Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020672 (hypothermia)
 17,327 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xiaobuxin-Tang (XBXT), a traditional Chinese herbal decoction, has been used for the treatment of depressive disorders for centuries in China. Herein, we explored the antidepressant-like effect and its monoaminergic mechanism of the total flavonoids (XBXT-2) isolated from the extract of XBXT. In present study, single XBXT-2 (25, 50, 100 mg/kg, p.o.) administration significantly potentiated the mouse head-twitch response induced by 5-hydroxytryptophan (5-HTP, a metabolic precursor to serotonin), and also, decreased the immobility time in mouse tail suspension test, which was completely prevented by p-chlorophenylalanine (PCPA, an inhibitor of serotonin synthesis) pretreatment. However, single treatment with XBXT-2 had no effect on yohimbine toxicity and high dose of apomorphine-induced hypothermia in mice. These results indicated that acute treatment with XBXT-2 produced serotonergic, but not noradrenergic activation. In addition, chronic XBXT-2 (25, 50 mg/kg, p.o., 28 days) treatments significantly reversed the depressive-like behaviors in chronically mildly stressed (CMS) rats, including the reduced sucrose preference, deficient locomotor activity and prolonged latency to novelty-suppressed feeding. Furthermore, XBXT-2 normalized the neurotransmitter changes, including the decreased serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) levels in hippocampus and prefrontal cortex in CMS rats. These findings confirm the antidepressant-like effect of XBXT-2 in CMS model of rats, which may be primarily based on its serotonergic activation.
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PMID:Role for serotonin in the antidepressant-like effect of a flavonoid extract of Xiaobuxin-Tang. 1836 39

The present study aimed to investigate the antidepressant potential of genipin and its possible mechanisms. Mouse models of depression including the forced swimming test (FST) and the tail suspension test (TST) were used to evaluate the effects of genipin. A possible mechanism was explored in the test of antagonism of reserpine-induced ptosis and hypothermia in mice. The contents of monoamine neurotransmitters and their metabolites including epinephrine (NE), 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) in mice hippocampi were determined by HPLC-ECD. The results showed that intra-gastric administration of genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days significantly reduced the duration of immobility in FST and TST, while it did not affect the locomotor activity in the open field test (OFT). However, the effect was not dose-dependent. When the mice were treated with genipin or fluoxetine for 7 days, both of them could antagonize reserpine-induced ptosis and hypothermia. The 5-HT and NE contents in mice hippocampi were decreased after the peritoneal injection of reserpine at 2.0mg/kg. The pre-treatment with genipin at 50, 100, 200mg/kg or fluoxetine at 7.5mg/kg for 7 days could elevate the contents of NE and 5-HT in mice hippocampi significantly. The results suggest that compared with fluoxetine, genipin exerts antidepressant-like effects significantly. A possible mechanism, at least in part, is the regulation of the 5-HT and NE levels in the hippocampus.
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PMID:Antidepressant-like effect of genipin in mice. 2056 35

Probably the foremost hypothesis of depression is the 5-hydroxytryptamine (5-HT, serotonin) deficiency hypothesis. Accordingly, anomalies in putative 5-HT biomarkers have repeatedly been reported in depression patients. However, whether such anomalies in fact reflect deficient central 5-HT neurotransmission remains unresolved. We employed a naturalistic model of 5-HT deficiency, the tryptophan hydroxylase 2 (Tph2) R439H knockin mouse, to address this question. We report that Tph2 knockin mice have reduced basal and stimulated levels of extracellular 5-HT (5-HT(Ext)). Interestingly, cerebrospinal fluid (CSF) 5-hydroxyindoleacetic acid (5-HIAA) and fenfluramine-induced plasma prolactin levels are markedly diminished in the Tph2 knockin mice. These data seemingly confirm that low CSF 5-HIAA and fenfluramine-induced plasma prolactin reflects chronic, endogenous central nervous system (CNS) 5-HT deficiency. Moreover, 5-HT(1A) receptor agonist-induced hypothermia is blunted and frontal cortex 5-HT(2A) receptors are increased in the Tph2 knockin mice. These data likewise parallel core findings in depression, but are usually attributed to anomalies in the respective receptors rather than resulting from CNS 5-HT deficiency. Further, 5-HT(2A) receptor function is enhanced in the Tph2 knockin mice. In contrast, 5-HT(1A) receptor levels and G-protein coupling is normal in Tph2 knockin mice, indicating that the blunted hypothermic response relates directly to the low 5-HT(Ext). Thus, we show that not only low CSF 5-HIAA and a blunted fenfluramine-induced prolactin response, but also blunted 5-HT(1A) agonist-induced hypothermia and increased 5-HT(2A) receptor levels are bona fide biomarkers of chronic, endogenous 5-HT deficiency. Potentially, some of these biomarkers could identify patients likely to have 5-HT deficiency. This could have clinical research utility or even guide pharmacotherapy.
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PMID:Deficient serotonin neurotransmission and depression-like serotonin biomarker alterations in tryptophan hydroxylase 2 (Tph2) loss-of-function mice. 2153 32

Peony is often used in Chinese herbal medicine for the treatment of depression-like disorders. Our previous studies have demonstrated that the total glycosides of peony exert antidepressant-like effects in animal models. Paeoniflorin is the main active glycoside of peony. The aim of this study was to evaluate the antidepressant-like effects of paeoniflorin in mice, as well as its active mechanisms. The results revealed that intraperitoneally injected paeoniflorin significantly reduced the duration of immobility in forced swimming and tail suspension tests. The doses that affected the immobility response did not affect locomotor activity. Furthermore, paeoniflorin antagonized reserpine-induced ptosis, akinesia and hypothermia. Paeoniflorin also significantly increased the levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampus. These results suggest that the upregulation of serotonergic systems may be an important mechanism for the antidepressant-like effects of paeoniflorin in mice.
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PMID:The antidepressant-like effects of paeoniflorin in mouse models. 2359 34

Catalpol is a natural iridoid glycoside with diverse bioactivities that is found in abundance in Rehmannia glutinosa Libosch. (Scrophulariaceae). The present study assessed whether catalpol treatment (5, 10, or 20 mg/kg for 14 days by intragastric administration (i.g.)) has an antidepressant-like effect on mice performing the forced swim test (FST), tail suspension test (TST), open field test (OFT), and tests for reversal of reserpine-induced ptosis, akinesia, and hypothermia. This study also examined the potential role that catalpol plays in the cerebral monoaminergic system. Results indicated that catalpol administration produced an antidepressant-like effect in mice, as indicated by the reduced duration of immobility in the FST and TST, but it had no effect on locomotor activity in the OFT. Catalpol treatment significantly counteracted the decrease in rectal temperature, akinesia, and eyelid ptosis induced by reserpine. Moreover, catalpol increased levels of serotonin (5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the brains of mice, but it did not affect levels of norepinephrine (NE) or dopamine (DA). These antidepressant-like effects of catalpol are essentially similar to the effects of the clinical antidepressant fluoxetine hydrochloride (FH). This is the first study to indicate that catalpol has an antidepressant-like effect and that its action may be mediated by the central serotonergic system, and not by noradrenergic or dopaminergic systems.
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PMID:Involvement of the central monoaminergic system in the antidepressant-like effect of catalpol in mice. 2538 40

The Radix Bupleuri and Radix Paeoniae Alba drug pair plays a pivotal role in Xiaoyaosan, a famous Chinese herbal preparation that is popular in clinical medicine. To investigate the antidepressant-like effects and potential mechanism of action of the Radix Bupleuri and Radix Paeoniae Alba drug pair, we carried out the forced swim test (FST) and tail suspension test (TST), as the mouse models of depression; and the open field test (OFT) to exclude false-positive results. Subsequently, ptosis and hypothermia induced by reserpine were assessed. Finally, the concentrations of monoamine neurotransmitters and their metabolites, namely epinephrine (NE), 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) in the hippocampal and cortical tissues of mice were detected with HPLC with electrochemical detector. The Radix Bupleuri and Radix Paeoniae Alba (1:1) drug pair at low, medium, and high doses decreased immobility time in both the FST and TST, and counteracted hypothermia induced by reserpine in mice. After the administration of reserpine, the concentrations of 5-HT and NE in the hippocampal and cortical tissues were decreased; however, pre-treatment with the Radix Bupleuri and Radix Paeoniae Alba drug pair significantly elevated the concentrations of 5-HT and NE in the hippocampal and cortical tissues. The results suggested that, compared with single dose of fluoxetine and the drugs used individually, the Radix Bupleuri and Radix Paeoniae Alba drug pair had an excellent antidepressant-like effect. These data revealed a possible mechanism of action, as the regulation of the central monoaminergic neurotransmitter system in the hippocampal and cortical tissues.
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PMID:Antidepressant-like effects of the Radix Bupleuri and Radix Paeoniae Alba drug pair. 2761 41


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