109-117

• A search of cancer for chemopreventive agents from spices revealed that the alcohol extracts of rosemary and sage showed strong antumorigenic activities. Rosemary and sage extracts contain active antioxidative factors such as phenolic diterpenes, flavonoids and phenolic acids.
  **Chemistry and antioxidative factors in rosemary and sage. Biofactors 2000;13(1-4):161-166

• In a test involving foodborne microorganisms, rosemary extract exhibited potent antibacterial activity against a variety of pathogenic bacteria.
  **Antimicrobial effect of rosemary extracts. J Food Prot 2000 Oct;63(10):1359-1368

• Extracts of rosemary modulate cytochrome P450 (CYP) and detoxication enzymes in animal studies, suggesting that these compounds may have significant chemopreventive potency.
  **Induction of cytochrome P450 and/or detoxication enzymes by various extracts of rosemary: description of specific patterns. Food Chem Toxicol 2001 Sep;39(9):907-918

• Three closely related furanones have been found in raspberry where they are important flavor compounds. These compounds are, in practice, very effective anti-carcinogenic agents in the diets of animals which are being treated with known cancer-inducing compounds. Two of the food-derived furanones have antioxidant activity comparable to that of ascorbic acid.
  **The naturally occurring furanones: formation and function from pheromone to food. Biol Rev Camb Philos Soc 1999 Aug;74(3):259-7

• Many women consume the raspberry leaf herb during their pregnancies in the belief that it shortens labor and makes labor "easier." In this study, raspberry leaf produced a shortening of the second stage of labor and a lower rate of forceps deliveries between the treatment group and the control group.
  **Raspberry leaf in pregnancy: its safety and efficacy in labor. J Midwifery Womens Health 2001 Mar-Apr;46(2):51-9

• In a study of the antimutagenic properties of juices of 20 vegetables and fruits, juice of raspberries protected cultured cells against genetic mutation in the presence of benzo[a]pyrene, a potent mutagen and carcinogen. Cooking did not reduce the antimutagenic properties of the juice.
  **Antimutagenic activity of vegetable and fruit extracts against in-vitro benzo(a)pyrene. Z Gesamte Hyg 1990 Mar;36(3):144-7

Super Oxide Dismutase

• The cellular enzyme super oxide dismutase (SOD) provides physiological defence against superoxide radicals.
  **A novel antioxidant alleviates heat hyperalgesia in rats with an experimental painful peripheral neuropathy. Neuroreport 1996 May 31;7(8):1382-1384

• Introduction of superoxide dismutase significantly reduced oxygen free radical activity in a rat heart treated with polymorphonuclear leukocytes (PMN).
  **Functional impairment in isolated rat hearts induced by activated leukocytes: protective effect of oxygen free radical scavengers. J Mol Cell Cardiol 1989 Sep;21(9):877-887

• Experimental results suggest that copper,zinc-superoxide dismutase may play a primary protective role against ultraviolet-B-induced injury of the human keratinocyte cell line HaCaT.
  **Protective role of copper, zinc superoxide dismutase against UVB-induced injury of the human keratinocyte cell line HaCaT. J Invest Dermatol 2000 Mar;114(3):502-7

• As we age we become less efficient at absorbing and retaining Cu, Zn and Mg. Since Cu and Zn are necessary for the synthesis of copper-zinc superoxide dismutase (CuZnSOD), which disables the noxious O2-, the deficiencies cause considerable damage as we age. Similarly, Mg is a cofactor for CuZnSOD and is necessary for NO to leave the cell and perform its vasodilating job. Furthermore, Se and vitamins B6 and D are required for Mg absorption and vitamin E is required to minimize the oxidative damage.
  Gradual micronutrient accumulation and depletion in Alzheimer's disease. Med Hypotheses 2001 Jun;56(6):595-7

• In laboratory tests, glutathione (reduced form), showed superoxide dismutase (SOD)-like activity, indicating that it is a natural antioxidant.
  **Measurement of superoxide dismutase-like activity of natural antioxidants. Biosci Biotechnol Biochem 1995 May;59(5):822-6

• Rosemary exhibits superoxide dismutase-like activity, indicating its effectiveness as an antioxidant.
  **Measurement of superoxide dismutase-like activity of natural antioxidants. Biosci Biotechnol Biochem 1995 May;59(5):822-6

• Oxidative stress has been associated with the development of blood-brain barrier disruption and cellular injury after ischemia. The cytosolic antioxidant, copper/zinc superoxide dismutase, has been shown to protect against blood-brain barrier disruption and infarction after cerebral ischemia-reperfusion.
  **The cytosolic antioxidant, copper/zinc superoxide dismutase, attenuates blood-brain barrier disruption and oxidative cellular injury after photothrombotic cortical ischemia in mice. Neuroscience 2001;105(4):1007-1018

• Results of an animal study suggest that superoxide anion radical is an important factor in blood-brain barrier disruption and oxidative cellular injury, and that copper/zinc superoxide dismutase could protect against the evolving infarction after thromboembolic cortical ischemia.
  **Ibid.

• SOD is an efficient suppressors of oxygen radical overproduction by rheumatoid arthritis neutrophils.
  **Oxidative stress in rheumatoid arthritis leukocytes: suppression by rutin and other antioxidants and chelators(1). Biochem Pharmacol 2001 Sep 15;62(6):743-746

Combined Therapies

• Combined therapy with Coenzyme Q 10 (CoQ 10), L-carnitine, Zn, Mg, N-acetyl cysteine, vitamin C, vitamin E and selenium were effective in reducing damage to liver cells in mice treated with Ochratoxin A, a potent liver toxin. The combined antioxidants enhanced the liver's antioxidant/detoxification system, as evidenced by an increase in the level of reduced glutathione in that organ.
  **Significance Of Apoptosis And Its Relationship To Antioxidants After Ochratoxin A Administration In Mice. J Pharm Pharmaceut Sci 3(3):281-291, 2000

• In a double blind, placebo-controlled study, the antioxidative defense system was measured in 34 healthy subjects before and after multinutrient supplementation. The results clearly demonstrated that short-term supplementation (16 weeks) with multinutrient could markedly improve antioxidative vitamin status and enzymatic activities. Plasma vitamin C, E and beta-carotene, erythrocyte vitamin E, as well as whole blood selenium all showed increase at 5 weeks of supplementation. These improvements also led to the reduction of red blood cell susceptibility to free radical peroxidation.
  **Effects of multinutrient supplementation on antioxidant defense systems in healthy human beings. J Nutr Biochem 2001 Jul;12(7):388-395

• A mixed antioxidant containing alpha-tocopherol (Vitamin E), ascorbic acid (Vitamin C), beta-carotene (Vitamin A) and grape seed catechins and milk thistle derived silybin suppressed lipid peroxidation and protected membrane proteins against degradation induced by peroxyl radicals, and effectively delayed AAPH induced haemolysis.
  **Oxidative insult to human red blood cells induced by free radical initiator AAPH and its inhibition by a commercial antioxidant mixture. Life Sci 2001 May 25;69(1):75-86