Kazumi Yokomizo

Glycyrrhizin Inhibits Interleukin-8 Production and Nuclear Factor–κB Activity in Lung Epithelial Cells, but Not Through Glucocorticoid Receptors

Abstract This study was designed to examine the glucocorticoid-like inhibitory effect of glycyrrhizin (GL) on interleukin (IL)-8 production in A549 lung epithelial cells. GL, as well as dexamethasone (DEX) inhibited both tumor necrosis factor (TNF)-α –and IL-1β –induced IL-8 production, mRNA expression, and promoter activity in A549 cells. Both GL and DEX inhibited transactivation of nuclear factor (NF)-κ B, without inhibiting translocation of the NF-κ B p65 subunit to the nucleus. However, the effect of GL was insensitive to RU486, a GR antagonist, and to GR knockdown by siRNA. Furthermore, only GL inhibited DNA binding of p65 to the IL-8 promoter region. These findings indicated that GL had a glucocorticoid-like inhibitory effect on IL-8 production via a mechanism that differs from that of glucocorticoids.

A broad antiviral neutral glycolipid, fattiviracin FV-8, is a membrane fluidity modulator.

To screen for an effective antiviral compound which acts as a membrane fluidity modulator, dichotomous effects on human immunodeficiency virus type 1 (HIV‐1) infection due to different treatments of several glycolipids and lipids were examined. Continuous treatment of infected cells with 40 μg ml−1 fattiviracin FV‐8, a neutral glycolipid isolated from Streptomycetes, inhibited HIV‐1 infection by 96%, whereas pretreatment with 400 μg ml−1 enhanced infectivity 4.7‐fold. The glycolipid showed similar effects as glycyrrhizin; it inhibited infection by broad enveloped viruses, blocked cell–cell fusion, reduced the infectivity of treated virions and enhanced susceptibility to viral infection and cell–cell fusion of cells pretreated with high doses of the compound. Suppression and enhancement was correlated with decreased and increased fluidity of plasma membrane of the fattiviracin FV‐8‐treated cells. Restricted movement of membrane molecules might impede the formation of a wide fusion pore, and therefore be critical to the entry of viruses. Thus, this can be applied as a new strategy to inhibit viral infections.

HSP70 inducers from Chinese herbs and their effect on melanin production

Please cite this paper as: HSP70 inducers from Chinese herbs and their effect on melanin production. Experimental Dermatology 2010; 19: e340–e342.

Structures of phytotoxins, AV-toxins C, D and E, produced by zonate leaf spot fungus of mulberry

Abstract The structures of phytotoxins, AV-toxins C, D and E, produced by zonate leaf spot fungus of mulberry, were characterized.

Antiviral Activity of Four New Resin Glycosides Calysolins XIV-XVII from Calystegia soldanella against Herpes Simplex Virus.

Four new resin glycosides, named calysolins XIV (1), XV (2), XVI (3), and XVII (4) were isolated from the leaves, stems, and roots of Calystegia soldanella ROEM.. et SCHULT. (Convolvulaceae). Their structures were determined based on spectroscopic and chemical evidence, and consisted of two different types: those (1) with a macrolactone structure and those (2-4) with a non-macrolactone structure. Their sugar moieties were partially acylated by specific organic acids, including tiglic, 2S-methylbutyric, and 2S,3S-nilic acids. Additionally, evaluation of the antiviral activity of 1-4 revealed effects against the herpes simplex virus type 1.

Low direct cytotoxicity and cytoprotective effects of nitric oxide releasing indomethacin

Nitric oxide (NO) releasing non-steroidal anti-inflammatory drugs (NSAIDs) have shown a marked reduction of gastrointestinal side effects and we here examined the cytotoxicity of NCX 530 (NO-indomethacin). Under conditions where indomethacin clearly induced both necrosis and apoptosis, NCX 530 induced neither. NCX 530 protected cells from celecoxib-induced necrosis and apoptosis. NCX 530 partially suppressed celecoxib-dependent membrane permeabilization and an inhibitor for guanylate cyclase suppressed the cytoprotective effect of NCX 530 against celecoxib. In vivo, NCX 530 alone produced fewer gastric lesions in rats than did indomethacin. A combination of the oral administration of celecoxib together with the intraperitoneal administration of indomethacin, but not of NCX 530, clearly resulted in the production of gastric lesions. The low direct cytotoxicity and the cytoprotective effect of NCX 530 observed in vitro may also act in vivo, thus ensuring that NCX 530 is safe for use on the gastric mucosa.

Low direct cytotoxicity of nabumetone on gastric mucosal cells

Prodrugs of non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for clinical purposes because they are not harmful to the gastrointestinal mucosa. We recently showed that NSAIDs have direct cytotoxicity in NSAID-induced gastric lesions. We show here that under conditions where the NSAIDs indomethacin and celecoxib clearly induce cell death, an NSAID prodrug, nabumetone, and its active metabolite 6-methoxy-2-naphthylacetic acid (6MNA), did not have such effects. Moreover, nabumetone and 6MNA exhibited much lower membrane permeabilizing activities than did indomethacin and celecoxib. We recently reported that when an orally administered NSAID was used in combination with a low dose of intravenously administered indomethacin, the severity of gastric lesions produced in rats depended on the cytotoxicity of the orally administered NSAID. Using a similar protocol, we show here that gastric lesions were produced when the orally administered NSAID was celecoxib, but not when nabumetone was used. We thus propose that the low direct cytotoxicity of nabumetone observed in vitro is maintained in vivo, and that the use of nabumetone does not harm the gastric mucosa.

Synthesis and Antiviral Evaluation of Some C(3)-Symmetrical Trialkoxy-Substituted 1,3,5-Triazines and Their Molecular Geometry.

As one of our projects, we here report some new molecular modifications of 2,4,6-trichloro-1,3,5-triazine (TCTAZ: 1) to symmetrical 2,4,6-trialkoxy- or 2,4,6-triaryloxy-substituted 1,3,5-triazine (TAZ) molecules, as well as the results of anti-herpes simplex virus type 1 (anti-HSV-1) activity evaluation of synthesized 2,4,6-trisubstituted TAZ derivatives. Among the tested 2,4,6-trisubstituted TAZ derivatives, we reconfirmed that a C3-symmetrical TAZ derivative, 4e, shows the highest level of anti-HSV-1 activity with a good selectivity index. In this paper, we also report the results of the preparation of newly targeted TAZ derivatives and the structure-activity relationships (SARs) of these trialkoxy-substituted TAZ derivatives and related compounds. The sugar recognition properties of C3-symmetrical TAZ derivative 4e are also described.

Carbohydrate recognition of C3-symmetrical tripodal receptor-type 2,4,6-trisubstituted 1,3,5-triazine derivatives with antiviral activities

In our search for new bioactive compounds that interfere with the sugar recognition process, we have designed and synthesized C3- and Cs-symmetrical tripodal receptor-type molecules. Among the synthesized C3-symmetrical 2,4,6-trisubstituted 1,3,5-triazine (TAZ) derivatives, compounds A [2,4,6-tris(2-propoxy)-TAZ] and B [2,4,6-tris(3,4-dimethoxyphenyl)-TAZ] showed high levels of anti-HSV-1 activity. We carried out isothermal titration calorimetry on compound B·HCl in aqueous 25% 2-PrOH solution with some sugar derivatives including methyl α/β-d-galactopyranoside (MeO-α/β-Gal), methyl α/β-d-mannopyranoside (MeO-α/β-Man) and methyl α/β-d-glucopyranoside (MeO-α/β-Glc). The reactions of compound B·HCl with MeO-β-Gal and MeO-α-Man were exothermic, and the obtained thermodynamic profiles indicated that both reactions are spontaneous and that there is a considerably large enthalpic contribution (ΔH) in total Gibbs free energy change (ΔG), indicating favorable hydrogen bonding interactions. The reaction of compound B·HCl showed a thermodynamic signature different from that of the entropically driven reaction of compound A.

Tomato juice saponin, esculeoside B ameliorates mice experimental dermatitis

Background : Allergic diseases like atopic dermatitis have recently increased. A naturally occurring glycoside, Esculeoside B, has been identified as a major component in tomato juice from the can. Accordingly, the present study investigated the effects of esculeoside B on experimental dermatitis mice. Results : Oral treatment with 10 mg/kg of esculeoside B on the experimental dermatitis mice for 4 weeks significantly decreased the skin clinical score of 2.0 compared to the control score of 5.0. Furthermore, the scratch frequency of mice treated with esculeoside B was lower compared to the control group. Overall, the administration of esculeoside B significantly inhibited T lymphocyte proliferation and demonstrated a tendency to decrease in IL-4 production. For example, the 121.2 pg/ml in the control group decreased to 96.1 pg/ml. There was also a decrease in serum IgE levels from 928.0 ng/ml in the control group to 687.8 ng/ml. Conclusion : Our study is the first to demonstrate how tomato juice saponin or esculeoside B may ameliorate mice experimental dermatitis by the inhibition of T cell proliferation. Keywords : tomato juice; experimental atopic dermatitis; IgE; cytokine; tomato saponin; esculeoside B