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Brain Sciences Jan 2023Gastrodin is the active ingredient in Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved...
Gastrodin is the active ingredient in Our previous studies demonstrated that gastrodin ameliorated cerebral ischemia-reperfusion and hypoperfusion injury and improved cognitive deficit in Alzheimer's disease. This study aims to examine the effects of gastrodin on REM sleep deprivation in rats. Gastrodin (100 and 150 mg/kg) was orally administered for 7 consecutive days before REM sleep deprivation. Seventy-two hours later, pentobarbital-induced sleep tests and a Morris water maze were performed to measure REM sleep quality and learning and memory ability. Histopathology was observed with hematoxylin-eosin staining, and the expression of the NF-κB and Wnt/β-catenin signaling pathways was examined using Western blot. After REM sleep deprivation, sleep latency increased and sleep duration decreased, and the ability of learning and memory was impaired. Neurons in the hippocampal CA1 region and the cortex were damaged. Gastrodin treatment significantly improved REM sleep-deprivation-induced sleep disturbance, cognitive deficits and neuron damage in the hippocampus CA1 region and cerebral cortex. A mechanism analysis revealed that the NF-κB pathway was activated and the Wnt/β-catenin pathway was inhibited after REM sleep deprivation, and gastrodin ameliorated these aberrant changes. Gastrodin improves REM sleep-deprivation-induced sleep disturbance and cognitive dysfunction by regulating the TLR4/NF-κB and Wnt/β-catenin signaling pathways and can be considered a potential candidate for the treatment of REM sleep deprivation.
PubMed: 36831722
DOI: 10.3390/brainsci13020179 -
Journal of Veterinary Emergency and... 2023To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital...
OBJECTIVE
To describe the clinical signs, electroencephalographic (EEG) findings, treatment, and outcome in a dog after successful resuscitation from out-of-hospital cardiopulmonary arrest (OHCA) induced by pentobarbital intoxication.
CASE SUMMARY
A 10-year-old, male intact Jack Russell Terrier was referred for management of refractory status epilepticus and presented dead on arrival. After 7 minutes of cardiopulmonary resuscitation, return of spontaneous circulation was achieved, but the dog remained comatose, apneic, and lacked brainstem reflexes on neurological examination 6 hours following resuscitation. Magnetic resonance imaging showed polioencephalomalacia consistent with prolonged epileptiform activity, and EEG was initially concerning for electrocerebral inactivity. Following supportive care that included short-term mechanical ventilation, the dog made a full recovery and was discharged from the hospital alive 7 days postresuscitation. It was later revealed that the dog had been administered an unknown amount of pentobarbital during transportation, which likely contributed to the OHCA, clinical, and EEG findings.
NEW INFORMATION PROVIDED
This is the first report to describe the full recovery and hospital discharge of a dog suffering OHCA and the first description of EEG findings in a clinical veterinary patient following cardiopulmonary arrest and successful resuscitation. Factors likely contributing to successful patient outcome and potential benefits and limitations of EEG in monitoring postcardiac arrest patients are discussed.
Topics: Male; Dogs; Animals; Pentobarbital; Heart Arrest; Cardiopulmonary Resuscitation; Drug Overdose; Hospitals; Dog Diseases
PubMed: 36815742
DOI: 10.1111/vec.13283 -
Ecotoxicology and Environmental Safety Mar 2023To explore the action time and molecular mechanism underlying the effect of acetaminophen (APAP) on liver injury. APAP was used to establish drug-induced liver injury...
To explore the action time and molecular mechanism underlying the effect of acetaminophen (APAP) on liver injury. APAP was used to establish drug-induced liver injury (DILI) model in mice. Mice in the model group were intraperitoneally injected 300 mg/kg APAP for 6, 12, and 24 h respectively, and control group mice were given the same volume of normal saline. The mice were anesthetized through intravenous injection of sodium pentobarbital at 6, 12, and 24 h after APAP poisoning. Analysis of ALT, AST and ALP in serum, liver histopathological observation, oxidative damage and western blot were performed. The livers in APAP exposed mice were pale, smaller, with a rough texture, and poorly arranged cells. Lesions, large areas of hyperemia, inflammation, swelling, poorly cell arrangement, necrosis, and apoptosis of liver cells were obvious in the liver tissue sections. Serum ALT, AST and ALP levels were significantly enhanced at 12 h of APAP adminstration mice than that of in control group mice (P<0.05). The histopathological alterations and proinflammatory cytokines (IL-1β, TNF-α and IL-6) levels were most severe at 12 h of APAP-induced hepatotoxicity. APAP treatment induced oxidative stress by decreasing hepatic activities of superoxide dismutase (SOD) and glutathione (GSH) (P<0.05), and enhancing malondialdehyde (MDA) content (P<0.05). Moreover, APAP inhibited erythroid 2-related factor 2 (Nrf2) antioxidative pathway with decreased of Nrf2 and HO-1 proteins levels. Furthermore, APAP aggravated the activation of NLRP3 inflammasome by increasing of NLRP3, caspase-1, ASC, IL-1β and IL-18 proteins levels. Finally, APAP further significantly activated the toll-like receptor 4 (TLR4), nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinases (MAPKs) signaling pathways. This study demonstrated that APAP-induced hepatotoxicity by inhibiting of Nrf2 antioxidative pathway and promoting TLR4-NF-κB-MAPK inflammatory response and NLRP3 inflammasome activation.
Topics: Animals; Mice; Acetaminophen; Antioxidants; Chemical and Drug Induced Liver Injury; Glutathione; Inflammasomes; Liver; NF-E2-Related Factor 2; NF-kappa B; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Toll-Like Receptor 4; Mitogen-Activated Protein Kinases
PubMed: 36738614
DOI: 10.1016/j.ecoenv.2023.114590 -
Journal of Orthopaedic Surgery and... Jan 2023Panax notoginseng saponins (PNSs) have been found as the major active ingredient of Panax notoginseng (Burkill) F.H.Chen (PN) leaves, which has the effect of reducing...
Study on the regulatory effect of Panax notoginseng saponins combined with bone mesenchymal stem cell transplantation on IRAK1/TRAF6-NF-κB pathway in patients with diabetic cutaneous ulcers.
UNLABELLED
Panax notoginseng saponins (PNSs) have been found as the major active ingredient of Panax notoginseng (Burkill) F.H.Chen (PN) leaves, which has the effect of reducing inflammatory response, facilitating fibroblast proliferation, as well as promoting angiogenesis. This study aimed to investigate the molecular basis of PNS combined with bone mesenchymal stem cells (BMSCs) for treating diabetic cutaneous ulcers (DCU) and its mechanism of action.
METHODS
A total of 75 SD rats were selected to make diabetic cutaneous ulcers model. According random number table method, the rats were randomly divided into a control group, a DCU group, a BMSCs group, a PNS group and BMSCs + PNS group. Five groups of rats were given without treatment. After being treated for 7 days, the rats were anesthetized with pentobarbital, and granulation tissue was collected from the central point of the wound. They were used for pathological analysis, Western blot (WB) and polymerase chain reaction (PCR) assays.
RESULTS
The wound healing area was the largest in the BMSCs + PNS group. HE staining results showed that the PNS + BMSCs group could promote the formation of new epidermis and reduce the infiltration of inflammatory cells. Immunohistochemistry (IHC) results showed that the PNS + BMSCs group could up-regulate the expression of Ki67 protein and cell proliferation. In addition, PNS combined with BMSCs up-regulated the expression of miR-146-5p and down-regulated the expression of IL-1β, IL-6 and TNF-α, IRAK1, TRAF6 and p65 in the NF-κB signaling pathway (p < 0.05).
CONCLUSIONS
PNS combined with bone mesenchymal stem cell transplantation up-regulated miR-146a-5p targeting and binding to IRAK1/TRAF6, inhibiting the activation of NF-κB pathway, which reduced the inflammatory response of DCU and facilitated the skin healing of DCU. Thus, this study provides a theoretical basis and a novel therapeutic option for the treatment of DFU with PNS combined with BMSCs.
Topics: Animals; Rats; Rats, Sprague-Dawley; NF-kappa B; Panax notoginseng; TNF Receptor-Associated Factor 6; Mesenchymal Stem Cell Transplantation; Ulcer; Diabetes Complications; MicroRNAs; Diabetes Mellitus; Interleukin-1 Receptor-Associated Kinases
PubMed: 36721171
DOI: 10.1186/s13018-022-03467-w -
Molecules (Basel, Switzerland) Jan 2023is a species that grows in various areas of Latin America. It was known to be useful for the treatment of different human ailments. The present work evaluated the...
is a species that grows in various areas of Latin America. It was known to be useful for the treatment of different human ailments. The present work evaluated the neuropharmacological and analgesic effects of hydroalcoholic and dichloromethane extracts of . The effect on the central nervous system (CNS) of both extracts obtained from bark, administered by the intraperitoneal route in mice, was evaluated by different tests: spontaneous motor activity, hole-board, motor coordination, pentobarbital induced hypnosis, and rectal temperature. Analgesic activity was evaluated using a hot plate test. Phytochemical analysis was performed by high-performance liquid chromatography (HPLC) using reversed-phase and gradient of elution. The hydroalcoholic extract (dose 0.5 g dry plant/kg weigh) administration caused an important reduction of the head-dipping response in the hole board test. A decrease in spontaneous motor activity test and a disturbance of motor coordination in the rotarod test was observed. The hydroalcoholic extract produced a significant prolongation of pentobarbital induced sleeping time. This extract prevented hot plate test induced nociception. The phytochemical analysis revealed the presence of catechin, epicatechin, and procyanidin B12. Therefore, this study revealed that the hydroalcoholic extract of possesses analgesic and sedative CNS activity.
Topics: Humans; Mice; Animals; Plant Extracts; Pentobarbital; Chromatography, High Pressure Liquid; Motor Activity; Plant Bark; Behavior, Animal; Analgesics; Models, Animal
PubMed: 36677821
DOI: 10.3390/molecules28020764 -
Renal Sympathetic Hyperactivity in Diabetes Is Modulated by 5-HT Receptor Activation via NO Pathway.International Journal of Molecular... Jan 2023Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in...
Renal vasculature, which is highly innervated by sympathetic fibers, contributes to cardiovascular homeostasis. This renal sympathetic outflow is inhibited by 5-HT in normoglycaemic rats. Considering that diabetes induces cardiovascular complications, we aimed to determine whether diabetic state modifies noradrenergic input at renal level and its serotonergic modulation in rats. Alloxan diabetic rats were anaesthetized (pentobarbital; 60 mg/kg i.p.) and prepared for in situ autoperfusion of the left kidney to continuously measure systemic blood pressure (SBP), heart rate (HR), and renal perfusion pressure (RPP). Electrical stimulation of renal sympathetic outflow induces frequency-dependent increases (Δ) in RPP (23.9 ± 2.1, 59.5 ± 1.9, and 80.5 ± 3.5 mm Hg at 2, 4, and 6 Hz, respectively), which were higher than in normoglycaemic rats, without modifying HR or SBP. Intraarterial bolus of 5-HT and 5-CT (5-HT agonist) reduced electrically induced ΔRPP. Only L-694,247 (5-HT agonist) reproduced 5-CT inhibition on sympathetic-induced vasoconstrictions, whereas it did not modify exogenous noradrenaline-induced ΔRPP. 5-CT inhibition was exclusively abolished by i.v. bolus of LY310762 (5-HT antagonist). An inhibitor of guanylyl cyclase, ODQ (i.v.), completely reversed the L-694,247 inhibitory effect. In conclusion, diabetes induces an enhancement in sympathetic-induced vasopressor responses at the renal level. Prejunctional 5-HT receptors, via the nitric oxide pathway, inhibit noradrenergic-induced vasoconstrictions in diabetic rats.
Topics: Rats; Animals; Serotonin; Rats, Wistar; Receptor, Serotonin, 5-HT1D; Diabetes Mellitus, Experimental; Kidney; Norepinephrine; Sympathetic Nervous System; Electric Stimulation; Blood Pressure
PubMed: 36674892
DOI: 10.3390/ijms24021378 -
Journal of Atherosclerosis and... Sep 2023Central systolic blood pressure (cSBP) was closely related to hypertension-related organ damage rather than peripheral systolic blood pressure (pSBP). We aimed to...
Estimation of Central Systolic Blood Pressure from Peripheral Pressure Waves using a Novel Second Systolic Pressure-Based Method in Normal and Heritable Hypercholesterolemic Rabbits.
AIM
Central systolic blood pressure (cSBP) was closely related to hypertension-related organ damage rather than peripheral systolic blood pressure (pSBP). We aimed to estimate cSBP from pSBP without generalized transfer function in normal and Kurosawa and Kusanagi-hypercholesterolemic (KHC) rabbits aged 12 months.
METHODS
Two catheter-tip transducers were advanced into the ascending aorta (AA) and distal end of the right brachial artery (Br) through the right common carotid and right radial arteries, respectively, under pentobarbital anesthesia. Pressure waves in response to the intravenous administration of angiotensin II and sodium nitroprusside were simultaneously recorded in AA and Br under regular cardiac pacing.
RESULTS
The first (pSBP) and second peaks (pSBP) of the brachial blood pressure and their average (pSBP) were significantly correlated with cSBP, despite Murgo's wave pattern of central pressure waves in both rabbit groups. In Bland-Altman plot and its modification as a function of the peripheral augmentation index (pAI) analyses, the differences between pSBP and cSBP decreased, and those between pSBP and cSBP increased significantly in their average- or pAI-dependent manner, with undeniable mean biases in both rabbit groups. When the same analyses for SBP were performed instead, the mean bias was around zero, with reduced variance in the two rabbit groups. The observed pressure or pAI-dependent systematic biases for pSBP and pSBP disappeared, representing the precise feature of pSBP as a cSBP estimate.
CONCLUSIONS
We conclude that pSBP could be more precise than pSBP as a cSBP estimate, irrespective of blood pressure levels, pAI, or the presence of atherosclerosis.
Topics: Animals; Rabbits; Blood Pressure; Hypertension; Blood Pressure Determination; Aorta; Angiotensin II
PubMed: 36642536
DOI: 10.5551/jat.63793 -
Frontiers in Pharmacology 2022To explore the mechanism of action of appling Radix Ginseng and Semen Ziziphi Spinosae Drug pair (R-S) in the treatment of insomnia by investigating the effect of R-S...
Effects of the Radix Ginseng and Semen Ziziphi Spinosae drug pair on the GLU/GABA-GLN metabolic cycle and the intestinal microflora of insomniac rats based on the brain-gut axis.
To explore the mechanism of action of appling Radix Ginseng and Semen Ziziphi Spinosae Drug pair (R-S) in the treatment of insomnia by investigating the effect of R-S on GLU/GABA-GLN metabolic cycle and intestinal microflora of rats with insomnia. Rats were intraperitoneally injected with 4-chloro-DL-phenylalanine (PCPA) to make sleep deprivation (SD) models. The rats were divided into 6 groups, with 8 rats in each group. The general status of the rats was observed and the pentobarbital sodium sleep synergy experiment was performed. The contents of GABA, GLU, GLN, GAD65, and GS in hippocampus of rats were determined by ELISA. The expressions of GABAARα1mRNA, mGluR5mRNA, NR1mRNA and GluR1mRNA in rats' hippocampal tissue were determined by Realtime PCR. 16SrRNA gene sequencing was used to analyze the intestinal microflora of insomnia rats. In PCPA-induced insomnia rats, the state of insomnia was relieved, the sleep rate was improved, the duration of sleep latency was shortened and the sleep duration was prolonged in each dose group of R-S ( < 0.05, < 0.01) compared with the model group. The contents of GABA, GLN, GAD65 and GS were increased ( < 0.05, < 0.01) while GLU content was decreased ( < 0.01) in both medium and high dose groups, especially in the high dose group. The expression of GABAARα1mRNA was increased ( < 0.01), and the expressions of mGluR5mRNA, NR1mRNA and GluR1mRNA were decreased ( < 0.01) in hippocampal tissue of rats in R-S groups, especially in the high dose group. At the same time, the various dose groups of R-S could improve the species diversity, microflora abundance of insomnia rats and regulate the KEGG metabolic pathway related to sleep. R-S can improve the sleep of PCPA-induced insomnia rats by regulating GLU/GABA-GLN metabolic cycle and intestinal microflora, which provides experimental basis for appling R-S in the treatment of insomnia.
PubMed: 36618926
DOI: 10.3389/fphar.2022.1094507 -
Journal of Toxicology 2022Local Ethiopians regularly use for cosmetic purposes. The plant's safety, however, is not supported by any solid facts. This investigation aimed to evaluate the acute...
BACKGROUND
Local Ethiopians regularly use for cosmetic purposes. The plant's safety, however, is not supported by any solid facts. This investigation aimed to evaluate the acute and subacute toxicities of essential oil in mice.
METHODS
The essential oil was analyzed using GC-MS. The approach outlined by Chinedu et al., 2013 has been used to calculate the median lethal dose. According to organization for economic cooperation and development (OECD) 407 standard, a 28-day repeated dose oral toxicity study was carried out on female mice. Three groups of ten experimental mice each were distributed at random. Group I received the same saline volume and was considered the control. Groups II and III were treated with doses of of 500 mg/kg and 1000 mg/kg, respectively, of body weight. Hematological and biochemical markers were assessed. The liver and kidney were taken out after the sacrifice using sodium pentobarbital for pathological analysis.
RESULTS
Geraniol (40.89%) was the predominant component in the essential oil composition of with cyclofenchene (13.91%), myrcene (9.34%), 2, 4, 6, octatriene, 2, 6, dimethyl (8.20%), and ocimene (5.93%) being present in small amounts. The LD of essential oil was discovered to be greater than 5000 mg/kg body weight. During a 4-week follow-up period, mice treated with , the essential oil, at doses of 500 mg/kg or 1000 mg/kg body weight showed no evidence of toxicity or mortality. Biochemical and hematological parameters were not significantly altered in mice treated with the essential oil of compared with the control group. Histopathological evaluation of the liver and kidney did not exhibit any adverse results.
CONCLUSIONS
The essential oil of from Ethiopia is considered relatively safe and nontoxic.
PubMed: 36573136
DOI: 10.1155/2022/1995578