Involvement of central noradrenaline, serotonin and dopamine system in the antidepressant activity of fruits of Solanum torvum (Solanaceae)

The methanolic extract (ME) of Solanum torvum seeds and its ethyl acetate fraction (EAF) were investigated for their antidepressant activity using behavioral (forced swim test, FST and tail suspension test, TST) and biochemical (monoamine oxidase, MAO reduced activity) tests. ME (10, 30 and 100?mg?kg(-1)) and EAF (10 and 30?mg?kg(-1)) dose dependently inhibited the immobility period, increased noradrenaline, serotonin and dopamine levels and inhibited the MAO enzymes in FST and TST using mice. Furthermore, we have observed antagonism between the threshold dose of ME (30 and 100?mg?kg(-1)) and EAF (10 and 30?mg?kg(-1)) with antagonists on behaviour mediated by neurotransmitters noradrenaline, serotonin and dopamine. MAO-A inhibition was more prominent as compared to MAO-B inhibition. The study provides evidence for antidepressant actions of S. torvum.     

Antidepressant activity of Ceratonia siliqua L. fruit extract, a source of polyphenols

A previous study from our laboratory has shown the facilitatory effect of Ceratonia siliqua L. (Fabaceae) on the dopaminergic function. This study investigates the involvement of monoamines in the antidepressant activity of the total polyphenol content of Ceratonia siliqua extract (CS) in mice using a tail suspension test (TST) and forced swim test (FST). The immobility time in the TST and FST were significantly reduced by CS (25 and 50 mg kg(-1), i.p.). The extract considerably attenuated the duration of immobility induced by prazosin (62.5 μg kg(-1), i.p., an α-adrenoceptor antagonist) and eticlopride (0.1 μg kg(-1), i.p., a classical D2-like dopamine receptor antagonist) in both TST and FST, whereas the extract could not modify the immobility in mice treated with p-chlorophenylalanine (100 mg kg(-1), i.p., ×3 days; an inhibitor of serotonin synthesis) and baclofen (10 mg kg(-1), i.p., GABAB agonist). This suggests that the antidepressant effect of CS is mediated by dopamine and noradrenaline.     

Pedicularis resupinata Extract Prevents Depressive-like Behavior in Repeated Corticosterone-Induced Depression in Mice: A Preliminary Study

Excessive corticosterone (CORT), resulting from a dysregulated hypothalamic–pituitary–adrenal (HPA) axis, is associated with cognitive impairment and behavioral changes, including depression. In Korean oriental medicine, Pedicularis resupinata is used for the treatment of inflammatory diseases such as rheumatoid arthritis. However, the antidepressant properties of P. resupinata have not been well characterized. Here, the antidepressant-like effects of P. resupinata extract (PRE) were evaluated in terms of CORT-induced depression using in vivo models. HPLC confirmed that acteoside, a phenylethanoid glycoside, was the main compound from PRE. Male ICR mice (8 weeks old) were injected with CORT (40 mg/kg, i.p.) and orally administered PRE daily (30, 100, and 300 mg/kg) for 21 consecutive days. Depressive-like behaviors were evaluated using the open-field test, sucrose preference test, passive avoidance test, tail suspension test, and forced swim test. Treatment with a high dose of PRE significantly alleviated CORT-induced, depressive-like behaviors in mice. Additionally, repeated CORT injection markedly reduced brain-derived neurotrophic factor levels, whereas total glucocorticoid receptor (GR) and GR phosphorylation at serine 211 were significantly increased in the mice hippocampus but improved by PRE treatment. Thus, our findings suggest that PRE has potential antidepressant-like effects in CORT-induced, depressive-like behavior in mice.     

In vivo microdialysis determination of collagen-induced serotonin release in rat blood

We developed a sensitive microbore HPLC method coupled with an on-line microdialysis system to simultaneously measure endogenous 5-hydroxytryptamine (serotonin; 5-HT) and its major metabolite 5-hydroxyindoleacetic acid (5-HIAA) in the rat blood in vivo. A dialysis tube was placed in the right jugular vein. The validity of the procedure is demonstrated because analysis of the aggregating agents, collagen (I mg/kg) plus epinephrine (0.3 mg/kg) after intravenous injection, showed that they induced an increase in 5-HT and 5-HIAA levels in the jugular vein of the rat.     

Antidepressant-like Effects of Combined Fluoxetine and Zinc Treatment in Mice Exposed to Chronic Restraint Stress Are Related to Modulation of Histone Deacetylase

Chronic stress is the key factor contributing to the development of depressive symptoms. Chronic restraint stress (CRS) is well validated and is one of the most commonly used models to induce depressive-like behavior in rodents. The present study aimed to evaluate whether fluoxetine (FLU 5 mg/kg) and zinc (Zn 10mg/kg) given simultaneously induce a more pronounced antidepressant-like effect in the CRS model than both those compounds given alone. Behavioral assessment was performed using the tail suspension and splash tests (TST and ST, respectively). Furthermore, the effects of CRS, FLU and Zn given alone and combined treatment with FLU + Zn on the expression of proteins involved in the apoptotic, inflammatory, and epigenetic processes were evaluated in selected brain structures (prefrontal cortex, PFC; and hippocampus, Hp) using Western blot analysis or enzyme-linked immunosorbent assays (ELISA). The results obtained indicated that three hours (per day) of immobilization for 4 weeks induced prominent depressive symptoms that manifested as increased immobility time in the TST, as well as decreased number and grooming time in the ST. Behavioral changes induced by CRS were reversed by both FLU (5 and 10 mg/kg) or Zn (10 mg/kg). Zinc supplementation (10 mg/kg) slightly increases the effectiveness of FLU (5 mg/kg) in the TST. However, it significantly increased the activity of FLU in the ST compared to the effect induced by FLU and Zn alone. Biochemical studies revealed that neither CRS nor FLU and Zn given alone or in combined treatment alter the expression of proteins involved in apoptotic or inflammatory processes. CRS induced major alterations in histone deacetylase (HDAC) levels by increasing the level of HADC1 and decreasing the level of HADC4 in the PFC and Hp, decreasing the level of HADC6 in the PFC but increasing it in Hp. Interestingly, FLU + Zn treatment reversed CRS-induced changes in HDAC levels in the Hp, indicating that HDAC modulation is linked to FLU + Zn treatment and this effect is structure-specific.     

Cinnamomum cassia: an implication of serotonin reuptake inhibition in animal models of depression

The aim of the study was to explore the traditional use of Cinnamomum cassia against depression. The standardised methanolic extract of the bark of C. cassia was evaluated for antidepressant activity using various behavioural tests, i.e. tail suspension test (TST), forced swim test (FST) and locomotor activity test. The serotonergic and noradrenergic modulation was assessed using 5-hydroxytryptophan (5-HTP)-induced head twitches and yohimbine potentiation tests, respectively. The fluoxetine and phenelzine were used as positive controls in the study. The C. cassia extract significantly decreased the immobility time in TST (maximum effective dose tested was 50 mg/kg) while no effect was observed in FST and locomotor activity test. The extract significantly increased the 5-HTP-induced head twitches while yohimbine-induced lethality remained unaltered. The aforementioned results are similar to that caused by fluoxetine. The standardised methanolic extract of C. cassia demonstrated antidepressant activity that can be attributed to rise in serotonin levels.     

Simultaneous HPLC Analysis of Catecholamines and Indoleamines in Mouse Brain Tissue Following Acetate Extraction and Treatment with Ascorbate Oxidase

Abstract

A refined HPLC Method for the determination of monoamine levels in six brain regions is presented. Analyses are made for the olfactory tubercles, prefrontal cortex, septum, striatum, amygdala and hypothalamus of adult male ICR mice. This system permits the simultaneous analysis of norepinephrine, dopamine, serotonin and their major metabolites during a single run of approximately twenty-five minutes without prior clean-up of samples.     

LC/ESI/TOF-MS Characterization,Anxiolytic and Antidepressant-like Effects of Mitragyna speciosa Korth Extract in Diabetic Rats

In this study, the attenuative effects of the hydro-alcoholic extract from Mitragyna speciosa (MSE) against diabetes-induced anxiety and depression-like behaviors were examined. In addition, UPLC/ESI/TOF-MS analysis was performed to identify the phytochemical nature of MSE. DM was induced using a combination of high fructose/streptozotocin, and the diabetic rats were treated with MSE (50 and 200 mg/kg) for 5 weeks. After treatment, the animals were subjected to a forced swim test, open field test and elevated plus-maze tests. Additionally, proinflammatory cytokines and oxidative stress parameters were evaluated in the brain tissues of the rats. UPLC/ESI/TOF-MS analysis revealed that MSE is abundantly rich in polyphenolic constituents, notably flavonoid and phenolic glycosides. Behavioral tests and biochemical analyses indicated that diabetic rats showed significantly increased anxiety and depressive-like behavioral deficits, brain oxidative stress and pro-inflammatory cytokines levels (IL-1β, IL-6 and TNF-α). Treatment with MSE (50 and 200 mg/kg) significantly attenuated increased blood glucose level, depressive and anxiety-like behaviors in diabetic rats. Additionally, the antioxidant enzymes activities were markedly increased in MSE-treated animals, while TNF-α, IL-1β and IL-6 cytokines were notably suppressed. Taken together, these results suggested that MSE has potentials as antidepressant and anxiolytic-like effects and improves the brain oxido-inflammatory status in diabetic rats.     

化妆品中8种呋喃香豆素的高效液相色谱法检测及质谱确证

建立了同时测定化妆品中8种呋喃香豆素类化合物(8-羟基补骨脂素、补骨脂素、异补骨脂素、8-甲氧基补骨脂素、5-甲氧基补骨脂素、三甲沙林、欧前胡素和异欧前胡素)的高效液相色谱分析方法及液相色谱-串联质谱确证方法。膏霜类、水剂类、香波类、散粉类、唇膏类等不同类型的化妆品样品分别经适宜的提取溶液进行超声提取,提取液以离心处理后,取上清液经微孔滤膜过滤后测定。采用Agilent Zorbax SB-Phenyl色谱柱(250 mm×4.6 mm, 5 μm)分离,以甲醇-乙腈-水三元流动相梯度洗脱,流速1.0 mL/min,柱温30 ℃,检测波长250 nm。8-羟基补骨脂素的定量限为0.25 mg/kg,补骨脂素、异补骨脂素、8-甲氧基补骨脂素、5-甲氧基补骨脂素、三甲沙林、欧前胡素、异欧前胡素的定量限为0.5 mg/kg。在低、中、高3种加标水平下,8种待测组分的平均回收率为85.0%～105.8%,相对标准偏差为0.41%～7.90%。采用本方法在一日内不同时间点(6个时间点,每隔1 h测定一次)和不同日期(6 d内)测定混合标准溶液,得到8个目标物峰面积的日内精密度均小于1%,日间精密度均小于2%。该方法准确、简便、快速,适用于不同类型化妆品中8种呋喃香豆素类化合物的测定。     

高效液相色谱-串联质谱法测定化妆品中的欧前胡素和异欧前胡素

建立了化妆品中欧前胡素和异欧前胡素的高效液相色谱-串联质谱(HPLC-MS/MS)测定与确证方法。样品经甲醇提取,以C18柱为分离柱,10 mmol/L乙酸铵/甲醇溶液-5 mmol/L乙酸铵水溶液(80:20, v/v)为流动相分离,采用电喷雾串联四极杆质谱进行检测。欧前胡素和异欧前胡素在0.25～20 μg/L内线性良好(相关系数大于0.999);方法定量限(LOQ)为0.50 mg/kg。在0.50～10.0 mg/kg内,欧前胡素和异欧前胡素的回收率范围分别为82.2%～105%和80.0%～103%,相对标准偏差分别为2.7%～4.9%和1.8%～4.6%。该方法能够满足化妆品中欧前胡素和异欧前胡素检测的需要。     

Antidepressant Effect of Crocin in Mice with Chronic Mild Stress

This study aimed to investigate the antidepressant property of crocin (Crocetin digentiobiose ester) using a chronic mild stress (CMS)-induced depression model in experimental mice. The tail suspension test (TST) and the sucrose preference test were used to evaluate the antidepressant effect on albino mice of either sex after three weeks of CMS. The period of immobility in the TST and percentage preference for sucrose solution were recorded. By monitoring brain malondialdehyde (MDA) level, catalase (CAT) activity, and reduced glutathione (GSH) level, the antioxidant potential was assessed. Three dosages of crocin (4.84, 9.69, and 19.38 mg/kg) were evaluated. When compared to controls, animals that received crocin administration during three periods of CMS had considerably shorter immobility times during the TST. Crocin treatment also raised the percentage preference for sucrose solution in a dose-dependent manner, bringing it to parity with the conventional antidepressant, imipramine. Animals that received a high dose of crocin had a much greater spontaneous locomotor activity. Furthermore, a high dose of crocin remarkably lowered plasma corticosterone and nitrite levels brought on by CMS. Additionally, high doses of crocin given during CMS greatly enhanced reduced glutathione levels while considerably reducing the brain’s MDA and catalase activities. In conclusion, high doses of crocin may have an antidepressant effect in an animal model through several mechanisms. However, further studies should be carried out to explore the role of neurotransmitters for their antidepressant property.     

Simultaneous determination of imperatorin and its metabolites in vitro and in vivo by a GC‐MS method: application to a bioavailability and protein binding ability study in rat plasma

In this study, a simple and sensitive gas chromatography–mass spectrometry method was developed for the study of bioavailability and protein binding and the metabolism of imperatorin in rat. The results showed that the pharmacokinetics of imperatorin after intravenous and oral administration in rats exhibited linear characteristics. The absolute bioavailability of imperatorin was calculated as ~3.85, ~33.51 and ~34.76% for 6.25, 12.5 and 25 mg/kg, respectively. The low bioavailability of imperatorin may be attributed to the poor absorption or extensive metabolism. The phase I metabolites of imperatorin formed in vitro by rat liver microsomes were studied, and two metabolites were isolated and identified as xanthotoxol and heraclenin. Following oral administration of imperatorin, one metabolite (heraclenin) was detected in rat plasma, and two potential metabolites (xanthotoxol and heraclenin) were detected in rat urine. However, none of potential metabolites was detected in rat feces and bile. The results showed that the metabolites of imperatorin were excreted by kidney, and heraclenin was associated with an active component. Demethylation and oxygenization were the main metabolic pathways. In vitro plasma protein binding of imperatorin was 90.1 and 92.6% for the spiked rat plasma concentrations of 1.0 and 50.0 µg/mL, respectively, indicating that imperatorin showed slow distribution into the intra‐ and extracellular space. Copyright © 2013 John Wiley & Sons, Ltd.     

LC/QTOF profile and preliminary stability studies of an enriched flavonoid fraction of Cecropia pachystachya Trécul leaves with potential antidepressant‐like activity

There is increasing interest in natural antioxidants that are candidates for the prevention of brain damage occurring in major depressive disorders. Cecropia pachystachya is a tropical tree species of Central and South America and a rich source of polyphenols, particularly flavonoids. The aim of this study was to characterize the flavonoid profile of an enriched flavonoid fraction of C. pachystachya (EFF‐Cp ) and evaluate the antidepressant‐like effects of its acute administration in behavior, cytokine levels, oxidative stress and energy metabolism parameters. The EFF‐Cp chemical characterization was performed by HPLC/DAD and LC/QTOF. The antidepressant‐like effects were performed by the forced swimming test, splash test and open field test. EFF‐Cp revealed 15 flavonoids, including seven new glycosyl flavonoids for C. pachystachya . Quantitatively, EFF‐Cp showed isoorientin (43.46 mg/g), orientin (23.42 mg/g) and isovitexin (17.45 mg/g) as major C ‐glycosyl flavonoids. In addition, EFF‐Cp at doses 50 and 100 mg/kg reduced the immobility time in the forced swimming test, without changing the locomotor activity and grooming time. In addition, EFF‐Cp was able to prevent the oxidative damage in some brain areas. In conclusion, the results of this study suggest that EFF‐Cp exerts antidepressant‐like effects with its antioxidant properties.     

Determination of N-acetylaspartic acid concentration in the mouse brain using HPLC with fluorescence detection

The concentration of brain N-acetylaspartic acid (NAA) in mice was determined by high-performance liquid chromatography (HPLC) using fluorescence detection after pre-column derivatization with 4-N,N-dimethylaminosulfonyl-7-N-(2-aminoethyl)amino-2,1,3-benzoxadiazole (DBD-ED). Six different brain parts, namely, the prefrontal cortex, olfactory bulb, nucleus accumbens, striatum, cerebellum and hippocampus, of male C57BL6/J mice, were investigated. The NAA concentration (nmol/mg protein) was highest in the olfactory bulb (58.2 ± 4.0, n = 8) and lowest in the hippocampus (42.8 ± 1.6, n = 8). The proposed HPLC method with fluorescence detection was successfully used to determine the NAA concentration in each investigated brain area.     

Quantitative determination of paroxetine and its 4-hydroxy-3-methoxy metabolite in plasma by high-performance liquid chromatography/electrospray ion trap mass spectrometry: application to pharmacokinetic studies

A high-performance liquid chromatography (HPLC) method with tandem mass spectrometric detection is described for the determination of paroxetine, an antidepressant drug, and its metabolite (3S,4R)-4-(4-fluorophenyl)-3-(4-hydroxy-3-methoxyphenoxymethyl)piperidine (HM paroxetine) in human plasma. Plasma samples were hydrolysed with hydrochloric acid and then analytes were extracted with ethyl acetate at alkaline pH. Extracts were analysed by HPLC coupled to an atmospheric pressure ionisation-electrospray (ESI) interface and an ion trap mass spectrometer. Chromatography was performed on a reversed-phase column using acetonitrile/0.02% formic acid (66:34, v/v) as a mobile phase. The mass spectrometer was operated in the multiple reaction monitoring mode. The method was validated over concentration ranges of 0.75-100 microg/L and 5-100 microg/L for paroxetine and HM paroxetine, respectively. Mean recoveries of 77% for paroxetine and 76% for HM paroxetine were found, with precision always better than 15%. The limits of detection and quantification were 0.20 and 0.70 microg/L for paroxetine, and 0.70 and 2.20 microg/L for its metabolite. The method was applied to the analysis of plasma samples obtained from nine healthy male volunteers administered with a single oral dose of 20 mg paroxetine. After the 20-mg dose, the mean peak plasma concentration was 8.60 microg/L for paroxetine and 92.40 microg/L for HM paroxetine showing a tenfold ratio between the metabolite and the parent drug along the entire time-concentration curve.     

Psychotropic effects of Japanese valerian root extract.

The psychotropic effects of "Hokkai-Kisso", i.e. roots of Japanese valerian, were compared with those of diazepam and imipramine. Both 30% EtOH extract of valerian root (11.2 g/kg) and diazepam (3 mg/kg) significantly prolonged hexobarbital-induced sleep in mice. Spontaneous ambulation and rearing during an open field test were significantly decreased by valerian extract (11.2 g/kg), but kessyl glycol diacetate (KGD, 400 mg/kg) and diazepam (3 mg/kg) significantly increased ambulation. Diazepam (10 mg/kg) significantly decreased approach-avoidance conflict in mice in a water-lick conflict test, but valerian extract and KGD did not. By contrast, valerian extract (4.1 g/kg) and imipramine (20 mg/kg) significantly inhibited immobility induced by a forced swimming test in rats, but did not increase spontaneous motor activity during an open field test just before the forced swimming test. In addition, valerian extract and imipramine significantly reversed reserpine-induced hypothermia in mice. These results indicate that valerian extract acts on the central nervous system and may be an antidepressant.     

Neurochemical studies on catecholamines and indoleamines by high-performance liquid chromatography with electrochemical detection

Summary This communication reports the HPLC separation and quantitative ECD assay of dopamine (DA) and its metabolites DOPAC and HVA, 5-HT and its metabolite 5-HIAA and the noradrenaline metabolites MHPG and VMA, in samples of rat brain extracts and human CSF. The separation is carried out by reversed-phase with a methanolic phosphate/citrate buffer as mobile phase. Response is linear within 10pg-20 ng. Rat brain homogenates of cortex plus striatum were centrifuged and 10–20 l aliquots injected in the column. CSF samples were directly injected without any further manipulation. The method has been applied to the study of the possible neuromodulating role of T on the catecholaminergic and serotonergic transmission. For this purpose rats are injected intraperitoneally (ip) with T (150 mg/kg) and killed after 30 min. Relative to control rats, the results show that for n=12, T does not affect the basal level of DA and DOPAC whereas HVA increases a 99.3% and 5HT and 5HIAA show variations of 23% and — 4.1%, respectively. Aside from the fall of 5HIAA, it is interesting to note that the turnover rate of 5HT decreases, which might prove of functional significance.Presented at the 14th International Symposium on Chromatography London, September, 1982     

Application of liquid chromatography-tandem mass spectrometry method for the simultaneous quantitative analysis of propentofylline and its chiral metabolite M1 in rats

A sensitive and selective liquid chromatographic–electrospray ionization mass spectrometric method for the simultaneous determination of propentofylline and enantiomers of its active metabolite M1 in rat serum, cortex and hippocampus was developed and validated according to GLP procedures. Sample preparations were carried out by liquid–liquid extraction using diethyl ether after the addition of the internal standard (pentoxifylline). The dried residue was reconstituted in mobile phase and injected onto a Chiralpak AD column (10 µm, 250 × 4.6 mm i.d.). The limit of quantification for propentofylline in serum, cortex and hippocampus was set at 0.25 ng/mL and for enantiomers of its metabolite M1 at 1.25 ng/mL. The established LC/ESI‐MS/MS method has been successfully applied to an initial pharmacokinetic study of propentofylline and also to assessment of distribution of parent drug and enantiomers of its pharmacologically active metabolite M1 to cortex and hippocampus after intravenous administration of propentofylline to rats at a dose of 5 mg/kg. Copyright © 2010 John Wiley & Sons, Ltd.     

The Potential of Parsley Polyphenols and Their Antioxidant Capacity to Help in the Treatment of Depression and Anxiety: An In Vivo Subacute Study

Depression and anxiety are major mental health problems in all parts of the world. These illnesses are associated with a number of risk factors, including oxidative stress. Psychotropic drugs of a chemical nature have demonstrated several side effects that elevated the impact of those illnesses. Faced with this situation, natural products appear to be a promising alternative. The aim of this study was to evaluate the anxiolytic and antidepressant effects of the Petroselinum sativum polyphenols in vivo, as well as its correlated antioxidant properties in vitro. Anxiolytic activity of the extract (50 and 100 mg/kg) was evaluated using the open field and the light-dark chamber tests, while the antidepressant activity was evaluated using the forced swimming test. The antioxidant activity of the extract was evaluated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical test and the FRAP (iron-reducing capacity) test. The phenolic extract showed very powerful anxiolytic and antidepressant-like effects, especially at a dose of 100 mg/kg, decreasing the depressive behavior in mice (decreased immobility time) and also the anxiolytic behavior (tendency for discovery in the center and illuminated areas) better even than those of paroxetine and bromazepam (classic drugs) concomitant with those results the extract also showed an important antioxidant capacity. These preliminary results suggest that Petroselinum sativum exhibits anxiolytic and antidepressant potential for use as a complement or independent phytomedicine to treat depression and anxiety.     

Determination of piquindone in canine plasma and urine by high-performance liquid chromatography

This report describes a rapid, sensitive and selective method for the determination of piquindone in canine plasma and piquindone and the N-demethyl metabolite of piquindone in canine urine, utilizing normal-phase high-performance liquid chromatography (HPLC) with isocratic elution at ambient temperature and monitoring the ultraviolet absorbance of the eluent at 254 nm. The trimethyl analogue of piquindone is used as the internal standard in the HPLC assay of plasma. The assay was applied to the measurement of concentrations of piquindone in the plasma and urine of a dog following single intravenous and oral administration of 5 mg/kg doses of piquindone hydrochloride dihydrate.