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Sedating animals is sometimes necessary in experimental research. This paper presents and discusses the influence of four of the most common anesthetic agents on cardiovascular parameters in rats. We also studied the influence of body temperature. Ten-week-old Sprague-Dawley rats were anesthetized with either isoflurane, pentobarbital, ketamine/xylazine or tiletamine/zolazepam (n = 12 in each group). A pressure-sensing catheter was placed in the right carotid artery for the continuous measurement of arterial pressure, and echocardiography was performed. Indices of cardiac function were significantly higher in the tiletamine/zolazepam rats compared with the other groups. Heart rate was highest but stroke volume lowest with pentobarbital. Left ventricular diastolic dimension was lower in the pentobarbital and tiletamine/zolazepam rats compared with the isoflurane or ketamine/xylazine rats. Intraventricular diastolic pressure was similar in all groups whereas intraventricular systolic pressure, as well as both systolic and diastolic aortic pressures, was significantly higher in the tiletamine/zolazepam rats compared with the other groups. No hemodynamic indices differed significantly among the isoflurane, pentobarbital and ketamine/xylazine rats. Lowering body temperature significantly reduced heart rate and cardiac output but had no apparent effect on hemodynamic parameters. In conclusion, although cardiac functional parameters differed between the different anesthetic agents in ways that could be of relevance to the researcher, they may all have a role in experimental cardiology. Importantly, tiletamine/zolazepam anesthesia resulted in significantly higher indices of cardiac function and elevated blood pressures compared with the other anesthetic agents, a finding that should be kept in mind when interpreting data obtained in rats sedated on this regimen.

A safe method for endotracheal intubation was successfully employed in rats weighing 300-400 g. A catheter from a commercial intravenous cannulation assembly was introduced into the trachea under direct visualization. A surgical operating microscope supplied magnification and light to facilitate the procedure.

A very reliable isocratic reverse phase high performance liquid chromatography (HPLC) system has been developed to separate angiotensins, which combined with a very sensitive radioimmunoassay, provided precise measurements of the endogenous angiotensin II (AII) concentration in the rat plasma in different experimental circumstances. The overall recoveries of AII were 95.2 +/- 15.8% (means +/- SD) when 10 pg of this peptide was added to 1 ml of human plasma. The coefficient of variation for within-assay precision was 10% (n = 6). The plasma AII, measured by this method, of normal male pentobarbital-anesthetized rats was 53.0-141.6 pg/ml (mean: 103.9 +/- 29.7 pg/ml). The plasma AII of rats fed a sodium deficient diet was 300.0 +/- 100.6 pg/ml, while that of rats given oral Enalapril, an angiotensin converting enzyme (ACE) inhibitor, for 1 week was 35.7 +/- 28.0 pg/ml. The plasma AII of bilaterally nephrectomized rats was 2.7 +/- 2.9 pg/ml 24 hours after nephrectomy and below the detection limit 48 hr after nephrectomy. This method, therefore, can be used to study AII in different pathophysiological states or after treatment with renin-angiotensin system inhibitors.

When used to restrain rats while obtaining cardiac blood, there was little difference between the effects of ether, pentobarbitone sodium, and fentanyl plus droperidol on acid-base balance, haemoglobin, haematocrit, plasma protein, calcium and magnesium. The use of manual restraint increased blood acidity, plasma protein, calcium and magnesium, but decreased blood glucose. Haemoglobin and haematocrit values were higher for tail blood than for blood removed from the heart or abdominal aorta.

Phytolacca dodecandra (L' Herit), or 'Endod', is one of the widely known medicinal plants in Ethiopia. Berries of the endod have been used as a detergent for centuries. The present study was aimed to test the hepatoprotective effects of the plant against acetaminophen (APAP)-induced liver injury in rats. Mice of either sex were used for oral acute toxicity tests and APAP-induced lethality tests. Hepatoprotective experiments were done on male rats using 2 g/kg of APAP to induce liver damage. Liver enzymes, total bilirubin (TB), and lipid profile were determined. Liver tissues were also examined histopathologically to see a morphologic change in the control and experiment groups. The protective effect of the plant extract was also tested through sodium pentobarbital (SPB)-induced sleeping time. A significant increase in serum levels of liver enzymes, TB, low-density lipoprotein (LDL), and triglycerides (TGs) was seen from oral administration of 2 g/kg APAP. Total cholesterol (TC) and high-density lipoprotein (HDL) levels were decreased. Serum levels of all parameters were reversed to normal after administration of silymarin 100 mg/kg and, 100, 200, and 400 mg/kg doses of the extract. A significant dose-dependent hepatoprotective effect of Phytolacca dodecandra Methanol Root Extract (PDME) was seen in terms of LDL. Histopathological investigations and SPB-induced sleeping time confirmed the findings of biochemical analysis. The findings of the present study indicate that PDME protected the liver from APAP injury. [ABSTRACT FROM AUTHOR]

Simple Summary: The present study aimed to assess the infrared thermal response of laboratory rats (Rattus norvegicus) during the application of six euthanasia methods (injectable, inhalational, and physical) to determine the method that prevents or diminishes the stress response. The surface temperature was assessed in four thermal windows: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). The results showed that inhalant methods (CO2 and isoflurane) had temperature alterations that could be suggestive of a marked stress response, in contrast to other methods such as pentobarbital, decapitation, and xylazine + ketamine. In conclusion, according to the thermal response of the rats, it is suggested that CO2 and isoflurane might cause distress and this needs to be considered when selecting these techniques as the method of euthanasia for laboratory rats. Refinement is one of the principles aiming to promote welfare in research animals. The techniques used during an experimental protocol, including euthanasia selection, must prevent and minimize suffering. Although the current euthanasia methods applied to laboratory rodents are accepted, the controversial findings regarding the potential stress/distress they can cause is a field of research. The objective was to assess the thermal response of Wistar rats during various euthanasia methods using infrared thermography (IRT) to determine the method that prevents or diminishes the stress response and prolonged suffering. Pentobarbital (G1), CO2 (G2), decapitation (G3), isoflurane (G4), ketamine + xylazine (G5), and ketamine + CO2 (G6) were evaluated at five evaluation times with IRT to identify changes in the surface temperature of four anatomical regions: ocular (T°ocu), auricular (T°ear), interscapular (T°dor), and caudal (T°tai). Significant differences (p < 0.05) were found in G2 and G4, registering temperature increases from the administration of the drug to the cessation of respiratory rate and heart rate. Particularly, isoflurane showed a marked thermal response in T°ocu, T°ear, T°dor, and T°tai, suggesting that, in general, inhalant euthanasia methods induce stress in rats and that isoflurane might potentially cause distress, an effect that must be considered when deciding humane euthanasia methods in laboratory rodents. [ABSTRACT FROM AUTHOR]

Dyslipidemia and inflammation have great roles in the development of diabetic nephropathy (DN). Oleanolic acid (OA) is a natural triterpenoid that possesses multiple pharmacological properties including anti-oxidation, anti-inflammatory and hypoglycemia. In the present study, the effects of OA on diabetic kidney disease (DKD) and its underlying mechanisms were investigated in DKD rats. Twenty-five of a total thirty-five male Sprague-Dawley (SD) rats were used to establish for Type 2 diabetes mellitus (T2DM) model by high-fat diet combined with streptozotocin (STZ). Then rats were randomly assigned into four group: control group (n = 10), T2DM group (n = 9), OA (50 mg/kg) group (n = 7), OA (100 mg/kg) group (n = 8). Rats were sacrificed at the end of 18 weeks after feeding by intraperitoneal injection of pentobarbital sodium. Body weight (BW), fasting blood glucose (FBG), kidney weight (KW), serum lipid, 24-h urinary microalbumin (UMA), serum creatinine (Scr) and uric acid (UA) were measured. Histopathological changes were observed by PAS staining and electron microscope. The expressions of nephrin, CD68, Collagen-IV, AMPK, p-AMPK, PGC-1α, TLR4, NF-κB and TGF-β1 in kidney were also detected by immunohistochemistry or western blot. OA significantly decreased the levels of FBG, kidney index (KI), serum lipid levels, 24 h UMA, Scr, UA in diabetic rats. Additionally, OA obviously attenuated renal lipid accumulation and renal structure abnormalities in diabetic rats. Furthermore, the expression levels of nephrin, p-AMPK/AMPK, PGC-1α were elevated, while CD68, Collagen-IV, TLR4, NF-κB and TGF-β1 expressions were decreased in renal tissues of OA treated diabetic rats. OA showed dose-independent. OA can alleviate renal injury in diabetic rats through improving lipid metabolism and inflammation via AMPK/PGC-1α and TLR4/NF-κB signaling pathway. • High fat diet combined STZ to establish diabetic nephropathy is more consistent with the diabetic kidney disease. • Oleanolic acid alleviates diabetic kidney disease by inhibiting renal inflammation in a dose-dependent manner. • Oleanolic acid attenuates diabetic kidney disease by improving renal lipid accumulation in a dose-dependent manner. • Oleanolic acid alleviates renal fibrosis in diabetic kidney disease in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Chinese herb pairs are the most basic and compressed examples of Chinese herbal combinations and can be used to effectively explain the fundamental concepts of traditional Chinese medicine prescriptions. These pairings have gained significant interest due to their subtle therapeutic benefits, minimal side effects, and efficacy in treating complicated chronic conditions. The Banxia–Xiakucao Chinese herb pair (BXHP) consists of Pinellia ternata (Thunb.) Breit. (Banxia) and Prunella vulgaris L. (Xiakucao). This formula was documented in The Medical Classic of the Yellow Emperor approximately 2000 years ago，and clinical research has demonstrated that BXHP effectively treats insomnia. This study aimed to evaluate the efficacy and therapeutic mechanism of the BXHP through a comprehensive strategy involving network pharmacology, molecular docking, transcriptomics, and molecular biology experimental validation. The composition of BXHP was characterized using the UPLC-Q-TOF-MS. The active compounds were screened to find drug-likeness compounds by analyzing the ADME data. To predict the molecular mechanism of BXHP in sleep deprivation (SD) by network pharmacology and molecular docking. We established a rat model of SD and the in vivo efficacy of BXHP was verified through the pentobarbital sodium righting reflex test, behavioral assays, enzyme-linked immunosorbent assay, transmission electron microscopy, HE staining, and Nissl staining, and the underlying molecular mechanism of BXHP in SD was revealed through transcriptomic and bioinformatic analyses in conjunction with quantitative real-time PCR, Western blot, and immunofluorescence staining. In the present study, we showed for the first time that BXHP reduced sleep latency, prolongs sleep duration, and improves anxiety; lowered serum CORT, IL6, TNF-α and MDA levels; decreased hypothalamic Glu levels; and elevated hypothalamic GABA and 5-HT levels in SD rats. We found 16 active compounds that acted on 583 targets, 145 of which are related to SD. By modularly dissecting the PPI network, we discovered three critical targets, Akt1, CREB1, and PRKACA, all of which play important roles in the effects of BXHP on SD. Molecular docking resulted in the identification of 16 active compounds that strongly bind to key targets. The results of GO and KEGG enrichment analyses of network pharmacology and transcriptomics focused on both the regulation of circadian rhythm and the cAMP signaling pathway, which strongly demonstrated that BXHP affects SD via the cAMP-PKA-CREB-Circadian rhythm pathway. Molecular biology experiments verified this hypothesis. Following BXHP administration, PKA and CREB phosphorylation levels were elevated in SD rats, the cAMP-PKA-CREB signaling pathway was activated, the expression levels of the biological clock genes CLOCK, p-BMAL1/BMAL1, and PER3 were increased, and the rhythmicity of the biological clock was improved. The active compounds in BXHP can activate the cAMP-PKA-CREB-Circadian rhythm pathway, improve the rhythmicity of the biological clock, promote sleep and ameliorate anxiety, which suggests that BXHP improves SD through a multicomponent, multitarget, multipathway mechanism. This study is important for the development of herbal medicines and clinical therapies for improving sleep deprivation. [Display omitted] [ABSTRACT FROM AUTHOR]

Scar formation and chronic ulcers can develop following a skin injury. They are the result of the over‐ or underproduction of collagen. It is very important to evaluate the quality and quantity of the collagen that is produced during wound healing, especially with respect to its structure, as these factors are very important to a complicated outcome. However, there is no standard way to quantitatively analyse dermal collagen. As prior work characterised some potentially fractal properties of collagen, it was hypothesised that collagen structure could be evaluated with fractal dimension analysis. Small‐angle X‐ray scattering technology (SAXS) was used to evaluate the dermis of rats exposed to graft harvest, burn, and diabetic pathologic states. It was found that almost all collagen structures could be quantitatively measured with fractal dimension analysis. Further, there were significant differences in the three‐dimensional (3‐D) structure of normal collagen versus that measured in pathologic tissues. There was a significant difference in the 3‐D structure of collagen at different stages of healing. The findings of this work suggest that fractal analysis is a good tool for wound healing analysis, and that quantitative collagen analysis is very useful for assessing the structure of dermal collagen. [ABSTRACT FROM AUTHOR]

Panax ginseng (P. ginseng) C. A. Meyer. has been used extensively globally as a medicine. It has a therapeutic effect on sleep and is an attractive alternative for patients with insomnia. The United States Patent of Invention has approved the use of P. ginseng alcohol extract (GAE) in nutraceuticals or food to improve sleep. It has shown promise as an effective therapeutic agent for improving sleep and cognition. However, its mechanism of action is not yet fully understood. To investigate the therapeutic benefits of GAE on sleep and cognition and its underlying mechanism in aged sleep-deprived rats, with a focus on orexin-mediated autophagy function. We conducted in vivo tests in an aged sleep-deprivation rat model produced using p-chlorophenylalanine (PCPA) coupled with modified multi-platform method to examine the therapeutic effects and mechanisms of GAE. A pentobarbital sodium-induced sleep test and water maze were used to assess sleep and cognitive performance, respectively. An enzyme-linked immunosorbent assay was used to determine orexin levels and aging and sleep markers in serum and hypothalamic tissues. Hematoxylin-eosin staining and Nissl staining were used to assess histopathological changes, and autophagy levels were assessed using transmission electron microscopy, immunofluorescence. Western blot and immunohistochemical staining were performed to detect the levels of orexin, orexin-receptor proteins, and autophagy-associated proteins to study the effects of GAE on hippocampal neurons, and the underlying mechanisms. In aged sleep-deprived rats, GAE treatment prolonged sleep duration, improved cognitive function, prevented hippocampal neuronal damage, increased the number of Nissl bodies, improved aging and sleep markers, and enhanced the LC3A/B expression in autophagosomes and neurons. The amount of orexin in serum and hypothalamic tissue and OX1R, OX2R, and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) proteins also reduced, which resulted in the inhibition of the PI3K/Akt/mTOR pathway and activation of the autophagy process. GAE may reduce hypothalamic orexin secretion and interact with orexin receptors to inhibit the PI3K/Akt/mTOR signalling network and activate autophagy. This may be a potential mechanism of action of GAE in regulating sleep-related cognitive function. [Display omitted] • GAE improved sleep duration and cognitive function in aged sleep-deprived rats. • GAE in aged sleep-deprived rats prevents hippocampal neuronal damage. • GAE promotes orexin mediated autophagy. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Sleep disorders induce anxiety and forgetfulness and change habits. The chemical hypnotic drugs currently used have serious side effects and, therefore, people are drawn towards using natural compounds such as plant-based healing agents. Abscisic acid (ABA) is produced in a variety of mammalian tissues and it is involved in many neurophysiological functions. Objective: To investigate the possible effect of ABA on pentobarbital-induced sleep and its possible signaling through GABA-A and PPAR (γ and β) receptors, in male Wistar rats. Methods: The possible effect of ABA (5 and 10 µg/rat, intracerebroventricularly) on sleep onset latency time and duration was evaluated in a V-maze model of sleep. Pentobarbital sodium (40 mg/kg, intraperitoneally) was injected to induce sleep 30 min after administration of ABA. PPARβ (GSK0660, 80 nM/rat), PPARγ (GW9662, 3 nM/rat) or GABA-A receptor (bicuculline, 6 µg/rat) antagonists were given 15 min before ABA injection. Diazepam (2 mg/kg, intraperitoneally) was used as a positive control group. Results: ABA at 5 µg significantly boosted the pentobarbital-induced subhypnotic effects and promoted induction of sleep onset in a manner comparable to diazepam treatment. Furthermore, pretreatment with bicuculline significantly abolished the ABA effects on sleep parameters, while the amplifying effects of ABA on the induction of sleep onset was not significantly affected by PPARβ or PPARγ antagonists. The sleep prolonging effect of ABA was significantly prevented by both PPAR antagonists. Conclusions: The data showed that ABA boosts pentobarbital-induced sleep and that GABA-A, PPARβ and PPARγ receptors are, at least in part, involved in ABA signaling.

Purpose: Anesthesia is necessary to conduct rodent electroretinograms (ERGs). We evaluated utility of the α2-agonist medetomidine versus xylazine for ERG studies in nondiabetic and diabetic rats. Pentobarbital was included as a comparator. Methods: Male Sprague-Dawley rats, with and without streptozotocin (STZ)-induced diabetes, were anesthetized with medetomidine (1 mg/kg), xylazine (10 mg/kg) (both with ketamine 75 mg/kg), or pentobarbital (70 mg/kg). The depth of anesthesia was assessed, and if adequate, scotopic ERGs were recorded. Blood glucose was monitored. Results: In nondiabetic rats, all three agents induced satisfactory anesthesia, but with differing durations: medetomidine > pentobarbital > xylazine. ERG responses were similar under medetomidine and xylazine, but relatively reduced under pentobarbital. Both α2-agonists (but not pentobarbital) elicited marked hyperglycemia (peak values 316.1 ± 42.6 and 300.3 ± 29.5 mg/dL, respectively), persisting for 12 h. In diabetic rats, elevated blood glucose concentrations were not affected by any of the agents, but the depth of anesthesia under medetomidine and xylazine was inadequate for ERG recording. Conclusions: In nondiabetic rats, medetomidine and xylazine elicited comparable effects on ERGs that differ from pentobarbital, but both perturbed glucose metabolism, potentially confounding experimental outcomes. In STZ-diabetic rats, neither α2-agent provided adequate anesthesia, while pentobarbital did so. Problems with α2-anesthetic agents, including medetomidine, must be recognized to ensure meaningful interpretation of experimental results. [ABSTRACT FROM AUTHOR]

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Purpose: The aim of this study was to investigate whether estrogen deficiency interrupts bone healing around titanium implants and to evaluate whether bone healing around implants under a condition of estrogen deficiency is affected by variations in implant surface characteristics. Materials and Methods: Forty-eight female rats were divided into two groups: ovariectomized rats (OVX; n = 24) and sham-operated rats (SHAM; n = 24). Each group was further divided into two groups: a machine-polished implants group and a sandblasted implants group. One implant was placed into the left femur of each rat 84 days after OVX or sham surgery. After 28 or 56 days, the rats were killed, and nondecalcified sections were obtained. Bone-toimplant contact (BIC) and bone area (BA) around the implants were assessed for cortical and cancellous bone. Furthermore, bone density (BD) was evaluated in a 500-mm-wide zone of cancellous bone lateral to the implants. Results: At 28 and 56 days after implantation, no significant differences were found between the OVX and SHAM groups for BIC and BA in cortical bone. BIC, BA, and BD with cancellous bone were lower in the OVX group than in the SHAM group. However, BIC and BA tended to increase with the sandblasted implant surface. Conclusions: Estrogen deficiency affected bone healing and bone density around titanium implants, especially in cancellous bone, but the sandblasted surface has the possibility to improve osseointegration. However, the positive effect of this rough surface is limited at the implant surface. [ABSTRACT FROM AUTHOR]

Suanzaoren decoction (SZRT), a classic Chinese herbal prescription, has been used as a treatment for insomnia for more than a thousand years. However, recent studies have found no significant effects of SZRT as a treatment for insomnia caused by gastric discomfort. Herein, we studied the effects of modified Suanzaoren decoction (MSZRD) on gastrointestinal disorder-related insomnia. The main constituents of MSZRD were spinosin (2.21 mg/g) and 6-feruloylspinosin (0.78 mg/g). A pentobarbital-induced animal model of insomnia showed that MSZRD shortened sleep latency and prolonged sleep time of the male Institute of Cancer Research (ICR) mice treated for 7 days with oral MSZRD. Sprague-Dawley male rats were treated daily with oral MSZRD or placebo for 11 days and then deprived of sleep for the last 4 days to establish a model of insomnia. Of note, MSZRD-treated animals had significantly improved body weight, organ index scores, and fecal moisture relative to placebo-treated animals, as well as reduced temperature. Sleep-deprived rats exhibited more exploratory behaviors in an open-field anxiety test; however, this effect was significantly reduced in MSZRD-treated animals. We found that MSZRD treatment decreased gastric acid pH, decreased the production of gastrin, pepsin, and Orexin-A, and increased the expression of MTL and CCK-8. Importantly, serum GABA concentration was increased by treatment with MSZRD, as reflected by a decreased Glu/GABA ratio. Treated animals had increased the expression of GAD1, GABARA1, and CCKBR but decreased the expression of Orexin R1. In summary, these results suggest that MSZRD has soporific and gastroprotective effects that may be mediated by differential expression of CCK-8 and Orexin-A. [ABSTRACT FROM AUTHOR]

Objectives. To evaluate the effects of pentobarbital dosages on lower urinary tract function and to define an appropriate dosage of sodium pentobarbital that would be suitable for urodynamic studies in which recovery from anesthesia and long term survive were needed for subsequent experiment. Methods. Twenty-four 8-week-old, female, virgin, Sprague-Dawley rats (200-250 g) were used in this study. Rats in study groups received gradient doses of pentobarbital intraperitoneally, and those in the control group received urethane intraperitoneally. External urethral sphincter electromyography (EUS-EMG) was recorded simultaneously during cystometry and leak point pressure tests. The toe-pinch reflex was used to determine the level of anesthesia. Results. Micturition was normally induced in both the urethane group and 32 mg/kg pentobarbital group. However, in groups of 40 mg/kg or 36 mg/kg pentobarbital, micturition failed to be induced; instead, nonvoiding contractions accompanied by EUS-EMG tonic activity were observed. There were no significant differences in leak point pressure or EUS-EMG amplitude or frequency between the urethane and 32 mg/kg pentobarbital groups. Conclusions. This study confirmed significant dose-dependent effects of pentobarbital on lower urinary tract function and 32 mg/kg pentobarbital as an appropriate dosage for recovery urodynamic testing, which enable the achievement of expected essential micturition under satisfactory anesthesia in female rats. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the chemopreventive effect of the ethanolic extract of Cordia lutea flowers (EECL) on N-methyl-N-nitrosourea- (MNU), cyproterone-, and testosterone-induced prostate cancer in rats. 40 Holtzman male rats were used and assigned to 5 groups (n = 8). In Group I, rats received normal saline (10 mL/Kg); Group II: rats were induced for prostate cancer with cyproterone, testosterone, and NMU; Groups III, IV, and V: rats received EECL daily, at doses of 50, 250, and 500 mg/kg body weight, respectively. After the period of treatment, animals were sacrificed by an overdose of pentobarbital and blood samples were collected for determination of prostate-specific antigen (PSA). The prostate was dissected and weighed accurately. The ventral lobe of the prostate was processed for histopathology analysis. The somatic prostate index decreased with EECL at dependent dose, from 0.34 ± 0.04 to 0.23 ± 0.05 (P < 0.05). The PSA levels also decreased significantly at doses of 250 and 500 mg/kg. Histopathological analysis showed a decrease in the number of prostatic layers with high-grade prostatic intraepithelial neoplasia (HG-PIN) and low-grade prostatic intraepithelial neoplasia (LG-PIN) at the dose of 500 mg/kg. The ethanolic extract of Cordia lutea flowers had a chemopreventive effect on induced prostate cancer in rats. [ABSTRACT FROM AUTHOR]

Background: Gongronema latifolium Benth. (family Apocynaceae) leaves (GL) has interesting medicinal properties. The effects of extracts from G. latifolium on blood pressure (BP) and the possible mechanisms of action were also investigated. Methods: The ultrahigh resolution liquid chromatography orbitrap MS analysis was used to identify the phytochemicals present. Normotensive Wistar rats were anesthetized with sodium pentobarbitone (40 mg/kg) intraperitoneally, and the jugular vein was cannulated for infusion of drugs while the carotid artery was cannulated for direct BP measurement. GL extract (5-20 mg) alone or with nifedipine (10 mg/kg), atropine (2 mg/kg), L-NAME (5 mg/kg), methyl blue (3 mg/kg) and propranolol (1 mg/kg) were administered intravenously to Wistar rats and direct BP measurements were carried out. Results: Systolic and diastolic BP levels (128/90 mm Hg; MAP 103 ± 3 mm Hg) and heart rates were all significantly (p < 0.01) decreased after GL administration. Raised mean arterial pressure (MAP) and heart rate by atropine, L-NAME and methyl blue were significantly (p < 0.01) reduced after GL administration, while propranolol significantly (p < 0.01) inhibited hypotension caused by GL. Infusion of GL reduced MAP (95 ± 3 mm Hg) comparable with nifedipine (93 ± 2 mm Hg), a calcium channel blocker. The phytochemicals identified were 34 compounds, including oleanolic acid derivatives, flavonoids, antioxidant fatty acids, 2 coumarins and 2 iridoids. Conclusions: These results suggest that G. latifolium has hypotensive properties mediated by the synergistic activity of the compounds, probably via the ß-adrenergic blockade mechanism. [ABSTRACT FROM AUTHOR]

Corticotropin-releasing hormone, a major neuromodulator of the neuroendocrine stress response, is expressed in the immature hippocampus, where it enhances glutamate receptor-mediated excitation of principal cells. Since the peptide influences hippocampal synaptic efficacy, its secretion from peptidergic interneuronal terminals may augment hippocampal-mediated functions such as learning and memory. However, whereas information regarding the regulation of corticotropin-releasing hormone's abundance in CNS regions involved with the neuroendocrine responses to stress has been forthcoming, the mechanisms regulating the peptide's levels in the hippocampus have not yet been determined. Here we tested the hypothesis that, in the immature rat hippocampus, neuronal stimulation, rather than neuroendocrine challenge, influences the peptide's expression. Messenger RNA levels of corticotropin-releasing hormone in hippocampal CA1, CA3 and the dentate gyrus, as well as in the hypothalamic paraventricular nucleus, were determined after cold, a physiological challenge that activates the hypothalamic pituitary adrenal system in immature rats, and after activation of hippocampal neurons by hyperthermia. These studies demonstrated that, while cold challenge enhanced corticotropin-releasing hormone messenger RNA levels in the hypothalamus, hippocampal expression of this neuropeptide was unchanged. Secondly, hyperthermia stimulated expression of hippocampal immediate-early genes, as well as of corticotropin-releasing hormone. Finally, the mechanism of hippocampal corticotropin-releasing hormone induction required neuronal stimulation and was abolished by barbiturate administration. Taken together, these results indicate that neuronal stimulation may regulate hippocampal corticotropin-releasing hormone expression in the immature rat, whereas the peptide's expression in the hypothalamus is influenced by neuroendocrine challenges.

Mist Antiaris is a herbal decoction for treatment of nervous disorders. Safety and efficacy were evaluated in Sprague-Dawley rats and human patients, respectively. Acute toxicity was assessed by administration of a single 5000 mg/kg oral dose of decoction to a group of six rats. For subchronic toxicity, four groups of six rats each received water (control) or 10, 100, or 200 mg/kg oral doses of decoction daily for eight weeks. Body weight, serum, urine, and hematological profile of the animals in each group were monitored over the period. Effects of treatment on pentobarbital-induced sleeping time and histology of liver, lung, heart, and kidney tissue were assessed at the end of the study. There was no evidence of acute toxicity within 48 hours of the oral dose. Over the 8-week period, body weight increases in Mist Antiaris treatment groups were reduced relative to the control group. There were no significant differences in urine profile, serum biochemistry, hematological parameters, and pentobarbital-induced sleeping time. Tissue histology revealed no differences relative to controls. Assessment of efficacy was by retrospective review of data on patients who presented with peripheral neuropathy. Treatment resulted in 53.7 % of patients reporting complete resolution and 15.7 % showing reduction in neuropathic symptoms. The data demonstrate that there is no toxicity due to subchronic administration of Mist Antiaris in Sprague-Dawley rats. The reduction or resolution of neuropathic symptoms indicated by patents' file data provides evidence to suggest that Mist Antiaris has antineuropathic effects. [ABSTRACT FROM AUTHOR]

Objective: To observe the effect of Quyu Chencuo Formula (去菀陈莝方, QCF) on renal fibrosis in rats with obstructive nephropathy.Methods: Twenty-four rats were randomly divided into three groups, 4 for sham operation as the control group, 10 for unilateral ureteral obstruction (UUO) model group, and the rest 10 for QCF treating UUO model group. All rats were sacrificed under 3% pentobarbital (50 mg/kg) anesthesia on the 14th day after surgery, then the right kidney samples of rats were harvested for hematoxylin eosin (HE) staining and Masson staining to observe the renal pathological changes. Immunohistochemistry and Western blotting were used to examine the expression of transforming growth factor β1 (TGF-β1), and real-time polymerase chain reaction (RT-PCR) was employed to examine the expressions of TGF-β1, α-smooth muscle actin (α-SMA) and E-cadherin mRNA.Results: HE and Masson staining showed that the renal interstitial of the rats in the control group had no significant fibrotic lesion; in the model group, there were obvious interstitial fibrosis; for the QCF group, there were epithelial cell necrosis, infiltration of lymphocytes and mononuclear cells, aggravated interstitial fibrosis in varied degrees, but the pathological changes were less in the QCF group than in the model group. The immunohistochemistry and Western blotting results showed that the TGF-β1 expression was increased significantly in the model group, while decreased significantly in the QCF group (P<0.05); RT-PCR showed that the mRNA expression of α-SMA and TGF-β1 increased significantly in the model group, while both were significantly decreased in the QCF group compared with the model group (P<0.05). The mRNA expression of E-cadherin was decreased significantly in the model group, and it was significantly increased in the QCF group as compared with the model group (P<0.05).Conclusion: QCF may improve renal fibrosis by regulating the expressions of TGF-β1, α-SMA and E-cadherin, and prevent the progress of kidney fibrosis. [ABSTRACT FROM AUTHOR]

Anxiety disorders are highly prevalent, chronic, and disabling conditions that impose enormous health and economic costs both on individuals and on society. Medicinal plants are an invaluable source of bioactive metabolites that can be useful as new pharmacological treatment. Teas from Mentha spicata and Plantago major are employed by Colombian populations to treat stress and insomnia. This work was conducted to evaluate their anxiolytic and hypnotic properties. For this, we employed the Elevated Plus-Maze test and the sodium pentobarbital-induced hypnosis method using Wistar rats. Oral administration of M. spicata extract (1000 mg/Kg) significantly increased the exploration and time spent in the open arms, which indicates its anxiolytic activity. On the other hand, both M. spicata and P. major extracts (1000 mg/Kg) remarkably augmented the sleeping time induced by pentobarbital, suggesting a sedative and hypnotic effect of the plants extracts. In addition, the acute toxicological study demonstrated that the doses used did not induce mortality or toxicity effects at hepatic or renal level. The bioactivity seems to be related to several kinds of constituents, mainly phenolic compounds such as flavonoids and tannins. In conclusion, these results reinforce the potential use of these species in the therapy of anxiety. [ABSTRACT FROM AUTHOR]