Pharmacokinetic Study of Allixin, a Phytoalexin Produced by Garlic.

Abstract

Intact constituents or transformation compounds derived from garlic (Allium sativum L.) have been investigated for more than 60 years, and numerous compounds have been isolated and investigated to reveal the relationship between the compounds and biological activities of garlic.1,2) Sulfur-containing compounds, such as allicin, diallylsulfides, dithiins, alliin and S-allylcysteine, have been well investigated by numerous researchers because garlic is rich in sulfur and its sulfur containing compounds were believed to be responsible for many biological activities of garlic.1,2) S-Allylcysteine has been investigated comprehensively, including its physical, chemical and biological properties. [1][2][3][4][5][6] On the other hand, other compounds such as saponins, proteins or maillard reaction products derived from garlic, which are non-sulfur containing compounds, have also been investigated to reveal the biological properties of garlic. 1,2,[7][8][9][10] Allixin (3-hydroxy-5-methoxy-6-methyl-2-penthyl-4H-pyran-4-one), a non-sulfur containing compound having a gpyrone skeleton structure (Fig. 1), was the first compound isolated from garlic as a phytoalexin, a product induced in plants by continuous stress.11) This compound has been shown to have unique biological properties, such as anti-oxidative effects, 11) anti-microbial effects, 11) anti-tumor promoting effects, 12) inhibition of aflatoxin B 2 DNA binding, 13) and neurotrophic effects.14) Allixin showed an anti-tumor promoting effect in vivo, inhibiting skin tumor formation by TPA in DMBA initiated mice.12) Analogs of this compound have exhibited anti tumor promoting effects in in vitro experimental conditions. 15) Herein, allixin and/or its analogs may be expected useful compounds for cancer prevention or chemotherapy agents for other diseases.Analysis of the biological mechanism of action of allixin is important for the study of cancer prevention or other biological properties, and also for drug development. Nishino et al. has reported that allixin interacts with the Ca 2ϩ -calmodulin complex.12) This in vitro study suggests that allixin may play an important role in signal transduction or regulation. However, the pharmacokinetic behavior of this compound has not been evaluated, and this is an important factor for in vivo studies. Therefore, this paper presents the pharmacokinetic behavior and identified metabolites of allixin. Result Preparation of Allixin and Allixin-d 11Allixin and allixin-d 11 were prepared as previously reported.16) The chemical structure of the obtained materials were confirmed by NMR and MS comparison with previous reporteds.11,16) Synthesized allixin-d 11 was used as the internal standard for the analysis of allixin content in blood samples. The yield of allixin and allixin-d 11 was 20% and 9%, respectively. Here, all The pharmacokinetic behavior of allixin (3-hydroxy-5-methoxy-6-methyl-2-penthyl-4H-pyran-4-one) was investigated in an experimental animal, mice. Allixin was administered using an inclusion compound because the solubili...

Dietary Agents and Phytochemicals in the Prevention and Treatment of Experimental Ulcerative Colitis

“…[9192] Different types of antioxidants are present in different garlic preparations, including water- and lipid-soluble organosulfur compounds like S-allylcysteine and S-allylmercaptocysteine[93] and non-metals like selenium and phytoalexin-like allixin, which are responsible for the protective effect of garlic in several disease models. [9495] Rats fed garlic (0.25 g/kg b. wt.)…”

Investigating the Phytochemicals and Antimicrobial Activities of Shoot and Root of Pycreus smithianus (Ridl.) C. B. Clarke (Family Cyperaceae)

“…The phytochemical screening showed that higher proportions of reducing sugars are present in the ethanolic extracts with only the root aqueous indicating appreciable presence while sugars are in low proportion in the shoot aqueous (Table 2). Kodera et al [9] and Dhalel and Markandeya [10] have remarked that the combination of the reducing sugars constitutes a building block in the production of phytoalexins which are antimicrobial substances synthesized by plants. Phytoalexins accumulate rapidly at areas of incompatible pathogen infection.…”

Action Mechanism of Insulin‐Mimetic Vanadyl–Allixin Complex

“…-During the study on the structure -activity relationship of vanadyl-3-hydroxypyronate [VO(3hp) 2 ]-related complexes (5 -7; Fig. ), we observed that a Figure. Chemical structures of vanadyl complexes complex with allixin, which is found in the extract of dry garlic after storage for two years in dark [22], has extremely high insulin-mimetic and antidiabetic activities [23]. Thus, we identified that bis(allixinato)oxovanadium(IV) [VO(alx) 2 ]; 7; Fig.…”