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.
Male ; Rats ; Animals ; Reserpine ; Dopamine ; Rats, Wistar ; Hypotension/chemically induced* ; Norepinephrine

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.
AMP-Activated Protein Kinases* ; Animals ; Cell Death ; Hypertension ; MCF-7 Cells ; PC12 Cells ; Phosphorylation ; Reserpine* ; Threonine

Although trimethoprim-sulfamethoxazole (TMP-SXT) is considered the first-line therapy for Stenotrophomonas maltophilia infections, there is debate on the use of the bacteriostatic drug in serious infections, and recently, there has been an increasing occurrence of acquired resistance to TMP-SXT. In the present study, the effect of efflux pump inhibitors on the susceptibility of TMP-SXT and other antibiotics were investigated in S. maltophilia complex. The sul and/or dfrA genes were identified in only up to 27.8% of all 36 TMP-SXT-resistant S. maltophilia complex isolates. Thus, TMP-SXT resistance in S. maltophilia was not explained completely by the presence of sul and dfrA genes. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) decreased the minimum inhibitory concentration (MIC) of TMP-SXT by eight to 128 folds in all 14 isolates. In contrast, 2,4-dinitrophenol (DNP), phenyl-arginine-β-naphthylamide (PAβN), and reserpine did not reduce the MIC of TMP-SXT. In addition to TMP-SXT, slight decrease in MICs was observed for tigecycline and piperacillin/tazobactam by CCCP (by two folds) in one isolate. Although efflux pump may play a role in TMP-SXT resistance in S. maltophilia, inhibition of the efflux pump could be done by active proton pore.
2,4-Dinitrophenol ; Anti-Bacterial Agents ; Carbonyl Cyanide m-Chlorophenyl Hydrazone ; Korea* ; Microbial Sensitivity Tests ; Protons ; Reserpine ; Stenotrophomonas maltophilia* ; Stenotrophomonas* ; Thiram* ; Trimethoprim, Sulfamethoxazole Drug Combination*

This project's aim was to determine the reserpine-induced gastric ulcer preventive effect of polysaccharide of Larimichthys crocea swim bladder (PLCSB) in ICR mice. The anti-gastric ulcer effects of polysaccharide of Larimichthys crocea swim bladder was evaluated in mice model using morphological test, serum levels assay, cytokine levels assay, tissue contents analysis, reverse transcription-polymerase chain reaction (RT-PCR) analysis and western bolt assay. High concentration (50 mg/kg dose) of PLCSB reduced IFN-gamma as compared to low concentration (25 mg/kg dose) and control mice. SS and VIP serum levels of PLCSB treated mice were higher than those of control mice, and MOT and SP serum levels were lower than control mice. Gastric ulcer inhibitory index of PLCSB treatment groups mice were much lower than control mice, and the high concentration treated mice were similar to the ranitidine treated mice. The SOD and GSH-Px activities of PLCSB treated mice were higher than control mice, close to normal mice and ranitidine treated mice. PLCSB treated mice also showed the similar contents of NO and MDA to normal group. By RT-PCR and western blot assay, PLCSB significantly induced inflammation in tissues of mice by downregulating NF-kappaB, iNOS, and COX-2, and upregulating IkappaB-alpha . These results suggest that PLCSB showed a good gastric ulcer preventive effect as the gastric ulcer drug of ranitidine. Polysaccharide of Larimichthys crocea swim bladder may be used as a drug material from marine products.
Animals ; Blotting, Western ; Inflammation ; Mice ; Mice, Inbred ICR* ; NF-kappa B ; Ranitidine ; Reserpine* ; Stomach Ulcer* ; Ulcer ; Urinary Bladder*

OBJECTIVES: Group B Streptococcus (GBS), a common bowel commensal, is a major cause of neonatal sepsis and an emerging cause of infection in immune-compromised adult populations. Fluoroquinolones are used to treat GBS infections in those allergic to beta-lactams, but GBS are increasingly resistant to fluoroquinolones. Fluoroquinolone resistance has been previously attributed to quinolone resistance determining regions (QRDRs) mutations. We demonstrate that some of fluoroquinolone resistance is due to efflux-mediated resistance. METHODS: We tested 20 GBS strains resistant only to norfloxacin with no mutations in the QRDRs, for the efflux phenotype using norfloxacin and ethidium bromide as substrates in the presence of the efflux inhibitor reserpine. Also tested were 68 GBS strains resistant only to norfloxacin not screened for QRDRs, and 58 GBS strains resistant to ciprofloxacin, levofloxacin or moxifloxacin. Isolates were randomly selected from 221 pregnant women (35-37 weeks of gestation) asymptomatically carrying GBS, and 838 patients with GBS infection identified in South Korea between 2006 and 2008. The VITEK II automatic system (Biomerieux, Durham, NC, USA) was used to determine fluoroquinolone resistance. RESULTS: The reserpine associated efflux phenotype was found in more than half of GBS strains resistant only to norfloxacin with no QRDR mutations, and half where QRDR mutations were unknown. No evidence of the efflux phenotype was detected in GBS strains that were resistant to moxifloxacin or levofloxacin or both. The reserpine sensitive efflux phenotype resulted in moderate increases in norfloxacin minimum inhibitory concentration (average=3.6 fold, range=>1-16 fold). CONCLUSIONS: A substantial portion of GBS strains resistant to norfloxacin have an efflux phenotype.
Adult ; beta-Lactams ; Ciprofloxacin ; Ethidium ; Female ; Fluoroquinolones ; Humans ; Korea ; Levofloxacin ; Microbial Sensitivity Tests ; Norfloxacin* ; Phenotype ; Pregnant Women ; Reserpine ; Sepsis ; Streptococcus*

OBJECTIVETo observe the effect of Sijunzi Decoction (SD) on the intestinal absorption of glucose in model rats of Pi-qi deficiency syndrome (PQDS).

METHODSPQDS rat model was established by subcutaneous injection of reserpine from the neck. The body weight and urine D-xylose excretion rates were measured. The glucose uptake rate was measured by jejunum perfusion. The intestinal mucosa was collected. The glucose transporter-2 (GLUT2) protein and mRNA expression levels were detected.

RESULTSCompared with the normal control group, the body weight and D-xylose excretion rates decreased in the model group. Meanwhile, the glucose uptake and GLUT2 protein and mRNA expression levels decreased in the model group. The aforesaid indices were improved in the SD group.

CONCLUSIONSD could promote the recovery of glucose uptake in the small intestine of reserpine induced PQDS rats.

Animals ; Drugs, Chinese Herbal ; pharmacology ; Female ; Glucose ; metabolism ; Glucose Transporter Type 2 ; metabolism ; Intestinal Absorption ; drug effects ; Intestinal Mucosa ; drug effects ; metabolism ; Intestine, Small ; drug effects ; metabolism ; Qi ; Rats ; Rats, Sprague-Dawley ; Reserpine ; adverse effects

OBJECTIVETo discuss the effect of Euodiae Fructus on hepatic energy metabolism-related mechanisms of mitochondria of hepatic tissues of asthenia cold syndrome rats.

METHODRats were subcutaneously injected with Reserpine to establish the model. After the oral administration with Euodiae Fructus for 12 d, the oxygen electrode method was adopted to determine the respiration efficiency. The expressions of Cox4, Atp5b, Ucp2,Pgc-1alpha, Nrf1, Tfam mRNA were assayed by using RT-PCR method.

RESULTEuodiae Fructus 4.2 g x kg(-1) could obviously increase ST3 and RCR of asthenia cold syndrome rats, and expressions of Cox4, Ucp2 Nrf1 mRNA. It could also increase expressions of Atp5b and Pgc-1alpha mRNA, but with no statistical significance. No obvious change was observed in Tfam mRNA expression. Euodiae Fructus 4.2 g x kg(-1) could significantly increase ST3 and RCR of asthenia cold syndrome rats and Pgc-1alpha mRNA and Nrf1 mRNA expressions, and significantly decrease P/O, with no obvious impact on Cox4, AtpSb, Ucp2, Tfam mRNA expressions.

CONCLUSIONEuodiae Fructus can promote mitochondrial respiratory function and oxidative phosphorylation efficiency by improving Pgc-1alpha mRNA and Nrf1 mRNA expressions and regulating Cox4 and Atp5b mRNA in mitochondrial respiratory chain. It can also strengthen mitochondrial uncoupling respiration and add heat production by activating Ucp2 mRNA expression in liver.

Animals ; Asthenia ; chemically induced ; drug therapy ; genetics ; metabolism ; Drugs, Chinese Herbal ; administration & dosage ; Energy Metabolism ; drug effects ; Evodia ; chemistry ; Fruit ; chemistry ; Humans ; Liver ; drug effects ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Reserpine ; adverse effects

This study is to offer a clinical pain-depression dyad therapy of ferulic acid, the pain-depression dyad induced by reserpine was established and the dose-effect relationship of ferulic acid on ameliorating pain-depression dyad was explored. Mice were randomly divided into control group, reserpine + vechile and reserpine + ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)) groups. The reserpine treated mice were tested with thermal hyperalgesia, mechanicial allodynia and forced swimming tests, and the SOD and NO levels of hippocampus and frontal cortex were measured. Moreover, the HPLC-ECD was used to detect the changes of central monoamines concentrations. Compared with control group, reserpine can induce a significant decrease in the nociceptive threshold and increase in the immobility time of the forced swimming test. The results suggested that reserpine significantly increased the level of nitrite in hippocampus and frontal cortex and reduced the levels of SOD, 5-HT and NE in these two brain regions. However, these indexes can be a dose-dependently reversed by ferulic acid (5, 10, 20, 40 and 80 mg x kg(-1)). Ferulic acid can reverse pain-depression dyad, especially at the dose of 80 mg x kg(-1). In addition, it can influence oxidative stress and monoamine level.
Animals ; Antidepressive Agents ; administration & dosage ; pharmacology ; Coumaric Acids ; administration & dosage ; pharmacology ; Depression ; chemically induced ; complications ; metabolism ; physiopathology ; Dopamine ; metabolism ; Dose-Response Relationship, Drug ; Frontal Lobe ; metabolism ; Hippocampus ; metabolism ; Hyperalgesia ; physiopathology ; Male ; Mice ; Mice, Inbred ICR ; Nitric Oxide ; metabolism ; Norepinephrine ; metabolism ; Pain ; chemically induced ; complications ; metabolism ; physiopathology ; Pain Measurement ; Random Allocation ; Reserpine ; adverse effects ; Serotonin ; metabolism ; Superoxide Dismutase ; metabolism ; Swimming ; physiology

Altered expression of neurotrophic factors as well as neuroinflammation is commonly associated with Major depressive disorder (MDD) and Alzheimer's disease (AD). To investigate whether or not reserpine-induced MDD affects the expression of AD-related proteins, the expression of gamma-secretase components and substrate were measured in brains of ICR mice following reserpine treatment for 15 days. In active avoidance test, total response time and peak slightly increased in the 2 mg/kg reserpine (RSP2)-treated group compared to vehicle-treated group (P<0.05). Expression and phosphorylation of MKP-1, which is a key factor in MDD pathology, were both higher in the RSP2-treated group than the vehicle- and 1 mg/kg reserpine (RSP1)-treated groups (P<0.02). Furthermore, full-length expression of amyloid precursor protein (APP) was enhanced in the RSP1 and RSP2-treated groups compared to the vehicle-treated group, whereas expression of gamma-secretase components decreased (P<0.03). Among the three components of the gamma-secretase complex, nicastrin protein underwent the largest decrease in expression, as detected by Western blotting (P<0.03). Therefore, the data presented here provide additional evidence about the pathological correlation between MDD and AD.
Alzheimer Disease ; Amyloid ; Amyloid Precursor Protein Secretases ; Animals ; Blotting, Western ; Brain ; Depressive Disorder, Major ; Membrane Glycoproteins ; Mice ; Mice, Inbred ICR ; Models, Animal ; Nerve Growth Factors ; Phosphorylation ; Proteins ; Reaction Time ; Reserpine

OBJECTIVETo study the effect of reserpine (RSP) for changing salivary protein secretion in Pi-deficient rats and to explore its possible mechanism.

METHODSTwenty rats allocated in the RSP group were given subcutaneous injection of RSP [0.4 mg/(kg x d)] for 9 successive days, while the other 20 rats in the control group were injected with same volume of saline instead. On the 10th day, ten rats randomly selected from each group were subjected for extracting saliva to detect salivary amylase activity (sAA) before and after an acid stimulation; and drawing blood from the orbital vein to measure the contents of vasoactive intestinal peptide (VIP) and cyclic adenosine monophosphate (cAMP). Then they were sacrificed and their parotids were taken out for pathological examination with HE staining, as well as for VIP and cAMP measuring, and zymogen granules counting under a transmission electron microscope. The remainder animals were stopped injecting and normally fed to 40 days, then subjected to be detected as above-mentioned.

RESULTSFood intake and body weight reduction were more significantly in the RSP group than in the control group. On the 10th day, the ratio of sAA before/after stimulation in the RSP group was 0.39 +/- 0.18, significantly lower than that in the control group (0.80 +/- 0.21, P < 0.01), but it was restored rapidly, reaching the normal range on the 25th day, on the 40th day, it became significantly different to the level on the 10th day (P < 0.05) and approached the level in the control group (P > 0.05). No significant pathological change of parotid was found in both groups; but the number of zymogen granules in the RSP group was remarkably more than that in the control group (41.4 +/- 4.9 vs 34.6 +/- 5.2, P < 0.01). Serum level of VIP in the RSP group was significantly less while that of cAMP was higher than that in the control group (22.5 +/- 13.1 mg/L vs 38.5 +/- 14.1 mg/L, and 125.8 +/- 15.5 micromol/L vs 105.3 +/- 16.7 micromol/L, both P < 0.05), but no inter-group difference was found in parotid tissue contents of both VIP and cAMP. All the indices detected became equivalent in the two groups on the 40th day.

CONCLUSIONThe reduction of salivary protein in Pi-deficient rats induced by RSP may be related to the regulatory pathway of VIP and cAMP.

Animals ; Cyclic AMP ; blood ; Male ; Medicine, Chinese Traditional ; Rats ; Rats, Sprague-Dawley ; Reserpine ; adverse effects ; pharmacology ; Salivary Proteins and Peptides ; metabolism ; Salivation ; drug effects ; Vasoactive Intestinal Peptide ; blood