Moon Young Heo

Anti-genotoxicity of galangin as a cancer chemopreventive agent candidate.

Flavonoids are polyphenolic compounds that are present in plants. They have been shown to possess a variety of biological activities at non-toxic concentrations in organisms. Galangin, a member of the flavonol class of flavonoid, is present in high concentrations in medicinal plants (e.g. Alpinia officinarum) and propolis, a natural beehive product. Results from in vitro and in vivo studies indicate that galangin with anti-oxidative and free radical scavenging activities is capable of modulating enzyme activities and suppressing the genotoxicity of chemicals. These activities will be discussed in this review. Based on our review, galangin may be a promising candidate for cancer chemoprevention.

Antioxidant and antigenotoxic activities of Korean fermented soybean

This study was aimed at evaluating the antioxidative and antigenotoxic activities of Korean fermented soybean (Chungkookjang) in vitro and in vivo. The 100% ethanol extract of Chungkookjang (CKJ) inhibited the generation of 1,1-diphenyl-2-picryl hydrazine (DPPH) radicals, and had an inhibitory effect on LDL oxidation. CKJ and its constituents (genistein and daidzein) also inhibited H(2)O(2)-induced DNA damage from NIH/3T3 fibroblasts. Furthermore, they showed the cytoprotective effects against H(2)O(2)-induced cell death. In vivo study also demonstrated that an oral administration of CKJ extract (800 mg/kg/day) for 2 weeks potently inhibited the formation of malondialdehyde, the damage of DNA and the formation of micronucleated reticulocytes in KBrO(3)-treated mice. The well-known antioxidants, trolox and vitamin C, also showed the potent inhibition on these parameters. All these results indicate that CKJ extract may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage. The isoflavones, genistein and daidzein, may contribute to these biological effects of CKJ extract at least in part. Korean fermented soybean (Chungkookjang) is suggested to be a promising functional food witch can prevent oxidative stress.

Inhibition of TPA-induced cyclooxygenase-2 expression and skin inflammation in mice by wogonin, a plant flavone from Scutellaria radix.

Wogonin (5,7-dihydroxy-8-methoxyflavone), isolated from Scutellaria radix, was previously reported to inhibit the expression and activity of the enzyme cyclooxygenase-2 in lipopolysaccharide (LPS)-stimulated cells of a mouse macrophage cell line, RAW 264.7. Here, in order to find in vivo effects, inhibition by wogonin of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cyclooxygenase-2 expression and anti-inflammatory activity in vivo were investigated. When applied topically to the dorsal skin of mice, wogonin at doses of 50-200 microg/site/treatment (total of five treatments in 3 days) inhibited cyclooxygenase-2 expression and prostaglandin E2 production induced by multiple treatments with TPA. At 200 microg/site/treatment, wogonin caused a 55.3% reduction of prostaglandin E2 production on the dorsal skin compared with an increased production in the TPA-treated control group. The same compound significantly inhibited mouse ear edema induced by TPA in both preventive (58.1% inhibition) as well as curative treatment (31.3% inhibition) schedules at 200 microg/ear/treatment. Inhibition of neutrophil infiltration was also observed. Therefore, wogonin may be beneficial for cyclooxygenase-2-related skin disorders.

Antioxidative constituents fromPaeonia lactiflora

The ethanol extract of the peony root (Paeonia Lactiflora Pall, Paeoniaceae) as well as its major active components including gallic acid and methyl gallate were evaluated for their protective effects against free radical generation and lipid peroxidation. In addition, the protective effects against hydrogen peroxide-induced oxidative DNA damage in a mammalian cell line were examined. The ethanol extracts of the peony root (PREs) and its active constituents, galdiphenyl-2-picryl hydrazine (DPPH) radical generation and had an inhibitory effect on lipid peroxidation, as measured by the level of malondialdehyde (MDA) formation. The PREs did not have any pro-oxidant effect. They strongly inhibited the hydrogen peroxide-induced DNA damage from NIH/3T3 fibroblasts, as assessed by single cell gel electrophoresis. Furthermore, the oral administration of 50% PRE (50% ethanol extract of peony root), gallic acid and methyl gallate potently inhibited the formation of micronucleated reticulocytes (MNRET) in the mouse peripheral blood induced by a KBrOP3 treatmentin vivo. Therefore, PREs containing gallic acid and methyl gallate may be a useful antigenotoxic antioxidant by scavenging free radicals, inhibiting lipid peroxidation and protecting against oxidative DNA damage without exhibiting any pro-oxidant effect.

Anticlastogenic effect of flavonoids against mutagen-induced micronuclei in mice

14 flavonoids, including flavone and flavonol derivatives, were tested for their anticlastogenic effect against induction of micronuclei by benzo[a]pyrene in polychromatic erythrocytes of mice. When each flavonoid was administered orally, together with intraperitoneally administered benzo[a]pyrene, most flavonol derivatives showed an anticlastogenic effect. The data suggest that the 2,3-double bond and 3,5,7-hydroxyl groups in the flavonoid molecules may be essential to produce anticlastogenic effects against benzo[a]pyrene. Galangin, one of the active compounds, and (-)-epicatechin, a weak one, were administered to mice in order to compare their anticlastogenic effect against 3 different kinds of carcinogens: ethyl methanesulfonate, 7,12-dimethylbenz[a]anthracene, and adriamycin. Galangin showed a stronger anticlastogenic effect than (-)-epicatechin against ethyl methanesulfonate and 7,12-dimethylbenz[a]anthracene. However, there was no significant effect against adriamycin-induced micronuclei by both compounds. Our study indicates that most flavonoids are anticlastogenic agents. Their anticlastogenic effects are apparently independent of their own clastogenic activities. Furthermore, their anticlastogenic activities do not apply universally to all types of genotoxic chemicals.

Pharmacological activities of water extracts ofUmbelliferae plants

In order to evaluate the pharmacological activities of Chinese medicine, nine Umbelliferae plants were selected and their restoring activity against dexamethasone-induced disorders, liver protective activity, antimicrobial activity, anti-inflammatory activity and antimutagenic activity were tested and compared.Angelica dahurica, Angelica acutiloba andOstericum koreanum showed various activities in these tests at the dose used in this study.

Anticlastogenic effects of galangin against bleomycin-induced chromosomal aberrations in mouse spleen lymphocytes

Galangin, a flavonoid derivative, was tested for its anticlastogenic effect against the induction of chromosome aberrations by bleomycin. For an in vitro assay, galangin (0, 2 x 10(-8), 2 x 10(-7), and 2 x 10(-6) M) was added to mouse spleen lymphocyte cultures together with bleomycin (3 microgram/ml) at 24 h after Con A initiation of cultures. In an in vivo/in vitro experiment, galangin (0, 0.1, 1, 10, and 100 mg/kg) was administered to mice orally twice with a 24-h interval. Mice were killed 8 h later. Spleen lymphocytes were isolated and cultures were made. Bleomycin (3 microgram/ml) was added to the mouse spleen lymphocyte cultures at 24 h after Con A initiation. Both in vitro and in vivo/in vitro cultures were harvested at 42 h after initiation. The harvested cells were used for cytogenetic analyses. The results showed that in vitro or in vivo treatment of lymphocytes with galangin suppressed the induction of chromosome aberrations by bleomycin in a galangin dose-dependent manner. The galangin doses used were non-clastogenic to cells. The data from our in vitro and in vivo/in vitro studies confirmed each other and indicate that galangin is an anticlastogenic agent. The in vivo/in vitro protocol may be a useful means to assay the chemoprotective effects of chemicals in humans.

Prenylated Flavonoids as Tyrosinase Inhibitors

In order to find new tyrosinase inhibitors and the effects of prenyl residue on flavonoid molecules, eight prenylated and three synthetic vinylated flavonoids were examined on their inhibitory effect against tyrosinase activity. From the results, kuwanon C, papyriflavonol A, sanggenon D and sophoflavescenol were found to possess the considerable inhibitory activity. Especially, sanggenon D is revealed as a potent inhibitor (IC50 = 7.3 μM), compared to the reference compound, kojic acid (IC50 = 24.8 μM). However, the prenylation with isoprenyl group or the vinylation to flavonoid molecules did not enhance tyrosinase inhibitory activity.

Anti-Inflammatory Activity of the Ethanol Extract of Chungkukjang, Korean Fermented Bean: 5-Lipoxygenase Inhibition

The anti-inflammatory activity of Chungkukjang, a Korean traditional fermented soybean food (Korean-style Natto), was examined for the first time. From the results, it was found that the ethanol extract of Chungkukjang inhibited 5-lipoxygenase from A23187-treated RBL-1 cells, reducing leukoriene production (50% inhibitory concentration = 54.1 microg/mL). However, it did not greatly affect cyclooxygenase-2-catalyzed prostaglandin E(2) and inducible nitric oxide synthase-catalyzed nitric oxide production from lipopolysaccharide-treated RAW 264.7 cells at the same concentration ranges. Since leukotrienes are intimately involved in some allergic disorders, the anti-allergic activity of Chungkukjang was further examined in animal models of passive cutaneous anaphylaxis (type I hypersensitivity) and arachidonic acid-induced ear edema, two well-known in vivo models sensitive to 5-lipoxygenase inhibitors. After oral administration for 5 consecutive days, Chungkukjang significantly reduced (27.3%) passive cutaneous anaphylaxis in rats at 400 mg/kg/day. It also showed in vivo anti-inflammatory activity against arachidonic acid-induced mouse ear edema. Therefore, it is suggested that Chungkukjang may be beneficial for several allergic conditions such as asthma and atopic dermatitis.

Anticlastogenic effects of galangin against mitomycin C-induced micronuclei in reticulocytes of mice

We investigated the suppressive effect of galangin on the induction of micronucleated reticulocytes (MNRETs) by mitomycin C (MMC) in mouse peripheral blood. When galangin was given to mice 24 h before the intraperitoneal injection of MMC (1 mg/kg), a more marked decrease in the frequency of MNRETs was observed than in mice with simultaneous and post-treatment of galangin. On the other hand, when galangin was given to mice for 7 consecutive days before MMC injection, galangin showed potent anticlastogenic effects, even at the lowest dose level of 0.1 mg/kg. Results from our in vivo studies indicate that galangin is capable of suppressing the clastogenic activity of the direct acting MMC. Together with our earlier observations, it appears that galangin is capable of protecting cells from the toxic effects of a variety of hazardous chemicals. Therefore, galangin may be an useful chemopreventive compound.