Sini Tang Prevents Depression-Like Behavior in Rats Exposed to Chronic Unpredictable Stress

2009 ◽  
Vol 37 (02) ◽  
pp. 261-272 ◽  
Author(s):  
Jian-You Guo ◽  
Hai-Ru Huo ◽  
Lan-Fang Li ◽  
Shu-Ying Guo ◽  
Ting-Liang Jiang

Sini Tang, a Chinese traditional prescription containing three herbs, has been widely used for Yang-deficiency. Recent clinical studies have shown that Sini Tang could treat and improve depression symptoms, but the mechanisms underlying the antidepressant effect of Sini Tang remains unknown. In rats with chronic unpredictable stress (CUS), we examined the effects of Sini Tang on sucrose preference and open field exploratory behavior. The levels of corticosterone level in plasma and corticotropin- releasing hormone (CRH) mRNA expression in hypothalamus were also measured by enzyme-linked immunosorbent assays (ELISA) and real-time reverse transcription PCR (RT-PCR), respectively. Rats subjected to CUS exhibited decreases in sucrose preference and ambulation in the open field test. These were all attenuated by Sini Tang in a dose-dependent manner. Biochemically, Sini Tang also reversed CUS-induced increases in corticosterone in plasma and CRH mRNA in the hypothalamus. The behavioral effects of the Sini Tang were correlated to the biochemical actions. These results suggest that Sini Tang produces an antidepressant-like effect, which appears to involve CRH in the brain.

2001 ◽  
Vol 91 (6) ◽  
pp. 2703-2712 ◽  
Author(s):  
Stephen M. Johnson ◽  
Julia E. R. Wilkerson ◽  
Daniel R. Henderson ◽  
Michael R. Wenninger ◽  
Gordon S. Mitchell

Brain stem preparations from adult turtles were used to determine how bath-applied serotonin (5-HT) alters respiration-related hypoglossal activity in a mature vertebrate. 5-HT (5–20 μM) reversibly decreased integrated burst amplitude by ∼45% ( P < 0.05); burst frequency decreased in a dose-dependent manner with 20 μM abolishing bursts in 9 of 13 preparations ( P < 0.05). These 5-HT-dependent effects were mimicked by application of a 5-HT1A agonist, but not a 5-HT1B agonist, and were abolished by the broad-spectrum 5-HT antagonist, methiothepin. During 5-HT (20 μM) washout, frequency rebounded to levels above the original baseline for 40 min ( P < 0.05) and remained above baseline for 2 h. A 5-HT3 antagonist (tropesitron) blocked the post-5-HT rebound and persistent frequency increase. A 5-HT3 agonist (phenylbiguanide) increased frequency during and after bath application ( P < 0.05). When phenylbiguanide was applied to the brain stem of brain stem/spinal cord preparations, there was a persistent frequency increase ( P < 0.05), but neither spinal-expiratory nor -inspiratory burst amplitude were altered. The 5-HT3receptor-dependent persistent frequency increase represents a unique model of plasticity in vertebrate rhythm generation.


Blood ◽  
2010 ◽  
Vol 116 (25) ◽  
pp. 5716-5723 ◽  
Author(s):  
Petr Klement ◽  
Leslie R. Berry ◽  
Peng Liao ◽  
Henry Wood ◽  
Paul Tressel ◽  
...  

AbstractTranscranial Doppler-detected high-intensity transient signals (HITS) during cardiopulmonary bypass (CPB) surgery have been associated with postoperative neurocognitive dysfunction, suggesting microemboli in the brain could be a contributing factor. HITS occur despite administration of unfractionated heparin (UFH). This study was done to determine whether antithrombin-heparin covalent complex (ATH), a more potent anticoagulant than heparin, can reduce HITS during CPB. In a pig CPB model, ATH, UFH, or UFH + antithrombin (AT) was intravenously administered to female Yorkshire pigs after sternotomy. Twenty minutes later, hypothermic CPB was initiated and continued for 1.25 hours, then normothermia was re-established for 45 minutes. Protamine sulfate was given to neutralize the anticoagulants, and pigs were allowed to recover. HITS were monitored using an arterial flow probe placed over the carotid artery. Compared with UFH (300 or 1000 U/kg), ATH reduced the number of HITS during CPB in a dose-dependent manner. AT (3 mg/kg) + UFH (300 U/kg) resulted in an intermediate HITS rate between UFH and ATH (2 mg/kg in terms of AT). Examination of brain sections for emboli formation confirmed that, similar to HITS, number of thrombi decreased in direct proportion to ATH dosage. These results support the hypotheses that the majority of HITS represent thromboemboli and that ATH reduces emboli formation during CPB.


2021 ◽  
Vol 12 ◽  
Author(s):  
Luping Zhang ◽  
Dengyuan Zhou ◽  
Qiuyan Li ◽  
Shuo Zhu ◽  
Muhammad Imran ◽  
...  

Flaviviruses are the major emerging arthropod-borne pathogens globally. However, there is still no practical anti-flavivirus approach. Therefore, existing and emerging flaviviruses desperately need active broad-spectrum drugs. In the present study, the antiviral effect of steroidal dehydroepiandrosterone (DHEA) and 23 synthetic derivatives against flaviviruses such as Japanese encephalitis virus (JEV), Zika virus (ZIKV), and Dengue virus (DENV) were appraised by examining the characteristics of virus infection both in vitro and in vivo. Our results revealed that AV1003, AV1004 and AV1017 were the most potent inhibitors of flavivirus propagation in cells. They mainly suppress the viral infection in the post-invasion stage in a dose-dependent manner. Furthermore, orally administered compound AV1004 protected mice from lethal JEV infection by increasing the survival rate and reducing the viral load in the brain of infected mice. These results indicate that the compound AV1004 might be a potential therapeutic drug against JEV infection. These DHEA derivatives may provide lead scaffolds for further design and synthesis of potential anti-flavivirus potential drugs.


Author(s):  
MAHESWARI REDDY B ◽  
DHANAPAL CK ◽  
LAKSHMI BVS

Objective: The current study evaluates anti-Parkinson’s activity of aqueous extracts of leaves of Murraya koenigii (MK) (AEMK) against paraquat (PQ)-induced Parkinsonism in rats. Methods: In this study, effects of MK (100, 200, and 400 mg/kg, p.o.) were studied using in vivo behavioral parameters such as catalepsy, muscle rigidity, and locomotor activity and its effects on neurochemical parameters malondialdehyde, catalase (CAT), glutathione (GSH) reductase, GSH peroxidase, and GSH in rats. Results: Parkinson’s disease was induced by administering PQ 10 mg/kg b.w/i.p once in a week for 4 weeks. The increased cataleptic scores were significantly (p<0.001) found to be reduced, with the AEMK in a dose-dependent manner. Chronic administration of PQ significantly induced motor dysfunction (muscle rigidity and hypolocomotion), showed a significant increase in lipid peroxidation level, and depleted the levels of GSH, CAT, and reduced GSH. Daily administration of AEMK significantly improved motor performance and also significantly attenuated oxidative damage. Conclusion: The study proved that MK treatment significantly attenuated motor defects and also protected the brain from oxidative stress.


Dose-Response ◽  
2019 ◽  
Vol 17 (4) ◽  
pp. 155932581989126 ◽  
Author(s):  
Hafiz Muhammad Asif ◽  
Abdul Hayee ◽  
Muhammad Rahil Aslam ◽  
Khalil Ahmad ◽  
Abdul Sattar Hashmi

The present work was carried out to assess the Onosma bracteatum anxiolytic and antidepressant properties. Swiss albino mice (male) were fed orally with hydroalcoholic extract at different doses 50, 100, and 200 mg 1 hour prior to test with the standard diazepam and fluoxetine. Anxiolytic and antidepressant activities were evaluated by using open field, elevated plus maze, force swimming, and tail suspension test. Results of open field test showed an increase in number of line crossing as well as number of rearing in dosage-dependent design. Although results of elevated plus maze test evidently showed antianxiety effect of O bracteatum by increasing the time spent in open arms along with decreasing the time spent in closed arms in dosage-dependent way. For the evaluation of antidepressant effect, O bracteatum diminished the immobility time and expanded mobility time in forced swim model in dosage-dependent way. Likewise, O bracteatum expanded time span of mobility along with diminished immobility time in tail suspension method in dosage-dependent way. Outcome demonstrated that plant at the dose of 200 mg/kg body weight showed significant potential which was similar to that standard diazepam and fluoxetine. Hence, O bracteatum may be used as potent natural psychotherapeutic agent against the mental disorders.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chunyan Hao ◽  
Zefeng Gao ◽  
XianJun Liu ◽  
Zhijiang Rong ◽  
Jingjing Jia ◽  
...  

AbstractPropionate has been reported to exert antidepressant effects, but high-dose propionate may induce autism-like symptoms in experimental animals through induction of dysbiosis of neurotransmitters. The bi-directional effects of propionate seem to be dose-dependent. However, due to the pathological discrepancies between depression and autism, conclusions drawn from autism may not be simply transferable to depression. The effect and underlying action mechanisms of high-dose propionate on depression remains undetermined. To investigate the effects of propionate on depression, propionate dose gradients were intravenously administrated to rats exposed to chronic unpredictable mild stress (CUMS) for 1 week. Results of these behavioral tests demonstrate that low-dose propionate (2 mg/kg body weight/day) induces antidepressant effect through bodyweight recovery, elevated reward-seeking behaviors, and reduced depression-like behaviors, while high-dose propionate (200 mg/kg body weight/day) induces prodepressant effects opposite of those of low-dose propionate. A comprehensive profiling of neurotransmitters in the hippocampus demonstrated that CUMS induces reduction of NE (Norepinephrine), DA (Dopamine). GABA (γ-aminobutyric acid) was recovered by low-dose propionate, while high-dose propionate exerted more complicated effects on neurotransmitters, including reduction of NE, DA, 5-Hydroxytryptamine and Tryptophan, and increase of GABA, Kynurenine, Homovanillic acid, 3-hydroxyanthranilic acid, 3-hydroxykynurenine, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine. The neurotransmitters disturbed by high-dose propionate suggest metabolic disorders in the hippocampus, which were confirmed by the clear group separation in PCA of metabolomic profiling. The results of this study demonstrate the double-edged dose-dependent effects of propionate on depression and suggest potential cumulative toxicity of propionate as a food additive to mood disorders.


2016 ◽  
Vol 14 (3) ◽  
pp. 46-52 ◽  
Author(s):  
Petr D. Shabanov ◽  
Andrei A. Lebedev ◽  
Natalia D. Yakushina ◽  
Anna G. Pshenichnaya ◽  
Eugenii R. Bychkov

A rodent marble test can be qualified as the most informative test of evaluation of obsessive-compulsive disorder as a neurobiological component of pathological gambling. Several behavioral components of obsession (obsessive and anxious ideas) and compulsions (obsessive actions) directed to anxiety reduction are modeled in this test. The effect of psychostimulant amphetamine on the rat behavior was studied in a marble test, anxiety-phobic model (scale), open field (evaluation of motor and emotional activity) and resident-intruder test (Intraspecies behavior). Amphetamine 0.5 and 1.5 mg/kg increased a number of burying bolls and elevated anxiety level in dose dependent manner. This accompanied with reduction of explorative activity, elevation of motor activity and number of individual behavioral patterns. Therefore, dopaminergic system of the brain activated with amphetamine is involved in obsessive-compulsive behavior and pathological gambling.


1979 ◽  
Vol 57 (6) ◽  
pp. 595-599 ◽  
Author(s):  
P. D. Hrdina ◽  
K. Elson

The effect of tricyclic antidepressants, chlorpromazine, and some monoamine oxidase inhibitors on the accumulation of [14C]choline by crude synaptosomal (P2) fraction from different regions of rat brain (cortex, striatum, and hippocampus) was investigated. Analysis of choline uptake kinetics resulted in high- and low-affinity components with different Michaelis constants. All tricyclic antidepressants tested inhibited in a dose-dependent manner the high-affinity choline uptake in the three regions, amitriptyline being the most potent. The IC50 values correlated significantly with the relative potencies of imipramine congeners in binding to muscarinic receptors in the brain. Neither tranylcypromine nor pargyline in concentrations up to 0.1 mM had any effect on choline transport. Concentrations of tricyclic antidepressants effective in inhibiting the uptake of choline failed to influence significantly the activity of choline acetyltransferase in brain regions examined. The results suggest that the effect of imipramine congeners on high-affinity choline uptake may be reflected in the anticholinergic properties of these compounds.


2018 ◽  
Vol 21 (2) ◽  
pp. 80-86 ◽  
Author(s):  
Shanta Islam ◽  
Md Shafiullah Shajib ◽  
Bidyut Kanti Datta ◽  
Mohammad A Rashid

Albizia lebbeck (Linn.) Benth. is a deciduous tree which is planted as ornamental and avenue tree almost all over Bangladesh. Leaves of the plant are used in ethnomedicine for the treatment of convulsion and CNS related disorder. This study was aimed to evaluate the neuropharmacological effects of the methanol extract of A. lebbeck leaves in Swiss albino mice. The locomotor effect of crude methanol extract of the plant was investigated by open field and hole cross tests while the anxiolytic activity was determined using elevated plus-maze (EPM) and light/dark box (LDB) tests. Furthermore, the sedative activity of the plant extract was assessed by sodium thiopental-induced sleeping time test. The results demonstrated that the methanol extract significantly (p < 0.001) reduced locomotion of the animals in both hole cross and open field tests in dose-dependent manner at 200-400 mg/kg b.w. In both EPM and LDB tests, the plant extract produced significant anxiolytic effect (p < 0.05) at the doses of 100-400 mg/kg b.w. In addition, it showed significant (p < 0.001) dose-dependent decrease in the onset of sleep and an increase in duration of sleep in sodium thiopental-induced sleeping time test. Preliminary phytochemical analyses of the plant extract revealed the presence of alkaloid, flavonoid, glycoside, saponin, tannin and resin. In acute toxicity test, the leaf extract did not exhibit any adverse effect in mice during 7 days treatment. The results of the present studies suggest that the crude methanol extract of A. lebbeck leaves possesses significant CNS depressant, anxiolytic and sedative properties and rationalize the traditional uses of the plant.Bangladesh Pharmaceutical Journal 21(2): 80-86, 2018


1991 ◽  
Vol 261 (5) ◽  
pp. R1104-R1108 ◽  
Author(s):  
T. Watanabe ◽  
A. Morimoto ◽  
N. Murakami

Injection of a low concentration (0.3 micrograms/kg iv) of interleukin-1 beta (IL-1 beta) produced monophasic fever, but high concentrations (15 micrograms/kg iv) produced biphasic fever in rats. Treatment with IL-1 beta caused dose-dependent rises in the plasma concentration of adrenocorticotropic hormone (ACTH) 30 min after injection. Moreover, significant increases in plasma levels of ACTH were observed 90 and 180 min after injection of the high dose of IL-1 beta. ACTH response induced by IL-1 beta (15 micrograms/kg iv) was suppressed by pretreatment with injection of indomethacin (Indo), a potent inhibitor of prostaglandin (PG) synthesis, in a dose-dependent manner (1 and 10 mg/kg iv). Also, biphasic fever induced by the high dose of IL-1 beta was completely abolished by pretreatment with the intravenous injection of Indo. Intracerebroventricular (icv) injection of Indo (50 micrograms) did not affect febrile and ACTH responses induced by intravenous IL-1 beta, whereas those responses induced by IL-1 beta (2 ng icv) were significantly suppressed by injection of Indo (50 micrograms icv). Although it is possible that intracerebroventricular Indo does not reach the site of intravenous IL-1 beta action within the brain, these results suggest that in rats febrile and ACTH responses induced by intravenous IL-1 beta are caused by IL-1 beta-acting structures outside the blood-brain barrier. It is likely that these structures subsequently synthesize and release PGE2, which in turn induces ACTH and febrile responses in rats.


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