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Biomedicine & Pharmacotherapy =... Dec 2020Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its... (Review)
Review
Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent.
Topics: Animals; Anti-Anxiety Agents; Anti-Inflammatory Agents; Antineoplastic Agents, Phytogenic; Ginkgo biloba; Ginkgolides; Humans; Lactones; Plant Leaves; Platelet Activating Factor
PubMed: 33254431
DOI: 10.1016/j.biopha.2020.110908 -
The Journal of Clinical Investigation Oct 2022The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing...
The TET family of dioxygenases promote DNA demethylation by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine (5hmC). Hypothalamic agouti-related peptide-expressing (AGRP-expressing) neurons play an essential role in driving feeding, while also modulating nonfeeding behaviors. Besides AGRP, these neurons produce neuropeptide Y (NPY) and the neurotransmitter GABA, which act in concert to stimulate food intake and decrease energy expenditure. Notably, AGRP, NPY, and GABA can also elicit anxiolytic effects. Here, we report that in adult mouse AGRP neurons, CRISPR-mediated genetic ablation of Tet3, not previously known to be involved in central control of appetite and metabolism, induced hyperphagia, obesity, and diabetes, in addition to a reduction of stress-like behaviors. TET3 deficiency activated AGRP neurons, simultaneously upregulated the expression of Agrp, Npy, and the vesicular GABA transporter Slc32a1, and impeded leptin signaling. In particular, we uncovered a dynamic association of TET3 with the Agrp promoter in response to leptin signaling, which induced 5hmC modification that was associated with a chromatin-modifying complex leading to transcription inhibition, and this regulation occurred in both the mouse models and human cells. Our results unmasked TET3 as a critical central regulator of appetite and energy metabolism and revealed its unexpected dual role in the control of feeding and other complex behaviors through AGRP neurons.
Topics: 5-Methylcytosine; Agouti-Related Protein; Animals; Anti-Anxiety Agents; Chromatin; Dioxygenases; Humans; Hypothalamus; Leptin; Mice; Neurons; Neuropeptide Y; gamma-Aminobutyric Acid
PubMed: 36189793
DOI: 10.1172/JCI162365 -
Agri : Agri (Algoloji) Dernegi'nin... Oct 2023Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and...
OBJECTIVES
Pregabalin (PGB) is used in drug-resistant epilepsy. Also, it has analgesic effects in painful syndromes. Depression and anxiety are commonly seen in epilepsy and neuropathic pain patients. PGB is often combined with anxiolytics and antidepressants. We aimed to investigate the antidepressant and anxiolytic effects of PGB and compare its effects with those of antidepressant and anxiolytic drugs and their combined use.
METHODS
Wistar Albino rats were used, and PGB (5, 10, 20, and 40 mg/kg), amitriptylin (AMT), fluoxetine (FLX), ketamine (KET), and diazepam (DZM), as well as combinations of PGB (20 mg/kg) with AMT, FLX, KET, and DZM, were administered. Elevated plus maze, forced swimming, and locomotor activity tests were performed.
RESULTS
In the elevated plus maze, PGB10, 20, 40, AMT, FLX, and DZM increased open arm time. The PGB20+FLX combination increased compared to PGB20. In forced swimming, PGB doses increased immobility time. AMT, FLX, DZM, and KET decreased compared to control and PGB doses. Other combinations of PGB20 reversed immobility time, except FLX. In locomotor activity, PGB20, AMT, KET, and DZM decreased distance.
CONCLUSION
PGB had a depressant effect in all doses and a dose-dependently anxiolytic effect. In combinations of PGB with AMT, KET, and DZM, it reversed their antidepressant effects. We assumed FLX could be preferred instead of AMT in patients using PGB. When PGB is used in combination, drug interactions should be considered. These results are also very remarkable in terms of pharmacoeconomics.
Topics: Rats; Humans; Animals; Anti-Anxiety Agents; Pregabalin; Rats, Wistar; Antidepressive Agents; Fluoxetine; Amitriptyline; Ketamine; Epilepsy
PubMed: 37886867
DOI: 10.14744/agri.2022.98474 -
Nutrients Jul 2021Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also... (Review)
Review
Propolis is produced by honeybees from materials collected from plants they visit. It is a resinous material having mixtures of wax and bee enzymes. Propolis is also known as bee glue and used by bees as a building material in their hives, for blocking holes and cracks, repairing the combs and strengthening their thin borders. It has been extensively used since ancient times for different purposes in traditional human healthcare practices. The quality and composition of propolis depend on its geographic location, climatic zone and local flora. The New Zealand and Brazilian green propolis are the two main kinds that have been extensively studied in recent years. Their bioactive components have been found to possess a variety of therapeutic potentials. It was found that Brazilian green propolis improves the cognitive functions of mild cognitive impairments in patients living at high altitude and protects them from neurodegenerative damage through its antioxidant properties. It possesses artepillin C (ARC) as the key component, also known to possess anticancer potential. The New Zealand propolis contains caffeic acid phenethyl ester (CAPE) as the main bioactive with multiple therapeutic potentials. Our lab performed in vitro and in vivo assays on the extracts prepared from New Zealand and Brazilian propolis and their active ingredients. We provided experimental evidence that these extracts possess anticancer, antistress and hypoxia-modulating activities. Furthermore, their conjugation with γCD proved to be more effective. In the present review, we portray the experimental evidence showing that propolis has the potential to be a candidate drug for different ailments and improve the quality of life.
Topics: Animals; Anti-Anxiety Agents; Antineoplastic Agents; Antioxidants; Brazil; Caffeic Acids; Humans; New Zealand; Phenylethyl Alcohol; Phenylpropionates; Propolis
PubMed: 34444688
DOI: 10.3390/nu13082528 -
Journal of Neurodevelopmental Disorders May 2022Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common,...
BACKGROUND
Rett syndrome (RTT) is a neurodevelopmental disorder most often related to a pathogenic variant in the X-linked MECP2 gene. Internalizing behaviors appear to be common, but standard methods of diagnosing anxiety are not readily applied in this population which typically has cognitive impairment and limited expressive language. This study aims to describe the frequency of anxiety-like behavior and anxiolytic treatments along with associated clinical features in individuals with RTT.
METHODS
Parental reports and medication logs provided data from 1380 females with RTT participating in two iterations of the multicenter U.S. RTT Natural History Study (RNHS) from 2006 to 2019.
RESULTS
Most participants with RTT (77.5%) had at least occasional anxious or nervous behavior. Anxiety was reported to be the most troublesome concern for 2.6%, and within the top 3 concerns for 10.0%, of participants in the second iteration. Parents directly reported treatment for anxious or nervous behavior in 16.6% of participants in the second iteration with most reporting good control of the behavior (71.6%). In the medication logs of both RNHS iterations, the indication of anxiety was listed for a similar number of participants (15% and 14.5%, respectively). Increased use of anxiolytics and selective serotonin reuptake inhibitors (SSRIs) was related to more frequent anxiety-like behaviors (P < 0.001), older age (P < 0.001), and mild MECP2 variants (P = 0.002).
CONCLUSION
Anxiety-like behavior is frequent at all ages and is a significant parental concern in RTT. Older individuals and those with mild MECP2 variants are more likely to be treated with medications. Better diagnosis and treatment of anxiety in RTT should be a goal of both future studies and clinical care.
TRIAL REGISTRATION
NCT00299312 and NCT02738281.
Topics: Anti-Anxiety Agents; Anxiety; Female; Humans; Rett Syndrome
PubMed: 35568815
DOI: 10.1186/s11689-022-09432-2 -
Nature Jun 2024Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds...
Psychedelic substances such as lysergic acid diethylamide (LSD) and psilocybin show potential for the treatment of various neuropsychiatric disorders. These compounds are thought to mediate their hallucinogenic and therapeutic effects through the serotonin (5-hydroxytryptamine (5-HT)) receptor 5-HT (ref. ). However, 5-HT also plays a part in the behavioural effects of tryptamine hallucinogens, particularly 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a psychedelic found in the toxin of Colorado River toads. Although 5-HT is a validated therapeutic target, little is known about how psychedelics engage 5-HT and which effects are mediated by this receptor. Here we map the molecular underpinnings of 5-MeO-DMT pharmacology through five cryogenic electron microscopy (cryo-EM) structures of 5-HT, systematic medicinal chemistry, receptor mutagenesis and mouse behaviour. Structure-activity relationship analyses of 5-methoxytryptamines at both 5-HT and 5-HT enable the characterization of molecular determinants of 5-HT signalling potency, efficacy and selectivity. Moreover, we contrast the structural interactions and in vitro pharmacology of 5-MeO-DMT and analogues to the pan-serotonergic agonist LSD and clinically used 5-HT agonists. We show that a 5-HT-selective 5-MeO-DMT analogue is devoid of hallucinogenic-like effects while retaining anxiolytic-like and antidepressant-like activity in socially defeated animals. Our studies uncover molecular aspects of 5-HT-targeted psychedelics and therapeutics, which may facilitate the future development of new medications for neuropsychiatric disorders.
Topics: Animals; Humans; Male; Mice; 5-Methoxytryptamine; Anti-Anxiety Agents; Antidepressive Agents; Cryoelectron Microscopy; Hallucinogens; Lysergic Acid Diethylamide; Methoxydimethyltryptamines; Models, Molecular; Receptor, Serotonin, 5-HT1A; Receptor, Serotonin, 5-HT2A; Serotonin Receptor Agonists; Structure-Activity Relationship
PubMed: 38720072
DOI: 10.1038/s41586-024-07403-2 -
The 5-HT7 receptor system as a treatment target for mood and anxiety disorders: A systematic review.Journal of Psychopharmacology (Oxford,... Dec 2023Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this... (Review)
Review
BACKGROUND
Preclinical animal and preliminary human studies indicate that 5-HT7 antagonists have the potential as a new treatment approach for mood and anxiety disorders. In this systematic review, we aimed to review the relationship between the 5-HT7 receptor system and mood and anxiety disorders, and to explore the pharmacology and therapeutic potential of medications that target the 5-HT7 receptor for their treatment.
METHODS
Medline, Cochrane Library, EMBASE, PsycINFO databases, the National Institute of Health website Clinicaltrials.gov, controlled-trials.com, and relevant grey literature were used to search for original research articles, and reference lists of included articles were then hand searched.
RESULTS
Sixty-four studies were included in the review: 52 animal studies and 12 human studies. Studies used a variety of preclinical paradigms and questionnaires to assess change in mood, and few studies examined sleep or cognition. Forty-four out of 47 (44/47) preclinical 5-HT7 modulation studies identified potential antidepressant effects and 20/23 studies identified potential anxiolytic effects. In clinical studies, 5/7 identified potential antidepressant effects in major depressive disorder, 1/2 identified potential anxiolytic effects in generalized anxiety disorder, and 3/3 identified potential antidepressant effects in bipolar disorders.
CONCLUSION
While there is some evidence that the 5-HT7 receptor system may be a potential target for treating mood and anxiety disorders, many agents included in the review also bind to other receptors. Further research is needed using drugs that bind specifically to 5-HT7 receptors to examine treatment proof of concept further.
Topics: Animals; Humans; Anti-Anxiety Agents; Antidepressive Agents; Anxiety Disorders; Depressive Disorder, Major
PubMed: 37994803
DOI: 10.1177/02698811231211228 -
International Journal of Clinical... Jul 2021This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between...
OBJECTIVE
This study was conducted to study the anxiety scores among undergraduate university students in Jordan during COVID-19 pandemic and to assess the relationship between quarantine and shifting to distance learning resulted from the governmental strict isolation measures and severity of anxiety among students.
METHODS
A cross-sectional design was conducted to meet the study objectives. A convenience sample of 736 undergraduate university students in Jordan was recruited, and anxiety was assessed using the Hamilton Anxiety Scale.
RESULTS
The results indicated that anxiety score was 22.76 and 40.6% of the participant experienced moderate to severe anxiety, whereas 23.5% experienced mild to moderate anxiety and 35.9% experienced mild anxiety. Factors like suffering from chronic illnesses, having chronic medications, grade point average, shifting to distance learning, quarantine during the pandemic, study duties, the newly developed evaluation methods and the experience of students towards the use of anti-anxiety drugs and herbs had significantly increased the anxiety scores.
CONCLUSION
Our findings indicate that quarantine and shifting to distance learning during COVID-19 pandemic have negatively affected the anxiety scores of the university students which should be taken in consideration by the policymakers in Jordan in order to support this vulnerable group.
Topics: Anti-Anxiety Agents; Anxiety; COVID-19; Cross-Sectional Studies; Humans; Jordan; Pandemics; Quarantine; SARS-CoV-2; Students; Surveys and Questionnaires
PubMed: 33884714
DOI: 10.1111/ijcp.14249 -
Annals of the Academy of Medicine,... Sep 2019
Topics: Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Commitment of Mentally Ill; Electroconvulsive Therapy; Health Literacy; Humans; Mental Health; Patient Safety; Psychotherapy; Suicidal Ideation; Suicide Prevention
PubMed: 31737892
DOI: No ID Found -
Neuroscience and Biobehavioral Reviews Dec 2022The validity of widely used rodent behavioural tests of anxiety has been questioned, as they often fail to produce consistent results across independent replicate... (Meta-Analysis)
Meta-Analysis Review
The validity of widely used rodent behavioural tests of anxiety has been questioned, as they often fail to produce consistent results across independent replicate studies. In this study, we assessed the sensitivity of common behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. We conducted a pre-registered systematic review of 814 studies reporting effects of 25 anxiolytic compounds using common behavioural tests for anxiety. Meta-analyses of effect sizes of treatments showed that only two out of 17 commonly used test measures reliably detected effects of anxiolytic compounds. We report considerable between-study variation in size and even direction of effects of most anxiolytics on most outcome variables. Our findings indicate a general lack of sensitivity of those behavioural tests and cast serious doubt on both construct and predictive validity of most of these tests. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests.
Topics: Humans; Mice; Animals; Anti-Anxiety Agents; Behavior Rating Scale; Reproducibility of Results; Anxiety; Anxiety Disorders
PubMed: 36341943
DOI: 10.1016/j.neubiorev.2022.104928