Antidepressant-like effect of ursolic acid isolated from Rosmarinus officinalis L. in mice: Evidence for the involvement of the dopaminergic system

Ursolic acid, a constituent from Rosmarinus officinalis, is a triterpenoid compound which has been extensively known for its anticancer and antioxidant properties. In the present study, we investigated the antidepressant-like effect of ursolic acid isolated from this plant in two predictive tests of antidepressant property, the tail suspension test (TST) and the forced swimming test (FST) in mice. Furthermore, the involvement of dopaminergic system in its antidepressant-like effect was investigated in the TST. Ursolic acid reduced the immobility time in the TST (0.01 and 0.1 mg/kg, p.o.) and in the FST (10 mg/kg, p.o.), similar to fluoxetine (10 mg/kg, p.o.), imipramine (1 mg/kg, p.o.) and bupropion (10 mg/kg, p.o.). The effect of ursolic acid (0.1 mg/kg, p.o.) in the TST was prevented by the pretreatment of mice with SCH23390 (0.05 mg/kg, s.c., a dopamine D₁ receptor antagonist) and sulpiride (50 mg/kg, i.p., a dopamine D₂ receptor antagonist). The administration of a sub-effective dose of ursolic acid (0.001 mg/kg, p.o.) in combination with sub-effective doses of SKF38393 (0.1 mg/kg, s.c., a dopamine D₁ receptor agonist), apomorphine (0.5 μg/kg, i.p., a preferential dopamine D₂ receptor agonist) or bupropion (1 mg/kg, i.p., a dual dopamine/noradrenaline reuptake inhibitor) reduced the immobility time in the TST as compared with either drug alone. Ursolic acid and dopaminergic agents alone or in combination did not cause significant alterations in the locomotor and exploratory activities. These results indicate that the antidepressant-like effect of ursolic acid in the TST is likely mediated by an interaction with the dopaminergic system, through the activation of dopamine D₁ and D₂ receptors.     

开环式微创痔上粘膜切除吻合术(TST术)与Milligan-Morgan术治疗痔病疗效及术后并发症对比

目的:比较开环式微创痔吻合术(TST术)与Milligan-Morgan术(M-M术)治疗痔病的临床疗效及并发症有无差异。方法:将86名Ⅲ、Ⅳ度痔患者,随机分为实验组(TST术组)和对照组(M-M术组),比较两组治疗的效果及术后并发症。结果:实验组在脱垂、出血症状的改善及远期复发率与对照组比较差异无统计学意义(P>0.05),而在手术时间、住院时间、术后肛门疼痛、水肿、小便情况方面与对照组比较差异有统计学意义(P<0.05)。结论:TST手术在疗效上与MMH手术相似,但具有手术时间短,住院时间短,术后肛门疼痛、水肿、尿潴留程度轻的优点。     

TST与PPH治疗Ⅲ~Ⅳ度内痔的临床疗效对比分析

目的比较选择性痔上黏膜吻合术（TST）与痔上黏膜环切术（PPH）治疗Ⅲ~Ⅳ度内痔的疗效。 方法回顾性分析郑州人民医院肛肠外科2017年5月至2017年7月间因Ⅲ~Ⅳ度内痔接受TST和PPH共60例住院患者的临床资料。 结果TST较PPH手术,两组疗效相当,均缓解了脱出、便血症状,但差异无统计学意义（P>0.05）,但两组在术后并发症上,肛门坠胀感差异有统计学意义（P<0.05）,而吻合口狭窄差异无统计学意义（P>0.05）。 结论TST是治疗非环状Ⅲ～Ⅳ度内痔的一种个体化、微创化、精准化治疗的方法。     

Melatonin agonists in primary insomnia and depression-associated insomnia: are they superior to sedative-hypnotics?

Current pharmacological treatment of insomnia involves the use of sedative-hypnotic benzodiazepine and non-benzodiazepine drugs. Although benzodiazepines improve sleep, their multiple adverse effects hamper their application. Adverse effects include impairment of memory and cognitive functions, next-day hangover and dependence. Non-benzodiazepines are effective for initiating sleep but are not as effective as benzodiazepines for improving sleep quality or efficiency. Furthermore, their prolonged use produces adverse effects similar to those observed with benzodiazepines. Inasmuch as insomnia may be associated with decreased nocturnal melatonin, administration of melatonin is a strategy that has been increasingly used for treating insomnia. Melatonin can be effective for improving sleep quality without the adverse effects associated with hypnotic-sedatives. Ramelteon, a synthetic analog of melatonin which has a longer half life and a stronger affinity for MT1 and MT2 melatonergic receptors, has been reportedly effective for initiating and improving sleep in both adult and elderly insomniacs without showing hangover, dependence, or cognitive impairment. Insomnia is also a major complaint among patients suffering from depressive disorders and is often aggravated by conventional antidepressants especially the specific serotonin reuptake inhibitors. The novel antidepressant agomelatine, a dual action agent with affinity for melatonin MT1 and MT2 receptors and 5-HT2c antagonistic properties, constitutes a new approach to the treatment of major depressive disorders. Agomelatine ameliorates the symptoms of depression and improves the quality and efficiency of sleep. Taken together, the evidence indicates that MT1/MT2 receptor agonists like ramelteon or agomelatine may be valuable pharmacological tools for insomnia and for depression-associated insomnia.     

Effect of various classes of antidepressants in behavioral paradigms of despair

The forced swim test (FST) and tail suspension test (TST) are widely used as animal models for screening potential antidepressants. Immobility or despair behavior produced in both FST and TST are taken as paradigm of depression and antidepressant drugs reduce the immobility period. Recent studies have suggested dissimilar hemodynamic, behavioral, physiological and pharmacological variations in these two models. Also, studies have proposed the significance of strain in these models of despair in an attempt to replicate results from one laboratory to another. The present study was undertaken to compare the antidepressant action of four major classes of antidepressants namely tricyclics (imipramine), selective serotonin reuptake inhibitor (fluoxetine), dual reuptake inhibitor of serotonin and norepinephrine (venlafaxine) and atypical antidepressants (mianserin and trazodone) using male laca mice in order to validate the two test procedures. Total immobility period was recorded during the period of 6 min in both the tests and the results were expressed as percentage decrease in immobility period with respect to vehicle control. Chlorpromazine (4 mg/kg, i.p.) or pentobarbitone (20 mg/kg, i.p.) were used as negative control. Imipramine (2, 5, 10 and 20 mg/kg), fluoxetine (5, 10, 20 and 40 mg/kg), or venlafaxine (2, 4, 8 and 16 mg/kg) dose dependently decreased the immobility period in mice. ED(50) values of imipramine, fluoxetine, and venlafaxine in FST and TST were found to be 9.2 and 10 mg/kg i.p, 18 and 20 mg/kg, i.p., and 8.5 and 12 mg/kg, i.p respectively. The relative potency of standard drugs in both FST and TST is imipramine=venlafaxine>fluoxetine. Mianserin (16 and 32 mg/kg., i.p.) or trazodone (1 and 2 mg/kg., i.p.) were ineffective to reduce the immobility period in both the tests showing the atypical nature of these antidepressants. Chlorpromazine or pentobarbitone was ineffective in reversing the immobility period thus validating the models for testing antidepressants. The present study further validated that both the test procedures are equi-sensitive to antidepressant drugs of different class in the strain of animals used.     

Respiratory patterns during sleep in obesity-hypoventilation patients treated with nocturnal pressure support: a preliminary report

BACKGROUND: The obesity-hypoventilation syndrome (OHS), commonly defined as a combination of obesity and diurnal hypercapnia, is efficiently treated using nasal positive pressure ventilation (NPPV). The present study aimed to determine whether nocturnal polysomnography allows detection of respiratory disturbances occurring in patients with OHS treated with NPPV that may interfere with the quality of sleep and of ventilatory support, and are not detected by nocturnal pulse oximetry and capnography. METHODS: Twenty OHS patients in stable clinical condition treated by NPPV for at least 3 months with a bilevel pressure support ventilator were studied. All patients underwent single-night polysomnography under NPPV including transcutaneous measurement of Pco(2) (TcPco(2)). Four types of respiratory events were defined and quantified: patient/ventilator desynchronization, periodic breathing (PB), autotriggering, and apnea-hypopneas. RESULTS: Eleven patients (55%) exhibited desynchronization occurring mostly in slow-wave sleep and rapid eye movement sleep and associated with arousals but not inducing significant changes in TcPco(2) or oxygen saturation using pulse oximetry (Spo(2)). Eight patients (40%) showed a high index of PB, mostly occurring in light sleep and associated with more severe nocturnal hypoxemia. Autotriggering was sporadic and usually limited to one or two breaths, although prolonged and asymptomatic autotriggering occurred in one patient during 10.6% of total sleep time. CONCLUSIONS: Patient/ventilatory asynchrony and PB are respiratory patterns occurring frequently in OHS patients treated using NPPV. Nocturnal monitoring of Spo(2) and TcPco(2), commonly used to assess the efficacy of ventilatory support, do not adequately explore this aspect of therapy that might influence its efficacy as well as sleep quality.     

Respiratory polygraphy with actigraphy in the diagnosis of sleep apnea-hypopnea syndrome

OBJECTIVE: To determine the utility and reliability of a respiratory polygraphy (RP) device with actigraphy (Apnoescreen II; Erich Jaeger GMBH & CoKg; Wuerzburg, Germany) in the diagnosis of sleep apnea-hypopnea syndrome (SAHS). DESIGN: A prospective randomized study with blinded analysis. PATIENTS: Sixty-two patients with suspected SAHS. MEASUREMENTS: the following two RP studies were performed: one in the sleep laboratory (sleep laboratory RP [LRP]), simultaneously with polysomnography; and the other at home (home RP [HRP]). To study the interobserver reliability of RP, two manual analyses were carried out by two different researchers. RESULTS: In LRP, when the respiratory disturbance index was calculated using the total sleep time estimated by actigraphy (RDI) as a denominator, the sensitivity ranged between 94.6% and 100%, and the specificity between 88% and 96.7% for the different cutoff points of the apnea-hypopnea indexes studied. When the respiratory disturbance index was calculated according to the total recording time (RDITRT), the sensitivity was slightly lower (91.6 to 96.9%) and the specificity was similar (92 to 96.7%). In HRP, the sensitivity of the RDI ranged between 83.8% and 95.8%, and the specificity between 92% and 100%, whereas, when the RDITRT was used, the sensitivity was between 83.8% and 87.5%, and the specificity was between 94.7% and 100%. With regard to interobserver reliability, the intraclass correlation coefficient for the RDI of the two analyses of the RP was 0.99 for both LPR and HPR. CONCLUSION: HPR is an effective and reliable technique for the diagnosis of SAHS, although it is less sensitive than LRP. Wrist actigraphy improves the results of HRP only slightly.     

Potential antidepressant properties of cysteamine on hippocampal BDNF levels and behavioral despair in mice

Several studies have demonstrated that antidepressants increase central brain-derived neurotrophic factor (BDNF) levels, suggesting that BDNF signaling is important for the therapeutic mechanism of antidepressants. Recent work has found that cysteamine and its related agent, cystamine, are neuroprotective in Huntington's disease mice, and act by enhancing the secretion of central BDNF. In the present study, the potential antidepressant effects of cysteamine were examined by behavioral paradigms and biochemical assay. Male BALB/CByJ mice were given a single dose of normal saline, 10 mg/kg of imipramine or either 50, 100 or 200 mg/kg of cysteamine (i.p.) 30 min before undergoing the forced-swimming test (FST) or the tail suspension test (TST). Other groups of mice treated with the same drugs and doses, without behavioral tests, were sacrificed for hippocampal BDNF measurements. We found that, compared with the control group, the cysteamine 200-mg/kg group showed a significant reduction in immobility time in the FST (P<0.01) and TST (P<0.01), and showed lower activity in the open field test (P<0.01). A significant increase in hippocampal BDNF levels was found in the cysteamine 200-mg/kg group (P<0.05). Our findings suggested that cysteamine may possess an antidepressant-like effect, which may be mediated by increasing central BDNF levels.     

Antidepressant-like effects of liquiritin and isoliquiritin from Glycyrrhiza uralensis in the forced swimming test and tail suspension test in mice

Two classic animal behavior despair tests--the Forced Swimming Test (FST) and the Tail Suspension Test (TST) were used to evaluate the antidepressant activity of liquiritin and isoliquiritin from Glycyrrhiza uralensis in mice. It was observed that both liquiritin and isoliquiritin at doses of 10, 20 and 40 mg/kg significantly reduced the immobility time in the FST and TST in mice 30 min after treatment. Measurement of locomotor activity indicated that liquiritin and isoliquiritin had no central nervous system (CNS)-stimulating effects. The main monoamine neurotransmitters and their metabolites in mouse brain regions were also simultaneously determined by HPLC-ECD. It was found that these two compounds significantly increased the concentrations of the main neurotransmitters 5-HT and NE in the hippocampus, hypothalamus and cortex. Liquiritin and isoliquiritin also significantly reduced the ratio of 5-HIAA/5-HT in the hippocampus, hypothalamus and cortex, slowing down 5-HT metabolism compared with mice treated with vehicle+stress. In conclusion, liquiritin and isoliquiritin produced significant antidepressant-like effects, and their mechanism of action may be due to increased 5-HT and NE in the mouse hippocampus, hypothalamus and cortex.