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.

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.

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.

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.

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.

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.

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.

Effects of Hemerocallis flava on motor activity and the concentration of central monoamines and its metabolites in rats.

In this study, we used behavioral and biochemical methods to investigate the effects of Hemerocallis flava (Liliaceae) (abbreviated as HF) on motor activity and the concentration of monoamines in rats. The water fraction of the resuspended HF extract was most active in reducing the motility in rats. The water fraction of the HF extract enhanced the reduction of locomotor activity produced by alpha-methyl-p-tyrosine and 5-hydroxytryptophan, but it reduced the increase of locomotor activity produced by L-dopa plus benserazide and p-chlorophenylalanine. Furthermore, the water fraction of the HF extract significantly decreased the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in the brain stem. It also increased the concentration of vanilylmandelic acid in the cortex, homovanillic acid and 5-hydroxyindole-acetic acid in the brain stem. These results suggest that the reduction of locomotor activity produced by the water fraction of HF extract may be related to the decrease in the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in brain stem.

Increase of locomotor activity by acupuncture on Bai-Hui point in rats.

The effect of acupuncture on locomotor activity was investigated in rats. Stimulation with acupuncture inserted in Bai-Hui point, which is located at the vertex of the head, increased the spontaneous locomotor activity of rats measured in ANIMEX meter. This effect was obtained in rats which received acupuncture significantly at 60 min later as compared with sham-treated control. The sleeping time induced by hexobarbital was also reduced markedly in rats receiving acupuncture. An activation of the central nervous system by acupuncture at Bai-Hui point can thus be considered. This action was unrelated to opioids because naloxone failed to modify it. Increase in locomotor activity was abolished by an intraperitoneal (i.p.) injection of alpha-methyl-p-tyrosine (200 mg/kg) at 2 h before insertion of acupuncture. Deprenyl at the dose sufficient to elevate monoamine enhanced this action of acupuncture. Mediation of cerebral monoamines can also be considered. This view was supported by the dose-dependent inhibition of chlorpromazine. Action of acupuncture was not observed in apomorphine (0.5 mg/kg, i.p.)-treated rats, probably due to an activated receptor of dopamine. Otherwise, action of acupuncture was enhanced by para-chlorophenylalanine, the depleter of endogenous 5-hydroxytryptamine (5-HT), and eliminated by 5-hydroxytryptophan, the precursor of 5-HT, in the initial stage of insertion. Participation of 5-HT can be considered as an initial way in rats that received acupuncture at Bai-Hui point. These results suggested that stimulation of Bai-Hui point with acupuncture can activate central neurotransmission of monoamines to increase the spontaneous locomotor activity in rats.

Hypotensive and bradycardic effects of dl-tetrahydropalmatine mediated by decrease in hypothalamic serotonin release in the rat.

In anesthetized rats, intravenous administration of dl-tetrahydropalmatine (dl-THP, 1-10 mg/kg) elicited proportional hypotension, bradycardia and decreases in hypothalamic serotonin (5-HT) release (measured by carbon-fiber electrodes in combination with voltammetry). In addition, postsynaptic blockade of 5-HT2 receptors with cyproheptadine (2-5 mg/kg, i.v.) or ketanserin (2-5 mg/kg, i.v.) produced both hypotension and bradycardia, while stimulation of 5-HT2 receptors with 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) (10-250 mg/kg, i.v.) produced both hypertension and tachycardia. The dl-THP-induced hypotension and bradycardia could be reversed by DOI treatment. The data indicate that dl-THP decreases both arterial pressure and heart rate through a serotonergic release process in the hypothalamus.

Effects of ginseng on the blood chemistry profile of dexamethasone-treated male rats.

Ginseng, a panacea in the Orient, has been widely investigated in the last two decades and found to possess a wide range of pharmacological activities including anti-fatigue properties, a transient regulatory action on metabolism and blood pressure, and an increase in the hypothalamo-pituitary-adrenocortical activities. However, a panoramic clinical chemistry study including adrenal and thyroid functions has never been done before. Two experiments with the same design but different concentrations of dexamethasone were performed in this study. The results obtained from the two experiments indicated that ginseng administration at this regime did not influence the blood chemistry profiles in normal rats, but significantly decreased AST and ALT levels from those in dexamethasone-treated ones. It implies that ginseng has a liver-protective effect. Meanwhile, ginseng therapy restores the adrenal and thyroid functions of rats inhibited by dexamethasone treatment.

Studies on the anticonvulsive, sedative and hypothermic effects of Periostracum Cicadae extracts.

The anticonvulsive, sedative and hypothermic effects of water and ethanol extracts of Periostracum Cicadae (PC), the cast off skin of Cryptotympana atrata were studied. The water-extract of whole Periostracum Cicadae (PCws) had anticonvulsive, sedative and hypothermic effects in rats. Orally, it decreased carrageenin-induced hyperthermia. The hypothermic effect of PCws was potentiated by 5-hydroxytryptophan and antagonized by p-chlorophenylalanine. PCws enhanced the decrease in locomotor activity induced by alpha-methyl-p-tyrosine or 5-hydroxytryptophan and reduced the increase in locomotor activity produced by levodopa plus benserazide or p-chlorophenylalanine. From these results, it was concluded that the sedative and hypothermic effect of PCws may be due to an increase in central serotonergic activity.

Long-term reno-cardiovascular effects of orally administered aconiti tuber in humans.

The reno-cardiovascular effects of Aconiti Tuber were studied. In a controlled, double-blind, and randomized clinical trial, it was found that in 9 months, Aconiti Tuber, after preparation (120 degrees C, 40 min), (1) had no apparent adverse effects, (2) showed positive inotropic, positive chronotropic, and vasodilator effects, (3) increased renal blood flow, and glomerular filtration rate, Na+/Cl-/K+ excretions. The renal function test results could be interpreted as secondary to hemodynamic changes. We conclude that specially prepared Aconiti Tuber may be a promising cardiotonic agent.

Effects of paweiwan on streptozotocin-induced hyperglycemia in rats.

The ancient Chinese remedy of Paweiwan was used by patients with polyuria, polydipsia, and polyphagia. The present study investigated the hypoglycemic effects of Paweiwan using streptozotocin-induced hyperglycemic rats. The effects on serum glucose in a 4-day course, in a 7-week course, on the standard oral glucose tolerance test, and on the liver glycogen content were studied. In the glucose tolerance test, chlorpropamide and insulin were used as the positive controls and 0.5% CMC (Carboxymethylcellulose) was used as the negative control. We found that Paweiwan decreased the baseline glucose concentration, ameliorated the blood glucose elevation after glucose challenge, and increased liver glycogen content. The results may imply that Paweiwan increases glucose entrance into cells.