Jian-Rong Zhou

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.

Direct Potentiation of Capsaicin Current by Histamine and Its Effect by Suplatast on Rat Trigeminal Ganglia Neurons

In this study, we investigated the effect of histamine on capsaicin-induced current and its influence by suplatast in rat trigeminal ganglia neurons using a patch-clamp technique. We found that histamine directly potentiated capsaicin-induced currents in rat sensory neurons, and suplatast had little effect on this potentiation. Since it has been known that suplatast suppresses histamine release from mast cells, it is possible that suplatast inhibits the activation of nociceptive fibers in the pathological condition via prevention of histamine-induced potentiation of the transient receptor potential vanilloid 1 receptor-mediated currents.

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

Preparation and Antiviral Activity of Some New C3- and CS-Symmetrical Tri-Substituted Triazine Derivatives Having Benzylamine Substituents

We report the preparation of new C3- and CS-symmetrical molecules constructed on a triazine (TAZ) template. Anti-herpes simplex virus type 1 (anti-HSV-1) and cytotoxic activities against Vero cells of synthesized TAZ derivatives were evaluated. The results suggested that the presence of an electron-donating group(s) on the benzene ring in benzylamine groups on the TAZ template is an important structural factor for expressing a high level of anti-HSV-1 activity and low cytotoxicity for these C3 types of TAZ derivatives. Among the tested TAZ derivatives, compounds 4f and 7h showed the highest anti HSV-1 activities (EC50=0.98 and 1.23 µM, respectively) and low cytotoxic activities to Vero cells (50% cytotoxic concentration (CC50)=292.2 and >200 µM, respectively).

Anti-hyaluronidase Activity in Vitro and Amelioration of Mouse Experimental Dermatitis by Tomato Saponin, Esculeoside A.

The increasing incidence of atopic dermatitis during recent decades has prompted the development of safe and effective agents for prevention of atopic diseases. Esculeoside A, a glycoside of spirosolane type, is identified as a major component in ripe tomato fruits. The present study investigated the effects of esculeoside A and its aglycon esculeogenin A on hyaluronidase activity in vitro and antiallergy in experimental dermatitis mice. Esculeogenin A/esculeoside A (esculeogenin A equivalent) with an IC50 of about 2 μM/9 μM dose-dependently inhibited hyaluronidase activity measured by a modified Morgan-Elson method. Oral treatment with esculeoside A 10 mg/kg of experimental dermatitis mice for 4 weeks significantly decreased the skin clinical score to 2.5 without any detectable side effects compared with 6.75 of the control. The scratching frequency of esculeoside A 100 mg/kg application was decreased significantly as 107.5 times compared with 296.67 times of the control. Thus, the present study showed that esculeoside A/esculeogenin A significantly blocks hyaluronidase activity in vitro and that esculeoside A ameliorates mouse experimental dermatitis.

Effects of lycium and lycium-composed formula on the peripheral coldness induced by local cooling in mice

Recently people appealing for peripheral coldness increase. Lycium fruits have a long tradition of use in nutrition and traditional medicine in East Asia, while its effect on peripheral coldness is not yet investigated. We study the effects of lycium and lycium-rich formula (Ligustrum lucidum ait, LLA) on the peripheral coldness induced by local cooling in mice. 7-week old male ddY mice were administered either water (control) or lycium or LLA for 2 weeks. After an aesthesia, the mouse body except for head was immersed into 10 ℃ water for 10 min. Then the skin surface and rectal temperature of mouse were measured with a thermocamera and a thermocouple thermometer, respectively. And two laser Doppler flow probes were set to measure the skin blood flow of plantar and tail, respectively. In the case of 1-week administration on mice, 10% lycium- and 10% LLA-treatments showed good recovery of whole body surface temperature measured by a thermocamera. After 2-week administration on mice, there were not significant differences in the recovery rates of rectal temperature compared with those of the control group. And the 30 min- and 50 min-recovery rates of dorsal skin surface temperature by 1% and 10% lycium-treatment were significantly higher than those of the respective control. Further, the 30 min- and 50 min-plantar skin blood flow by 10% LLA-treatment were significantly higher than those of the respective control. The 50 min-tail skin blood flow by 10% LLA-treatment and 60 min-tail skin blood flow by 1% LLA-treatment were significantly higher than those of the control, respectively. It can be concluded that the administration of lycium or LLA on mouse led to an increase of peripheral blood blow, and thus a recovery of skin surface temperature.

New spirostanol glycosides from Solanum nigrum and S. jasminoides

A new characteristic steroidal glycoside possessing a hydroxyl group at C-23, inunigroside A (1), was isolated from the withered berries of Solanumnigrum L. On the basis of spectroscopic analysis, the structure of 1 was characterized as (5α,22S,23S,25R)-3β,23-dihydroxyspirostane 3-O-β-lycotetraoside. Next, a major steroidal sapogenol, (22R, 25S)-3β,15α-dihydroxy-spirost-5-ene (3), was obtained from the acid hydrolysate of the methanolic extract of the aerial parts of Solanum jasminoides L. A new bisdesmoside, 3-O-β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranosyl (22R,25S)-3β,15α-dihydroxyspirost-5-ene 15-O-α-l-rhamnopyranoside (4), named jasminoside A, was isolated from the methanolic extract of S. jasminoides.