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

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          Abstract

          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-alpha release assay, we studied Acer nikoense (Megusurino-ki in Japanese), one of the herbal medicines. The inhibitory activity of TNF-alpha 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 IC50 values of TNF-alpha release inhibition were 43 microM for geraniin and 76 microM for corilagin, whereas that for (-)-epigallocatechin gallate (EGCG) was 26 microM. 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 from 3.8 to 1.1 in week 20. Thus, geraniin has slightly weaker inhibitory activity than EGCG. Since geraniin and corilagin have been well investigated as representative tannins, we discuss here the new possibility of classical herbal medicine in the development of preventive agents for cancer and other life-style related diseases.

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          Most cited references16

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          Resveratrol Suppresses TNF-Induced Activation of Nuclear Transcription Factors NF- B, Activator Protein-1, and Apoptosis: Potential Role of Reactive Oxygen Intermediates and Lipid Peroxidation

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            Cross sectional study of effects of drinking green tea on cardiovascular and liver diseases.

            To investigate the association between consumption of green tea and various serum markers in a Japanese population, with special reference to preventive effects of green tea against cardiovascular disease and disorders of the liver. Cross sectional study. Yoshimi, Japan. 1371 men aged over 40 years resident in Yoshimi and surveyed on their living habits including daily consumption of green tea. Their peripheral blood samples were subjected to several biochemical assays. Increased consumption of green tea was associated with decreased serum concentrations of total cholesterol (P for trend < 0.001) and triglyceride (P for trend = 0.02) and an increased proportion of high density lipoprotein cholesterol together with a decreased proportion of low and very low lipoprotein cholesterols (P for trend = 0.02), which resulted in a decreased atherogenic index (P for trend = 0.02). Moreover, increased consumption of green tea, especially more than 10 cups a day, was related to decreased concentrations of hepatological markers in serum, aspartate aminotransferase (P for trend = 0.06), alanine transferase (P for trend = 0.07), and ferritin (P for trend = 0.02). The inverse association between consumption of green tea and various serum markers shows that green tea may act protectively against cardiovascular disease and disorders of the liver.
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              Phase I trial of oral green tea extract in adult patients with solid tumors.

              This trial was designed to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) once daily or three times daily. Cohorts of three or more adult cancer patients were administered oral GTE with water after meals one or three times daily for 4 weeks, to a maximum of 6 months, depending on disease response and patient tolerance. Pharmacokinetic analyses were encouraged but optional. Dose levels of 0.5 to 5.05 g/m(2) qd and 1.0 to 2.2 g/m(2) tid were explored. A total of 49 patients were studied. median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%; 98% had PS of 1; and 21 had non-small-cell lung, 19 had head & neck cancer, three had mesothelioma, and six had other. Mild to moderate toxicities were seen at most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting toxicities were caffeine related and included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m(2) once daily or 1.0 g/m(2) three times daily. No major responses occurred; 10 patients with stable disease completed 6 months of GTE. Pharmacokinetic analyses found accumulation of caffeine levels that were dose dependent, whereas epigallocatechin gallate levels did not accumulate nor appear dose related. A dose of 1.0 g/m(2) tid (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is recommended for future studies. The side effects of this preparation of GTE were caffeine related. Oral GTE at the doses studied can be taken safely for at least 6 months.
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                Author and article information

                Journal
                Biological & Pharmaceutical Bulletin
                Biol. Pharm. Bull.
                Pharmaceutical Society of Japan
                09186158
                13475215
                2001
                : 24
                : 10
                : 1145-1148
                Article
                10.1248/bpb.24.1145
                11642320
                f3ffe2a1-469e-48e6-8845-d9099e0156e5
                © 2001
                History

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