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Objective:To compare the sedative and anti-anxiety effects of levo-tetrahydropalmatine (L-THP) and diazepam on conditioned fear model rats.Methods:According to the random number table method, 32 adult male rats were divided into blank group, model group, diazepam group and L-THP group(with 8 rats in each group). The conditioned fear model was reproduced by the plantar electric shock method. Four days after the modeling, the rats in diazepam group and L-THP group were given diazepam (3.6 mg/kg) and L-THP (25 mg/kg) were respectively gavaged once a day for 10 days, the rats in blank group and model group were given the same volume of saline. After the administration, the elevated plus maze test and the open field test were used to measure the anxiety behavior of the rats, and the sleep energy monitoring system was used to detect changes in sleep and energy-related indicators. SPSS 23.0 and Graphpad Prism 7.0 softwares were used for data analysis, multiple samples between groups were compared by one-way ANOVA, and LSD test was used for pairwise comparison.Results:The results of the elevated plus maze experiment showed that compared with the model group, the percentage of open-arm entry times ((11.27±8.78)%, (30.11±14.59)%, P<0.05) and the percentage of open-arm residence time ((1.94±1.48)%, (17.53±8.21)%, P<0.05) in diazepam group were all significantly increased. Compared with the model group, the open arm residence time, the percentage of open arm residence time and the percentage of open arm entry times in L-THP group showed an upward trend, but there was no statistical significance (all P>0.05). The results of the open field experiment showed that compared with the model group, the time of entering the central grid ((2.99±1.83) s, (6.94±3.52) s, P<0.05) and the time of entering the peripheral field ((297.01±1.83) s, (293.30±3.52) s, P<0.05) in diazepam group both increased. Compared with the model group, there was no significant difference in the changes of various indexes in L-THP group (all P>0.05). The results of locomotor activities showed that the autonomic activity times of model group in nighttime was significantly lower than that of blank group((758.79±375.37)times/h, (1 101.93±525.96)times/h, P<0.05). Compared with the model group, the number of autonomous activities of rats in L-THP group in daytime ((820.57±364.60) times/min, (502.40±228.54)times/min, P<0.05) decreased, and the number of autonomous activities in the nighttime ((758.79±375.37) times/min, (1 146.85±309.69)times/min, P<0.05) increased, but there was no significant change in the number of autonomous activities in the whole day. Correlation analysis of energy metabolism related indexes and sleep time of rats in each group were analyzed. The experimental results showed that the daytime sleep time were negatively correlated with heat value ( r=-0.335, P<0.05), and the night sleep time was positively correlated with daytime heat value ( r=0.352, P<0.05). Conclusion:L-tetrahydropalmatine has no significant anti-anxiety effect in the concentration range used in this study, but its sedative and improving sleep activity rhythm are better than diazepam.
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To investigate the effects of Corydalis Rhizoma and L-tetrahydropalma-tine (L-THP) on the levels of dopamine neurotransmitter (DA), dopamine transporter (DAT) and the second dopamine receptor (D2R) in learning and memory-related brain areas, hippocampus and striatum, the DA, DAT and D2R were detected in conditioned place preference (CPP) rats suffered from morphine. And comparation the degree of similarity and consistency of the pharmacological effects was also studied. The rats were trained in black compartments and white ones (drug-paired compartment) with the increasing doses of morphine for 10 days (hypodermically injected from 10 mg•kg⁻¹ to 100 mg•kg⁻¹). Models of CPP were validated in those psychological dependence rats after 48 h training. The dopamine contents were detected as soon as the materials of hippocampus and striatum are harvested from rats of NS control group and model group. The DAT and D2R levels are measured by Western blot. The high, medium and low dose group of Corydalis Rhizoma are given Corydalis Rhizoma 2, 1, 0.5 g•kg⁻¹ water extraction liquid respectively (which contains L-THP were 0.274, 0.137 and 0.137 mg respectively), and the high, medium and low dose group of L-THP were given L-THP 3.76, 1.88, 0.94 mg•kg⁻¹ lavage treatment respectively, NS treatment group were lavaged normal saline for 6 days and they were killed after test of CPP, again tested DA levels and expression of DAT and D2R similar to the front of materials. The reduction effects of CPP were observed in the groups of both Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) subjected to medicine for 6 days (P<0.01). Compared with the NS treatment group and the model group, the higher values including in the contents of neurotransmitter dopamine were detected of hippocampus and striatum (P<0.01, P<0.05), the DAT and D2R protein expression of Corydalis Rhizoma (2, 1 g•kg⁻¹) and L-THP (3.76, 1.88 mg•kg⁻¹) increased in hippocampus and striatum (P<0.01). Learning and memory-related brain regions hippocampus and striatum was another neuroanatomical sites of action in the treatment of mental dependence of fumarate and L-THP, its mechanism was related to lowering its elevated DA neurotransmitter levels, and increasing the expression of DAT and D2R. Corydalis Rhizoma could be play 14-times roles in effect of L-THP. The similar effects were observed on the neurotransmitter dopamine, DAT and D2R in learning and memory-related brain areas, hippocampus and striatum of the morphine- dependent rats.
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Objective: To prepare the molecularly imprinted polymer (MIPs) of L-tetrahydropalmatine (L-THP) by the molecular imprinting technique and study on solid-phase extraction. Methods: Using L-THP as template, methyl acrylic acid (MAA) as functional monmer, and ehtylene glycol dimethacrylate (EDMA) as a cross-linking agent to prepare the L-THP-MIPs. A test was conducted to investigate the selectivity and the specificity of solid-phase extraction. Results: The experiment showed that the MIPs had the specific adsorption to L-THP, but did not have the specific adsorption to corydaline the structural analogue with L-THP. Conclusion: The L-THP-MIPs have a good selectivity and the specificity of L-THP.
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Abnormal adaptation of the stress-response system following traumatic stress can lead to alterations in the hypothalamic-pituitary-adrenal (HPA) axis that may contribute to the development of post-traumatic stress disorder (PTSD). The present study used several behavioral tests to investigate the anxiolytic-like and antidepressant activity of L-tetrahydropalmatine (L-THP) in an experimental rat model of anxiety and depression induced by single prolonged stress (SPS), an animal model of PTSD. Male rats were treated intraperitoneally (i.p.) with vehicle or varied doses of THP 30 min prior to SPS for 8 consecutive days. Daily THP (50 mg/kg) administration significantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index, increased the risk assessment, and increased the number of head dips over the borders of the open arms after SPS. THP was also associated with increased time spent at the center of the open field, reduced grooming behaviors in the EPM test, and reduced time spent immobile in the forced swimming test (FST). It also blocked the decrease in neuropeptide Y (NPY) and the increase in corticotrophin-releasing factor (CRF) expression in the hypothalamus. This is the first study to determine that THP exerts pronounced anxiolytic-like and antidepressant effects on the development of the behavioral and biochemical symptoms associated with PTSD, indicating its prophylactic potential. Thus, THP reversed several behavioral impairments triggered by the traumatic stress of SPS and is a potential non-invasive therapeutic intervention for PTSD.
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Animals , Humans , Male , Rats , Anxiety , Arm , Axis, Cervical Vertebra , Depression , Grooming , Head , Hypothalamus , Models, Animal , Neuropeptide Y , Physical Exertion , Risk Assessment , Stress Disorders, Post-TraumaticABSTRACT
Objective To observe effects of conditioned place preference (CPP) of morphine dependent rats,variation of dopamine neurotransmitter and its receptor 2 of the striatum in rats suffered from 1-tetrabydropalmatine(l-THP).Methods The CPP model was established by morphine injection in rats with a increasing dose for 10 days,with the initial dose of 10 mg · kg-1 and the final dose of 100 mg · kg-1,10 mg · kg-1 was increased each day,thus 100 nmg · kg-1 Was injected by day 10.Treatments with administration of 1-THP(3.76,1.88 and 0.94 mg/kg) were performed respectively for 6 days,and the effects of CPP for psychological dependence in these rats were observed.Striatum samples were taken out and their variable contents of dopamine neurotransmitter and its receptor 2 in striatum were detected by high performance liquid chromatography and immunohistochemisty,respectively.Results Compared with the NS treatment group,the time of animals treated with 1-THP (3.76 and 1.88 mg/kg) staying in drug-paired compartment were reduced (354 ± 58,373 ± 79) (P＜ 0.01) ;the raised of variation contents of dopamine neurotransmitter were reduced in striatum from those rats(5.49 ± 1.95,6.11 ± 1.05),while the expression level of dopamine receptor 2 was increased(0.08 ± 0.02,0.07 ± 0.03) (P ＜ 0.01 or P ＜0.05).Conclusion Reversing dopamine neurotransmitter and its receptor 2 in striatum of morphine dependent rats may be one of the possible mechanisms that 1-THP effectively inhibit the effects of morphine CPP.
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Objective: To observe the changes of hemeoxygenase-1 (HO-1) activity in cerebral tissue, carboxyhemoglobin (COHb) level in blood of rats during global cerebral ischemia/reperfusion (I/R) and the influence of L-tetrahydropalmatine (L-THP) on them. Methods: Seventy-seven Sprague-Dawley (SD) rats were randomly divided into sham-operated group (S group, n=7), I/R group (I group, n=35) and L-2THP treatment group (T group, n=35). Cerebral I/R model was reproduced in SD rats of I group and T group. HO-1 activity, cyclic GMP (cGMP) in the brain and COHb in blood were evaluated respectively at 1, 3, 12, 24, and 48 hours after global cerebral I/R and compared to those of the S group. Results: ① HOCD*21 activity, COHb content and cGMP level in I group increased as compared with those in S group after global cerebral I/R (all P
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One of the constituents of the oriental traditional pill named Balok was Tuber Stephaniae rotundae, the active principle of which was rotundine. The test solutions used for the analysis of rotundine were standardized after ISO/IEC 17027 and GLP, the equipment was adjusted after ISO/IEC 17025. The proposed HPLC technique was proved to be appropriate and stable for the quantitative determination of rotundine. The examined concentration showed the linear correlation between the rotundine concentration and the pic surface. The reproducibility of the method was high, with RSD = 0.98%. The accuracy rate of the method was 100.01%, with RSD = 2.0%.
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Chromatography, High Pressure Liquid , Berberine AlkaloidsABSTRACT
Objective To study the counteraction of l- tetrahydropalmatine (l- THP) against bromocriptine (Bro)- induced hypoprolactin in lactational rats and to prove that l- THP is an antagonist of dopamine D2 receptors. Methods The lactational rat model with hypoprolactin was established by subcutaneous injection of Bro (0.5 mg/kg).The counteraction of l- THP (6 and 18 mg/kg, ip)was evaluated by observing serum prolactin (PRL) level, weight growing in newly born rats, and histology changes of mammary gland. Results Bro (0.5 mg/kg, sc) reduced the PRL level and induced the dysplasia of mammary gland in lactational rats. Bro also caused the retardation of the weight growing in newly- born rats. l- tetrahydropalmatine 6 and 18 mg/kg ip remarkably increased the prolactin level and promoted the development of mammary gland in lactational rats models and promoted the weight growing in newly- born rats. Conclusion l- tetrahydropalmatine(l- THP) has an antagonism against dopamine D2 receptors.
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Hemodynamic study of L-THP in anaesthetized rats showed that 6 mg/kg iv decreased only blood pressure (BP) significantly, and decreased left ventricular pressure ( LVP ) temporarily. At the dose of 18 mg/kg, L-THP lowered the BP, LVP, ? ( dP/dt ) max, ( dP/dt ) P-1 and HR. But the degrees o?diminutions of BP were greater than that of cardiac contractility. The inhibitory percentage of L-THP on DAP was greater than that of SAP. In addition, the extent of decrease of DAP was shown dose dependently. The results suggest that L-THP reduces the peripheral vessel resistance, and it inhibits the cardiac contractibility in high dosage.
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The antagonistic effects of L-THP, Ver and Pap to contraction of isolated guinea pig trachea preparations induced by BaCl2 10-3mol/L ,KC1 3?10-2mol/L, 5-HT 2?10-5mol/L, Ach 2?10-5mol/L and His 2? 10-5mol/L were studied.The antagonistic effects of L-THP were different from Ver and Pap. The IC50 value of L-THP for contraction induced by BaCl2, KC1, 5-HT and His was 3 .5? 10-5mol/L , 4.5 ? 10-5mol/L , 2.5?10-3 mol/L and 8.9? 10-5mol/L respectively. It was showed that sensibility of several agonists to inhibition by L-THP was correlated with dependence of extracellular Ca2+. The potencies of L-THP on anti-KCl and anti-5-HT actions were similar. The results suggested that LTHP possesses anti-calcium and anti-5-HT action on guinea pig trachea.