Establishment of a Rat Model of Hypotension Induced by Reserpine / 中国医学科学院学报

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.

Effects of thymoquinone in a rat model of reserpine-induced depression

The objective of this study is to examine the antidepressant and antioxidant effects of thymoquinone (TQ) on reserpine-induced depression, and to investigate the antidepressant and antioxidant activity of combined treatment of TQ+citalopram. In total, 36 male Wistar rats were randomly divided into 6 groups: 1)control1, 2)control2, 3)reserpine, 4)reserpine+TQ 5)reserpine+citalopram and 6)reserpine+TQ+citalopram. Depression was induced by administering intraperitoneal reserpine of 0.2mg/kg/14days. For antidepressant effects, 10 mg/kg TQ and/or 10 mg/kg citalopram was administered intragastrically 30 minutes prior to the administration of reserpine. Rat behavior was examined using the Behavioral Test following the completion of treatment protocol. Total nitric oxide (NOx) levels, malondialdehyde (MDA) levels, total oxidants status (TOS), total antioxidant status (TAS) in brain cortex, plasma as well as brain cortex glutathione (GSH) and levels of plasma total sulfhydryl groups (RSH) were examined. Treatment with TQ ameliorated the reserpine-induced changes in the Behavioral Test (p<0.05). TQ treatment significantly increased dopamine (DA) and noradrenaline (NA) expressions when compared to the R group (p<0.01). Serotonin (5-HT) expression also increased significantly (p<0.05). Brain cortex and plasma TOS, MDA and NOx levels decreased, whereas TAS, GSH and RSH levels increased (p< 0.05). TQ has the ability to prevent depression induced by reserpine. The combination of TQ+citalopram can be used in the treatment of depression with a stronger antioxidant effect

Use of network pharmacology to analyze compound reserpine and triamterene tablets in the treatment of hypertension / 药学学报

Compound reserpine and triamterene tablets (CRTT), a compound antihypertensive drug developed by Chinese scientists, is still widely used in clinical practice. However, the mechanisms by which CRTT treats hypertension remain to be fully understood. This study used network pharmacology to analyze CRTT's antihypertensive mechanisms with in vitro experiments. The targets of the four chemical components of CRTT were collected from the Swiss Target Prediction database; 1 828 protein targets related to hypertension were collected from the Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The CRTT-hypertension network model was constructed using a search tool for recurring instances of neighbouring genes (STRING). Gene ontology (GO) and pathway enrichment analysis of targets of interest was conducted with the Metascape database. In the in vitro study, human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) were treated with 1 μmol·L-1 angiotensin Ⅱ (AngⅡ) and CRTT was administered at concentrations of 0.01, 0.1, and 1 μmol·L-1. Changes in the phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway in HUVEC and the cyclic guanosine monophosphate/cGMP-dependent protein kinase (cGMP/PKG) pathway in VSMC were determined by Western blot. Network pharmacological analysis revealed that the antihypertensive effect of CRTT is closely associated with biological pathways such as vascular tone regulation, adrenergic receptor activation, protein kinase activity and signaling pathways such as the cGMP/PKG signaling pathway, vascular smooth muscle contraction, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes and calcium signaling pathways. The in vitro study confirmed that CRTT increased the levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated protein serine threonine kinase (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) in HUVEC and the levels of eNOS, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), and PKG in VSMC through multiple targets and pathways. These results suggest that the activation of PI3K/Akt/eNOS pathway and endothelial-dependent NO/cGMP signaling may be involved in the CRTT-mediated hypotensive effect.

Anti-depressant activities of Theobroma cacao Extract on Reserpine-induced Depression in Female Wistar Rats.

Background: Depression is one of the most commontypes of neurological disorder, which is a markedpattern of disturbances in emotional behavior, memoryand hedonic processing. Aim and Objectives: Toinvestigate the role of ethanolic extract of Theobromacacao seed on the prefrontal cortex of female Wistarrats following reserpine-induced depression. Materialand Methods: Thirty-six (36) female Wistar rats wereused for this study. They were divided into six (A - F)groups (n = 6). Group A- control, Group B - 0.2 mg/kgreserpine, Group C - 10 mg/kg fluoxetine, Group D -500 mg/kg Theobroma cacao seed extract, Group E -0.2 mg/kg reserpine + 500mg/kg Theobroma cacaoseed extract, Group F - 0.2 mg/kg reserpine + 10mg/kgfluoxetine. Animals were euthanized via cervicaldislocation after the last day of administration and theprefrontal cortex and hippocampus were excised andfixed in 10% formalin solution for routine histologicalprocessing while the part used for biochemical assaywere homogenized in phosphate buffer beforecentrifugation. Results: Morphological alteration andreduced population of prefrontal cortex andhippocampus neurons, reduced protein synthesis, poorbehavioral patterns, reduced neurotransmission andinduction of oxidative stress in reserpine exposedanimal. Conclusion: Theobroma cacao seed extractwas able to mitigate these aberrations.

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Effect of daidzein on Parkinson disease induced by reserpine in rats

Parkinson disease is a neurodegenerative disorder characterised by the cardinal symptoms of stiffness, resting tremor, slowness (bradykinesia) and reduction of movement (hypokinesia). Involvement of oxidative damage has been reported in the pathophysiology of Parkinson disease and its related complications. The purpose of this study was to examine the effect of daidzein to quench the free radicals produced as a result of the increased oxidative stress in Parkinson disease.Parkinson disease is induced by administration of reserpine (5 mg/kg/day, i.p) for 5 consecutive days. The symptoms of PD such as tremors, akinesia and rigidity were evaluated. The effect was evaluated by assessing various behavioral parameters (grip strength and locomotor activity), biochemical parameters (lipid peroxidation, and reduced glutathione), as well as histopathological parameters in brain tissue. Daidzein (an antioxidant) was administered at the dose of 50 and 100 mg/kg, p.o. once daily for 5 days. Reserpine significantly causes tremor, rigidity, akinesia and oxidative damage which were reversed by daily administration of daidzein when compared toreserpine group. There was a significant histological improvement in the neuronal degeneration in brain tissue with daidzein. So, the results indicated the protective effect of daidzein against PD.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Serotonergic-like profile of 4-propyl-2hbenzo[h]-chromen-2-one (FCS-304) in mice and rats / Perfil de tipo serotoninérgico de 4-propil-2h-benzo[h]-cromen-2-ona (FCS-304) en ratones y ratas

Background: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) is a semisynthetic coumarin with MAO-A inhibitory activity and positive results in forced swimming and tail suspension test in mice, but until now, it has not been studied in other screening antidepressant models in mice and rats. Objectives: The aim of this work was to assess the serotonin like effect of FCS-304 in the 5-hydroxytryptophan (5-HTP) test in mice, in the behavioral despair test in rats, and in the reserpine test in rats. Methods: Potentiation of 5-HTP (100 mg/kg, i.p.), induced head twitches were assessed in mice, previously treated with FCS-304 (50-75-150 mg/kg, p.o.). The behavioral despair test was performed in rats treated with FCS-304, recording the immobility time attained by the animals subjected to forced swimming. Antagonism of reserpine-induced ptosis was examined in rats, assessing the level of palpebral closure. Imipramine (30 mg/kg, p.o.) and vehicle (canola oil) served as positive and negative controls, respectively. Results: FCS-304 significantly potentiated 5-HTP induced head twitches in mice, in a dose dependent manner. In rats, FCS-304 significantly decreased the immobility time in the behavioral despair test and antagonized reserpine induced ptosis. Conclusions: These results add support to propose that FCS-304 could elicit antidepressant effects related to MAO-A inhibitory activity.

Antecedentes: 4-propil-2H-benzo[h]-cromen-2-ona (FCS-304) es una cumarina semisintética inhibidora de MAO-A con efectos positivos en las pruebas de nado forzado y suspensión por la cola en ratones, sin embargo, hasta ahora no se había estudiado en otros modelos de tamizado antidepresivo en ratones y ratas. Objetivos: el objetivo de este trabajo fue evaluar el efecto de tipo serotoninérgico de FCS-304 en la prueba de potenciación de 5-hidroxitriptofano (5-HTP) en ratones, y su respuesta en la prueba de desesperanza conductual en ratas y en la prueba de reserpina en ratas. Métodos: se evaluó la potenciación de las sacudidas de cabeza inducidas por 5-HTP (100 mg/kg, i.p.), en ratones tratados con FCS-304 (50-75-150 mg/Kg, v.o.). La prueba de desesperanza conductual se realizó en ratas tratadas con FCS-304, expuestas a nado forzado. El antagonismo de la ptosis palpebral inducida por reserpina se examinó en ratas determinando el grado de apertura ocular. Imipramina (30 mg/kg, v.o.) y el vehículo (aceite de canola, 0,1 mL/10 g), sirvieron como controles positivo y negativo, respectivamente. Resultados: FCS-304 incrementó significativamente el recuento de sacudidas de cabeza inducidas por 5-HTP en ratones, en función de la dosis. En ratas, FCS-304 fue efectiva para disminuir el tiempo de inmovilidad en la prueba de desesperanza inducida por nado forzado y el grado de ptosis palpebral inducido por reserpina. Conclusiones: estos resultados dan soporte para proponer que FCS-304 ejercería efectos de tipo antidepresivo relacionados con la inhibición de MAO-A.

Regulation of Chaihu Shugan Powder on kynurenine in raphe nucleus of depressive rats induced by reserpine / 中华行为医学与脑科学杂志

Objective To investigate the antidepressant effects of Chaihu Shugan Powder(CSP) on depressive rats induced by reserpine and its influences on the kynurenine (KYN),indoleamine 2,3-dioxyge-nase(IDO),interleukin-6(IL-6) and tumor necrosis factor-α( TNF-α). Methods Forty rats with similar behavior results were divide into 4 groups randomly,including Control group(Con),Model group(Res),Flu- oxetine group(Res+Flu) and Chaihu Shugan Powder group(CSP). The depressive rat model was established by intraperitoneal injection reserpine. The rats in Res+Flu group were administered with fluoxetine by intrap-eritoneal and rats in Res+CSP group were administered with CSP by intraperitoneal. After 14 days,the be-havior of rats was measured and then the rats were executed and sampled. The content of tryptophan and kynurenine in raphe nuclei tissue were detected. The mRNA expression level of IDO,IL-6,TNF-α in raphe nuclei tissue were detected. Results ( 1) Compared with Con group (( 81. 81 ± 36. 13) s, ( 83. 51 ± 5. 34)%), the swimming immobility time((150. 50±31. 45)s) in Res group increased(t=68. 7, P<0. 05) and the sucrose perference (59. 73±11. 30)%) in Res group decreased(t=23. 8,P<0. 05). Compared with Res group, the swimming immobility time in Res+Flu group((114. 90± 14. 29) s) and Res+CSP group ((111. 7±11. 34)s) decreased(t=35. 6,35. 8,both P<0. 05). Compared with Res group, the sucrose pref-erence in Res+Flu group((78. 21±10. 07)%) increased(t=18. 3, P<0. 05). (2)Compared with Con group (KYN/TRP:(0. 023±0. 016),IDO mRNA:(1. 00±0. 05),IL-6 mRNA:(1. 00±0. 58),TNF-α mRNA:(1. 00±0. 32)), the activity of IDO(KYN/TRP(0. 039±0. 003)) and the mRNA levels of IDO mRNA(3. 63± 0. 31),IL-6 mRNA(2. 36±0. 23),TNF-α mRNA( 3. 56± 0. 14) of Raphe Nuclei tissue in Res group were significantly increased (t=21. 2,12. 9,38. 3,19. 7,all P<0. 05). Compared with Res group, the activity of IDO(KYN/TRP(0. 030±0. 013)),the mRNA expression levels of IDO mRNA( 1. 56±0. 36),IL-6 mRNA (1. 62±0. 16),TNF-α mRNA(2. 64±0. 20)of Raphe Nuclei tissue in Res+Flu group were significantly de-creased(t=38. 8,15. 8,12. 8,26. 4,all P<0. 05). And compared with Res group,the activity of IDO( KYN/TRP(0. 028±0. 021)) ,the mRNA expression level of IDO mRNA( 1. 33± 0. 29),IL-6 mRNA(1. 36± 0. 34),TNF-α mRNA(1. 93±0. 21)of raphe nuclei tissue in Res+CSP group were also significantly decreased (t=23. 21,17. 3,19. 8,29. 8,all P<0. 05). Compared with Res+Flu group,the level of IDO mRNA and in-flammatory factors' mRNA in Res+CSP group were significantly decreased(t=18. 3,20. 8,31. 5,all P<0. 05). Conclusion Chaihu Shugan Powder has antidepressant effect,and the mechanism is related with de-creasing the inflammatory factors,inhibiting IDO activation and decreasing the IDO mRNA.

Changes of behavioral and serum inflammatory factors in rats with acute reserpine-induced comor-bidity of pain and depression / 中华行为医学与脑科学杂志

Objective To investigate the effects of acute reserpine-induced pain and depression co-morbidity model on behavior and related inflammatory cytokines in rats. Methods Twelve male 8-week-old SD rats were randomly divided into control group and model group,6 in each group. Rats in the model group were intraperitoneally injected with reserpine(1 mg/kg/d)for 3 days to establish the model. Rats in the con-trol group were injected with the same amount of distilled water. The pain threshold of rats was measured by Von Frey Hairs and Hot Plate Analgesia Test. The depression behavior of rats was evaluated by open-field test,Forced Swimming Test and Sucrose Consumption Test. Serum IL-1β, IL-6, IL-18 and TNF-α content were detected by ELISA. Results Compared with the control group(1d (15. 00±0. 00) g;3d ( 13. 20±4. 03)g),the PWTs of the model group (1d (6. 20±0. 45) g;3d (4. 20±1. 64) g) decreased significantly(t=44. 00,4. 63,both P<0. 05). Compared with the control group (( 8. 82 ± 1. 08) s),the PWTL (( 3. 16 ± 0. 24)s) was significantly reduced on the first day in model group,and the difference was statistically signifi-cant (t=11. 48,P<0. 05). Compared with the control group (( 1 815. 18± 541. 40) cm,(98. 20± 26. 25) s, (87. 78±9. 38)g),the total distance of the open-field test ((948. 91±494. 35)cm)significantly shortened (t=2. 64,P<0. 05),swimming time ((143. 60±21. 45)s) was significantly prolonged (t=-2. 65,P<0. 05), and the sucrose consumption (( 22. 23 ± 6. 97) g) significantly decreased (t=12. 55,P<0. 05) in model group. Compared with the control group (( 285. 80 ± 11. 93) ng/ml, ( 233. 07 ± 8. 47) ng/ml,( 280. 41 ± 14. 31) ng/ml,( 213. 10 ± 33. 87) ng/ml), serum levels of IL-1β, IL-6, IL-18, TNF-α in model group ((471. 23±24. 15) ng/ml,(364. 82±17. 16) ng/ml,(471. 81± 28. 98) ng/ml,(821. 19±93. 16) ng/ml) increased significantly(F=-15. 39,-15. 39,-13. 24,-13. 72,all P<0. 05). Conclusion A large number of intraperitoneal injections of acute reserpine can cause hyperalgesia,depressive behavior and serum inflamma-tory factors in rats,effectively simulating the symptoms of pain and depression,and can be used as a model of pain and depression comorbidity for biological mechanisms and treatment research.

Reserpine treatment activates AMP activated protein kinase (AMPK)

Reserpine is a well-known medicine for the treatment of hypertension, however the role of reserpine in cell signaling is not fully understood. Here, we report that reserpine treatment induces the phosphorylation of AMP activated protein kinase (AMPK) at threonine 172 (T172) in PC12 cells. Phosphorylation of AMPK T172 is regulated by upstream signaling molecules, and the increase of phospho-T172 indicates that AMPK is activated. When we examined the FOXO3a dependent transcription by using the FHRE-Luc reporter assay, reserpine treatment repressed the FHRE-Luc reporter activity in a dose dependent manner. Finally, we showed that reserpine treatment induced the phosphorylation of AMPK as well as cell death in MCF-7 cells. These results suggest that AMPK is a potential cellular target of reserpine.

Clinical Observation of Atorvastatin Combined with Levamlodipine Besylate in the Treatment of Elderly Patients with Hypertension Combined with Carotid Plaque / 中国药房

OBJECTIVE:To observe the clinical efficacy and safety of atorvastatin combined with levamlodipine besylate in the treatment of elderly patients with hypertension combined with carotid plaque. METHODS:160 elderly patients with hyperten-sion combined with carotid plaque were randomly divided into control group(80 cases)and observation group(80 cases). Control group orally received Atorvastatin tablet 3 mg,qd+compound reserpine tablets 2 tablets,tid;observation group was received Atorv-astatin tablet(the same dosage and usage with control group)+Levamlodipine besylate tablet 2.5 mg,qd. They were treated for 8 months. Antihypertensive efficacy,blood pressure,and carotid intima-media thickness (IMT) before and after treatment,and the incidence of adverse reactions in 2 groups were observed and recorded. RESULTS:The antihypertensive effective rate in observa-tion group was significantly higher than control group,with statistical significance(P0.05). After treatment,blood pressure and IMT levels in 2 groups were significantly lower than before,and observation group was lower than control group,with statistical significance(P0.05). CONCLUSIONS:Atorv-astatin combined with levamlodipine besylate shows good efficacy in the treatment of elderly patients with hypertension combined with carotid plaque,which can not only effectively control patients'blood pressure,but also improve atherosclerosis,reversing plaques and does not increase the incidence of adverse veactions.

A validated and densitometric HPTLC method for the simultaneous quantification of reserpine and ajmalicine in Rauvolfia serpentina and Rauvolfia tetraphylla

ABSTRACT High performance thin layer chromatographic method (HPTLC) has been developed for the quantification of reserpine and ajmalicine in root part of two different population of Rauvolfia serpentina (L.) Benth. ex Kurz and Rauvolfia tetraphylla L., Apocynaceae, collected from Punjab and Uttarakhand. HPTLC of methanolic extract of root containing indole alkaloids, i.e., reserpine and ajmalicine, was performed on TLC Silicagel 60 F254 (10 cm × 10 cm) plates with toluene:ethyl acetate:formic acid (7:2:1), as mobile phase. Quantification of the reserpine and ajmalicine was performed in the absorption–reflection mode at 268 nm. The recovery of reserpine and ajmalicine were 99.3 and 98.7% respectively. The calibration curves were linear for both the reserpine and ajmalicine, in the range of 200–1200 ng. HPTLC densitometry has been performed for the estimation of reserpine and ajmalicine in root part of R. serpentina and R. tetraphylla for the first time. The method is simple, rapid and cost effective and can be used for routine analysis of ajmalicine and reserpine in different Rauvolfia species as well as for quality control of herbal drugs containing Rauvolfia species.

Research Progress on Animal Modeling Methods and Model Evaluation of Spleen-yang Deficiency / 世界科学技术-中医药现代化

The paper was aimed to review the modeling methods of spleen-yang deficiency, which can be classified into imitating traditional Chinese medicine (TCM) etiology methods and modern medicine methods. At present, methods of modeling were not generally accepted and the main presented problems were as follows. Modern medicine methods did not conformed to the rules of TCM etiology and pathogenesis. The evaluation of yang deficiency models was not accurate. Some modeling methods can lead to other diseases at the same time. The names of spleen deficiency model were not unified. It was difficult to distinguish the modeling methods of spleen-yang deficiency and spleen-qi deficiency, and etc. Model evaluation of spleen-yang deficiency was various. However, the domestic standard evaluation system had not been formed. The main model evaluation problems were as follows. Macro symptoms of the model lacked of objective and quantitative evaluation. It lacked of evaluation indexes of pulse and tongue with TCM characteristics. The disproof of prescription selection was not unified. Similar syndromes had not been ruled out. The microscopic indexes were fragmented, and etc. This paper reviewed on animal modeling methods of spleen-yang deficiency.

Effect of Saraswatarishta in animal models of behavior despair.

Background: Saraswatarishta (SA) is a herbo-mineral formulation consisting of 18 plants some of which are Medhyarasayanas. It has been claimed to be useful in treating central nervous system disorders. Objective: To evaluate antidepressant effect of ‘Saraswatarishta’(SA) alone and in combination with imipramine and fluoxetine in animal models of depression. Materials and Methods: After obtaining IAEC permission, 144 rats (n = 36/part) were randomized into 6 groups‑ Group 1: Distilled water (1 mL), Group 2: Imipramine (30 mg/kg), Group 3: Fluoxetine (10 mg/kg), Group 4: SA (1.8 mL/kg), Group 5: Imipramine + SA, Group 6: Fluoxetine + SA. Effects of study drugs were evaluated in forced swim test (FST) with single exposure to FST (Part 1) and repeated exposure for 14 days (Part 2). In Part 3, reserpine was used with FST and effects of study drugs were evaluated against single exposure to FST. Same model was used with repeated exposures to FST (Part 4). In each part, rats were subjected to open field test (OFT) for 5 min prior to final FST. The variables measured: Immobility time in FST; line crossing, rearing and defecation in the OFT. Results: In all four parts, individual drugs and combinations thereof produced significant decrease in immobility time as compared to control, and extent of decrease was comparable amongst these groups. However, values for combination of fluoxetine with SA group were found to be lesser than that for individual agents in Parts 2 and 3. Combination of SA with imipramine did not enhance its anti‑depressant effect in any of the parts. OFT findings did not vary significantly amongst the study groups. Conclusion: Decreased immobility in FST and absence of generalized stimulation or depression of motor activity in OFT point towards potential antidepressant effect of Saraswatarishta. Its co‑administration with fluoxetine showed more promising effects.

Fluoroquinolone resistance and active drug efflux in Enterococci / 中华检验医学杂志

Objective To investigate the effect of reserpine,an efflux pumps inhibitor,on the activities of fluoroquinolones (FQNs) against Enterococci,and the distribution of efflux pump genes emeA and its correlation with the resistance of Enterococci.To elucidate the relationship between FQN resistance in Enterococci and active efflux.Methods One hundred isolates of enterococci were identified by VITEK microbe automatic system.The antibacterial agent susceptibility tests were performed by the disc diffusion method (K-B) in accordance with the CLSI standards.The minimum inhibitory concentration (MIC) of each FQN was tested by the agar dilution method,and the MIC changes were detected after adding reserpine.The distribution of emeA in 100 isolates of Enterococci was determined by PCR.Thex2 test was used to compare the differences of statistical results.Results After reserpine was used,three-FQN resistance in Enterococci was reduced.Ciprofloxacin,gatifloxacin and levofloxacin resistance was reduced from 42％ (42/100) to 28％ (28/100),from 30％ (30/100) to 17％ (17/100),and from 33％ (33/100) to 23％ (23/100),respectively.The positive rate of emeA gene in 100 strains of Enterococci was 55％ (55/100).There were 45 positive strains(72.6％) in 62 E.faecalis and 10 positive strains (26.4％) in 38 E.faecium.The positive rate of emeA gene in the resistant strains against ciprofloxacin,gatifloxacin and levofloxacin was 73.8％ (31/42),76.7％ (23/30),75.8％ (25/33),respectively,and the positive rate of emeA gene in the susceptible strains against above 3 antibacterials were 41.4％ (24/58),45.7％ (32/70),44.8％ (30/67).Efflux pump genes emeA in resistant strains is higher than the sensitive strains,with the statistically significant difference(x2 =13.02,8.13 and 8.57,P ＜ 0.005).Conclusions Reserpine could inhibit the active efflux of in FON Enterococci and reduce the MIC for drug-resistant strains in vitro.Multidrug-resistant efflux pump gene emeA was relevant to antimicrobial drug resistance in Enterococci.

Antidepressant-like effect of extracts from dried root of Rehmannia glutinosa (Dihuang) / 中国药学杂志

OBJECTIVE: To investigate the antidepressant-like effect of extracts from dried root of Rehmannia glutinosa Libosch. (Dihuang) (RG).

Determination of hydrochlorothiazide, prazosin hydrochloride, promethazine hydrochloride, reserpine, and nifedipine illegally added into Qingnao Jiangya Tablets by HPLC method / 中草药

Objective: To set up an HPLC method for the determination of hydrochlorothiazide, prazosin hydrochloride, romethazine hydrochloride, reserpine, and nifedipine illegally added into Qingnao Jiangya Tablets (QJT). Methods: HPLC method was used. Octadecyl silane bonded silica as a filler (APOLLO C18 column, 250 mm × 4.6 mm) was used with the mobile phase consisting of water containing 0.02% phosphoric acid and acetonitrile in gradient mode. The flow rate was 1.0 mL/min, column temperature was 25℃, and detection wavelength was set at UV 251 nm. Results: The calibration curve showed the good linearity for hydrochlorothiazide, prazosin hydrochloride, romethazine hydrochloride, reserpine, and nifedipine in the ranges of 21.24-2 124.0 ng (r = 1.000 0), 16.184-1 618.4 ng (r = 1.000 0), 19.72-1 972.0 ng (r = 1.000 0). 18.976-1 897.6 ng (r = 1.000 0), and 22.504-2 250.4 ng (r = 1.000 0), respectively; The average recovery rates (n = 6) were 100.93%, 101.61%, 103.07%, 97.58%, and 96.36%, respectively; RSD values were 1.52%, 1.21%, 1.08%, 0.73%, and 0.48%, respectively. Conclusion: The accurate and reproducible method can be used for the determination of hydrochlorothiazide, prazosin hydrochloride, romethazine hydrochloride, reserpine, and nifedipine illegally added into QJT.

Anti-depressant like activity of N-n-butyl-3-methoxyquinoxaline-2-carboxamide (6o) a 5-HT3 receptor antagonist.

The compound 6o (at 0.5, 1 and 2 mg/kg, ip) with optimum log P and pA2 value, was subjected to forced swim test (FST) and tail suspension test (TST). The compound 6o significantly reduced the duration of immobility in mice without affecting the base line locomotion in actophotometer. Moreover, 6o (2 mg/kg, ip), potentiated the 5-hydroxytryptophan (5-HTP)-induced head twitch responses in mice and at 1 and 2 mg/kg, ip antagonized the reserpine-induced hypothermia (RIH) in rats. In interaction studies with various standard drugs/ligands using FST, 6o (1 and 2 mg/kg, ip) potentiated the anti-depressant effect fluoxetine (5 mg/kg, ip) and reversed the depressant effect of parthenolide (1 mg/kg, ip) by reducing the duration of immobility. Furthermore, 6o (1 and 2 mg/kg, ip) potentiated the effect of bupropion (10 mg/kg, ip) in TST. The behavioural anomalies of the olfactory bulbectomised (OBX) rats were augmented by chronic 6o (1 and 2 mg/kg) treatment as observed from the modified open field test (parameters: ambulation, rearing, fecal pellet). The results suggest that compound 6o exhibited anti-depressant like effect in rodent models of depression.

Ação da fluoxetina sobre a dor aguda em ratos submetidos à constrição do nervo ciático / Fluoxetine action on acute pain in rats submitted to sciatic nerve constriction

JUSTIFICATIVA E OBJETIVOS: Os inibidores seletivos da recaptação de serotonina como a fluoxetina, têm sido apontados como alternativa ao uso dos antidepressivos tricíclicos para o tratamento da dor crônica, pela menor incidência de efeitos colaterais. O objetivo deste estudo foi estudar o efeito da serotonina na modulação da dor aguda, pela administração de fluoxetina, por meio do teste da formalina, em ratos, anteriormente submetidos à constrição do nervo ciático. MÉTODO: Foram estudados 24 ratos Wistar, machos, com peso médio de 300 g, distribuídos em 5 grupos: 1. Controle sem tratamento; 2. Constrição do nervo ciático; 3. Constrição do nervo ciático tratados com 5 mg.kg-1.dia de fluoxetina, por via oral durante 15 dias; 4. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina, por via oral a cada 72h e com 5 mg.kg-1.dia de fluoxetina por via oral, durante 15 dias; 5. Constrição do nervo ciático tratados com 5 mg.kg-1 de reserpina por via oral em intervalos de 72h, durante 15 dias. Todos os animais foram submetidos ao teste da formalina modificado após os tratamentos especificados. RESULTADOS: A resposta na fase I, na fase intermediária e na fase II do teste da formalina não foi alterada pela constrição do ciático. O tratamento com reserpina ou fluoxetina não interferiu com as fases I e intermediária do teste da formalina nos grupos submetidos à constrição do ciático. O número de elevações da pata na fase II do teste da formalina aumentou nos animais tratados com fluoxetina e diminuiu nos animais tratados com reserpina. Nos animais tratados com a associação reserpina e fluoxetina houve redução do número de elevações da pata em comparação com os animais tratados apenas com a fluoxetina. CONCLUSÃO: O tratamento com fluoxetina aumentou a sensação dolorosa após estímulo agudo em ratos submetidos à constrição do ciático, evidenciando ação algogênica do fármaco neste modelo experimental.

BACKGROUND AND OBJECTIVES: Selective serotonin reuptake inhibitors, such as fluoxetine, have been suggested as alternative to tricyclic antidepressants to treat chronic pain, due to the lower incidence of side effects. This study aimed at observing the effects of serotonin on acute pain modulation, by the administration of fluoxetine through the formalin test in rats previously submitted to sciatic nerve constriction. METHOD: We used 24 male Wistar rats, with mean weight of 300 g and distributed in 5 groups: 1. Control untreated; 2. Sciatic nerve constriction; 3. Sciatic nerve constriction and treated with 5 mg.kg-1.day oral fluoxetine for 15 days; 4. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours and with 5 mg.kg-1.day oral fluoxetine for 15 days; 5. Sciatic nerve constriction treated with 5 mg.kg-1 oral reserpine every 72 hours for 15 days. All animals were submitted to modified formalin test after treatment. RESULTS: Response in the phase I, intermediate and phase II formalin test was not changed by sciatic nerve constriction. Treatment with reserpine or fluoxetine has not interfered with first and intermediate formalin test phases in the groups submitted to sciatic nerve constriction. The number of flinches in the second formalin test phase has increased in animals treated with fluoxetine and has decreased in animals treated with reserpine. There has been decrease in the number of flinches in animals treated with the association reserpina and fluoxetine as compared to animals treated with fluoxetine alone. CONCLUSION: Fluoxetine has increased painful sensation after acute stimulation in rats submitted to sciatic nerve constriction, showing the algogenic action of the drug in this experimental model.