scholarly journals Acupuncture and oxytocinergic system: The promising treatment for autism

2021 ◽  
Vol 12 (1) ◽  
pp. 96-102
Author(s):  
Tangfeng Su ◽  
Lei Pei
Keyword(s):  
Animal Studies ◽  
Molecular Mechanisms ◽  
Alternative Therapy ◽  
Endocannabinoid System ◽  
Autism Spectrum ◽  
Therapeutic Effects ◽  
Promising Target ◽  
Socioemotional Competence ◽  
Promising Treatment ◽  
Core Symptoms

Abstract Autism spectrum disorder (ASD) is a group of heterogeneous neurodevelopmental disorders characterized by impairments activities without efficient pharmacological therapies in social interaction, speech and stereotypic patterns. Clinical studies have shown the efficacy of acupuncture as an alternative therapy for autism. The effectiveness of acupuncture as an alternative treatment for autism has been demonstrated through clinical trials. However, the molecular mechanisms that underlie these effects remain unclear. Due to its profound pro-social, anxiolytic, stress management effects, and its potential use for the treatment of psychiatric disorders associated with altered socioemotional competence, oxytocin (OT) released from the hypothalamus has attracted considerable interest. In the past decade, a number of clinical and animal studies have shown that OT administration effectively reduces core symptoms of ASD, especially social behavior deficits. Recently, the endocannabinoid system has emerged as a promising target for the treatment of autism. OT was found to facilitate the endocannabinoid-mediated social reward processes in the nucleus accumbens of the mouse brain. Furthermore, serotonin and dopamine are involved in the reward response mediated by OT. In view of these findings, we conclude that acupuncture may produce therapeutic effects on autism by triggering the hypothalamic oxytocin system, which in turn activates the release of neurotransmitters such as endocannabinoids, dopamine and serotonin. This would be a valuable guide for further research on the mechanism of treatment of autism with acupuncture.

scholarly journals Xiaoxuming Decoction: A Traditional Herbal Recipe for Stroke With Emerging Therapeutic Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Qian Zhang ◽  
Yue Wang ◽  
Aiwen Chen ◽  
Xinwei Huang ◽  
Qianyu Dong ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Molecular Mechanisms ◽  
Neurovascular Unit ◽  
Alternative Therapy ◽  
Acute Stage ◽  
Therapeutic Effects ◽  
Active Compounds ◽  
Endovascular Thrombectomy ◽  
Therapeutic Mechanisms ◽  
New Perspective

Xiaoxuming decoction (XXMD) has been traditionally used to manage stroke though debates on its clinical efficacy were present in the history. Till nowadays, it is still one of the most commonly used herbal recipes for stroke. One of the reasons is that a decent proportion of ischemic stroke patients still have residue symptoms even after thrombolysis with rt-PA or endovascular thrombectomy. Numerous clinical studies have shown that XXMD is an effective alternative therapy not only at the acute stage, but also at the chronic sequelae stage of ischemic stroke. Modern techniques have isolated groups of compounds from XXMD which have shown therapeutic effects, such as dilating blood vessels, inhibiting thrombosis, suppressing oxidative stress, attenuating nitric oxide induced damage, protecting the blood brain barrier and the neurovascular unit. However, which of the active compounds is responsible for its therapeutic effects is still unknown. Emerging studies have screened and tested these active compounds aiming to find individual compounds that can be used as drugs to treat stroke. The present study summarized both clinical evidence of XXMD in managing stroke and experimental evidence on its molecular mechanisms that have been reported recently using advanced techniques. A new perspective has also been discussed with an aim to provide new targets that can be used for screening active compounds from XXMD.

scholarly journals Resveratrol in Autism Spectrum Disorders: Behavioral and Molecular Effects

Antioxidants ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 188 ◽  
Author(s):  
Michele Malaguarnera ◽  
Haroon Khan ◽  
Omar Cauli
Keyword(s):  
Oxidative Stress ◽  
Animal Models ◽  
Molecular Mechanisms ◽  
Autism Spectrum ◽  
Immune Alteration ◽  
Stress Markers ◽  
Behavioral Abnormalities ◽  
Spectrum Disorders ◽  
Core Symptoms ◽  
And Oxidative Stress

Resveratrol (RSV) is a polyphenolic stillbenoid with significant anti-oxidative and anti-inflammatory properties recently tested in animal models of several neurological diseases. Altered immune alteration and oxidative stress have also been found in patients with autism spectrum disorders (ASD), and these alterations could add to the pathophysiology associated with ASD. We reviewed the current evidence about the effects of RSV administration in animal models and in patients with ASD. RSV administration improves the core-symptoms (social impairment and stereotyped activity) in animal models and it also displays beneficial effects in other behavioral abnormalities such as hyperactivity, anxiety and cognitive function. The molecular mechanisms by which RSV restores or improves behavioral abnormalities in animal models encompass both normalization of central and peripheral immune alteration and oxidative stress markers and new molecular mechanisms such as expression of cortical gamma-amino butyric acid neurons, certain type of miRNAs that regulate spine growth. One randomized, placebo-controlled clinical trial (RCT) suggested that RSV add-on risperidone therapy improves comorbid hyperactivity/non-compliance, whereas no effects where seen in core symptoms of ASD No RCTs about the effect of RSV as monotherapy have been performed and the results from preclinical studies encourage its feasibility. Further clinical trials should also identify those ASD patients with immune alterations and/or with increased oxidative stress markers that would likely benefit from RSV administration.

A Review on Molecular Mechanisms and Patents of Marine-derived Anti-thrombotic Agents

2020 ◽  
Vol 21 ◽  
Author(s):  
Gaurav Doshi ◽  
Namrata Nailwal
Keyword(s):  
Sea Cucumber ◽  
Marine Algae ◽  
Molecular Mechanisms ◽  
Alternative Therapy ◽  
Extraction Process ◽  
Risk Profile ◽  
Age Group ◽  
Preparation Methods ◽  
Life Threatening ◽  
Promising Treatment

Abstract: Thrombosis is a condition of major concern worldwide as it is associated with life-threatening diseases related to the cardiovascular system. The condition affects annually 1 in 1000 adults whereas 1 in 4 dies due to thrombosis and this increases as the age group increases. The major outcomes are considered to be a recurrence, bleeding due to commercially available anticoagulants and deaths. The side effects associated with available anti-thrombotic drugs are a point of concern. Therefore, it is necessary to discover and develop an improvised benefit-risk profile drug, so in search of alternative therapy for the treatment of thrombosis, marine sources have found to be used as promising treatment agents. They have shown the presence of sulfated fucans/galactans, fibrinolytic proteases, diterpenes, glycosaminoglycan, glycoside, peptides, amino ac-ids, sterols, polysaccharides, polyphenols, vitamins, and minerals. Out of these marine sources, many chemicals are found to be have anti-thrombotic activities. This review focuses on the recent discovery of anti-thrombotic agents obtained from marine algae, sponges, mussels and sea cucumber along with their mechanism of action and patents on its extraction process, preparation methods and their applications. Further, the article concludes with the author insight related to marine drugs which have a promising future.

scholarly journals Phase-IIa randomized, double-blind, sham-controlled, parallel group trial on anodal transcranial direct current stimulation (tDCS) over the left and right tempo-parietal junction in autism spectrum disorder—StimAT: study protocol for a clinical trial

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Christina Luckhardt ◽  
Magdalena Schütz ◽  
Andreas Mühlherr ◽  
Hannah Mössinger ◽  
Sara Boxhoorn ◽  
...  
Keyword(s):  
Cognitive Abilities ◽  
Social Cognitive ◽  
Autism Spectrum ◽  
Social Responsiveness ◽  
Post Intervention ◽  
Double Blind ◽  
Parallel Group ◽  
Promising Treatment ◽  
Core Symptoms

Abstract Background Autism spectrum disorder (ASD) is characterized by impaired social communication and interaction, and stereotyped, repetitive behaviour and sensory interests. To date, there is no effective medication that can improve social communication and interaction in ASD, and effect sizes of behaviour-based psychotherapy remain in the low to medium range. Consequently, there is a clear need for new treatment options. ASD is associated with altered activation and connectivity patterns in brain areas which process social information. Transcranial direct current stimulation (tDCS) is a technique that applies a weak electrical current to the brain in order to modulate neural excitability and alter connectivity. Combined with specific cognitive tasks, it allows to facilitate and consolidate the respective training effects. Therefore, application of tDCS in brain areas relevant to social cognition in combination with a specific cognitive training is a promising treatment approach for ASD. Methods A phase-IIa pilot randomized, double-blind, sham-controlled, parallel-group clinical study is presented, which aims at investigating if 10 days of 20-min multi-channel tDCS stimulation of the bilateral tempo-parietal junction (TPJ) at 2.0 mA in combination with a computer-based cognitive training on perspective taking, intention and emotion understanding, can improve social cognitive abilities in children and adolescents with ASD. The main objectives are to describe the change in parent-rated social responsiveness from baseline (within 1 week before first stimulation) to post-intervention (within 7 days after last stimulation) and to monitor safety and tolerability of the intervention. Secondary objectives include the evaluation of change in parent-rated social responsiveness at follow-up (4 weeks after end of intervention), change in other ASD core symptoms and psychopathology, social cognitive abilities and neural functioning post-intervention and at follow-up in order to explore underlying neural and cognitive mechanisms. Discussion If shown, positive results regarding change in parent-rated social cognition and favourable safety and tolerability of the intervention will confirm tDCS as a promising treatment for ASD core-symptoms. This may be a first step in establishing a new and cost-efficient intervention for individuals with ASD. Trial registration The trial is registered with the German Clinical Trials Register (DRKS), DRKS00014732. Registered on 15 August 2018. Protocol version This study protocol refers to protocol version 1.2 from 24 May 2019.

scholarly journals β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Niraj Kumar Jha ◽  
Charu Sharma ◽  
Hebaallah Mamdouh Hashiesh ◽  
Seenipandi Arunachalam ◽  
MF Nagoor Meeran ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Cb2 Receptors ◽  
Anti Inflammatory

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.

scholarly journals Oxytocin-induced increase in N,N-dimethylglycine and time course of changes in oxytocin efficacy for autism social core symptoms

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods The current study explored metabolites representing the molecular mechanisms of oxytocin’s efficacy using high-throughput metabolomics analysis on plasma collected before and after 6-week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N = 106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial. Results Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (false discovery rate (FDR) corrected P = 0.043, d = 0.74, N = 83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR = 0.004, d = 1.13, N = 60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR = 0.006, r = − 0.485, N = 43) and deteriorations between 2 and 4 weeks (PFDR = 0.032, r = 0.415, N = 37). Limitations The metabolites changes caused by oxytocin administration were quantified using peripheral blood and therefore may not directly reflect central nervous system changes. Conclusion Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-methyl-D-aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy. Trial registration: A multi-center, parallel-group, placebo-controlled, double-blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders (the date registered: 30 October 2014; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264).

Ketogenic diet as possible therapy of autism spectrum disorder — review and implication

2019 ◽  
Vol 87 (4) ◽  
pp. 218-224
Author(s):  
Aleksander Rajczewski ◽  
Magdalena Gibas-Dorna
Keyword(s):  
Autism Spectrum Disorder ◽  
Ketogenic Diet ◽  
Animal Studies ◽  
Neurodevelopmental Disorder ◽  
Treatment Strategies ◽  
Medium Chain Triglyceride ◽  
Autism Spectrum ◽  
Human Studies ◽  
Spectrum Disorder ◽  
Therapeutic Effects

Autism spectrum disorder (ASD) has become widespread neurodevelopmental disorder, which currently can be treated with only few therapeutic options. Furthermore, their effectiveness is limited therefore novel treatment strategies for ASD are needed. This review seeks to address this need by discussing a ketogenic diet (KD) in the context of ASD therapy. KD effects have been examined in animal and human studies. They indicate effectiveness of KD by improving autistic features. Moreover, animal studies have revealed clinically useful information about caloric restriction component of KD, which is not necessary to achieve therapeutic effects. Significantly administration of KD but not β-hydroxybutyrate or acetone has a therapeutic effect on social interactions. Human studies are scarce, however previous researches imply KD as an effective treatment at least in certain types of autism. KD in an altered form as: modified Atkins diet (MAD), ketogenic gluten-free diet with supplemental medium-chain triglyceride (MCT), and John Radcliffe ketogenic diet is an alternative to classic KD. These variants provide better quality of nutrition and are less strict, thus less difficult to maintain. KD is described as safe with limited, easily manageable adverse effects. Taken together human and animal studies would seem to suggest that KD will become part of ASD treatment. However, in order to determine accurate recommendations for all ASD patients, further studies are required.

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

2020 ◽  
Author(s):  
Yasuhiko Kato ◽  
Hitoshi Kuwabara ◽  
Takashi Okada ◽  
Toshio Munesue ◽  
Seico Benner ◽  
...  
Keyword(s):  
Effect Size ◽  
Neural Plasticity ◽  
Time Course ◽  
Molecular Mechanisms ◽  
Controlled Trial ◽  
Autism Spectrum ◽  
Medium Effect ◽  
Double Blind ◽  
Parallel Group ◽  
Core Symptoms

Abstract Background: Oxytocin is expected as a novel therapeutic agent for autism spectrum disorder (ASD) core symptoms. However, previous results on the efficacy of repeated administrations of oxytocin are controversial. Recently, we reported time-course changes in the efficacy of the neuropeptide underlying the controversial effects of repeated administration; however, the underlying mechanisms remained unknown. Methods: The current study explored metabolites representing the molecular mechanisms of oxytocin's efficacy using high-throughput metabolomics analysis on plasma collected before and after 6 week repeated intranasal administration of oxytocin (48 IU/day) or placebo in adult males with ASD (N=106) who participated in a multi-center, parallel-group, double-blind, placebo-controlled, randomized controlled trial.Results: Among the 35 metabolites measured, a significant increase in N,N-dimethylglycine was detected in the subjects administered oxytocin compared with those given placebo at a medium effect size (False discovery rate (FDR) corrected P=0.043, d=0.74, N=83). Furthermore, subgroup analyses of the participants displaying a prominent time-course change in oxytocin efficacy revealed a significant effect of oxytocin on N,N-dimethylglycine levels with a large effect size (PFDR=0.004, d=1.13, N=60). The increase in N,N-dimethylglycine was significantly correlated with oxytocin-induced clinical changes, assessed as changes in quantifiable characteristics of autistic facial expression, including both of improvements between baseline and 2 weeks (PFDR=0.006, r=-0.485, N=43) and deteriorations between 2 and 4 weeks (PFDR=0.032, r=0.415, N=37).Limitations: The metabolites changes caused by oxytocin administration were quantified using peripheral blood, and therefore may not directly reflect central nervous system changes. Conclusion: Our findings demonstrate an association of N,N-dimethylglycine upregulation with the time-course change in the efficacy of oxytocin on autistic social deficits. Furthermore, the current findings support the involvement of the N-Methyl-D-Aspartate receptor and neural plasticity to the time-course change in oxytocin’s efficacy.Trial registration: A multicenter, parallel group, placebo-controlled, double blind, confirmatory trial of intranasal oxytocin in participants with autism spectrum disorders. (The date registered: 30th Oct 2020; UMIN Clinical Trials Registry: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000017703) (UMIN000015264)

scholarly journals Perspectives on the Use of Stem Cells for Autism Treatment

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Dario Siniscalco ◽  
James Jeffrey Bradstreet ◽  
Nataliia Sych ◽  
Nicola Antonucci
Keyword(s):  
Stem Cells ◽  
Adult Stem Cells ◽  
Molecular Mechanisms ◽  
Intestinal Inflammation ◽  
Autism Spectrum ◽  
Great Expectations ◽  
Cell Therapies ◽  
Autism Treatment ◽  
Core Symptoms ◽  
Chronic Intestinal Inflammation

Autism and autism spectrum disorders (ASDs) are complex neurodevelopmental disorders. ASDs are clinically defined by deficits in communication, social skills, and repetitive and/or restrictive interests and behaviours. With the prevalence rates for ASDs rapidly increasing, the need for effective therapies for autism is a priority for biomedical research. Currently available medications do not target the core symptoms, can have markedly adverse side-effects, and are mainly palliative for negative behaviours. The development of molecular and regenerative interventions is progressing rapidly, and medicine holds great expectations for stem cell therapies. Cells could be designed to target the observed molecular mechanisms of ASDs, that is, abnormal neurotransmitter regulation, activated microglia, mitochondrial dysfunction, blood-brain barrier disruptions, and chronic intestinal inflammation. Presently, the paracrine, secretome, and immunomodulatory effects of stem cells would appear to be the likely mechanisms of application for ASD therapeutics. This review will focus on the potential use of the various types of stem cells: embryonic, induced pluripotential, fetal, and adult stem cells as targets for ASD therapeutics.

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