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Medicina (Kaunas, Lithuania) Jan 2023: This study aimed to identify the analgesic properties of immature extract (iROE) using a postoperative-pain rat model. We also aimed to compare the analgesic effects...
: This study aimed to identify the analgesic properties of immature extract (iROE) using a postoperative-pain rat model. We also aimed to compare the analgesic effects of iROE to those of mature extract (mROE) and examine the proinflammatory cytokine response and associated underlying mechanisms. : In adult male Sprague Dawley rats, acute postoperative pain was induced through plantar hind-paw incisions. After the plantar incisions were made, the rats were intraperitoneally administered with normal saline or various doses of iROE and mROE to investigate and compare the analgesic effects of iROE and mROE. The mechanisms underlying iROE-induced analgesia were investigated via post-incisional administration of yohimbine, dexmedetomidine, prazosin, naloxone, atropine, or mecamylamine, followed by iROE. Mechanical withdrawal threshold (MWT) evaluations with von Frey filaments were carried out at different time points. Serum levels of tumor necrosis factor α, interleukin (IL)-1β, and IL-6 were measured to assess inflammatory responses. Multivariate analysis of variance (MANOVA) and linear mixed-effects model (LMEM) analysis were used to analyze the analgesic effect data. : The MWTs demonstrated significant increases in iROE in a dose-dependent manner up to 2 h after the plantar incisions were made. An LMEM analysis demonstrated that iROE yielded a significantly greater analgesic effect than mROE, but there was no significant difference between the two according to MANOVA. Dexmedetomidine enhanced the MWT-confirmed iROE response, while yohimbine and naloxone diminished it. Administration of iROE significantly attenuated the post-incisional increases in serum IL-1β and IL-6 levels. : The iROE demonstrated analgesic and anti-inflammatory effects in a rat model of incisional pain, which were more pronounced than those associated with mROE. The analgesic activity of iROE may be associated with α-adrenergic and opioid receptors.
Topics: Animals; Male; Rats; Analgesics; Dexmedetomidine; Hyperalgesia; Interleukin-6; Naloxone; Pain, Postoperative; Rats, Sprague-Dawley; Rubus; Yohimbine; Plant Extracts
PubMed: 36837466
DOI: 10.3390/medicina59020264 -
International Journal of Molecular... Feb 2023Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The...
Mechanisms for the α-adrenoceptor-mediated positive inotropy in neonatal mouse ventricular myocardium were studied with isolated myocardial preparations. The phenylephrine-induced positive inotropy was suppressed by prazosin, nifedipine, and chelerythrine, a protein kinase C inhibitor, but not by SEA0400, a selective Na/Ca exchanger inhibitor. Phenylephrine increased the L-type Ca channel current and prolonged the action potential duration, while the voltage-dependent K channel current was not influenced. In the presence of cromakalim, an ATP-sensitive K channel opener, the phenylephrine-induced prolongation of action potential duration, as well as the positive inotropy, were smaller than in the absence of cromakalim. These results suggest that the α-adrenoceptor-mediated positive inotropy is mediated by an increase in Ca influx through the L-type Ca channel, and the concomitant increase in action potential duration acts as an enhancing factor.
Topics: Mice; Animals; Action Potentials; Cromakalim; Myocardial Contraction; Myocardium; Phenylephrine; Receptors, Adrenergic
PubMed: 36835338
DOI: 10.3390/ijms24043926 -
Annals of Medicine Dec 2023The sympathetic nervous system and the immune system are responsible for producing neurotransmitters and cytokines that interact by binding to receptors; due to this,... (Review)
Review
The sympathetic nervous system and the immune system are responsible for producing neurotransmitters and cytokines that interact by binding to receptors; due to this, there is communication between these systems. Liver immune cells and nerve fibres are systematically distributed in the liver, and the partial overlap of both patterns may favour interactions between certain elements. Dendritic cells are attached to fibroblasts, and nerve fibres are connected via the dendritic cell-fibroblast complex. Receptors for most neuroactive substances, such as catecholamines, have been discovered on dendritic cells. The sympathetic nervous system regulates hepatic fibrosis through sympathetic fibres and adrenaline from the adrenal glands through the blood. When there is liver damage, the sympathetic nervous system is activated locally and systemically through proinflammatory cytokines that induce the production of epinephrine and norepinephrine. These neurotransmitters bind to cells through α-adrenergic receptors, triggering a cellular response that secretes inflammatory factors that stimulate and activate hepatic stellate cells. Hepatic stellate cells are key in the fibrotic process. They initiate the overproduction of extracellular matrix components in an active state that progresses from fibrosis to liver cirrhosis. It has also been shown that they can be directly activated by norepinephrine. Alpha and beta adrenoblockers, such as carvedilol, prazosin, and doxazosin, have recently been used to reverse CCl-induced liver cirrhosis in rodent and murine models.KEY MESSAGESNeurotransmitters from the sympathetic nervous system activate and increase the proliferation of hepatic stellate cells.Hepatic fibrosis and cirrhosis treatment might depend on neurotransmitter and hepatic nervous system regulation.Strategies to reduce hepatic stellate cell activation and fibrosis are based on experimentation with α-adrenoblockers.
Topics: Mice; Humans; Animals; Hepatic Stellate Cells; Neuroimmunomodulation; Liver Cirrhosis; Liver; Norepinephrine; Fibrosis; Cytokines; Neurotransmitter Agents
PubMed: 36826975
DOI: 10.1080/07853890.2022.2164047 -
Biological & Pharmaceutical Bulletin 2023We examined whether the α-adrenoceptor (AR), which shows low affinity (pA < 9) for prazosin (an α-AR antagonist) and high affinity (pA ≈ 10) for...
Phenylephrine-Induced Contraction in Guinea Pig Thoracic Aorta Is Triggered by Stimulation of α-Adrenoceptors Functionally Coupled with Store-Operated Ca Channels and Voltage-Dependent Ca Channels.
We examined whether the α-adrenoceptor (AR), which shows low affinity (pA < 9) for prazosin (an α-AR antagonist) and high affinity (pA ≈ 10) for tamsulosin/silodosin (α-AR antagonists), is involved in phenylephrine-induced contractions in the guinea pig (GP) thoracic aorta (TA). Intracellular signaling induced by α-AR activation was also examined by focusing on Ca influx pathways. Tension changes of endothelium-denuded TAs were isometrically recorded and mRNA encoding α-ARs/Ca channels and their related molecules were measured using RT-quantitative PCR. Phenylephrine-induced contractions were competitively inhibited by prazosin/tamsulosin, and their pA value were calculated to be 8.53/9.74, respectively. These contractions were also inhibited by silodosin concentration-dependently. However, the inhibition was not competitive fashion with the apparent pA value being 9.48. In contrast, phenylephrine-induced contractions were not substantially suppressed by L-765314 (an α-AR antagonist), BMY 7378 (an α-AR antagonist), yohimbine, and idazoxan (α-AR antagonists). Phenylephrine-induced contractions were markedly inhibited by YM-254890 (a Gq protein inhibitor) or removal of extracellular Ca, and partially inhibited by verapamil (a voltage-dependent Ca channel (VDCC) inhibitor). The residual contractions in the presence of verapamil were slightly inhibited by LOE 908 (a receptor-operated Ca channel (ROCC) inhibitor) and strongly inhibited by SKF-96365 (a store-operated Ca channel (SOCC) and ROCC inhibitor). Among the mRNA encoding α-ARs/SOCC-related molecules, α-AR (Adra1a)/Orai3, Orai1, and Stim2 were abundant in this tissue. In conclusion, phenylephrine-induced contractions in the GP TA can be triggered by stimulation of Gq protein-coupled α-AR, followed by activation of SOCCs and VDCCs.
Topics: Guinea Pigs; Animals; Phenylephrine; Adrenergic alpha-Antagonists; Aorta, Thoracic; Tamsulosin; GTP-Binding Protein alpha Subunits, Gq-G11; Prazosin; Verapamil; RNA, Messenger; Muscle Contraction
PubMed: 36724959
DOI: 10.1248/bpb.b22-00754 -
Frontiers in Immunology 2022Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating...
α-adrenoceptor stimulation ameliorates lipopolysaccharide-induced lung injury by inhibiting alveolar macrophage inflammatory responses through NF-κB and ERK1/2 pathway in ARDS.
INTRODUCTION
Catecholamines such as norepinephrine or epinephrine have been reported to participate in the development of acute respiratory distress syndrome (ARDS) by activating adrenergic receptors (ARs). But the role of α1-AR in this process has yet to be elucidated.
METHODS
In this study, ARDS mouse model was induced by intratracheal instillation of lipopolysaccharide. After treatment with α1-AR agonist phenylephrine or antagonist prazosin, lung pathological injury, alveolar barrier disruption and inflammation, and haemodynamic changes were evaluated. Cytokine levels and cell viability of alveolar macrophages were measured in vitro. Nuclear factor κB (NF-κB), mitogen-activated protein kinase, and Akt signalling pathways were analysed by western blot.
RESULTS
It showed that α1-AR activation alleviated lung injuries, including reduced histopathological damage, cytokine expression, and inflammatory cell infiltration, and improved alveolar capillary barrier integrity of ARDS mice without influencing cardiovascular haemodynamics. experiments suggested that α1-AR stimulation inhibited secretion of TNF-α, IL-6, CXCL2/MIP-2, and promoted IL-10 secretion, but did not affect cell viability. Moreover, α1-AR stimulation inhibited NF-κB and enhanced ERK1/2 activation without significantly influencing p38, JNK, or Akt activation.
DISCUSSION
Our studies reveal that α1-AR stimulation could ameliorate lipopolysaccharide-induced lung injury by inhibiting NF-κB and promoting ERK1/2 to suppress excessive inflammatory responses of alveolar macrophages.
Topics: Mice; Animals; NF-kappa B; Macrophages, Alveolar; MAP Kinase Signaling System; Lung Injury; Lipopolysaccharides; Proto-Oncogene Proteins c-akt; Respiratory Distress Syndrome; Cytokines; Receptors, Adrenergic
PubMed: 36685596
DOI: 10.3389/fimmu.2022.1090773 -
Cureus Dec 2022Scorpion stings are painful but harmless and are rarely life-threatening. There is emerging evidence of the association of electrocardiographic (ECG) changes in patients...
Scorpion stings are painful but harmless and are rarely life-threatening. There is emerging evidence of the association of electrocardiographic (ECG) changes in patients following scorpion stings. We report a case of scorpion sting in a patient in central rural India and provide a review of similar published cases. A 55-year-old previously healthy female was hospitalized in the department of medicine at our institute within two hours of a scorpion sting. She presented with severe pain at the site of the sting and profuse sweating. Her routine investigations (complete blood count renal function test, liver function tests, and arterial blood gas analysis) results were normal. Her electrocardiogram revealed acute myocardial infarction, and serial ECG showed ST and T-wave changes. On laboratory investigation, it was found that her troponin-T was positive and creatinine phosphokinase levels were raised. There was apical wall hypokinesia on transthoracic echocardiography on Day 1 and Day 2. The patient recovered completely and was discharged within five days of hospitalization once her symptoms improved. This case highlights the severe presentation of scorpion stings in otherwise healthy females. The chances of improved clinical symptoms are more if prazosin (125-250 ug) is administered early after scorpion-stung patients experience cardiac abnormalities. This treatment can dramatically alter scorpion envenomation's morbidity and mortality depending on the duration after which it is administered. This case raised our interest due to cardiovascular manifestations in the patient and the early treatment with prazosin for the scorpion sting. Hence, this case was reported for the purpose of creating awareness among physicians and protecting the more vulnerable population.
PubMed: 36654648
DOI: 10.7759/cureus.32536 -
Journal of Ethnopharmacology Apr 2023The seeds of Cajanus cajan (L) Millsp, are used in Traditional medicine for the treatment of anxiety and other neurological disorders. Hence, this study is designed to...
ETHNOPHARMACOLOGICAL RELEVANCE
The seeds of Cajanus cajan (L) Millsp, are used in Traditional medicine for the treatment of anxiety and other neurological disorders. Hence, this study is designed to investigate the antidepressant- and anxiolytic-like properties of ethanol seed extract of Cajanus cajan (CC) in mice.
MATERIALS AND METHODS
CC (50, 100 or 200 mg/kg, p.o.) was administered 1h before subjecting the animals to different behavioral models: forced swim test (FST) and tail suspension test (TST) (depressive-like behaviour), open field test (OFT), elevated plus maze (EPM), light-dark test (LDT) and hole-board test (HBT) for anxiety-like behaviour. To ascertain the pharmacodynamic of CC mice were pretreated with monoaminergic, nitrergic and GABAergic receptors antagonists. As well as molecular docking analysis of about 19 flavonoids present in CC on GABA, α adrenoceptors and 5-HT receptors.
RESULTS
CC (50, 100 or 200 mg/kg, p.o.) treatment significantly reduced immobile time in both FST and TST when compared with vehicle-treated control. However, the pretreatment of mice with prazosin/yohimbine (α adrenoceptor antagonists, respectively), WAY100635 (5-HT receptor antagonist), ketanserin (5-HT receptor antagonist), sulpiride (dopamine D receptor antagonist), L-N-Nitro arginine methyl ester (L-NAME), or methylene blue reversed the antidepressant-like effect of CC. In anxiety model, CC produced significant (p < 0.05) increase in open arms exploration and head dipping behavior which was reversed by flumazenil (benzodiazepine receptor antagonist) in the EPM. Docking analysis showed significant binding affinity of orientin, vitexin, pinostrobin and quercetin with 5HT, α-adrenoceptor and GABA receptors.
CONCLUSION
Findings from this study showed that C.cajan seeds extract exerts antidepressant-like effect through participation of monoaminergic systems (5-HT receptor, α/α-adrenoceptors, and dopamine D-receptors), nitric oxide-cyclic GMP pathway and anxiolytic-like effect via GABA benzodiazepine receptors. Moreso, presence of flavonoids with significant binding energies with monoaminergic and GABAergic systems support the potential of the extract in the management of mixed anxiety-depressive illness.
Topics: Animals; Mice; Anti-Anxiety Agents; Nitric Oxide; Dopamine; Molecular Docking Simulation; Serotonin; Antidepressive Agents; Plant Extracts; Receptors, Serotonin; gamma-Aminobutyric Acid; Flavonoids; Receptors, Adrenergic; Depression; Behavior, Animal; Hindlimb Suspension
PubMed: 36638856
DOI: 10.1016/j.jep.2023.116142 -
International Journal of Environmental... Dec 2022Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and... (Meta-Analysis)
Meta-Analysis Review
Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size ( = 1.86), followed by the histamine H-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of = 1.17 and = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.
Topics: Humans; Dreams; Randomized Controlled Trials as Topic; Prazosin; Adrenergic alpha-1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Hydroxyzine
PubMed: 36613097
DOI: 10.3390/ijerph20010777 -
Pharmaceuticals (Basel, Switzerland) Dec 2022(Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. bark was extracted in ethanol, and the extract (CAE) was chemically...
(Kunth) Britten & Baker f (Malvaceae) is used for the folk treatment of mood disorders. bark was extracted in ethanol, and the extract (CAE) was chemically standardized using gas chromatography-mass spectrometry (GC-MS). This study evaluated the effects of CAE (10-100 mg/kg p.o.) on anxiolytic-like activity, sedation, locomotor activity, depression-like activity, and spatial working memory using in vivo rodent models. A possible mechanism for the anxiolytic-like and antidepressant-like actions induced by CAE was assessed using neurotransmission pathway inhibitors. Myristic acid was one of the compounds found in CAE using GC-MS. This study also evaluated the anxiolytic-like activity and the sedative actions of myristic acid and assessed a possible mechanism of action using neurotransmission pathway inhibitors and an in silico analysis. CAE elicited anxiolytic-like activity and antidepressant-like effects (ED = 57 mg/kg). CAE (10-100 mg/kg) did not affect locomotor coordination or induce sedation. The anxiolytic-like and antidepressant-like actions of CAE were reverted by prazosin, suggesting a possible participation of the noradrenergic system. The anxiolytic-like activity of myristic acid was reverted by the co-administration of prazosin and partially reverted by ketanserin. The docking study revealed that myristic acid can form favorable interactions within 5-HT2A and α1A-adrenoreceptor binding pockets.
PubMed: 36559031
DOI: 10.3390/ph15121580 -
Journal of Family Medicine and Primary... Sep 2022Scorpion envenomation is a life-threatening condition, particularly for children. Therefore, it is essential for primary care health providers to suspect, identify, and...
INTRODUCTION
Scorpion envenomation is a life-threatening condition, particularly for children. Therefore, it is essential for primary care health providers to suspect, identify, and manage this condition early to prevent death and minimize morbidity.
OBJECTIVE
To identify the key epidemiological characteristics of scorpion envenomation and update the primary care health workers regarding the latest management practices of scorpion envenomation.
METHODOLOGY
A non-systematic review was performed by searching the key terms on databases such as PubMed, Medline, Scopus, Google Scholar, and ResearchGate.
RESULTS
Worldwide, over 2.5 billion people are living at risk of scorpion stings. Every year, over 1.2 million are stung by scorpions leading to the death of at least 3,250 people globally. The most vulnerable group includes farmers, laborers, and those living in rural areas. Adults are most frequently stung but envenomation is more severe among children. Prazosin is a key drug to prevent death due to cardiovascular complications.
CONCLUSION
Most of these stings and deaths could be preventable with proper awareness, safety precautions, and timely access to treatment. Government and local hospitals should ensure the availability of key drugs such as prazosin.
PubMed: 36505581
DOI: 10.4103/jfmpc.jfmpc_2300_21