Harunobu Amagase

Bio: Harunobu Amagase is an academic researcher from Hiroshima University. The author has contributed to research in topics: Epidermal growth factor & Allicin. The author has an hindex of 8, co-authored 17 publications receiving 1639 citations.

Intake of Garlic and Its Bioactive Components

Abstract: The health benefits of garlic likely arise from a wide variety of components, possibly working synergistically. The complex chemistry of garlic makes it plausible that variations in processing can yield quite different preparations. Highly unstable thiosulfinates, such as allicin, disappear during processing and are quickly transformed into a variety of organosulfur components. The efficacy and safety of these preparations in preparing dietary supplements based on garlic are also contingent on the processing methods employed. Although there are many garlic supplements commercially available, they fall into one of four categories, i.e., dehydrated garlic powder, garlic oil, garlic oil macerate and aged garlic extract (AGE). Garlic and garlic supplements are consumed in many cultures for their hypolipidemic, antiplatelet and procirculatory effects. In addition to these proclaimed beneficial effects, some garlic preparations also appear to possess hepatoprotective, immune-enhancing, anticancer and chemopreventive activities. Some preparations appear to be antioxidative, whereas others may stimulate oxidation. These additional biological effects attributed to AGE may be due to compounds, such as S-allylcysteine, S-allylmercaptocysteine, N(alpha)-fructosyl arginine and others, formed during the extraction process. Although not all of the active ingredients are known, ample research suggests that several bioavailable components likely contribute to the observed beneficial effects of garlic.

Clarifying the Real Bioactive Constituents of Garlic

Abstract: Compounds in garlic work synergistically to produce various effects, but, because of garlic's chemical complexity, processing methods yield preparations with differing efficacy and safety. Although thiosulfinates such as allicin have been long misunderstood to be active compounds due to their characteristic odor, it is not necessary for garlic preparations to contain such odorous compounds to be effective, and they decompose and disappear during any processing. Garlic exhibits hypolipidemic, antiplatelet, and procirculatory effects. It prevents cold and flu symptoms through immune enhancement and demonstrates anticancer and chemopreventive activities. In addition, aged garlic extract possesses hepatoprotective, neuroprotective, antioxidative activities, whereas other preparations may stimulate oxidation. Additional effects may be caused by S-allylcysteine, S-allyl mercaptocysteine), saponins, Nalpha-fructosyl arginine, and other substances formed during a long-term extraction process. Although not all of active ingredients of garlic are known, and allicin-like transient components are not directly active, ample research suggests that an allicin-free garlic preparation that is standardized with a bioavailable component such as S-allylcysteine, is active and various effects of garlic may be attributed to it. Furthermore, various chemical constituents in garlic products, including nonsulfur compounds such as saponins, may contribute to the essential biological activities of garlic. Further studies are needed to confirm their bioavailability and associated activities.

Aged Garlic Extract May Be Safe for Patients on Warfarin Therapy

Abstract: Garlic has been known to have antiplatelet properties. Because of the lack of major clinical data regarding the safety of concomitant use of garlic supplements and anticoagulants, we decided to evaluate the safety of using garlic extract along with oral anticoagulation therapy. During this project we tested aged garlic extract (AGE), a commercial garlic preparation, with warfarin (Coumadin). Sixty-six (66) patients were screened for a double-blind, randomized, placebo-controlled pilot study. Fifty-two (52) patients were randomized for the project. Forty-eight patients (30 men and 18 women, with a mean age of 56+/-10 years) completed the study. Eighteen patients (14 before randomization, 4 after randomization) were dropped from the study. The study medication (AGE or placebo) was administered at a dose of 5 mL twice a day for 12 wk. Potential bleeding and thromboembolic episodes were monitored. There was no evidence of increased hemorrhage in either the placebo or the AGE group. Adverse events included headache, fatigue, colds, and dizziness. However, no significant difference was found in the incidence of these minor adverse events between the groups. Thus, the adverse events are unlikely to be attributable to AGE. The results suggest that AGE is relatively safe and poses no serious hemorrhagic risk for closely monitored patients on warfarin oral anticoagulation therapy. Although the risk-benefit ratio of AGE use needs to be considered carefully when warfarin therapy is necessary, its positive effects may be beneficial to people with a high-risk background or who are taking cardiovascular medications.

Significance of Garlic and Its Constituents in Cancer and Cardiovascular Disease

Abstract: Compounds in garlic work synergistically to produce various effects, but, because of garlic’s chemical complexity, processing methods yield preparations with differing efficacy and safety. Although thiosulfinates such as allicin have been long misunderstood to be active compounds due to their characteristic odor, it is not necessary for garlic preparations to contain such odorous compounds to be effective, and they decompose and disappear during any processing. Garlic exhibits hypolipidemic, antiplatelet, and procirculatory effects. It prevents cold and flu symptoms through immune enhancement and demonstrates anticancer and chemopreventive activities. In addition, aged garlic extract possesses hepatoprotective, neuroprotective, antioxidative activities, whereas other preparations may stimulate oxidation. Additional effects may be caused by S-allylcysteine, S-allyl mercaptocysteine), saponins, N-fructosyl arginine, and other substances formed during a long-term extraction process. Although not all of active ingredients of garlic are known, and allicin-like transient components are not directly active, ample research suggests that an allicinfree garlic preparation that is standardized with a bioavailable component such as S-allylcysteine, is active and various effects of garlic may be attributed to it. Furthermore, various chemical constituents in garlic products, including nonsulfur compounds such as saponins, may contribute to the essential biological activities of garlic. Further studies are needed to confirm their bioavailability and associated activities. J. Nutr. 136: 716S–725S, 2006.

Aged garlic extract is a potential therapy for sickle-cell anemia.

Abstract: Sickle-cell anemia is one of the most prevalent hereditary disorders with prominent morbidity and mortality. Oxidative phenomena play a significant role in the disorder's pathophysiology. A forumlation of garlic (Allium sativum), AGE, has been reported to exert an antioxidant effect in vitro. We evaluated the antioxidant effect of AGE on sickle red blood cells (RBCs). Five patients (two men and three women, mean age 40+/-15 years, range 24-58 years) with sickle-cell anemia participated in the study. AGE was administered at a dose of 5 mL daily. Whole blood samples were obtained at baseline and at 4 wk, primarily for Heinz body analysis. In all patients, the number of Heinz bodies decreased over the 4-wk period (58.9+/-20.0% at baseline to 29.8+/-15.3% at follow-up; P=0.03). These data suggest that AGE has a significant antioxidant activity on sickle RBCs. AGE may be further evaluated as a potential therapeutic agent to ameliorate complications of sickle-cell anemia.

Natural antioxidants: sources, compounds, mechanisms of action, and potential applications

Abstract: While use of synthetic antioxidants (such as butylated hydroxytoluene and butylated hydroxyanisole) to maintain the quality of ready-to-eat food products has become commonplace, consumer concern regarding their safety has motivated the food industry to seek natural alternatives. Phenolic antioxidants can inhibit free radical formation and/or interrupt propagation of autoxidation. Fat-soluble vitamin E (α-tocopherol) and water-soluble vitamin C (L-ascorbic acid) are both effective in the appropriate matrix. Plant extracts, generally used for their flavoring characteristics, often have strong H-donating activity thus making them extremely effective antioxidants. This antioxidant activity is most often due to phenolic acids (gallic, protocatechuic, caffeic, and rosmarinic acids), phenolic diterpenes (carnosol, carnosic acid, rosmanol, and rosmadial), flavonoids (quercetin, catechin, naringenin, and kaempferol), and volatile oils (eugenol, carvacrol, thymol, and menthol). Some plant pigments (anthocyanin and anthocyanidin) can chelate metals and donate H to oxygen radicals thus slowing oxidation via 2 mechanisms. Tea and extracts of grape seeds and skins contain catechins, epicatechins, phenolic acids, proanthocyanidins, and resveratrol, all of which contribute to their antioxidative activity. The objective of this article is to provide an overview of natural antioxidants, their mechanisms of action, and potential applications.

Hydrogen sulfide mediates the vasoactivity of garlic

Abstract: The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H2S), an endogenous cardioprotective vascular cell signaling molecule. This H2S production, measured in real time by a novel polarographic H2S sensor, is supported by glucose-maintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H2S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the α carbon of the allyl substituent, thereby forming a hydropolysulfide (RSnH), a key intermediate during the formation of H2S. Organic polysulfides (R-Sn-R′; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RSnH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H2S. The vasoactivity of garlic compounds is synchronous with H2S production, and their potency to mediate relaxation increases with H2S yield, strongly supporting our hypothesis that H2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H2S can be used to standardize garlic dietary supplements.

Interactions between herbal medicines and prescribed drugs: an updated systematic review.

Abstract: The concomitant use of herbal medicines and pharmacotherapy is wide spread. We have reviewed the literature to determine the possible interactions between seven popular herbal medicines (ginkgo, St John's wort, ginseng, garlic, echinacea, saw palmetto and kava) and conventional drugs. Literature searches were performed using MEDLINE, Cochrane Library and EMBASE and we identified 128 case reports or case series, and 80 clinical trials. Clinical trials indicate that St John's wort (Hypericum perforatum), via cytochrome P450 (CYP) and/or P-glycoprotein induction, reduces the plasma concentrations (and/or increases the clearance) of alprazolam, amitriptyline, atorvastatin, chlorzoxazone, ciclosporin, debrisoquine, digoxin, erythromycin, fexofenadine, gliclazide, imatinib, indinavir, irinotecan, ivabradine, mephenytoin, methadone, midazolam, nifedipine, omeprazole, oral contraceptives, quazepam, simvastatin, tacrolimus, talinolol, verapamil, voriconazole and warfarin. Case reports or case series suggest interactions of St John's wort with adrenergic vasopressors, anaesthetics, bupropion, buspirone, ciclosporin, eletriptan, loperamide, nefazodone, nevirapine, oral contraceptives, paroxetine, phenprocoumon, prednisone, sertraline, tacrolimus, theophylline, tibolone, tryptophan, venlafaxine and warfarin. Ginkgo (Ginkgo biloba) decreases the plasma concentrations of omeprazole, ritonavir and tolbutamide. Clinical cases indicate interactions of ginkgo with antiepileptics, aspirin (acetylsalicylic acid), diuretics, ibuprofen, risperidone, rofecoxib, trazodone and warfarin. Ginseng (Panax ginseng) may interact with phenelzine and warfarin. Kava (Piper methysticum) increases the clearance of chlorzoxazone (a CYP2E1 substrate) and may interact with alprazolam, levodopa and paroxetine. Garlic (Allium sativum) interacts with chlorpropamide, fluindione, ritonavir and warfarin; it also reduces plasma concentrations of chlorzoxazone (a CYP2E1 probe). Echinacea might affect the clearance of caffeine (a CYP1A2 probe) and midazolam (a CYP3A4 probe). No interactions have been reported for saw palmetto (Serenoa repens). Numerous interactions between herbal medicines and conventional drugs have been documented. While the significance of many interactions is uncertain, several interactions, particularly those with St John's wort, may have serious clinical consequences.

Biological properties of onions and garlic

Abstract: Garlic (Allium sativum) and onion (Allium cepa) are two food ingredients widely used in our gastronomy. Moreover, garlic and onion extracts have been recently reported to be effective in cardiovascular disease, because of their hypocholesterolemic, hypolipidemic, anti-hypertensive, anti-diabetic, antithrombotic and anti-hyperhomocysteinemia effects, and to possess many other biological activities including antimicrobial, antioxidant, anticarcinogenic, antimutagenic, antiasthmatic, immunomodulatory and prebiotic activities. Given the importance of these vegetables and derived supplements as much in feeding as in therapeutic, in the present work, their main biological activities have been reviewed, indicating the compounds responsible for each one of them. In addition, the influence of the processing on the bioactivity and the adverse effects and interactions with different medications have also been considered.