Anti-stress effects of combined block of glucocorticoid and mineralocorticoid receptors in the paraventricular nucleus of the hypothalamus.

BACKGROUND AND PURPOSE: Mineralocorticoid receptors (MRs), glucocorticoid receptors (GRs) and corticotropin-releasing factor (CRF) in the paraventricular nucleus of hypothalamus (PVN) are involved in the response to stress. The present study investigated the role of GRs and MRs in the PVN in regulating depressive and anxiety-like behaviours. EXPERIMENTAL APPROACH: To model chronic stress, rats were exposed to corticosterone treatment via drinking water for 21 days, and GR antagonist RU486 and MR antagonist spironolactone, alone and combined, were directly injected in the PVN daily for the last 7 days of corticosterone treatment. Behavioural tests were run on days 22 and 23. Depressive- and anxiety-like behaviours were evaluated in forced swim test, sucrose preference test, novelty-suppressed feeding test and social interaction test. The expression of GRs, MRs and CRF were detected by western blot. KEY RESULTS: Rats exposed to corticosterone exhibited depressive- and anxiety-like behaviours. The expression of GRs and MRs decreased, and CRF levels increased in the PVN. The intra-PVN administration of RU486 increased the levels of GRs and CRF without influencing depressive- or anxiety-like behaviours. The spironolactone-treated group exhibited an increase in MRs without influencing GRs and CRF in the PVN and improved anxiety-like behaviours. Interestingly, the intra-PVN administration of RU486 and spironolactone combined restored expression of GRs, MRs and CRF and improved depressive- and anxiety-like behaviours. CONCLUSION AND IMPLICATIONS: In this rat model of stress, the simultaneous restoration of GRs, MRs and CRF in the PVN might play an important role in the treatment of depression and anxiety.

Prophylactic effects of sporoderm-removed Ganoderma lucidum spores in a rat model of streptozotocin-induced sporadic Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (G. lucidum, Lingzhi), also known as "immortality mushroom" has been broadly used to improve health and longevity for thousands of years in Asia. G. lucidum and its spores have been used to promote health, based on its broad pharmacological and therapeutic activity. This species is recorded in Chinese traditional formula as a nootropic and has been suggested to improve cognitive dysfunction in Alzheimer's disease. However, little is known about the nootropic effects and molecular mechanism of action of G. lucidum spores. AIM OF THE STUDY: The present study investigated the protective effects of sporoderm-deficient Ganoderma lucidum spores (RGLS) against learning and memory impairments and its mechanism of action. MATERIALS AND METHODS: In the Morris water maze, the effects of RGLS on learning and memory impairments were evaluated in a rat model of sporadic Alzheimer's disease that was induced by an intracerebroventricular injection of streptozotocin (STZ). Changes in amyloid ß (Aß) expression, Tau expression and phosphorylation, brain-derived neurotrophic factor (BDNF), and the BDNF receptor tropomyosin-related kinase B (TrkB) in the hippocampus were evaluated by Western blot. RESULTS: Treatment with RGLS (360 and 720 mg/kg) significantly enhanced memory in the rat model of STZ-induced sporadic Alzheimer's disease and reversed the STZ-induced increases in Aß expression and Tau protein expression and phosphorylation at Ser199, Ser202, and Ser396. The STZ-induced decreases in neurotrophic factors, including BDNF, TrkB and TrkB phosphorylation at Tyr816, were reversed by treatment with RGLS. CONCLUSION: These findings indicate that RGLS prevented learning and memory impairments in the present rat model of STZ-induced sporadic Alzheimer's disease, and these effects depended on a decrease in Aß expression and Tau hyperphosphorylation and the modulation of BDNF-TrkB signaling in the hippocampus.

Tenuifolin, a saponin derived from Radix Polygalae, exhibits sleep-enhancing effects in mice.

BACKGROUND: Radix Polygalae, the dried root of Polygala tenuifolia, has been extensively used as a traditional Chinese medicine for promoting intelligence and tranquilization. Polygalasaponins extracted from the root of P. tenuifolia possess evident anxiolytic and sedative-hypnotic activities. Previous studies have reported that tenuifolin was a major constituent of polygalasaponins. PURPOSE: The currently study aims to investigate the hypnotic effect and possible mechanism of tenuifolin in freely moving mice. DESIGN/METHODS: The hypnotic effects of tenuifolin (20, 40 and 80mg/kg, p.o.) were assessed by electroencephalographic (EEG) and electromyographic (EMG) analysis. Double-staining immunohistochemistry test was performed to evaluate the neuronal activity of sleep-wake regulating brain areas. High performance liquid chromatograph- electrochemical detection (HPLC-ECD) and ultrafast liquid chromatography-mass spectrometry (UFLC-MS) were used for the detection of neurotransmitters. Locomotor activity was measured by Open-field Test. RESULTS: Tenuifolin at doses of 40 and 80mg/kg (p.o.) significantly prolonged the total sleep time by increasing the amount of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep, associated with the significant increase in the bouts of episodes respectively. After administration of tenuifolin, the cortical EEG power spectral densities during NREM and REM sleep were similar to that of natural sleep (vehicle) and thus compatible with physiological sleep. Double-immunohistochemistry staining test showed that tenuifolin increased the c-Fos positive ratios of GABAergic NREM sleep-promoting neurons in ventrolateral preoptic area (VLPO), cholinergic REM sleep-promoting neurons in laterodorsal tegmental area (LDT) and pontomesencephalic tegmental area (PPT) and decreased the c-Fos positive ratios in wake-promoting neurons (locus coeruleus (LC) and perifornical area (Pef)). Neurotransmitter detections revealed that tenuifolin significantly reduced the noradrenaline (NA) levels in LC, VLPO, PPT and LDT, elevated the GABA levels in VLPO, LC and Pef and increased the acetylcholine (Ach) levels in LDT and PPT. In addition, tenuifolin did not cause any change to locomotor activity. CONCLUSION: Taken together, these results provide the first experimental evidence of the significant sleep-enhancing effect of tenuifolin in mice. This effect appears to be mediated, at least in part, by the activation of GABAergic systems and/or by the inhibition of noradrenergic systems. Moreover, this study adds new scientific evidence and highlights the therapeutic potential of the medicinal plant P. tenuifolia in the development of phytomedicines with hypnotic properties.

Tetrandrine, an alkaloid from S. tetrandra exhibits anti-hypertensive and sleep-enhancing effects in SHR via different mechanisms.

BACKGROUND: Sleep disorders have been found to be associated with hypertension in both cross-sectional and longitudinal epidemiological studies. Tetrandrine, a major component of Stephania tetrandra, is well known as an antihypertensive agent. The anti-hypertension mechanism mainly relies on its L-type calcium channel blocking property. In the previous study, tetrandrine revealed both anti-hypertension and hypnotic effects in spontaneously hypertensive rats (SHRs). PURPOSE: This study aims to elucidate whether the antihypertensive mechanism of tetrandrine in SHRs is relevant to its hypnotic effect. DESIGN/METHODS: Sleep-wake behavior of the SHRs was detected by electroencephalography (EEG) and electromyography (EMG) recordings. Blood pressure was measured by noninvasive blood pressure tail cuff test. Immunohistochemistry was performed to evaluate the noradrenergic neuronal activity. The level of norepinephrine (NE) was detected by HPLC-ECD. RESULTS: Amlodipine (100mg/kg, i.g.), the well-known L-type Ca2+ channel blockers (CCBs) exhibited remarkable antihypertensive activities in SHRs, but did not show effects on sleep of SHRs. Tetrandrine (30 and 60mg/kg/day, i.g.) significantly suppressed blood pressure of SHRs. Meanwhile, tetrandrine (60mg/kg/day, i.g.) remarkably increased non-rapid eye movement sleep (NREMS) time, bouts and mean duration. The hypnotic effect of tetrandrine was potentiated by prazosin (0.5mg/kg, i.p.) but attenuated by yohimbine (2mg/kg, i.p.). Administration of tetrandrine (60mg/kg/day, i.g.) not only significantly decreased c-Fos positive ratio of noradrenergic neurons in the locus coeruleus (LC), but also significantly decrease NE in the endogenous sleep-wake regulating pathways including LC, hypothalamus and ventrolateral preoptic nucleus (VLPO). CONCLUSION: In spite of a good potency in blocking L-type Ca2+ channel, the hypnotic effects of tetrandrine may be related to its suppressing effects on the noradrenergic system other than to block calcium channels. As a multi-targets drug, tetrandrine might be favorable to the hypertension patients who suffered poor sleep.

Phosphorylation of CaMKII in the rat dorsal raphe nucleus plays an important role in sleep-wake regulation.

The Ca(2+) modulation in the dorsal raphe nucleus (DRN) plays an important role in sleep-wake regulation. Calmodulin-dependent kinase II (CaMKII) is an important signal-transducing molecule that is activated by Ca(2+) . This study investigated the effects of intracellular Ca(2+) /CaMKII signaling in the DRN on sleep-wake states in rats. Maximum and minimum CaMKII phosphorylation was detected at Zeitgeber time 21 (ZT 21; wakefulness state) and ZT 3 (sleep state), respectively, across the light-dark rhythm in the DRN in rats. Six-hour sleep deprivation significantly reduced CaMKII phosphorylation in the DRN. Microinjection of the CAMKII activation inhibitor KN-93 (5 or 10 nmol) into the DRN suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REM sleep (NREMS). Application of a high dose of KN-93 (10 nmol) increased slow-wave sleep (SWS) time, SWS bouts, the mean duration of SWS, the percentage of SWS relative to total sleep, and delta power density during NREMS. Microinjection of CaCl2 (50 nmol) in the DRN increased CaMKII phosphorylation and decreased NREMS, SWS, and REMS. KN-93 abolished the inhibitory effects of CaCl2 on NREMS, SWS, and REMS. These data indicate a novel wake-promoting and sleep-suppressing role for the Ca(2+) /CaMKII signaling pathway in DRN neurons. We propose that the intracellular Ca(2+) /CaMKII signaling in the dorsal raphe nucleus (DRN) plays wake-promoting and sleep-suppressing role in rats. Intra-DRN application of KN-93 (CaMKII activation inhibitor) suppressed wakefulness and enhanced rapid-eye-movement sleep (REMS) and non-REMS (NREMS). Intra-DRN application of CaCl2 attenuated REMS and NREMS. We think these findings should provide a novel cellular and molecular mechanism of sleep-wake regulation.

Glucocorticoid receptors in the locus coeruleus mediate sleep disorders caused by repeated corticosterone treatment.

Stress induced constant increase of cortisol level may lead to sleep disorder, but the mechanism remains unclear. Here we described a novel model to investigate stress mimicked sleep disorders induced by repetitive administration of corticosterone (CORT). After 7 days treatment of CORT, rats showed significant sleep disturbance, meanwhile, the glucocorticoid receptor (GR) level was notably lowered in locus coeruleus (LC). We further discovered the activation of noradrenergic neuron in LC, the suppression of GABAergic neuron in ventrolateral preoptic area (VLPO), the remarkable elevation of norepinephrine in LC, VLPO and hypothalamus, as well as increase of tyrosine hydroxylase in LC and decrease of glutamic acid decarboxylase in VLPO after CORT treatment. Microinjection of GR antagonist RU486 into LC reversed the CORT-induced sleep changes. These results suggest that GR in LC may play a key role in stress-related sleep disorders and support the hypothesis that repeated CORT treatment may decrease GR levels and induce the activation of noradrenergic neurons in LC, consequently inhibit GABAergic neurons in VLPO and result in sleep disorders. Our findings provide novel insights into the effect of stress-inducing agent CORT on sleep and GRs' role in sleep regulation.

Tetrandrine, an antihypertensive alkaloid, improves the sleep state of spontaneously hypertensive rats (SHRs).

ETHNOPHARMACOLOGICAL RELEVANCE: Radix of Stephania tetrandrae S. Moore has been used since antiquity in China as an antirheumatic, antihypertension, analgesic and antipyretic agent. Tetrandrine is the major component of Stephania tetrandrae. This study aims to evaluate the antihypertensive and hypnotic effect of tetrandrine on spontaneously hypertensive rats (SHR) and the possible mechanisms. MATERIALS AND METHODS: Electroencephalography (EEG) and electromyography (EMG) were recorded in freely moving rats and the sleep parameters were analyzed with SleepSign software. The levels of serotonin (5-HT), norepinephrine (NE), dopamine (DA) and their metabolites were examined to investigate the underlying mechanisms by using HPLC-ECD. Blood pressure was measured by noninvasive blood pressure tail cuff test. RESULTS: Tetrandrine (100mg/kg, i.g.) significantly suppressed blood pressure of SHR rats day by day during three days treatment. Meanwhile, tetrandrine remarkably improved the sleep efficiency by increasing total sleep time, rapid eye movement (REM) sleep and non-REM (NREM) sleep (including deep sleep and light sleep) time from the first day. Three days treatment of tetrandrine induced 5-HT concentration decrease in DRN, 5-HIAA concentration increase in LC and 5-HIAA/5-HT ratio increase in VTA and LC. In contrast, no changes in NE and DA concentrations in the DRN, VTA and LC occurred in SHR after tetrandrine treatment. These results indicate that modulation of 5-HT, its metabolite 5-HIAA and the 5-HIAA/5-HT ratio in DRN, VTA and LC are likely the mechanism of antihypertensive and hypnotic effects of tetrandrine at least in part. CONCLUSION: This is the first observation that tetrandrine possesses both anti-hypertension and hypnotic effects in SHR and suggested that tetrandrine may be useful for the treatment of hypertension patients who accompanied with short sleep time and poor sleep efficiency.

Extract of Ganoderma lucidum prolongs sleep time in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ganoderma lucidum (Ling Zhi) is a basidiomycete white-rot macrofungus that has been used as a tranquilizing agent (i.e., An-Shen effect) for the treatment of restlessness, insomnia, and palpitation in China for hundreds of years. AIM OF THE STUDY: The present study aimed to investigate whether Ganoderma lucidum extract (GLE) influences the sleep of freely moving rats and the potential mechanism. MATERIALS AND METHODS: Ganoderma lucidum extract was extracted from fruiting bodies of Ganoderma lucidum. Rats were treated with GLE orally for 3 days, and on the third day, electroencephalographic and electromyographic recordings were made for 6h from 9:00 p.m. to 3:00 a.m. in freely moving rats. Sleep parameters were analyzed using SleepSign software. Tumor necrosis factor-α (TNF-α) levels were measured using the enzyme-linked immunosorbent assay. RESULTS: Three-day administration of GLE significantly increased total sleep time and non-rapid eye movement (NREM) sleep time at a dose of 80 mg/kg (i.g.) without influencing slow-wave sleep or REM sleep in freely moving rats. TNF-α levels were significantly increased concomitantly in serum, the hypothalamus, and dorsal raphe nucleus. The hypnotic effect of GLE (80 mg/kg, i.g.) was significantly inhibited by intracerebroventricular injection of TNF-α antibody (2.5 µg/rat). Co-administration of GLE (40 mg/kg, i.g.) and TNF-α (12.5 ng/rat, i.c.v.), both at ineffective doses, revealed an additive hypnotic effect. CONCLUSION: These results suggest that GLE has hypnotic effects in freely moving rats. The mechanism by which the extract promoted sleep remains unclear, but this effect appears to be primarily related to the modulation of cytokines such as TNF-α. Furthermore, these data at least partially support the ethnomedical use of Ganoderma lucidum.

Diltiazem potentiates pentobarbital-induced hypnosis via 5-HT1A and 5-HT2A/2C receptors: role for dorsal raphe nucleus.

It has been reported that the sedative component of pentobarbital is mediated by GABA receptors in an endogenous sleep pathway and the ventrolateral preoptic area (VLPO)-tuberomammillary nucleus (TMN) or VLPO-dorsal raphe nucleus (DRN) neural circuit is important in the sedative response to pentobarbital. Our previous findings indicated that the VLPO-TMN neuronal circuit may play crucial part in the augmentative effect of diltiazem on pentobarbital sleep and the serotonergic system may be involved. This study was designed to investigate the role of DRN and the serotonergic receptors 5-HT(1A) and 5-HT(2A/2C) in the augmentative effect of diltiazem on pentobarbital-induced hypnosis in rats. The results showed that diltiazem (5mg/kg, i.g.) significantly reversed pentobarbital-induced (35 mg/kg, i.p.) reduction of c-Fos expression in 5-HT neurons of DRNV (at -7.5mm Bregma), DRND, DRNVL and MRN (at -8.0mm Bregma). However it did not influence this reducing effect of pentobarbital on non-5-HT neurons either in DRN or in MRN. Moreover, the effect of diltiazem (1 or 2mg/kg, i.g.) on pentobarbital-induced (35 mg/kg, i.p.) hypnosis was significantly inhibited by 5-HT(1A) agonist 8-OH-DPAT (0.5mg/kg, i.p.) and 5-HT(2A/2C) agonist DOI (0.5mg/kg, i.p.), and potentiated by 5-HT(1A) antagonist p-MPPI (2mg/kg, i.p.) and 5-HT(2A/2C) antagonist ritanserin (2mg/kg, i.p.), respectively. From these results, it should be presumed that the augmentative effect of diltiazem on pentobarbital-induced sleep may be related to 5-HT(1A) and 5-HT(2A/2C) receptors, and DRN may be involved. In addition, it also suggested that the DRN may play a multi-modulating role in sleep-wake regulation rather than being recognized simply as arousal nuclei.

Ca²+ modulation in dorsal raphe plays an important role in NREM and REM sleep regulation during pentobarbital hypnosis.

Our previous studies indicated that L-type calcium channel blocker diltiazem could potentiate pentobarbital-induced hypnosis through serotonergic system. In view of the important role of dorsal raphe nucleus (DRN) on the sleep regulation and the pharmacological actions of calcium channel blocker, we presumed that Ca(2+) in the DRN may play an important role in sleep regulation in pentobarbital treated rats. Therefore, we investigated whether the Ca(2+) modulation in DRN by the microinjection of L-type Ca(2+) channel antagonist diltiazem, agonist BAY-K-8644, Ca(2+) chelator EGTA and CaCl(2) would alter the sleep parameters in pentobarbital treated rats. Results showed that perfusion of the agents attenuating Ca(2+) function, such as diltiazem (5 or 20 nmol) or EGTA (3 or 6 pmol) into DRN significantly increased pentobarbital (35 mg/kg, i.p.)-induced total sleep (TS), non-rapid eye movement (NREM) sleep and the slow wave sleep (SWS) ratio in NREM sleep. On the contrary, the DRN injection of the agents improving Ca(2+) function, such as BAY-K-8644 (10 nmol) or CaCl(2) (50 or 100 nmol) significantly reduced pentobarbital (35 mg/kg, i.p.)-induced TS, NREM sleep, rapid eye movement (REM) sleep and REM sleep ratio in TS without influence on SWS. These results suggested that the suppression of Ca(2+) function in DRN could increase NREM sleep including SWS, and the elevation of Ca(2+) function could reduce both NREM and REM sleep in pentobarbital treated rats.

Hypnotic effect of jujubosides from Semen Ziziphi Spinosae.

ETHNOPHARMACOLOGICAL SIGNIFICANCE: Semen Ziziphi Spinosae, the seed of Ziziphus jujuba Mill. var. spinosa (bunge) Hu ex H.F. Chow has been widely used in treating insomnia and anxiety. AIM OF THE STUDY: In this study, we investigated the hypnotic effect of jujubosides, one of the major components (saponin) of Semen Ziziphi Spinosae, in both day and night period. MATERIALS AND METHODS: After the administration of jujubosides (9 mg/kg once per day for 3 days), sleep parameters were examined by EEG and EMG analysis in normal rats and the action of jujubosides on pentobarbital-induced sleep assessed by the loss-of righting reflex. RESULTS: During daytime (9:00-15:00), jujubosides significantly increased the total sleep and rapid eye movement (REM) sleep without significant influence on non-REM (NREM) sleep. During nighttime (21:00-3:00), jujubosides significantly increased the total sleep and NREM sleep especially the light sleep while showed no significant effect on REM sleep and slow wave sleep (SWS). In pentobarbital-treated mice, jujubosides significantly augmented the hypnotic effect of pentobarbital (45 mg/kg, i.p.), proved by increasing sleep time and this augmentative effect was potentiated by 5-hydroxytryptophan (2mg/kg, i.p.). Furthermore, jujubosides inhibited the para-chlorophenylalanine-induced suppression of pentobarbital-induced hypnosis. CONCLUSIONS: These results suggested that the hypnotic effect of jujubosides on normal rats may be influenced by circadian rhythm and the serotonergic system may involve in the hypnotic effect of jujubosides. Jujubosides may be good source of lead compounds for novel hypnotics.

Potentiating effect of diltiazem on pentobarbital-induced hypnosis is augmented by serotonergic system: the TMN and VLPO as key elements in the pathway.

To investigate the mechanism by which L-type Ca+ channel blockers exerted potentiating effects on pentobarbital-induced hypnosis, the present study was undertaken to determine if the interaction of diltiazem and serotonergic system influences the architecture of pentobarbital sleep in rats and examined c-Fos expression in the ventrolateral preoptic nucleus (VLPO) and the tuberomammillary nucleus (TMN). The polysomnogram consisting of EEG and EMG was recorded for analyzing sleep architecture. The results showed that diltiazem (2.0 and 5.0 mg/kg, p.o.) increased both total pentobarbital sleep and slow wave sleep (SWS), but decreased rapid eye movement (REM) sleep. These effects were potentiated by 5-hydroxytryptophan (5-HTP), a precursor of serotonin, but abolished by p-chlorophenylalanine (PCPA), an inhibitor of tryptophan hydroxylase. Diltiazem (1 mg/kg, p.o.) or 5-HTP (2 mg/kg, i.p.) alone did not change the architecture of pentobarbital sleep and pentobarbital-induced c-Fos expression in the VLPO and the TMN, but co-administration of them significantly increased both total pentobarbital sleep and SWS, whereas decreased REM sleep, with increasing c-Fos expression in the VLPO and concomitantly decreasing c-Fos expression in the TMN. These findings indicate that the serotonergic system may be involved in the augmentative effect of diltiazem on pentobarbital sleep and the VLPO-TMN neuronal circuit may play a key role.

Extract of Ganoderma lucidum potentiates pentobarbital-induced sleep via a GABAergic mechanism.

Ganoderma lucidum has been used for the treatment of a variety of diseases. For the first time here we report a detailed study on the mechanisms and effects of G. lucidum aqueous extract (GLE) on sleep and its sedative activity. GLE showed no effects on sleep architecture in normal rats at doses of 80 and 120 mg/kg. However, GLE significantly decreased sleep latency, increased sleeping time, non-REM sleep time and light sleep time in pentobarbital-treated rats. Suppression of locomotor activity in normal mice induced by GLE was also observed. Flumazenil, a benzodiazepine receptor antagonist, at a dose of 3.5 mg/kg showed a significant antagonistic effect on the shortening in sleep latency, increase in sleeping time, non-REM sleep time or light sleep time in pentobarbital-treated rat induced by GLE. Significant effect was also observed with GLE on delta activity during non-REM sleep and flumazenil did not block this effect. In conclusion, GLE may be a herb having benzodiazepine-like hypnotic activity at least in part.

[Selective reduction of NO over indium catalysts prepared by different methods].

Alumina-supported indium catalysts with different metal loadings were prepared by various methods including impregnation, co-precipitation and sol-gel. Activity tests were carried out on the selective catalytic reduction (SCR) of NO by propene in excess O2 over the catalysts. And the effects of oxygen concentration in reaction gas feed on catalytic activities were examined. The results show that In/Al2O3 catalysts possess high deNO2 activity, and the preparation methods have obvious effects on catalytic activities. The catalysts prepared by co-precipitation or sol-gel method exhibited high NO, conversion to N2 about 90%; the impregnation samples have poor activities, the highest conversion rate not exceeding 60%. The O2 concentration in gas feed has significant effects on the highest conversion rates of NOx reduction and the corresponding reaction temperatures. Along with the increasing of O2 concentration, the temperatures mentioned above declined. The introduction of water into the gas feed depressed greatly the deNO2 activities of In/Al2O3 catalysts. Compared to many other metals as active components of deNOx catalysts, indium has a prominent different behavior that the respective best metal loadings of the catalysts prepared by these three diverse preparation methods have little difference, being all around 1% to approximately 2%.

Antioxidative and acute antiinflammatory effects of Torreya grandis.

The present study was undertaken to investigate the antioxidative and antiinflammatory activities of the ethanolic extract of seeds of Torreya grandis (EST). Exposure of human dermal fibroblasts to the extract at 50 and 250 microg/ml showed significant protective effect against hydrogen peroxide (300 microM). EST not only protected cell survival from H(2)O(2)-induced toxicity, but also inhibited the H(2)O(2)-induced LDH release significantly. It was also found that EST at 100 and 1000 microg/ml showed scavenging activities of radicals and reactive oxygen species with 29.8% and 100.0% of inhibition against DPPH radical and 41.2% and 98.4% against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Topically applied EST dose-dependently inhibited arachidonic acid (AA)- and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced ear edema in mice.

Antioxidative and acute anti-inflammatory effects of Campsis grandiflora flower.

The present study was undertaken to investigate the antioxidative and anti-inflammatory activities of the extract of the flower of Campsis grandiflora (Thunb.) K. Schum. Exposure of human dermal fibroblasts to 50% EtOH extract of Campsis grandiflora flower (ECG) at 10 and 100 microg/ml showed significant protective effect against hydrogen peroxide (300 microM). ECG not only protected cell survival from H(2)O(2)-induced toxicity, but also inhibited the H(2)O(2)-induced leakage of lactate dehydrogenase (LDH) enzyme release and DNA fragmentation significantly. It was also found that ECG showed scavenging activities of radicals and reactive oxygen species with IC(50) values of 20 microg/ml against 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical and 52 microg/ml against superoxide radicals in the xanthine/xanthine oxidase system, respectively. Topically applied ECG dose-dependently inhibited arachidonic acid (AA)- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear edema in mice. Consistent with its antioxidative properties in vitro, the present results suggest the therapeutic potential of ECG for acute skin inflammation that may involve oxidative tissue damage.

Tetrandrine, a bisbenzylisoquinoline alkaloid from Chinese herb Radix, augmented the hypnotic effect of pentobarbital through serotonergic system.

This is the first study of hypnotic activity of tetrandrine (a major component of Stephania tetrandrae) in mice by using synergism with pentobarbital as an index for the hypnotic effect. The results showed that tetrandrine potentiated pentobarbital (45 mg/kg, i.p.)-induced hypnosis significantly by reducing sleep latency and increasing sleeping time in a dose-dependent manner, and this effect was potentiated by 5-hydroxytryptophan (5-HTP). In the subhypnotic dosage of pentobarbital (28 mg/kg, i.p.)-treated mice, tetrandrine (60 and 30 mg/kg, p.o.) significantly increased the rate of sleep onset and also showed synergic effect with 5-HTP. Pretreatment of p-chlorophenylalanine (PCPA, 300 mg/kg, s.c.), an inhibitor of tryptophan hydroxylase, significantly decreased pentobarbital-induced sleeping time and tetrandrine abolished this effect. From these results, it should be presumed that serotonergic system may be involved in the augmentative effect of tetrandrine on pentobarbital-induced sleep.

[Selective reduction of NOx with propene over SnO2/Al2O3 catalyst].

In the study, a series of SnO2/Al2O3 catalysts with various Sn loading were prepared by three different methods (impregnation, co-precipitation and single step sol-gel) and their catalytic activities for the selective reduction of NOx with propene were investigated. It was found that the catalyst preparation method as well as the Sn loading exerted a significant influence on the catalyst activity. Catalysts prepared by sol-gel method exhibited the highest activity toward NOx reduction and the optimal Sn loading is 5%. 5% SnO2/Al2O3 catalyst prepared by sol-gel method was found to be less inhibited by the presence of H20 than those prepared by other methods. Even in the co-presence of H2O and SO2, it still showed the highest activity. The increase of oxygen and propene concentration promotes the NOx reduction, respectively.

[Selective catalytic reduction of NO on Ag, Co and Cu/Al2O3 in excess oxygen].

The catalytic activities of alumina-supported Ag, Co and Cu for selective reduction of NO with propene as reductant in the presence of excess oxygen were investigated. The catalytic performances of single-component catalysts with different metal loadings and of samples prepared by various methods such as mechanical mixing, one-step impregnation, two-step impregnation, etc. were studied. The experimental results showed that the Ag exhibited the highest conversion of NO to N2 (approximately 89% with 2% loading, wt.) among single-component catalysts, the lower was Co, and the lowest was Cu. The sequence of the temperature for the maximum conversion was on the order of Cu < Co < Ag. For Ag catalysts, the activities between samples of identical loadings prepared by one-step and two-step impregnation were almost the same. The activities of mixed samples were not the simple sum of the single-component catalysts. The mixed Ag-Co sample possessed the highest activity (80% above). The activities of the combinatorial samples declined comparatively to some extent. The activities of one-step impregnation samples descended more markedly and the highest conversion was only over 30%.

[Alumina-supported catalysts for the catalytic purification of lean-burn automobile exhaust].

Catalytic properties of Ag/Al2O3, In/Al2O3, Sn/Al2O3, Co/Al2O3, Pt/Al2O3 and a two-stage catalyst composed of Ag/Al2O3 and Pt/Al2O3 were investigated for the selective reduction of NO by C3H6 or C2H5OH in excess oxygen. The Ag/Al2O3 showed the highest NO reduction activity among the catalysts studied. A substantial amount of CO was formed over alumina-based transient metal oxides. HC and CO oxidations over Pt/Al2O3 occurred in relatively low temperatures, compared with the other catalysts. The sequential use of Ag/Al2O3 and Pt/Al2O3 was effective to broaden the temperature window for the reduction of NO, to improve oxidation of HC and CO and to inhibit the formation of N2O and CH3CHO.