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Journal of Ethnopharmacology Oct 2023Although lettuce is traditionally known to have hypnotic and sedative effects, to date, only a few studies have documented its sleep-promoting effects and elucidated the...
ETHNOPHARMACOLOGICAL RELEVANCE
Although lettuce is traditionally known to have hypnotic and sedative effects, to date, only a few studies have documented its sleep-promoting effects and elucidated the related mechanisms.
AIM OF THE STUDY
We aimed to investigate the sleep-promoting activity of Heukharang lettuce leaf extract (HLE) with increased lactucin content, known as a sleep-promoting substance in lettuce, in animal models.
MATERIALS AND METHODS
To evaluate the effect of HLE on sleep behavior, analysis of electroencephalogram (EEG), gene expression of brain receptors, and activation mechanisms using antagonists were investigated in rodent models.
RESULTS
High-performance liquid chromatography analysis showed that HLE contained lactucin (0.78 mg/g of extract) and quercetin-3-glucuronide (1.3 mg/g of extract). In the pentobarbital-induced sleep model, the group administered 150 mg/kg of HLE showed a 47.3% increase in sleep duration time as compared to the normal group (NOR). The EEG analysis showed that the HLE significantly increased non-rapid eye movement (NREM), where delta waves were improved by 59.5% when compared to the NOR, resulting in increased sleep time. In the caffeine-induced arousal model, HLE significantly decreased the awake time increased by caffeine administration (35.5%) and showed a similar level to NOR. In addition, HLE increased the gene and protein expression of gamma-aminobutyric acid receptor type A (GABA), GABA type B, and 5-hydroxytryptamine (serotonin) receptor 1A. In particular, in comparison to the NOR, the group administered 150 mg/kg HLE showed an increase in expression levels of GABA and protein by 2.3 and 2.5 times, respectively. When the expression levels were checked using GABA receptor antagonists, HLE showed similar levels to NOR, as the sleep duration was reduced by flumazenil (45.1%), a benzodiazepine antagonist.
CONCLUSIONS
HLE increased NREM sleep and significantly improved sleep behavior due to its action on the GABA receptors. The collective findings suggest that HLE can be used as a novel sleep-enhancing agent in the pharmaceutical and food industries.
Topics: Animals; Receptors, GABA-A; Lactuca; Caffeine; Plant Extracts; Sleep; Hypnotics and Sedatives; gamma-Aminobutyric Acid
PubMed: 37149068
DOI: 10.1016/j.jep.2023.116602 -
Journal of Traditional Chinese Medicine... Jun 2023To evaluate the effect of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia...
OBJECTIVE
To evaluate the effect of needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3) on cerebral cortical blood oxygen level in rats with insomnia identified as liver- stagnation pattern in terms of Traditional Chinese Medicine.
METHODS
Sixty Wistar rats were randomly divided into blank group ( 10), the rest of the rats were clamped tail as stimulation combined with injected intraperitoneally p-chlorophenylalanine (PCPA) to establish sleep deprivation model. After the successful replication of the model, they were randomly divided into model group, grabbing group, Western Medicine group, acupuncture group and sham acupuncture group, with 10 rats in each group. The model group was given normal saline; The grasping group was grasped in the same way as the two treatment groups; Western medicine group was given estazolam solution; The acupuncture group was treated with the acupuncture method of "soothing the liver and regulating mind" needling Baihui (GV20), Neiguan (PC6), Shenmen (HT7) and Taichong (LR3); The sham acupuncture group were needled with four non-acupoint sites. After 7 d of treatment of rats in each group, sodium pentobarbital sleep experiment was used to evaluate the sleep latency (SL) and sleep time (ST). The percentage of rats entering the open arm (OE%) and the percentage of time entering the open arm (OT%) in each group were monitored by elevated cross maze, and the vertical score, horizontal crossing times, central grid score and modification times were monitored by open field test, functional near infrared spectroscopy (fNIRs) was used to monitor the changes of oxygenated hemoglobin (Oxy-Hb), deoxyhemoglobin (Deoxy-Hb) and total hemoglobin (Total-Hb) in the cerebral cortex of rats in each group under light stimulation and dark stimulation, the statistically significant channel combinations were selected from 8 light sources and 12 detectors (S-D). According to the position of the light source detector covering the cerebral cortex, Preliminarily determine the key brain areas of insomnia (the preliminary experiment found that 6S-8D and 7S-9D were the key channels of insomnia under light stimulation, and the corresponding brain areas were prefrontal lobe and occipital lobe respectively; 7S-7D channel under dark stimulation, and the corresponding brain area was occipital lobe); The hemodynamic map of cerebral cortex was constructed through the absolute value of whole brain blood oxygen level. Further identify key brain regions for insomnia.
RESULTS
Compared with the blank group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score, the concentration of Deoxy-Hb in prefrontal and occipital lobes were decreased significantly (<0.01), and the concentrations of SL, modification times, Oxy-Hb and Total-Hb were increased significantly (<0.01); There was no difference in the above indexes between the model group and the grabbing group (>0.05); After treatment, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and Deoxy-Hb concentration in acupuncture group and Western medicine group increased significantly, while SL, modification times, Oxy-Hb and Total-Hb concentrations were decreased significantly (<0.01, <0.05), Compared with the Western Medicine group, the values of OE% and OT% were more significantly higher in the acupuncture group (<0.05), while the rest of the indexes were not significantly different between the two groups (>0.05); Compared with the acupuncture group, ST, OE%, OT%, the vertical score, horizontal crossing times, central grid score and the concentration of deoxy Hb in the sham acupuncture group decreased significantly (<0.01), and the concentrations of SL, modification times, Oxy-Hb and Total-Hb increased significantly (<0.01).
CONCLUSIONS
The needling method for soothing the liver and regulating mind could improve the abnormal behavior of insomnia rats with liver stagnation, and its effect on the improvement of abnormal mood caused by insomnia with liver stagnation is better than that of Western Medicine, and the mechanism of action may be related to the regulation of blood oxygen metabolism in the prefrontal and occipital lobes of the cerebral cortex by acupuncture.
Topics: Rats; Animals; Sleep Initiation and Maintenance Disorders; Oxygen Saturation; Rats, Wistar; Acupuncture Therapy; Acupuncture Points; Cerebral Cortex; Hemoglobins
PubMed: 37147754
DOI: 10.19852/j.cnki.jtcm.20230404.005 -
American Journal of Veterinary Research Jul 2023To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta).
OBJECTIVE
To determine the ability of transmucosal euthanasia solution to induce euthanasia in pond slider turtles (Trachemys scripta).
ANIMALS
16 pond slider turtles (T. scripta).
PROCEDURES
Pentobarbital 100 mg/kg was delivered through esophageal gavage (n = 8) or cloacal administration (8). The presence of voluntary movement, heart rate (HR), respiratory rate (RR), palpebral reflex, corneal reflex, and response to noxious stimuli were recorded until death, confirmed via the absence of reflexes, movement, heartbeat, and absence of cardiac electrical activity.
RESULTS
No signs of irritation were observed in any turtles. Leakage after administration occurred in 75% (6/8) of the cloacal group, including 2 turtles with marked leakage or expulsion. Two of eight turtles in the cloacal group regained movement and required euthanasia by a standard method and 1 turtle in the oral group was excluded from further analysis due to a miscalculated dose. The remaining 13 turtles (7/8 oral, 6/8 cloacal) had cessation of a heartbeat at a median of 18 hours (range = 6 to 26 hours) with respiratory arrest occurring within 15 minutes. The median time to loss of corneal reflex was 45 minutes (range = 15 minutes to 4 hours). Time-to-loss of parameters was similar between oral and cloacal routes, respectively.
CLINICAL RELEVANCE
Transmucosally administered pentobarbital via the oral and cloacal routes both result in euthanasia within approximately 24 hours. Given that 25% of the turtles in the cloacal group required a secondary method of euthanasia, the oral route is a preferred route to induce euthanasia in pond turtles.
Topics: Animals; Turtles; Pentobarbital; Euthanasia, Animal; Blinking; Heart Rate
PubMed: 37142234
DOI: 10.2460/ajvr.23.01.0011 -
Experimental and Therapeutic Medicine May 2023Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear...
Chronic fragmented sleep is a very common type of insomnia that affects the daily lives of numerous people around the world. However, its pathogenesis is not very clear and a corresponding rat model has not been reported for this purpose at present. The present study aimed to establish a rat model of chronic insomnia with sleep fragmentation using self-made multiple strings of unstable platforms surrounded by shallow water. During the establishment of the models, changes in body weight and differences in food and water intake in the daytime and at night were acquired. The rat models were assessed using several tests, including the Morris water maze test, pentobarbital sodium-induced sleep, infrared monitoring and electroencephalogram/electromyography during sleep. The expression levels of certain inflammatory factors and orexin A were detected in the serum and brain tissues using ELISAs, immunohistochemistry and immunofluorescence. The expression levels of orexin 1 receptor (orexin 1r) were also detected in the brain. Polysomnography indicated that the model rats were successfully prepared with reduced non-rapid eye movement (non-REM) sleep in the daytime, which was increased at night, and considerably lower REM duration during the day and night. The number of instances of sleep arousals were also increased in the day and at night, and the average duration of each sleep bout was decreased in the daytime. The body weights of the model rats increased at a normal rate. However, the reduction of body weight in the daytime and increased in body weight at night were significantly less than those of the control rats. The daytime food and water consumption of the model rats increased significantly compared with that of the control rats, but was similar to that of the control group at night. The Morris water maze test indicated that the model rats were slow to learn to escape the platforms and performed a lower number of target crossings. The pentobarbital-induced sleep experiment confirmed that the model rats exhibited a longer sleep latency and shorter sleep time. The serum IL-1β, IL-6, TNF-α and orexin A levels of the model rats were significantly increased, whereas their serum IL-10 levels were significantly decreased compared with those of the control rats. The expression levels of IL-1β, IL-6, orexin A and orexin 1r in the brain tissues of the model rats were also significantly increased. In conclusion, these data indicate that learning and memory function, sleep time, arousal times, diurnal and nocturnal body weight changes, food and water intake, and expression levels of the specific inflammatory factors orexin A and orexin 1r were altered in the model rats. This suggests the chronic insomnia rat model with sleep fragmentation was successfully established using multiple strings of unstable platforms surrounded by water.
PubMed: 37114171
DOI: 10.3892/etm.2023.11932 -
Molecules (Basel, Switzerland) Apr 2023Neophytadiene (NPT) is a diterpene found in the methanolic extracts of and , plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like...
Neophytadiene (NPT) is a diterpene found in the methanolic extracts of and , plants reported with anxiolytic-like activity, sedative properties, and antidepressant-like actions; however, the contribution of neophytadiene to these effects is unknown. This study determined the neuropharmacological (anxiolytic-like, antidepressant-like, anticonvulsant, and sedative) effects of neophytadiene (0.1-10 mg/kg p.o.) and determined the mechanisms of action involved in the neuropharmacological actions using inhibitors such as flumazenil and analyzing the possible interaction of neophytadiene with GABA receptors using a molecular docking study. The behavioral tests were evaluated using the light-dark box, elevated plus-maze, open field, hole-board, convulsion, tail suspension, pentobarbital-induced sleeping, and rotarod. The results showed that neophytadiene exhibited anxiolytic-like activity only to the high dose (10 mg/kg) in the elevated plus-maze and hole-board tests, and anticonvulsant actions in the 4-aminopyridine and pentylenetetrazole-induced seizures test. The anxiolytic-like and anticonvulsant effects of neophytadiene were abolished with the pre-treatment with 2 mg/kg flumazenil. In addition, neophytadiene showed low antidepressant effects (about 3-fold lower) compared to fluoxetine. On other hand, neophytadiene had no sedative or locomotor effects. In conclusion, neophytadiene exerts anxiolytic-like and anticonvulsant activities with the probable participation of the GABAergic system.
Topics: Animals; Anti-Anxiety Agents; Anticonvulsants; Flumazenil; Molecular Docking Simulation; Hypnotics and Sedatives; Seizures; Plant Extracts; Antidepressive Agents; Behavior, Animal
PubMed: 37110691
DOI: 10.3390/molecules28083457 -
Cureus Mar 2023Concomitant prescriptions of psychotropic drugs such as sleeping pills, antidepressants, and anti-anxiety medications are common. The relationship between the number of...
Concomitant prescriptions of psychotropic drugs such as sleeping pills, antidepressants, and anti-anxiety medications are common. The relationship between the number of psychotropic drug prescriptions and the incidence of drug overdose has not been reported. However, efforts have been made to reduce the number of concomitant prescriptions hoping that fewer prescriptions of multiple drugs will lower the incidence of drug overdoses. Furthermore, among sleeping pills, prescriptions of barbiturates have been gradually decreasing due to the risk of severe side effects and addiction. This report features a case of an overdose of pentobarbital tablets that caused the classic medical triad (impaired consciousness, hypotension, and hypothermia) of barbiturate intoxication under the characteristics of borderline personality disorder.
PubMed: 37090268
DOI: 10.7759/cureus.36498 -
Evidence-based Complementary and... 2023The use of medicinal plants in the treatment of mental illnesses is a reality that accompanies the history of civilizations, and the Piper genus exhibits many species...
AIM
The use of medicinal plants in the treatment of mental illnesses is a reality that accompanies the history of civilizations, and the Piper genus exhibits many species with pharmacologically proven central effects. Then, this study evaluated the neuropharmacological effects of the hydroalcoholic extract from (HEPC) leaves to validate its uses in folk medicine.
MATERIALS AND METHODS
Primarily Swiss mice (female, 25-30 g) were pretreated with HEPC (50-150 mg/kg, p.o.), vehicle, or the positive control, and submitted to open-field test (OFT), inhibitory avoidance test (IAT), tail suspension test (TST), and forced swim test (FST). Also, mice were exposed to pentylenetetrazol- and strychnine-induced seizure assay, pentobarbital-induced hypnosis test, and elevated plus-maze (EPM). The GABA levels and MAO-A activity were measured in the animal's brain after 15 days of HEPC administration (150 mg/kg, p.o.).
RESULTS
Mice pretreated with HEPC (100 and 150 mg/kg) and exposed to pentobarbital presented decreased sleep latency and increased sleep duration (HEPC 150 mg/kg). In EPM, the HEPC (150 mg/kg) increased the frequency of entry and the time of exploration of mice in the open arms. The antidepressant-like properties of HEPC were demonstrated by the decrease in the mice's immobility time when tested in FST and TST. The extract did not show anticonvulsant activity, in addition to not improving the memory parameters of animals (IAT) or interfering with their locomotor activity (OFT). Besides, HEPC administration decreased the MAO-A activity and increased the GABA levels in the animal's brain.
CONCLUSION
HEPC induces sedative-hypnotic, anxiolytic-, and antidepressant-like effects. These neuropharmacological effects of HEPC could be, at least in part, related to the modulation of the GABAergic system and/or MAO-A activity.
PubMed: 37078066
DOI: 10.1155/2023/1183809 -
American Journal of Translational... 2023To explore the mechanism by which mechanical ventilation improves myocardial injury in rats with acute heart failure (AHF).
OBJECTIVE
To explore the mechanism by which mechanical ventilation improves myocardial injury in rats with acute heart failure (AHF).
METHODS
Thirty-six male Sprague Dawley rats were randomized into a sham group, heart failure (HF) group, and mechanical ventilation (MV) group. The AHF rat model was established by pentobarbital perfusion under right internal jugular vein monitoring. The symptoms of heart failure, changes in hemodynamic parameters, cardiac function, N-terminal pro-B-type natriuretic peptide (NT-proBNP), oxidative stress-related indicators, myocardial apoptosis index, and expression of apoptosis-related proteins were compared in an AHF rat model with or without mechanical ventilation.
RESULTS
Compared to the sham group, the hemodynamics and cardiac function of MV and HF groups were markedly reduced (<0.05), and the serum levels of NT-proBNP of MV and HF groups were elevated (<0.05). The levels of malondialdehyde (MDA) were lowest in the sham group, followed by the MV group, and highest in the HF group. Glutathione (GSH) and superoxide dismutase (SOD) were lowest in the HF group, inermediate in MV group, and highest in the sham group (<0.05). Mechanical ventilation improved myocardial injury and reduced apoptosis of myocardial cells in a rat model of AHF.
CONCLUSION
Mechanical ventilation in the early stage of heart failure can significantly reduce the excessive occurrence of oxidative stress in rats and significantly improve apoptosis in myocardial cells in AHF rats, so as to effectively improve the symptoms of AHF and reduce the mortality of AHF rats.
PubMed: 37056811
DOI: No ID Found -
Frontiers in Endocrinology 2023The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset...
OBJECTIVES
The time of onset of puberty has been increasingly earlier, but its mechanism is still unclear. This study aimed to reveal the mechanism of leptin and NPY in the onset of puberty in male offspring rats after androgen intervention during pregnancy.
METHODS
Eight-week-old specific pathogen-free (SPF) healthy male Sprague-Dawley (SD) rats and 16 female SD rats were selected and caged at 1:2. The pregnant rats were randomly divided into the olive oil control group (OOG) and testosterone intervention group (TG), with 8 rats in each group. Olive oil and testosterone were injected from the 15th day of pregnancy, for a total of 4 injections (15th, 17th, 19th, 21st day). After the onset of puberty, the male offspring rats were anesthetized with 2% pentobarbital sodium to collect blood by ventral aorta puncture and decapitated to peel off the hypothalamus and abdominal fat. Serum testosterone (T), free testosterone (FT), dihydrotestosterone (DHT), dehydroepiandrosterone (DHEA), sex hormone binding globulin (SHBG), and leptin were detected by ELISA, and then the free androgen index (FAI) was calculated. The mRNA levels of androgen receptor (AR), estrogen receptor α (ERα), NPY, leptinR, and NPY2R in the hypothalamus and abdominal fat were detected by RT-PCR. Protein expression levels of AR, ERα, NPY, leptinR, and NPY2R in the arcuate nucleus (ARC) of the hypothalamus were detected by immunohistochemistry.
RESULTS
The time of onset of puberty was significantly earlier in the TG than in the OOG ( 0.05) and was positively correlated with body weight, body length, abdominal fat, and leptinR mRNA levels in adipose tissue in the OOG ( 0.05), while it was positively correlated with serum DHT and DHEA concentrations and FAI and AR mRNA levels in the hypothalamus in the TG ( 0.05). The NPY2R mRNA level and protein expression levels of ERα, NPY2R, and leptinR in the TG were significantly higher than those in the OOG, while the protein expression levels of AR and NPY in the TG were significantly lower than those in the OOG ( 0.05).
CONCLUSIONS
Testosterone intervention during pregnancy led to an earlier onset of puberty in male offspring rats, which may render the male offspring rats more sensitive to androgens, leptin, and NPY at the onset of puberty.
Topics: Pregnancy; Rats; Male; Female; Animals; Androgens; Leptin; Estrogen Receptor alpha; Olive Oil; Rats, Sprague-Dawley; Sexual Maturation; Testosterone; Dihydrotestosterone; Dehydroepiandrosterone; RNA, Messenger
PubMed: 37056673
DOI: 10.3389/fendo.2023.1090552 -
Frontiers in Pharmacology 2023Rhizoma Gastrodia (Orchidaceae; Blume), the rhizome of Blume (GE), is traditionally used as both a medicinal and functional food, with proven efficacy in treating...
Rhizoma Gastrodia (Orchidaceae; Blume), the rhizome of Blume (GE), is traditionally used as both a medicinal and functional food, with proven efficacy in treating mental disorders. In traditional processing, GE is washed, steamed with water, dried, and sliced. In this study, a novel processing technology-alcohol steamed GE (AGE) was proposed as an alternative. Totally, 17 compounds were identified in fresh GE and AGE. Compared with fresh GE, the relative content of parishin A and parishin E decreased after alcohol steaming, whereas gastrodin (GAS), p-hydroxylbenzyl alcohol (HBA), Parishin B, and Parishin C were increased. Additionally, the pentobarbital-induced sleep mice model and Chronic Restraint Stress (CRS) model were applied to evaluate the pharmacological effects of fresh GE and steamed GE, and both fresh and steamed GE showed an intensive hypnotic and anti-anxiety effect. Furthermore, the anti-anxiety mechanism based on serum metabolic was investigated and the tryptophan metabolic pathway was considered the response to the anti-anxiety effect of GE. Although the optimization of the processing technology of AGE still needs to be further explored, the current results have provided new thoughts for the processing technology and clinical application of GE.
PubMed: 37033659
DOI: 10.3389/fphar.2023.1092693