Formation of Isolable Dearomatized [4 + 2] Cycloadducts from Benzenes, Naphthalenes, and N-Heterocycles Using 1,2-Dihydro-1,2,4,5-tetrazine-3,6-diones as Arenophiles under Visible Light Irradiation.

We report that the dearomative [4 + 2] cycloaddition between 1,2-dihydro-1,2,4,5-tetrazine-3,6-diones (TETRADs) and benzenes, naphthalenes, or N-heteroaromatic compounds under visible light irradiation affords the corresponding isolable cycloadducts. Several synthetic transformations including transition-metal-catalyzed allylic substitution reactions using the isolated cycloadducts at room temperature or above were demonstrated. Computational studies revealed that the retro-cycloaddition of the benzene-TETRAD adduct proceeds via an asynchronous concerted mechanism, while that of the benzene-MTAD adduct (MTAD = 4-methyl-1,2,4-triazoline-3,5-dione) proceeds via a synchronous mechanism.

A trial study of propranolol and Zhigancao decoction on the central depressant and anti-osteoporosic action in ovariectomized rats.

OBJECTIVE: This study was originally designed to observe the effects of propranolol (a beta-blocker) and Zhigancao Decoction ([Chinese characters: see test] ZGCD) on bone mass in ovariectomized rats. METHODS: Thirty-eight female Sprague-Dawley rats were divided into four groups initially, a sham-operated group (Sham, n=7), a model ovariectomized (OVX) group (Model, n=7), a propranolol group (Pro, n=12) and a ZGCD group (ZGCD, n=12). After 15 weeks of treatment, the expected effects were not found. In order to verify the situations of the experiment, we modified the study by administering calcitonin to a subgroup of the tested Pro and ZGCD rats. RESULTS: The Pro and ZGCD treatments showed decreased heart rate and plasma norepinephrine level, but neither an increased bone mass nor any bone metabolism differences from the model rats were found. However, the OVX-induced bone loss was prevented by the sequent treatment of calcitonin. CONCLUSIONS: The results provide no evidence that the beta-blocker propranolol may stimulate bone formation, and do not justify its use for clinical treatment of osteoporosis.

1-Aminocyclopropanecarboxylic acid, an antagonist of N-methyl-D-aspartate receptors, causes hypotensive and antioxidant effects with upregulation of heme oxygenase-1 in stroke-prone spontaneously hypertensive rats.

1-Aminocyclopropanecarboxylic acid (ACPC) has been shown to protect neurons against glutamate-induced neurotoxicity by reducing N-methyl-D-aspartate (NMDA) receptor activation. Recent studies have demonstrated that several antagonists of NMDA receptors have important cardiovascular effects. In this study, we examined whether the cardiovascular effects of ACPC involve the role of heme oxygenase-1 (HO-1) and its antioxidant effect in stroke-prone spontaneously hypertensive rats (SHRSP). Male SHRSP were divided into two groups: a control group and an ACPC group administered ACPC at 50 mg/kg per day for 4 weeks by peritoneal injection. Systolic blood pressure (SBP) and mortality of stroke were significantly lower in the ACPC group than in the control group. Urinary Na(+) and Cl(-) excretion and plasma superoxide dismutase (SOD) activity were increased in the ACPC group. Western analysis detected proteins that were immunoreactive to anti-nitrotyrosine antibody and showed lower levels of expression in the cerebral cortex compared to that in the control group. Immunohistochemical analysis revealed that 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation in the hippocampus and cerebral cortex was reduced in the ACPC group. Quantitative reverse-transcription-polymerase chain reaction (RT-PCR) showed that administration of ACPC also significantly decreased the expression of neuronal nitric oxide synthase (nNOS) mRNA in the hippocampus and endotherial nitric oxide synthase (eNOS) mRNA in the cerebral cortex, and drastically increased HO-1 mRNA in the cerebral cortex. Enhanced HO-1 staining on sections from the hippocampus and cerebral cortex was observed in the ACPC group. These data suggest that the normalization by ACPC of blood pressure elevation and mortality of stroke involves induction of the expression of HO-1, which exerts antioxidant and vascular relaxation effects, in SHRSP.