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Rikkosan is a traditional Kampo medicine using the control of oral pain caused by dental caries, pulpitis, periodontitis and stomatitis. In order to provide evidence for its clinical effects, we herein investigated whether Rikkosan inhibits the production of pro-inflammatory substances in human and mouse models of inflammation. Rikkosan alone did not induce prostaglandin E2 (PGE2) production, but inhibited interleukin-1β (IL-1β) (5 ng/ml)-stimulated PGE2 production in human gingival fibroblasts and human periodontal ligament fibroblasts, with a selectivity index higher than 4.0 and 4.3, respectively. Rikkosan alone dose-dependently stimulated tumor necrosis factor-α (TNF-α) production, reaching a peak level slightly lower than that attained by lipopolysaccharide (LPS) at 0.4 mg/ml in mouse macrophage-like RAW264.7 cells. At a higher concentration of Rikkosan (4 mg/ml), TNF-α production, however, declined significantly regardless of the presence or absence of LPS. Rikkosan dose-dependently inhibited IL-1β production by LPS-stimulated RAW264.7 cells, with a selective index of 7.6. Five constituent extracts of Rikkosan, either alone or in combination, showed similar effects on TNF-α and IL-1β productions in activated RAW264.7 cells, but to lower extents than that of Rikkosan. These results demonstrated that Rikkosan inhibited both IL-1β production by LPS-activated macrophages and PGE2 production by IL-1β-stimulated human gingival fibroblasts and human periodontal ligament fibroblasts, suggesting that anti-inflammatory effects of Rikkosan may partially be generated by the inhibition of these pro-inflammatory substances via the IL-1β network through macrophages to oral tissue cells.

Recently, a prominent antiviral and macrophage stimulatory activity of cacao lignin-carbohydrate complex (LCC) has been reported. However, the solubility and sterility of LCC have not been considered yet. In the present study, complete solubilisation and sterilisation was achieved by autoclaving under mild alkaline conditions and the previously reported biological activities were re-examined.LCCs were obtained by 1% NaOH extraction and acid precipitation, and a repeated extraction-precipitation cycle. Nitric oxide (NO) and cytokine productions were assayed by the Griess method and ELISA, respectively. Inducible NO synthase (iNOS) expression was determined by Western blot analysis. Superoxide anion, hydroxyl radical and nitric oxide radical-scavenging activity was determined by ESR spectroscopy.Cacao mass LCC showed reproducibly higher anti-HIV activity than cacao husk LCC. Cacao mass LCC, up to 62.5 μg/ml, did not stimulate mouse macrophage-like cells (RAW264.7 and J774.1) to produce NO, nor did it induce iNOS protein, in contrast to lipopolysaccharide (LPS). Cacao mass LCC and LPS synergistically stimulated iNOS protein expression, suggesting a different point of action. Cacao mass LCC induced tumour necrosis factor-α production markedly less than LPS, and did not induce interleukin-1β, interferon-α or interferon-γ. ESR spectroscopy showed that cacao mass LCC, but not LPS, scavenged NO produced from NOC-7.This study demonstrated several new biological activities of LCCs distinct from LPS and further confirmed the promising antiviral and immunomodulating activities of LCCs.

We have previously investigated a total of 173 azulene-, tropolone- and azulenequinone-related compounds for their tumor-specificity and anti-inflammatory activity. In this study, we selected six compounds that showed tumor-specific cytotoxicity (referred to as group I compounds) and five compounds that inhibited nitric oxide production by activated macrophages (referred to as group II compounds) to investigate their possible hormetic and anti-radiation effects. We have established three oral normal cell type, human gingival fibroblast HGF-1, pulp cell HPC-1 and periodontal ligament fibroblast HPLF-1, from extracted teeth and periodontal tissue. These normal cells expressed p53 protein, regardless of the growth stage (either at growing or near confluent phase), more than oral squamous cell carcinoma cell line (HSC-2). Group I compounds slightly stimulated the growth of HPL-1 cells only at restricted durations and concentrations, but did not affect that of HGF-1 and HPC-1 cells, suggesting the minor hormetic effects displayed by these compounds. We established a new evaluation system for UV-induced cellular damage using an intact HSC-2 cell system in which sodium ascorbate (vitamin C) and gallic acid, but not N-acetyl-l-cysteine nor catalase, exerted protective effects. Three group I compounds and two group II compounds significantly protected the cells from UV-induced injury, suggesting their possible anti-UV effect.

Synthetic triazoles are widely used for the treatment of fungal infection. In order to understand their possible anti-inflammatory action, we investigated the effect of itraconazole and its hydroxylated derivative (hydroxyitraconazole) on the production of various pro-inflammatory substances by mouse macrophage-like RAW264.7 cells.These compounds did not apparently show any growth inhibitory or stimulatory effects over a wide range of concentrations (0.2-50 μg/ml). Itraconazoles dose-dependently increased the production of prostaglandin E₂ (PGE₂) and tumor necrosis factor-α (TNF-α) without affecting the production of interleukin-1β (IL-1β) and nitric oxide (NO). LPS treatment significantly enhanced the production of NO, PGE₂, TNF-α and IL-1β. The addition of itraconazoles to LPS-stimulated RAW264.7 cells significantly reduced the production of NO, but rather enhanced the production of PGE₂, TNF-α and IL-1β. ESR spectroscopy demonstrated that itraconazoles did not significantly scavenge NO and superoxide anion radicals, indicating that the inhibition of NO production by itraconazoles is not due to their radical-scavenging activity. Hydroxyitraconazole was slightly more cytostatic, and more efficiently inhibited NO production, but enhanced the production of other pro-inflammatory substances.These data suggest that itraconazoles regulate NO and other pro-inflammatory substances differently in activated macrophages.

We have previously reported that among 12 major ingredients of Sairei-to, Scutellariae radix inhibited prostaglandin E(2) (PGE(2)) production by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells more efficiently than other ingredients, and wogonin, a major flavonoid from Scutellariae radix, showed greater inhibitory activity and membrane permeability than baicalein and baicalin. Here the effects of six other flavonoids, with similar structures, on membrane permeability and PGE(2) production were investigated. 7-Methoxyflavone inhibited the LPS-stimulated PGE(2) production to the greatest extent, followed by flavonewogonin (5,7-dihydroxy-8-methoxyflavone)7,8-dimethoxyflavonechrysin (5,7-dihydroxyflavone)baicalein (5,6,7-trihydroxyflavone)chromone. 7-Methoxyflavone also showed the highest membrane permeability, followed by flavonechrysin7,8-dimethoxy-flavonewogoninbaicalein. When PGE(2) inhibitory activity was expressed per molecule incorporated into the cells, wogonin produced the greatest inhibition, further substantiating its anti-inflammatory potency.

Alkaline extract of Sasa senanensis Rehder (SE) has shown diverse biological activity. As an extension, whether SE affects the function of activated macrophages was investigated. SE inhibited the nitric oxide (NO) production by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells. Western blot and RT-PCR analyses demonstrated that this was due to the inhibition of inducible NO synthase (iNOS) expression at both protein and mRNA levels. ESR spectroscopy shows that SE dose-dependently scavenged the NO radical produced by NOC-7. In order to confirm the anti-inflammatory potency, possible effects on prostaglandin (PG) E(2) production and expression of enzymes involved in the arachidonic acid pathway were next investigated. It was found that SE effectively inhibited the PGE(2) production by LPS-stimulated RAW264.7 cells, although the extent of inhibition of PGE(2) was slightly less than that of NO production. SE inhibited cyclooxygenase (COX)-2 expression at both protein and mRNA levels, but to much lesser extents as compared with those for iNOS expression. SE contained much lower concentration of arginine, precursor of NO, as compared with the culture medium. These data suggest that SE exerts a weak anti-inflammatory activity.

We previously reported that Sairei-to concentration-dependently modified lipopolysaccharide (LPS)-stimulated prostaglandin E(2) (PGE(2)) production in mouse macrophage-like RAW264.7 cells. Among twelve major ingredients of Sairei-to, Scutellariae radix inhibited the LPS-stimulated PGE(2) production to the greatest extent, followed by Zingiberis rhizoma, Glycyrrhizae radix, Atractylodis lanceae rhizoma and Pinelliae tuber. Scutellariae radix contained several major flavonoids such as baicalin, baicalein and wogonin. We investigated the effect of these flavonoids on PGE(2) production and COX-2 expression by LPS-activated RAW264.7 cells. Wogonin inhibited PGE(2) production most efficiently, followed by baicalein and then baicalin, in the same order as their membrane permeability. It was unexpected that wogonin and all other compounds would fail to inhibit the expression of COX-2 at both protein and mRNA levels, suggesting the importance of re-evaluating the point of action of wogonin.

Three Chinese herbal extracts, Drynaria baronii, Angelica sinensis and Cornus officinalis Sieb. et Zucc (referred to as DB, AS, CO, respectively), were investigated for their possible anti-inflammatory activity. DB, AS and CO inhibited nitric oxide (NO) production by lipopolysaccharide (LPS)-activated mouse macrophage-like RAW264.7 cells. Western blot and RT-PCR analyses demonstrated that this was due to the inhibition of inducible NO synthase (iNOS) expression at both protein and mRNA levels. Electron-spin resonance spectroscopy showed that DB, AS and CO dose-dependently scavenged the NO radical produced by NOC-7 in the presence of carboxy-PTIO. In order to confirm the anti-inflammatory potency, effects on prostaglandin (PG) E(2) production and the expression of enzymes involved in the arachidonic acid pathway were next investigated. DB and CO effectively inhibited the PGE(2) production by LPS-stimulated RAW264.7 cells, although the extent of inhibition of PGE(2) production was slightly lower than that of NO production. AS only marginally inhibited the LPS-stimulated PGE(2) production. DB, AS and CO inhibited cyclooxygenase (COX)-2 expression at both protein and mRNA levels, but to much lesser extents as compared with that for iNOS expression. These data further substantiate the anti-inflammatory potency of DB, AS and CO.

Mastic is a resinous exudate obtained from the stem and the main leaves of Pistacia lentiscus. We have reported the antiplaque effect of mastic-containing chewing gum on the oral cavity. We hypothesize that mastic may be a multifunctional food which has some beneficial pharmaceutical properties. The aim of this study was to assess the biological activity of solid and liquid types of mastic by cytotoxicity against fibroblasts, radical-scavenging activities and inhibitory effect on cell death of oral polymorphonuclear leukocytes (OPMNs). Mastic showed selective antibacterial action against Porphyromonas gingivalis and Prevotella melaninogenica, but no anti-HIV activity. Among a total of thirteen human cell types, promyelocytic leukemia HL-60 was the most sensitive to the cytotoxicity of mastic, followed by myeloblastic leukemia (ML-1, KG-1), erythroleukemia (K-562), oral squamous cell carcinoma (HSC-2, HSC-3, HSC-4), hepatocellular carcinoma (HepG2), glioblastoma (T98G, U87MG) and normal oral cells (gingival fibroblast, pulp cell, periodontal ligament fibroblast, most resistant). Mastic did not induce the differentiation of myelogenous leukemic cells into maturing cells with higher nitroblue tetrazolium-reducing activity, but induced apoptotic cell death, characterized by internucleosomal DNA fragmentation, caspase-3 activation and a decline in the intracellular concentration of putrescine. The cytotoxicity of mastic against leukemic cells did not diminish during its storage. On the other hand, mastic inhibited the spontaneous apoptosis of OPMNs. Mastic showed hydroxyl radical-scavenging activity. The selective antibacterial and apoptosis-modulating activity of mastic suggests its possible beneficial effects on oral health.

Glycyrrhizin is a major constituent of Kanzo, a popular herbal medicine used in food and cosmetics. Glycyrrhizin alone did not stimulate nitric oxide (NO) or prostaglandin E2 (PGE2) production by RAW 264.7 cells, but modified lipopolysaccharide (LPS)-stimulated NO and PGE2 production in a bimodal fashion: it was stimulatory at lower concentrations, whereas it was inhibitory at higher concentrations. Electron-spin resonance spectroscopy showed that glycyrrhizin slightly scavenged the superoxide anion generated by hypoxanthine-xanthine oxidase reaction, but did not scavenge the DPPH and NO radicals. The present study demonstrates the concentration-dependent action of glycyrrhizin on both PGE2 and NO production by activated macrophages.

Sairei-to and its twelve ingredients were investigated for their activity to stimulate prostaglandin E2 (PGE2) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like RAW 264.7 cells. LPS significantly stimulated the production and extracellular secretion of PGE2 by RAW 264.7 cells. Sairei-to concentration-dependently modified the LPS-stimulated PGE2 production. Among Sairei-to ingredients, Scutellariae radix inhibited the LPS-stimulated PGE2 production to the greatest extent, followed by Zingiberis rhizoma, Glycyrrhizae radix, Atractylodis lanceae rhizoma and Pinelliae tuber. On the other hand, Bulpeuri radix, Alismatis rhizoma, Zizyphi fructus, Polyporus, Hoelen, ginseng radix and Cinnamomi cortex further enhanced the LPS-stimulated PGE2 production. Western blot analysis demonstrated that Sairei-to unexpectedly enhanced the expression of cyclooxygenase-2 (COX-2) protein level, but did not significantly affect phospholipase A2 protein level. The present study suggests that the modification of the enzyme activity of COX-2 may be involved in the concentration-dependent effect of Sairei-to on PGE2 production by macrophages.

We have previously reported that Rikko-san (RKS) inhibited the lipopolysaccharide (LPS)-stimulated prostaglandin (PG) E2 in mouse macrophage-like RAW264.7 cells without affecting the expression of cyclooxygenase (COX)-2. Here RKS inhibition of the enzyme activity of both COX-1 and COX-2 proteins was investigated. Western blot analysis showed that RKS did not significantly change the S-nitrosylated COX-2 protein level. On the other hand, RKS inhibited the PG production catalyzed by purified COX-2, more effectively than that catalyzed by purified COX-1. These results suggest that RKS inhibits the PGE2 production by selectively inhibiting the COX-2 activity in activated macrophages.

There are very few studies on the interaction between dental alloys and oral tissues. The effect of direct contact with copper (Cu) on the cellular function of human gingival fibroblast (HGF) derived from the periodontal tissues was investigated. When HGF cells were inoculated onto a Cu plate, the viability of HGF cells immediately declined. This was accompanied by vacuolization and chromatin condensation near the nuclear membrane. The intracellular concentration of spermidine and spermine declined, whereas that of putrescine slightly increased. Amino acid analysis of the medium revealed that glutamine was consumed at the greatest rate, amounting to more than half of the total amino acid consumption. Contact with the Cu plate resulted in the complete elimination of glutamine utilization and a simultaneous increase in the production of most amino acids, possibly due to enhanced proteolysis. This was accompanied by a time-dependent increase in the consumption of cystine, possibly due to oxidative reactions, and the enhanced production of glycine and glutamic acid. These data suggest that the contact with the Cu plate induced non-apoptotic cell death in HGF cells, which was tightly coupled with a rapid dysfunction of amino acid and polyamine metabolism.

Rikko-san (RKS) and its ingredients were investigated for their activity to stimulate prostaglandin E2 (PGE2) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. LPS significantly stimulated the production and extracellular secretion of PGE2 by Raw 264.7 cells. RKS dose-dependently modified the LPS-stimulated PGE2 production. A lower concentration (0.04-0.4 mg/ml) of RKS stimulated PGE2 production without or with LPS, whereas a higher concentration (4 mg/ml) of RKS inhibited the LPS-stimulated PGE2 production, suggesting the presence of both stimulator(s) and inhibitor(s) for PGE2 production. The inhibitory effect of a higher concentration of RKS was slightly neutralized by supplementation of exogenous arachidonic acid. Among five RKS ingredients, Kanzo inhibited the LPS-stimulated PGE2 production to the greatest extent, whereas other ingredients (Shoma, Ryutan, Saishin, Bofu) stimulated PGE2 production. Western blot analysis demonstrated that RKS and all its ingredients enhanced the intracellular concentration of cyclooxygenase-2, whereas RKS did not significantly affect the phospholipase A2 protein level. The present study demonstrates that the concentration-dependent effect of RKS on the PGE2 production by macrophage cannot be explained only by the expression levels of cyclooxygenase-2 or phospholipase A2.

A total of 6 newly-synthesized styrylchromones (SC-1 approximately SC-6) were compared for their cytotoxic activity against three normal oral human cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF) and four human tumor cell lines (squamous cell carcinoma HSC-2, HSC-3, submandibular gland carcinoma HSG, promyelocytic leukemia HL-60). All compounds showed higher cytotoxic activity against tumor cell lines than against normal cells. Among the 6 compounds, SC-3, SC-4 and SC-5, which have one to three methoxy groups, showed higher tumor specificity and water solubility. The cytotoxic activity of SC-3 and SC-5 was slightly reduced by a lower concentration of NADH, a quinone reductase, but that of SC-3 was enhanced by higher concentrations of NADH, possibly due to demethylation of the methoxy groups. Agarose gel electrophoresis demonstrated that SC-3 and SC-5 induced intemucleosomal DNA fragmentation in HL-60 cells and production of large DNA fragment in HSC-2 cells. Both SC-3 and SC-5 enhanced the enzymatic activity to cleave the substrates for caspases 3, 8 and 9, suggesting the activation of both extrinsic and intrinsic apoptosis pathways. ESR spectroscopy showed that these compounds produced no detectable amount of radical and did not scavenge superoxide anion generated by the hypoxanthine-xanthine oxidase reaction. The highly tumor-specific cytotoxic action and apoptosis-inducing capability of SC-3 and SC-5 suggest their applicability for cancer chemotherapy.

The biological activities of Moxa, used as moxibustion, have not been well documented. We investigated the effect of Moxa smoke on nitric oxide (NO) production by mouse macrophage-like Raw 264.7 cells. Moxa smoke failed to stimulate the Raw 264.7 cells to produce detectable amounts of NO, but rather inhibited the NO production by lipopolysaccharide (LPS)-activated Raw 264.7 cells. The 50% inhibitory concentration (IC50) of NO production by Moxa smoke (0.16%) was one order lower than the 50% cytotoxic concentration (CC50) (4.67%). Western blot and RT-PCR analyses demonstrated that a slightly higher concentration of Moxa is required to reduce the iNOS expression at protein and mRNA levels (IC50 = 0.99 and 2.03%, respectively). The inhibition of NO production by Moxa smoke is, thus, probably due to both the inhibition of iNOS expression and radical-scavenging activity. The present data suggest the possible anti-inflammatory effect of Moxa smoke.

Rikko-san and its ingredients were investigated for their activity to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells. LPS significantly stimulated the NO production by Raw 264.7 cells, and Rikko-san effectively inhibited the stimulation effect of LPS even at non-cytotoxic concentrations. Among 5 Rikko-san ingredients, Kanzo showed a similar magnitude of inhibition of NO production. Shoma was also slightly inhibitory. On the other hand, Ryutan, Saishin and Bofu did not show such a clear-cut stimulation effect, due to the co-existence of both inhibitory and stimulatory substance(s) for NO production. Thus NO stimulators were present in Rikko-san and its four ingredients except for Kanzo. Western blot analysis demonstrated that LPS induced the production of inducible NO synthase (iNOS), and that non-cytotoxic concentrations of Rikko-san and Kanzo significantly inhibited the LPS-stimulated iNOS expression. ESR spectroscopy showed that Rikko-san, Kanzo, Shoma and Saishin, but not Ryutan and Bofu, produced radical(s) under alkaline condition. All samples scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by 1-hydroxy-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC-7)), possibly by their general reducing activity. These data suggest that the inhibition of NO production by Chinese medicines investigated here may be the result of both the inhibition of iNOS expression and their radical scavenging activity.

The biological activities of Moxa, used as moxibustion, have not been well documented. We investigated here Moxa smoke for its tumor-specific cytotoxicity, anti-HIV activity, radical intensity and radical scavenging activity, in comparison with previously published data of Moxa extract. Moxa smoke showed slightly higher cytotoxicity against human tumor cell lines (oral squamous cell carcinoma HSC-2, HSC-3, promyelocytic leukemia HL-60) than against normal oral cells (gingival fibroblast HGF, pulp cell HPC, periodontal ligament fibroblast HPLF), yielding a tumor specificity index of 1.29. Moxa smoke dose-dependently induced internucleosomal DNA fragmentation, activation of caspases 3, 8 and 9, and slightly modified the expression of apoptosis-related proteins (Bcl-2, Bad, Bax) in HL-60 cells, but to much lesser extents than attained by positive controls (UV irradiation, actinomycin D treatment). ESR spectroscopy showed that Moxa smoke generated semiquinone-type radicals under alkaline conditions, and scavenged O2(-), hydroxyl radical, singlet oxygen and NO. All Moxa smoke preparations showed no apparent anti-HIV activity. These data demonstrate the antitumor potential of Moxa smoke.

Seven Chinese medicines were investigated for their ability to modify nitric oxide (NO) production by unstimulated and lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells, in comparison with their radical intensity and scavenging activity. LPS significantly stimulated the NO production by Raw 264.7 cells. Three Chinese medicines, Shosaiko-to, Hange-shashin-to and Sairei-to (tentatively classified as Group I), significantly reduced the extracellular concentration of NO in the LPS-stimulated cells, slightly below their cytotoxic concentrations. On the other hand, another four Chinese medicines, Byakko-ka-ninjin-to, Hochu-ekki-to, Juzen-taiho-to and Ninjin-yoei-to (tentatively classified as Group II), showed similar effects, but required higher concentrations due to the co-existence of both the inhibitors and stimulators for NO production by activated macrophages. Western blot analysis demonstrated that LPS stimulated the expression of inducible NO synthase (iNOS) at both protein and mRNA levels, and that Sairei-to reduced the LPS-induced iNOS expression more potently than did Juzen-taiho-to. ESR spectroscopy shows that Group I medicines generally produced higher amounts of radicals under alkaline condition, and scavenged superoxide (produced by hypoxanthine-xanthine oxidase reaction) and NO (produced by NOC-7, NO generator) more potently than Group II medicines. These data support the classification of Chinese medicines into two groups: Group I and Group II. The net inhibition of NO production by Group I medicines may be the summation of the radical scavenging activity and the inhibition of iNOS expression due to higher cytotoxicity. Group II medicines showed lower cytotoxicity, lower radical intensity, lower radical scavenging activity, but higher stimulation activity for NO production by macrophages than Group I, suggesting their possible application for immunopotentiation.

We investigated six endodontic agents for their ability to induce apoptosis and modify the cytotoxic activity of NaF against human squamous cell carcinoma (HSC-2) and human promyelocytic leukemia (HL-60) cell lines. Four Group I agents (Form Cresol, Cam Phenic, Eucaly Soft, GC Fuji Varnish), but not two Group II agents (Caviton, Canals-N), induced internucleosomal DNA fragmentation and activated caspases 3, 8 and 9 in HL-60 cells. Only Cam Phenic among these agents additively enhanced the cytotoxic activity of NaF in HSC-2 and HL-60 cells. Form Cresol and Cam Phenic reduced the glucose consumption at early stage, possibly due to their toxic effect. Amino acid analysis suggests that the higher cytotoxicity of Form Cresol may be derived, at least in part, from its oxidizing action.

Three hot water extracts of black tea, green tea and powdered green tea and five Chinese medicines (Shosaiko-tou, Orengedoku-tou, Goshuyu-tou, Choto-san, Keishininjinn-tou) were investigated for their ability to modify nitric oxide (NO) production by lipopolysaccharide (LPS)-stimulated mouse macrophage-like Raw 264.7 cells, and for their cytotoxicity, radical intensity and scavenging activity. All eight materials significantly reduced the extracellular concentration of NO in the LPS-stimulated Raw 264.7 cells. ESR spectroscopy shows that tea extracts, which had higher cytotoxicity, generated higher amounts of radicals, and more efficiently scavenged O2- (generated by hypoxanthine-xanthine oxidase reaction), hydroxyl radical (generated by Fenton reaction) and NO (generated by 1-hydroxyl-2-oxo-3-(N-3-methyl-3-aminopropyl)-3-methyl-1-triazene) than Chinese medicines. Close association between the radical intensity and radical scavenging activity suggests their bimodal (anti-oxidant and pro-oxidant) action. Pretreatment of mice with tea extracts significantly reduced the lethality of Escherichia coli-infection. All tea extracts showed no apparent anti-HIV activity. The present study demonstrates, for the first time, several attractive features of tea extracts in comparison with Chinese medicines, suggesting the possible application of the tea extracts for radical-mediated diseases.