Evaluation of the potential hypoglycemic and Beta-cell protective constituents isolated from Corni fructus to tackle insulin-dependent diabetes mellitus.

Corni fructus is the fruit of Cornus officinalis Sieb. et Zucc. and has attracted much interest due to its traditional applications and active fraction that reportedly possesses antidiabetic effects. In this study, we isolated 12 compounds from Corni fructus including three flavonoids, two iridoid glycosides, three phenolic compounds, and two triterpenoids, together with cornuside (11) and 2-butoxybutanedioic acid (12). Chemical structures were identified by (1)H, (13)C NMR, DEPT, COSY, HSQC, and HMBC spectral analyses. Furthermore, the glucose uptake efficiency, messenger (m)RNA expression of phosphoenolpyruvate carboxykinase (PEPCK), and prevention of cytokine-mediated cytotoxicity in the presence of test agents were evaluated. While CH and CB significantly increased glucose uptake from muscle, compounds 3 and 8, each at 50 µM, significantly suppressed PEPCK mRNA expression. Finally, compound 5, at 50 and 100 µM, effectively attenuated ß-cell death. In conclusion, those compounds could contribute to the antihyperglycemic and ß-cell-protective actions of Corni fructus against diabetes mellitus.

Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats.

The antihyperglycemic effect of catalpol (1) purified from the roots of Rehmannia glutinosa was investigated in streptozotocin-induced diabetic rats (STZ-diabetic rats) representing insulin-dependent diabetes mellitus. Bolus intravenous injection of 1 showed antihyperglycemic activity in a dose-dependent manner in STZ-diabetic rats. An effective dose of 0.1 mg/kg 1 significantly attenuated the increase of plasma glucose induced by an intravenous glucose challenge test in normal rats. Catalpol enhanced the uptake of radioactive glucose in the isolated soleus muscle of STZ-diabetic rats in a concentration-related manner. Moreover, an effect by 1 was established on glycogen incorporation in hepatocytes isolated from STZ-diabetic rats. Catalpol was found to increase glycogen synthesis in STZ-diabetic rats. These results suggest that 1 can increase glucose utilization to lower plasma glucose in diabetic rats lacking insulin.

Synthesis of N-hydroxycinnamides capped with a naturally occurring moiety as inhibitors of histone deacetylase.

Histone deacetylase (HDAC) inhibitors are regarded as promising therapeutics for the treatment of cancer. All reported HDAC inhibitors contain three pharmacophoric features: a zinc-chelating group, a hydrophobic linker, and a hydrophobic cap for surface recognition. In this study we investigated the effectiveness of osthole, a hydrophobic Chinese herbal compound, as the surface recognition cap in hydroxamate-based compounds as inhibitors of HDAC. Nine novel osthole-based N-hydroxycinnamides were synthesized and screened for enzyme inhibition activity. Compounds 9 d, 9 e, 9 g exhibited inhibitory activities (IC(50)=24.5, 20.0, 19.6 nM) against nuclear HDACs in HeLa cells comparable to that of suberoylanilide hydroxamic acid (SAHA; IC(50)=24.5 nM), a potent inhibitor clinically used for the treatment of cutaneous T-cell lymphoma (CTCL). While compounds 9 d and 9 e showed SAHA-like activity towards HDAC1 and HDAC6, compound 9 g was more selective for HDAC1. Compound 9 d exhibited the best cellular effect, which was comparable to that of SAHA, of enhancing acetylation of either alpha-tubulin or histone H3. Molecular docking analysis showed that the osthole moiety of compound 9 d may interact with the same hydrophobic surface pocket exploited by SAHA and it may be modified to provide class-specific selectivity. These results suggest that osthole is an effective hydrophobic cap when incorporated into N-hydroxycinnamide-derived HDAC inhibitors.

Fungichromin: a substance from Streptomyces padanus with inhibitory effects on Rhizoctonia solani.

Streptomyces padanus strain PMS-702 is an antagonist of Rhizoctonia solani AG-4, the causal agent of damping-off of cabbage. Treatment of cabbage seeds with the culture filtrate of S. padanus strain PMS-702 was effective in reducing the incidence of damping-off of cabbage. The major active ingredient from the culture filtrate of S. padanus strain PMS-702 was purified by silica gel column chromatography and identified as the polyene macrolide, fungichromin, by NMR and mass spectral data. Bioassay studies showed that fungichromin had a strong antifungal activity against R. solani AG-4, and its minimum inhibitory concentration (over 90% inhibition) was found to be 72 microg/mL. This is the first report of fungichromin from S. padanus as an active ingredient for the control of Rhizoctonia damping-off of cabbage.

Antitumor agents. Part 3: synthesis and cytotoxicity of new trans-stilbene benzenesulfonamide derivatives.

A new series of trans-stilbene benzenesulfonamide derivatives were designed and synthesized as potential antitumor agents. These new compounds were evaluated in the National Cancer Institute's 60 human tumor cell line in vitro screen. Compounds 9-13 were cytotoxic against several cell lines. Notably, two compounds, 9 and 12, demonstrated selective cytotoxic activity against BT-549 breast cancer (GI(50)=0.205 microM) and HT-29 colon cancer (GI(50)=0.554 microM), respectively.