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Journal of Ethnopharmacology May 2024Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress...
ETHNOPHARMACOLOGICAL RELEVANCE
Sleep plays a critical role in several physiologic processes, and sleep disorders increase the risk of depression, dementia, stroke, cancer, and other diseases. Stress is one of the main causes of sleep disorders. Ginseng Radix et Rhizoma and Polygalae Radix have been reported to have effects of calming the mind and intensifying intelligence in Chinese Pharmacopoeia. Traditional Chinese medicine prescriptions composed of Ginseng Radix et Rhizoma and Polygalae Radix (Shen Yuan, SY) are commonly used to treat insomnia, depression, and other psychiatric disorders in clinical practice. Unfortunately, the underlying mechanisms of the SY extract's effect on sleep are still unknown.
AIM OF THE STUDY
This study aimed to investigate the hypnotic effect of the SY extract in normal mice and mice with chronic restraint stress (CRS)-induced sleep disorders and elucidate the underlying mechanisms.
MATERIALS AND METHODS
The SY extract (0.5 and 1.0 g/kg) was intragastrically administered to normal mice for 1, 14, and 28 days and to CRS-treated mice for 28 days. The open field test (OFT) and pentobarbital sodium-induced sleep test (PST) were used to evaluate the hypnotic effect of the SY extract. Liquid chromatography-tandem mass spectrometry and enzyme-linked immunosorbent assay were utilized to detect the levels of neurotransmitters and hormones. Molecular changes at the mRNA and protein levels were determined using real-time quantitative polymerase chain reaction and Western blot analysis to identify the mechanisms by which SY improves sleep disorders.
RESULTS
The SY extract decreased sleep latency and increased sleep duration in normal mice. Similarly, the sleep duration of mice subjected to CRS was increased by administering SY. The SY extract increased the levels of tryptophan (Trp) and 5-hydroxytryptamine (5-HT) and the expression of tryptophan hydroxylase 2 (TPH2) in the cortex of normal mice. The SY extract increased the Trp level, transcription and expression of estrogen receptor beta and TPH2 in the cortex in mice with sleep disorders by decreasing the serum corticosterone level, which promoted the synthesis of 5-HT. Additionally, the SY extract enhanced the expression of arylalkylamine N-acetyltransferase, which increased the melatonin level and upregulated the expressions of melatonin receptor-2 (MT2) and Cryptochrome 1 (Cry1) in the hypothalamus of mice with sleep disorders.
CONCLUSIONS
The SY extract exerted a hypnotic effect via the Trp/5-HT/melatonin pathway, which augmented the synthesis of 5-HT and melatonin and further increased the expressions of MT2 and Cry1.
Topics: Humans; Mice; Animals; Hypnotics and Sedatives; Tryptophan; Serotonin; Drugs, Chinese Herbal; Melatonin; Sleep Initiation and Maintenance Disorders
PubMed: 38428654
DOI: 10.1016/j.jep.2024.117992 -
Journal of Ethnopharmacology May 2024Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the...
Guhan Yangsheng Jing mitigates hippocampal neuronal pyroptotic injury and manifies learning and memory capabilities in sleep deprived mice via the NLRP3/Caspase1/GSDMD signaling pathway.
ETHNOPHARMACOLOGICAL RELEVANCE
Guhan Yangsheng Jing (GHYSJ) is a traditional Chinese patent medicine, that has the function of nourishing the kidney and replenishing the essence, invigorating the brain and calming the mind. It is often used to treat dizziness, memory loss, sleep disorders, fatigue, and weakness, etc. However, its mechanism for improving sleep has not yet been determined.
AIM OF THE STUDY
This study aims to explore the effects of GHYSJ on Sleep Deprivation (SD)-induced hippocampal neuronal pyroptotic injury, learning and cognitive abilities, and sleep quality in mice.
METHODS
In this study, a PCPA-induced SD mouse model was established. We assessed the influence of GHYSJ on sleep quality and mood by using the pentobarbital-induced sleep test (PIST) and sucrose preference test (SPT). The pharmacological effects of GHYSJ on learning and memory impairment were evaluated by the Morris Water Maze (MWM) and Open Field Test (OFT). Pathological changes in the hippocampal tissue of the SD rats were observed via HE staining and Nissl staining. The severity of neuronal damage was evaluated by detecting the expression of the neuronal marker Microtubule-associated protein 2 (MAP2), via immunohistochemistry and immunofluorescence. Furthermore, the levels of neurotransmitter 5-hydroxytryptophan (5-HTP), 5-hydroxy tryptamine (5-HT), γ-aminobutyric acid (GABA), and Glutamic acid (Glu) in hippocampal tissues, as well as the expression of inflammatory factors Interleukin-1β (IL-1β) and Interleukin-18 (IL-18) in serum, were determined by ELISA. The expressions of mRNA and protein NOD-like receptor thermal protein domain associated protein 3 (NLRP3), Gasdermin D (GSDMD), Cysteinyl aspartate specific proteinase1 (Caspase1), High mobility group box-1 protein (HMGB1) and Apoptosis-associated speck-like protein containing CARD (ASC) related to the cellular ferroptosis pathway were tested and analyzed by RT-PCR and WB respectively.
RESULTS
PCPA significantly diminishes the sleep span of experimental animals by expediting the expenditure of 5-HT, consequently establishing an essentially direct SD model. The intervention of GHYSJ displays remarkable efficacy in mitigating insomnia symptoms, encompassing difficulties in initiating sleep and insufficient sleep duration. Likewise, it ameliorates memory function impairments induced by sleep deprivation, along with symptoms such as fatigue and depletion of vitality. GHYSJ exerts a protective influence on hippocampal neurons facilitated by inhibiting the down regulation of MAP2 and maintaining the equilibrium of neurotransmitters (5-HTP, 5-HT, GABA, and Glu). It diminishes the expression of intracellular pyroptosis-associated inflammatory factors (IL-1β and IL-18) and curbs the activation of the NLRP3/Caspase1/GSDMD pyroptosis-related signaling pathways, thereby alleviating the damage caused by hippocampal neuronal pyroptosis.
Topics: Mice; Animals; Rats; Aspartic Acid; Interleukin-18; Sleep Deprivation; NLR Family, Pyrin Domain-Containing 3 Protein; 5-Hydroxytryptophan; Serotonin; Sleep; Signal Transduction; Neurons; Memory Disorders; gamma-Aminobutyric Acid; Caspase 1
PubMed: 38403005
DOI: 10.1016/j.jep.2024.117972 -
Journal of Applied Physiology... Apr 2024Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are...
Opioids are well-known to cause respiratory depression, but despite clinical evidence of dysphagia, the effects of opioids on swallow excitability and motor pattern are unknown. We tested the effects of the clinically relevant opioid buprenorphine on pharyngeal swallow and respiratory drive in male and female rats. We also evaluated the utility of 5-HT agonists (8-OH-DPAT and buspirone) to improve swallowing and breathing following buprenorphine administration. Experiments were performed on 44 freely breathing Sprague-Dawley rats anesthetized with sodium pentobarbital. Bipolar fine wire electrodes were inserted into the mylohyoid, thyroarytenoid, posterior cricoarytenoid, thyropharyngeus, and diaphragm muscles to measure electromyographic (EMG) activity of swallowing and breathing. We evaluated the hypotheses that swallowing varies by stimulus, opioids depress swallowing and breathing, and that 5-HT agonists improve these depressions. Our results largely confirmed the following hypotheses: ) swallow-related EMG activity was larger during swallows elicited by esophageal distension plus oral water infusion than by either stimulus alone. ) Buprenorphine depressed swallow in both sexes, but females were more susceptible to total swallow suppression. ) Female animals were also more vulnerable to opioid-induced respiratory depression. ) 8-OH-DPAT rescued breathing following buprenorphine-induced respiratory arrest, and pretreatment with the partial 5-HT agonist buspirone prevented buprenorphine-induced respiratory arrest in female animals. ) 8-OH-DPAT enhanced mylohyoid and thyropharyngeus EMG amplitude during swallow but did not restore excitability of the swallow pattern generator following total suppression by buprenorphine. Our results highlight sex-specific and behavior-specific effects of buprenorphine and provide preclinical evidence of a 5HT agonist for the treatment of respiratory depression and dysphagia. This is the first study, to our knowledge, to evaluate sex-specific effects of opioid administration on pharyngeal swallow. We expand on a small but growing number of studies that report a lower threshold for opioid-induced respiratory depression in females compared with males, and we are the first to produce this effect with the partial μ-opioid-receptor agonist buprenorphine. This is the first demonstration, to our knowledge, that activation of 5-HT receptors can improve swallow and breathing outcomes following systemic buprenorphine administration.
Topics: Rats; Female; Male; Animals; Analgesics, Opioid; Serotonin; 8-Hydroxy-2-(di-n-propylamino)tetralin; Buspirone; Rats, Sprague-Dawley; Deglutition Disorders; Respiratory Insufficiency; Buprenorphine
PubMed: 38385184
DOI: 10.1152/japplphysiol.00509.2023 -
Journal of Pain Research 2024Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using...
PURPOSE
Few studies have assessed the effects of sphingosine kinase 1/sphingosine-1-phosphate (SPHK1/S1P) on microangiogenesis at rat myofascial trigger points (MTrPs) using contrast-enhanced ultrasonography (CEUS). This study aimed to address these deficiencies. Here, we investigated the effects of SPHK1/S1P on MTrP microangiogenesis and the value of CEUS in evaluating these effects.
METHODS
Forty Sprague‒Dawley rats were subdivided into two groups: control and MTrP groups. MTrPs were established by 8 weeks of the strike procedure combined with eccentric motion and 4 weeks of recovery. All rats were euthanized after having undergone CEUS with an overdose of pentobarbital sodium. MTrP and control tissue samples were removed for haematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM) imaging. The tissue was dehydrated, cleared, and embedded before sectioning. The sections were then incubated overnight at 4°C, and immunohistochemistry was carried out with primary antibodies including rabbit anti-CD31, rabbit anti-SPHK1and rabbit anti-S1PR1.
RESULTS
MTrP rats exhibited spontaneous electrical activity (SEA) and a local twitch response (LTR) during electromyography (EMG) examination. The CEUS time-intensity curves (TICs) showed that the perfusion intensity in the MTrPs and surrounding tissue area was increased, with faster perfusion than in normal sites, while the TICs in the control group slowly increased and then slowly decreased. The correlation coefficient between the microvessel density (MVD) and sphingosine 1-phosphate receptor 1 (S1PR1) was 0.716 ( <0.01). Spearman correlation analysis revealed that Spearman's rho () values between the MVD and peak intensity (PI), between the MVD and area under the curve (AUC), and between the MVD and SPHK1 were > 0.5 ( <0.05), > 0.7 ( <0.01), and > 0.7 ( <0.01), respectively.
CONCLUSION
CEUS is valuable for detecting microangiogenesis within MTrPs, and SPHK1/S1P plays an important role in promoting MTrP tissue microangiogenesis.
PubMed: 38371480
DOI: 10.2147/JPR.S437111 -
The Journal of Pediatric Pharmacology... 2024Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when...
OBJECTIVE
Difficult analgosedation is common and challenging in the pediatric intensive care unit (PICU). It is important to study alternative and supplemental sedatives for when the first-line agents become -insufficient.
METHODS
In this retrospective chart-review study, we report our center's experience in using intermittent doses of enteral pentobarbital as an adjunct sedative in 13 difficult to sedate critically ill and mechanically ventilated children. We compare the average sedation score and cumulative doses of other -sedatives (opioids, benzodiazepines and alpha-2 agonists) in the 24 hours before and 24 hours after enteral -pentobarbital initiation.
RESULTS
The addition of enteral pentobarbital was associated with lower State Behavioral State (SBS) scores in 8 out of the 13 patients and on average smaller doses of opioids (decreased by 11%), benzodiazepines (BZD) (decreased by 5%) and alpha-agonists (decreased by 20%). No adverse effects were noted attributable to pentobarbital administration.
CONCLUSION
Enteral pentobarbital seems to be safe and effective agent in the difficult to sedate critically ill child.
PubMed: 38332954
DOI: 10.5863/1551-6776-29.1.32 -
Veterinary World Dec 2023Potato ( L.) is mainly characterized by its antioxidant and healing properties. Therefore, this study aimed to evaluate the effects of an ointment based on L. "papa...
BACKGROUND AND AIM
Potato ( L.) is mainly characterized by its antioxidant and healing properties. Therefore, this study aimed to evaluate the effects of an ointment based on L. "papa tumbay" on burns induced in Balb/c mice ().
MATERIALS AND METHODS
The experimental animals were divided into four groups (n = 5/group) 48 h before second-degree burns were inducted. After epilating the loin areas of the mice and anesthetizing them with ketamine/xylazine (80 mg/kg/10 mg/kg) through intraperitoneal (i.p.) route, a round metal rod (0.7 cm in diameter) was placed on the depilated skin at a temperature of 100°C for 5 s. Group I was not given any treatment, Group II was treated with silver sulfadiazine (1%), and the other two groups (III and IV) were treated with the ointment formulated based on L. "papa tumbay" at 1% and 2%, respectively. After performing the treatment for 21 days, the mice were euthanized using i.p. sodium pentobarbital (185 mg/kg) to obtain skin samples. The samples were preserved in 10% neutral-buffered formalin and subjected to histopathological analysis.
RESULTS
We found statistically significant differences in the histopathological sections between the groups (p < 0.05). The abundant collagen and fibroblasts observed in the direction of the dermis in Groups III and IV indicate that the phytoconstituents present in the potato might promote the healing of the second-degree burns until day 21 of treatment.
CONCLUSION
Our findings showed that the ointments based on the ethanolic extracts of L. "papa tumbay," especially the 2% ointment, might accelerate the healing of second-degree burns induced in Balb/c mice.
PubMed: 38328356
DOI: 10.14202/vetworld.2023.2440-2445 -
Journal of Integrative Neuroscience Jan 2024Levodopa (L-DOPA) is the primary treatment for Parkinson's disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to...
Levodopa Improves Behavioral Deficits of Mice with Parkinson's Disease Symptoms via Curbing NLRP3 Inflammasome Activation and Enhancing Tyrosine Hydroxylase Levels in the Striatum and Substantia Nigra.
OBJECTIVE
Levodopa (L-DOPA) is the primary treatment for Parkinson's disease (PD). Nevertheless, the underlying mechanism of its action is not entirely learned. This study aims to probe the action of L-DOPA on NLR pyrin domain containing 3 (NLRP3) inflammasome activation and tyrosine hydroxylase (TH) levels in the striatum (STR) and substantia nigra (SN) of mice with PD symptoms.
METHODS
PD was simulated by administering 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 25 mg/kg/d) to induce mice, followed by L-DOPA (8 mg/kg/d) treatment. The behavioral performance of the mice was assessed using the pole test, balance beam, and rotarod test. After euthanasia with 120 mg/kg sodium pentobarbital, STR and SN were collected for evaluation of protein level of TH, NLR pyrin domain containing 3 (NLRP3), ASC and Cleaved caspase-1 using Western blot and mRNA levels of , inflammatory factors and using reverse transcription-quantitative polymerase chain reaction (RT-qPCR).
RESULTS
Treatment with L-DOPA significantly ameliorated the behavioral deficits caused by MPTP in mice with PD symptoms. L-DOPA administration resulted in reduced levels of apoptosis-associated speck-like protein containing a CARD (caspase recruitment domain) (ASC), NLRP3, and Cleaved caspase-1 protein levels, and decreased mRNA levels of and in the STR and SN. L-DOPA increased the mRNA and TH protein levels, while suppressing NLRP3 inflammasome activation in the STR and SN of mice with PD symptoms.
CONCLUSIONS
L-DOPA improves the behavioral deficits in mice with PD symptoms possibly by suppressing NLRP3 inflammasome activation and increasing TH levels in the STR and SN TH levels. These findings provide further perceptions into the property of L-DOPA in PD.
Topics: Mice; Animals; Parkinson Disease; Levodopa; Inflammasomes; NLR Family, Pyrin Domain-Containing 3 Protein; Interleukin-18; Tyrosine 3-Monooxygenase; Substantia Nigra; RNA, Messenger; Caspases; Mice, Inbred C57BL; Disease Models, Animal
PubMed: 38287845
DOI: 10.31083/j.jin2301002 -
Anti-inflammatory & Anti-allergy Agents... 2024, sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have...
INTRODUCTION
, sometimes called Indian jujube or Ber, belongs to the Rhamnaceae group of plants. The aqueous and ethanolic Ziziphus mauritiana formulations were shown to have analgesic, antipyretic, potent analgesic, anti-inflammatory, and anti-emetic properties.
AIMS & OBJECTIVES
The aim of this study is to investigate the sedative and anticonvulsant activities of extract by governing 200 and 400 mg/kg body weight orally.
MATERIALS AND METHODS
The leaves are extracted with ethanol and lukewarm water with a soxhlet apparatus for 72 hours. After that acute extract toxicity study was performed and then locomotor activity, pentobarbital induced sleeping time and anticonvulsant activity were performed with the extract.
RESULTS
Oral administration of extract at dosages of 200 & 400 mg/kg was employed after an immediate toxicity test. At a dosage of 400 mg/kg, the number of locomotions was reduced significantly lengthened the period of time spent sleeping and there was showed a dosage-dependent reduction in all phases of an epileptic episode.
CONCLUSION
In this study, the extract reduced locomotor activity, however, it had a superior profile for an antiepileptic action than phenytoin since it decreased locomotor activity to a lesser level. The considerable increase in pentobarbitone sleep hours with the extracts at a higher dose supported the sedative action of .
Topics: Animals; Anticonvulsants; Ziziphus; Plant Extracts; Hypnotics and Sedatives; Mice; Male; Rats; Sleep; Plant Leaves; Female; Seizures; Rats, Wistar
PubMed: 38279726
DOI: 10.2174/0118715230276586231215045816