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Kimura, Yoshiyuki; OKUDA, Hiromichi; Mori, Kazuko; OKUDA, Takuo; Arichi, Shigeru

doi:10.4327/jsnfs.37.223

Cited by 40 publications

(42 citation statements)

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“…Our results suggest that geraniin as an active constituent has systemic effects similar to those of EGCG and green tea: It was previously reported that oral administration of geraniin to rats (50 mg/kg/d or 100 mg/kg/d) inhibited the elevation of serum total cholesterol, lipid peroxide, free fatty acid, triglyceride, glutamic oxaloacetic transaminase and glutamic pyruvic transaminase induced by treatment with peroxidized oil. 19) All the results indicate that this megusurino-ki should be more intensively studied as a cancer preventive agent than as a simple folk medicine.…”

Section: Inhibition Of Tumor Promotion By Geraniinmentioning

confidence: 99%

New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

Okabe

Suganuma

Imayoshi

et al. 2001

Biological & Pharmaceutical Bulletin

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We have recently reported that inhibition of tumor necrosis factor-a (TNF-a) release is a useful method for screening of cancer preventive agents, 1) because TNF-a and other inflammatory cytokines stimulate tumor promotion and progression of initiated cells as well as premalignant cells. 2,3) Since TNFa and interleukin-1 (IL-1), as endogenous tumor promoters, activate nuclear factor kB (NF-kB), 4,5) inhibitors of NF-kB activation are also assumed to be cancer preventive agents. 6) However, in a practical sense, it is quantitatively easier to measure inhibition of TNF-a release from cells treated with a tumor promoter such as okadaic acid than inhibition of NFkB activation using a gel mobility shift assay. 7) Based on the study of green tea as cancer preventive agent in the United States 8) and as cancer preventive beverage in Japan, 9) we decided to take a closer look at Japanese herbal medicine for other likely cancer preventives. One classical Japanese herb, Geranium thunbergii SIEB. et ZUCC. (Gennoshoko in Japanese), is used as an antidiarrhetic 10) ; it contains geraniin, which has been intensively studied as a representative tannin. 11) And the bark of Acer nikoense MAXIM (Megusurino-ki in Japanese), which contains diarylheptanoids, is sold as a folk medicine for eye and liver diseases in Japan. 12) The Forestry Experiment Station of Saitama Prefecture succeeded in culturing young plants of A. nikoense collaborated with us on the scientific utilization of the plant. We received four water extracts-leaves, bark, small branches, and timber-from the Station and subjected them to inhibition of TNF-a release assay using BALB/3T3 cells treated with okadaic acid 13) : The leaves showed the strongest activity among the four extracts. Each extract was subjected to highperformance liquid chromatography (HPLC) with CAP-CELL PAK C18, and geraniin and corilagin were identified in the active leaf extract (Fig. 1).In The success of green tea as a cancer preventive is based on evidence that green tea contains tannins and antioxidants, does not show toxicity in humans and has long traditional use in Asia. In the light of this, herbal medicines are now also attracting attention as potential sources of cancer preventive agents. Using the inhibition of TNF-a a release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-a a release was found in the leaf extract rather than the bark extract, and the main active constituents were identified as geraniin and corilagin, which are present in another Japanese traditional herb, Geranium thunbergii (Genno-shoko). The IC 50 values of TNF-a a release inhibition were 43 m mM for geraniin and 76 m mM for corilagin, whereas that for (؊)-epigallocatechin gallate (EGCG) was 26 m mM. Treatment with geraniin prior to application of okadaic acid, a tumor promoter on mouse skin initiated with 7,12-dimethylbenz(a)anthracene, reduced the percentage of tumor-bearing mice from 80.0 to 40.0% and the average numbers of tumor per mouse ...

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Section: Inhibition Of Tumor Promotion By Geraniinmentioning

confidence: 99%

New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

Okabe

Suganuma

Imayoshi

et al. 2001

Biological & Pharmaceutical Bulletin

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“…This provides a possible explanation for the cardioprotective action of wine [8]. Furthermore, resveratrol has been shown to reduce the hepatic synthesis of cholesterol and triglyceride in rats [9], to inhibit the synthesis of eicosanoids and rat leukocytes [10], to interfere with arachidonate metabolism [11], to inhibit the activity of some protein kinases [12], and is a more powerful antioxidant than vitamin E in preventing LDL oxidation [13]. The demonstrated biological and pharmacological activities of resveratrol are attributed to its antioxidant property [14].…”

Section: Introductionmentioning

confidence: 99%

Study of phenolic compounds as natural antioxidants by a fluorescence method

López

Martínez

Valle

et al. 2003

Talanta

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Much work has been carried out in recent years on the beneficial effect of phenolic compounds as natural antioxidants which help to neutralize free radicals. In fact, researchers have focused their attention on the pathological role of free radicals in a variety of diseases, among which the most important are atherosclerosis and cancer. Thus, among the components of the so-called 'Mediterranean Diet', phenolic compounds have received increased attention as epidemiological studies have shown that consumption of foods and beverages rich in phenolics is correlated with reduced incidence of heart disease. In this study, four phenolic compounds: (1) 3,4,5-trihydroxybenzoic acid (gallic acid); (2) trans 3,4?,5-trihydroxystilbene (trans -resveratrol); (3) 3,3?,4?,5,7-pentahydroxyflavone (quercetin) and its glycoside (4) 3,3?,4?,5,7-pentahydroxyflavone Á/3-rutinoside (Rutin) have been subjected to antioxidant study by a fluorimetric assay. In this method, the rate of peroxidation induced by 2,2?-azobis (2-methylpropionamidine) dihydrochloride was monitored through the loss of fluorescence of the protein B-phycoerythrin (B-PE). Under appropriate conditions, the loss of B-PE fluorescence in the presence of reactive species is an index of oxidative damage of the protein. The inhibition of the action of reactive species by phenolic compounds, reflected in the protection against the loss of B-PE fluorescence in the fluorimetric assay, is a measure of its antioxidant capacity against the reactive species. The antioxidant effects of phenolic compounds have been investigated at different concentrations to relate activity to structural effects. It has been observed that the fluorescence decay due to peroxyl radical attack on B-PE decreases exponentially with time. As a reference compound for antioxidant capacity we used 6-hydroxy-2,5,7,8-tetramethyl-chroman-2-carboxylicacid (trolox), a water soluble tocopherol analogue. This compound reacts rapidly with peroxyl radicals, and, until the trolox is consumed, no loss in phycoerythrin fluorescence is observed. A linear correlation of the net protection value with the concentration of trolox was demonstrated. The phenolic compounds studied react with peroxyl radicals in a similar way to trolox. Quercetin and rutin were shown to have strong antioxidant activities. The results obtained here are in agreement with previous studies confirming that quercetin is the most antioxidant of the four polyphenolics. #

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“…Indeed, the phytoalexin has been reported to prevent atherosclerosis (6) by modulating the synthesis of hepatic apolipoproteins and lipids (7), inhibiting platelet aggregation (8 -10) and the synthesis of proatherogenic eicosanoids in human platelets and neutrophils (8,11).…”

Section: Resveratrolmentioning

confidence: 99%

p21 Gene Expression Is Modulated by Egr1

Ragione

Cucciolla

Criniti

et al. 2003

Journal of Biological Chemistry

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Epidemiological observations indicate that resveratrol, a natural antioxidant stilbene, exerts cardioprotective and chemopreventive effects. Moreover, the molecule induces in vitro cell growth inhibition and differentiation. Using human erythroleukemic K562 cells as model system, we demonstrated that resveratrol induces a remarkable ␥-globin synthesis, the erythroid differentiation being linked to impairment of cell proliferation, increased p21Cip1 expression and inhibition of cdk2 activity. The up-regulation of p21 an Egr1 consensus sequence in the p21Cip1 promoter suggested the hypothesis that this transcription factor directly regulates the expression of the cdk inhibitor. Transfection studies with deleted gene promoter constructs, as well as EMSA, pull-down, and chromatin immunoprecipitation experiments substantiated this view, demonstrating that Egr1 binds in vitro and in vivo to the identified consensus sequence of the p21 Cip1 promoter. Moreover, an Egr1 phosphorothioate antisense hinders p21Cip1 accumulation and the antiproliferative effects of resveratrol. In conclusion, this is the first demonstration that Egr1 controls p21Cip1 expression by directly interacting with a specific sequence on its gene promoter. The identified regulatory mechanism also contributes to the clarification of the complex chemopreventive and antiproliferative properties of resveratrol.

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Cited by 40 publications

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New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

New TNF-.ALPHA. Releasing Inhibitors, Geraniin and Corilagin, in Leaves of Acer nikoense, Megusurino-ki.

Study of phenolic compounds as natural antioxidants by a fluorescence method

p21 Gene Expression Is Modulated by Egr1

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