The hypothermic effects of dl-tetrahydropalmatine in rats.

Systemic administration of dl-tetrahydropalmatine (THP; 10-50 mg x kg(-1) intraperitoneally) produced a proportional decrease in both colonic temperature and release of hypothalamic serotonin (5-hydroxytryptamine (5-HT)) in rats at room temperature. The hypothermia was brought about by cutaneous vasodilation and decreased metabolism. The THP- induced hypothermia was significantly attenuated in rats with brain 5-HT depletion produced by control injection of 5,7-dihydroxytryptamine or in rats with 5-HT2A receptor activation produced by 1-(2,5-dimethoxy-4-iodophenyl) -2-aminopropane, or in rats with 5-HT1A receptor antagonist produced by (-)-pindolol. The results suggest involvement of serotoninergic antagonism in the THP-induced hypothermia in rats

Reversal caused by n-butylidenephthalide from the deficits of inhibitory avoidance performance in rats.

The present study was designed to investigate the mechanism of action of n-butylidenephthalide on the deficits of inhibitory avoidance performance induced by drugs in rats with piracetam as a positive control. n-Butylidenephthalide attenuated the scopolamine-induced and mecamylamine-induced acquisition impairment, and also attenuated the acquisition impairment induced by scopolamine plus mecamylamine. Furthermore, scopolamine methylbromide, a peripheral cholinergic muscarinic receptor antagonist, did not block the counteracting effect of n-butylidenephthalide on the scopolamine-induced acquisition impairment. n-Butylidenephthalide attenuated the impairment of inhibitory avoidance performance induced by the central acetylcholinergic neurotoxin AF64A administered intracisternally. From the above results, we suggest that n-butylidenephthalide attenuated the deficits of inhibitory avoidance performance induced by drugs, which are the effects related to activating the central but not the peripheral cholinergic neuronal system via muscarinic and nicotinic receptors.

The ameliorating effect of the water layer of Fructus Schisandrae on cycloheximide-induced amnesia in rats: interaction with drugs acting at neurotransmitter receptors.

Our previous study indicated that the water layer present in Fructus Schisandra(FS(w)) at 10 and 25 mg kg(-1)significantly counteracted cycloheximide (CXM)-induced amnesia. Therefore, the mechanism of action of the ameliorating effect of FS(w)on CXM-induced amnesia in the passive avoidance task was investigated in rats. The ameliorating effect of FS(w)on CXM-induced amnesia was depressed by scopolamine. The serotonin releaser, p -chloroamphetamine significantly antagonized the ameliorating effect of FS(w)on CXM-induced amnesia. Furthermore, the ameliorating effect was also inhibited by the 5-HT(1A)receptor agonist 8-OH-DPAT, but potentiated by the 5-HT(2)receptor antagonist ritanserin. Finally, the GABA(A)receptor antagonist bicuculline blocked the ameliorating effect of FS(w). These results suggest that the beneficial effect of FS(w)on CXM-induced amnesia is amplified by treatment with serotonergic 5-HT(2)receptor antagonists, but reduced by serotonergic 5-HT(1A)receptor agonists as well as GABA(A)and cholinergic receptor antagonists.

Anti-inflammatory and neuroprotective effects of magnolol in chemical hypoxia in rat cultured cortical cells in hypoglycemic media.

Our previous studies demonstrated that magnolol protects neurons against chemical hypoxia by KCN in cortical neuron-astrocyte mixed cultures (14). In the present study, we examined whether the neuroprotective effect of magnolol involve modulating inflammatory mediators, prostaglandin E2 (PGE2) and nitric oxide (NO), induced by KCN (hypoxia) or KCN plus lipopolysaccharide (LPS). In glucose-absent (hypoglycemia) media, KCN or KCN plus LPS induced increases in lactate dehydrogenase (LDH) activity by 32% and 34%, and PGE2 production by 12% and 32%, respectively. Both LDH and PGE2 increases were suppressed by 100 microM magnolol. In addition, although KCN or LPS alone did not increase NO generation, KCN plus LPS increased NO generation. This increase was reduced by 100 microM magnolol or 10 microM L-NAME, but the LDH increase and PGE2 production were not reduced by L-NAME. These findings suggest that the protective effects of magnolol against brain damage by KCN or KCN plus LPS in hypoglycemic media may involve inhibition of PGE2 production, but inhibition of NO generation may not be important.

Radix Angelica Sinensis extracts ameliorate scopolamine- and cycloheximide-induced amnesia, but not p-chloroamphetamine-induced amnesia in rats.

The effects of the methanolic extract of Radix Angelica Sinensis (Umbellifera) (abbreviated as RAS extract) and n-hexane fraction of RAS extract (RAS(H) fraction) on the various drugs-induced amnesia in rats were studied by using passive avoidance task. RAS extract (1 g/kg) significantly prolonged the shortened step-through latency induced by SCOP and CXM, but not PCA. Furthermore, RAS(H) fraction (1 g/kg) also significantly prolonged the shortened step-through latency induced by SCOP and CXM but not PCA. RAS extract at any dose alone did not influence the step-through latency in the training trial produced by non-shocked rats, but it plus PCA prolonged the latency compared with PCA alone. However, RAS(H) fraction (1 g/kg) prolonged the latency in the training trial produced by non-shocked rats, but it plus any induced drugs did not differ from any induced drugs alone. These results suggest that the attenuating effects of RAS extract on the various drugs-induced amnesia were related to the memory processes. n-Hexane fraction of RAS extract might be one of the active fractions of RAS extract in the treatment of amnesia.

Anxiolytic effect of seed of Ziziphus jujuba in mouse models of anxiety.

The aim of the present study was to investigate the ethanolic extract of Semen Ziziphi jujuba (SZJE) induced anxiolytic effect. The SZJE was orally administered to male ICR mice, at 0.5, 1.0 and 2. 0 g/kg, 30 min before the behavioral evaluation in the black and white test (BWT) and elevated plus maze (EPM). The SZJE at the dosage 0.5-2.0 g/kg increased the first time entry, total changes and times spent in the white chamber of the BWT. The SZJE at the dosage 0.5-1.0 g/kg increased the percentage of time-spent and the percentage of arm entries in the open arms of the EPM and decreased the percentage of time-spent and the percentage of arm entries in the closed arms of the EPM. Furthermore, the SZJE at the dosage of 1. 0 g/kg prolonged the hexobarbital-induced sleeping time in mice and decreased the locomotor activity in rats. These results suggested that SZJE possessed anxiolytic effect at lower dose and sedative effect at higher dose.

The ameliorating effects of the cognitive-enhancing Chinese herbs on scopolamine-induced amnesia in rats.

Ameliorating effects were investigated of the cognitive-enhancing Chinese herbs administered orally for 1 week-Panax ginseng (PG), Panax notoginseng (PNG), Dioscorea opposita (DO), Gastrodia elata (GE), Salvia miltiorrhiza (SM), Acorus gramineus (AG), Coptis chinensis (CC), Polygonum multiflorum (PM), Cyperus rotundus (CR) and Psoralea corylifolia (PC)-on the scopolamine (SCOP)-induced amnesia by using a passive avoidance task in rats. Of ten Chinese herbs, only PG, PNG, GE and CC prolonged the SCOP-shortened STL. These results revealed that PG, PNG GE and CC administered orally for 1 week improved the SCOP-induced learning and memory deficit in rats.

Anti-hepatitis B virus effects of wogonin isolated from Scutellaria baicalensis.

By using an HBV-producing cell line (MS-G2) in vitro culture system, we found that wogonin isolated from Scutellaria baicalensis can suppress HBV surface antigen production (P < 0.001) without evidence of cytotoxicity. By assaying the endogenous HBV DNA polymerase activity, we found that both the relaxed circular and the linear forms of HBV DNA are significantly reduced in the wogonin-treated group. Wogonin deserves to be further evaluated for the treatment of human HBV infection.

The neuroprotective effect of DL-tetrahydropalmatine in rat heatstroke.

After the onset of heatstroke, rats with saline injection displayed hyperthermia, decreased mean arterial pressure, decreased cerebral blood flow, increased brain monoamine release, and increased neuronal damage score compared with those of normothermia, control rats. The heatstroke-induced hyperthermia, arterial hypotension, cerebral ischemia, brain monoamine overload, and cerebral neuronal injury were attenuated by pretreatment with dl-tetrahydropalmatine. The data indicate that DL-tetrahydropalmatine pretreatment provides neuroprotective effect in heatstroke.

Effects of Fructus schizandrae on cycloheximide-induced amnesia in rats.

The effects of Fructus Schisandrae (Schizandra Chinensis, (FS) on cycloheximide (CXM)-induced amnesia by using a passive avoidance task were studied in rats. FS at 0.25 and 0.75 g/kg administered for 1 week significantly prolonged the CXM-shortened step-through latency (STL). Of the fractions (n-hexane, chloroform and water), only the water fraction at 25 mg/kg administered for 1 week prolonged the CXM-shortened STL. These results suggest that the water fraction is the main active fraction of FS.

Effects of palmatine on isometric force and intracellular calcium levels of arterial smooth muscle.

The effects of palmatine on isometric force and intracellular free calcium levels ([Ca2+]i) were determined in isolated rat arterial strips. Palmatine dose-dependently relaxed the contractile responses stimulated by phenylephrine (PE) in aortic strips. In contrast, it only partially relaxed aortic strips contracted by 51 mM KCl. Pretreatment with palmatine shifted the dose-response curves of PE both rightwards and downwards in a dose-dependent manner. When Ca2+-free solution and re-addition of Ca2+ were applied to assess PE-induced phasic and tonic contractions, palmatine was found to be effective in inhibiting both contractions. The effects of palmatine on intracellular calcium levels were measured with the bioluminescent calcium indicator aequorin in rat tail artery strips. Palmatine caused a concomitant, dose-dependent decrease in PE-activated isometric force and [Ca2+]i, resulting in small changes in the [Ca2+]i-force relationship. These results suggest that vasodilatory effect of palmatine was mediated by reducing [Ca2+]i as well as affecting [Ca2+]i sensitivity of the contractile apparatus. Palmatine-induced [Ca2+]i decreases appeared to involve decreases in both Ca2+ release from intracellular stores and Ca2+ influx through calcium channels.

Magnolol decreases body temperature by reducing 5-hydroxytryptamine release in the rat hypothalamus.

1. The effects of magnolol, isolated and purified from the cortex of Magnolia officinalis Rehd. et Wils, on thermoregulation and hypothalamic release of 5-hydroxytryptamine (5-HT) by in vivo microdialysis were assessed in normothermic rats and in febrile rats treated with interleukin-1 beta. 2. Intraperitoneal administration of magnolol (25-100 mg/kg) produced a decrease in colon temperature, an increase in foot skin temperature, a decrease in metabolic rate and a decrease in the endogenous release of 5-HT in the rat hypothalamus. 3. Depletion of rat brain 5-HT, produced by intracerebroventricular pretreatment with 5,7-dihydroxytryptamine, attenuated the magnolol-induced hypothermia, cutaneous vasodilation and decreased metabolism. 4. Intracerebroventricular administration of (+/-)-2,5-dimethoxy-4-iodoamphetamine (a 5-HT2 receptor agonist; 5-10 micrograms/5 microL) increased basal colon temperature and reversed the magnolol-induced hypothermia. 5. The increases in both colon temperature and hypothalamic 5-HT release produced by interleukin-1 beta injection were attenuated by treatment with magnolol. 6. The data suggest that magnolol decreases body temperature (due to increased heat loss and decreased heat production) by reducing 5-HT release in rat hypothalamus.

Ameliorating effect of p-hydroxybenzyl alcohol on cycloheximide-induced impairment of passive avoidance response in rats: interactions with compounds acting at 5-HT1A and 5-HT2 receptors.

The effect of p-hydroxybenzyl alcohol (HBA) on cycloheximide (CXM)-induced impairment in the step-through passive avoidance task was investigated in rats and compared to the effect of the nootropic piracetam. HBA and piracetam significantly counteracted the CXM-induced shortening of retention latencies. The effect of HBA was a bell-shaped dose-response curve with a maximal effect of 5 mg/kg. The counteractive effect of HBA was not depressed by either scopolamine or mecamylamine. The serotonin (5-HT) releaser, p-chloroamphetamine, and presursor, 5-hydroxytryptophan, significantly antagonized the counteractive effect of HBA on the CXM-induced shortening of retention latencies. Furthermore, the counteractive effect was also inhibited by the 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and the 5-HT2 receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2 aminopropane [(+/-)-DOI], but potentiated by the 5-HT1 receptor antagonist (+/-)-pindolol and the 5-HT2 receptor antagonist ritanserin. There results suggest that the beneficial effect of HBA on CXM-induced impairment is amplified by treatment with serotonergic receptor antagonists but reduced by serotonergic 5-HT1A and 5-HT2 receptor agonists, and insensitive to cholinergic manipulations.

Catecholaminergic mechanisms-mediated hypothermia induced by magnolol in rats.

Intraperitoneal administration of magnolol (25-100 mg/kg) produced a dose-related fall in rats' colonic temperature. The magnolol-induced hypothermia was attenuated by pretreatment with intracerebroventricular 6-hydroxydopamine (200 microg/rat). The L-DOPA (200 mg/kg, i.p.) plus benserazide (50 mg/kg, i.p.)-induced hyperthermia was attenuated by magnolol. On the other hand, the alpha-methyltyrosine (100 mg/kg, i.p.)-induced hypothermia was potentiated by magnolol. Furthermore, magnolol (50 mg/kg, i.p.) decreased the dopamine and norepinephrine release in the hypothalamus, but did not change the concentrations for their metabolites (3,4-dihydroxyphenylacetic acid and homovanillic acid). The data suggest that magnolol decreases colonic temperature by reducing catecholaminergic activity in rat hypothalamus.

Effect of long-term administration of berberine on scopolamine-induced amnesia in rats.

The effect of berberine (BER) on scopolamine (SCOP)-induced amnesia was investigated in a step-through passive avoidance task in rats. It was observed that BER at the doses of 0.1 and 0.5 g/kg after 7-day or 14-day administration significantly improved SCOP-induced amnesia. The anti-amnesic effect of BER after 14-day administration on the SCOP-induced amnesia was significantly augmented by physostigmine or neostigmine, and completely reversed by scopolamine N-methylbromide. These results suggest that the antiamnesic effect of BER after 14-day administration may be related to the increase in the peripheral and central cholinergic neuronal system activity.

Gastrodin and p-hydroxybenzyl alcohol facilitate memory consolidation and retrieval, but not acquisition, on the passive avoidance task in rats.

Gastrodin (GAS) and p-hydroxybenzyl alcohol (HBA) which is an aglycone of gastrodin, are active ingredients of Gastrodia elata Blume. In this study, we attempted to investigate the effects of acute administration of GAS and HBA on learning and memory processes such as acquisition, consolidation and retrieval, on the passive avoidance task in rats; piracetam was used as a positive control. Scopolamine, impairing learning acquisition, shortened the step-through latency in the retention test in rats. GAS and HBA did not prolong the step-through latency induced by scopolamine in the passive avoidance task, but piracetam could prolong the step-through latency induced by scopolamine. Cycloheximide, impairing memory consolidation, shortened the step-through latency in the retention test in rats. GAS at 50 mg/kg, HBA at 5 mg/kg and piracetam at 100 mg/kg could prolong the step-through latency induced by cycloheximide in the passive avoidance task. Apomorphine, impairing memory retrieval, shortened the step-through latency in the retention test in rats. GAS at 5 mg/kg, HBA at 1 mg/kg and piracetam at 300 mg/kg could prolong the step-through latency induced by apomorphine in the passive avoidance task. From the above results, we concluded that the facilitating effects of HBA on learning and memory are better than those of GAS. In conclusion, GAS and HBA can improve cycloheximide- and apomorphine-induced amnesia, but not scopolamine-induced acquisition impairment in rats. Thus, GAS and HBA can facilitate memory consolidation and retrieval, but not acquisition. The facilitating effects of GAS and HBA are different from those of piracetam.

Biphasic effects of pu-chung-i-chi-tang on sedation and excitation.

The biphasic effects of Pu-Chung-I-Chi-Tang (PCT) on sedation and excitation in acute treatment or after one-week consecutive treatment were studied. The results indicated that PCT produces sedation in acute treatment and excitation after one-week consecutive treatment. The sedative mechanism of PCT in acute treatment might be due to an increase in serotonergic activity and a decrease in dopaminergic activity. However, the excitatory mechanism of PCT after one-week consecutive treatment might involve the increase in dopaminergic activity and the decrease in serotonergic activity.

Inhibitory effects of (+/-)-tetrahydropalmatine on thyrotropin-stimulating hormone concentration in hyperthyroid rats.

The effects of (+/-)-tetrahydropalmatine ((+/-)-THP) on the hypothalamus-pituitary-thyroid system in rats were investigated. Thyroid function experiments indicated that (+/-)-THP produces significant decreases in thyroid function in hyperthyroid rats after 14 days of treatment. These effects were the same as those of propylthiouracil. However, propylthiouracil also decreased thyroid function in normal rats. Measurements of thyrotropin-stimulating hormone (TSH) demonstrated that (+/-)-THP decreased TSH in hyperthyroid rats after 14 days of treatment; however, propylthiouracil increased TSH in hyperthyroid rats. (+/-)-THP had no influence on TSH, or thyroid and pituitary weight in normal and hyperthyroid rats. We conclude that (+/-)-THP has an antithyroid function and the mechanism of action may be related to the inhibition of TSH in the pituitary.

Effects of Gastrodia elata and its active constituents on scopolamine-induced amnesia in rats.

The effects of the rhizome of Gastrodia elata Blume (Orchidaceae) (abbreviated as GE) and its active constituents on learning and memory by using the one-trial passive avoidance task were studied in rats. At the 1.0 g/kg dose administered for one week, the methanol extract of GE significantly prolonged the shortened step-through latency induced by scopolamine in the passive avoidance task. Furthermore, at the 50.0 mg/kg dose administered for one week, the ethyl acetate and n-butanol fractions of the methanol extract prolonged the shortened step-through latency induced by scopolamine in rats. Gastrodin, isolated from the n-butanol fraction of the methanol extract, and p-hydroxybenzyl alcohol, isolated from the ethyl acetate fraction of the methanol extract, also significantly prolonged the shortened step-through latency induced by scopolamine on the passive avoidance task. These results suggested that gastrodin and p-hydroxybenzyl alcohol may be the active constituents of GE.

Antihypertensive effects of DL-tetrahydropalmatine: an active principle isolated from Corydalis.

1. The effects of DL-tetrahydropalmatine (DL-THP) on cardio-vascular function and hypothalamic release of monoamines were assessed in rats under urethane anaesthesia. 2. Intravenous administration of DL-THP (1-10 mg/kg) produced hypotension, bradycardia, a decrease in hypothalamic serotonin and noradrenaline release and an increase in hypothalamic dopamine release in rats. 3. Intrahypothalamic administration of DOI (a serotonergic 5-HT2 receptor antagonist) or apomorphine (a dopamine D2-receptor agonist) produced the opposite effects and reversed DL-THP-induced hypotension and bradycardia. 4. The data suggest that DL-THP acts through the 5-HT2 and/or D2-receptor antagonism in the hypothalamus to induce hypotension and bradycardia in rats.