Hypericum perforatum
            in the treatment of psychiatric and neurodegenerative disorders: Current evidence and potential mechanisms of action

Background: Neuroinflammation plays a critical role in the development and progression of various neurological disorders. Therefore, various studies have focused on the development of neuroinflammation inhibitors as potential therapeutic tools. Recently, the involvement of autophagy in the regulation of neuroinflammation has drawn substantial scientific interest, and a growing number of studies support the role of impaired autophagy in the pathogenesis of common neurodegenerative disorders. Objective: The purpose of this article is to review recent research on the role of autophagy in controlling neuroinflammation. We focus on studies employing both mammalian cells and animal models to evaluate the ability of different autophagic modulators to regulate neuroinflammation. Methods: We have mostly reviewed recent studies reporting anti-neuroinflammatory properties of autophagy. We also briefly discussed a few studies showing that autophagy modulators activate neuroinflammation in certain conditions. Results: Recent studies report neuroprotective as well as anti-neuroinflammatory effects of autophagic modulators. We discuss the possible underlying mechanisms of action of these drugs and their potential limitations as therapeutic agents against neurological disorders. Conclusion: Autophagy activators are promising compounds for the treatment of neurological disorders involving neuroinflammation.

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Prion Diseases: A Unique Transmissible Agent or a Model for Neurodegenerative Diseases?

Biomolecules ◽

10.3390/biom11020207 ◽

2021 ◽

Vol 11 (2) ◽

pp. 207

Author(s):

Diane L. Ritchie ◽

Marcelo A. Barria

Keyword(s):

Public Health ◽

Neurodegenerative Diseases ◽

Prion Protein ◽

Neurodegenerative Disorders ◽

Prion Diseases ◽

Experimental Models ◽

Misfolded Proteins ◽

Current Evidence

The accumulation and propagation in the brain of misfolded proteins is a pathological hallmark shared by many neurodegenerative diseases such as Alzheimer’s disease (Aβ and tau), Parkinson’s disease (α-synuclein), and prion disease (prion protein). Currently, there is no epidemiological evidence to suggest that neurodegenerative disorders are infectious, apart from prion diseases. However, there is an increasing body of evidence from experimental models to suggest that other pathogenic proteins such as Aβ and tau can propagate in vivo and in vitro in a prion-like mechanism, inducing the formation of misfolded protein aggregates such as amyloid plaques and neurofibrillary tangles. Such similarities have raised concerns that misfolded proteins, other than the prion protein, could potentially transmit from person-to-person as rare events after lengthy incubation periods. Such concerns have been heightened following a number of recent reports of the possible inadvertent transmission of Aβ pathology via medical and surgical procedures. This review will provide a historical perspective on the unique transmissible nature of prion diseases, examining their impact on public health and the ongoing concerns raised by this rare group of disorders. Additionally, this review will provide an insight into current evidence supporting the potential transmissibility of other pathogenic proteins associated with more common neurodegenerative disorders and the potential implications for public health.

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Antimicrobial Peptides: Mechanisms of Action and Resistance

Journal of Dental Research ◽

10.1177/0022034516679973 ◽

2016 ◽

Vol 96 (3) ◽

pp. 254-260 ◽

Cited By ~ 177

Author(s):

B. Bechinger ◽

S.-U. Gorr

Keyword(s):

Cell Wall ◽

Cell Membrane ◽

Antimicrobial Peptides ◽

Bacterial Resistance ◽

Rare Event ◽

Mechanisms Of Action ◽

Current Evidence ◽

Aggregation State ◽

Host Defense Peptides ◽

Bacterial Membranes

More than 40 antimicrobial peptides and proteins (AMPs) are expressed in the oral cavity. These AMPs have been organized into 6 functional groups, 1 of which, cationic AMPs, has received extensive attention in recent years for their promise as potential antibiotics. The goal of this review is to describe recent advances in our understanding of the diverse mechanisms of action of cationic AMPs and the bacterial resistance against these peptides. The recently developed peptide GL13K is used as an example to illustrate many of the discussed concepts. Cationic AMPs typically exhibit an amphipathic conformation, which allows increased interaction with negatively charged bacterial membranes. Peptides undergo changes in conformation and aggregation state in the presence of membranes; conversely, lipid conformation and packing can adapt to the presence of peptides. As a consequence, a single peptide can act through several mechanisms depending on the peptide’s structure, the peptide:lipid ratio, and the properties of the lipid membrane. Accumulating evidence shows that in addition to acting at the cell membrane, AMPs may act on the cell wall, inhibit protein folding or enzyme activity, or act intracellularly. Therefore, once a peptide has reached the cell wall, cell membrane, or its internal target, the difference in mechanism of action on gram-negative and gram-positive bacteria may be less pronounced than formerly assumed. While AMPs should not cause widespread resistance due to their preferential attack on the cell membrane, in cases where specific protein targets are involved, the possibility exists for genetic mutations and bacterial resistance. Indeed, the potential clinical use of AMPs has raised the concern that resistance to therapeutic AMPs could be associated with resistance to endogenous host-defense peptides. Current evidence suggests that this is a rare event that can be overcome by subtle structural modifications of an AMP.

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Antiarrhythmic drugs: mechanisms of action, clinical effects, indications for use

Ukrainian Journal of Cardiology ◽

10.31928/1608-635x-2019.2.7690 ◽

2019 ◽

Vol 26 (2) ◽

pp. 76-90

Author(s):

G. M. Solovyan ◽

T. V. Mikhalieva

Keyword(s):

Clinical Practice ◽

Cardiac Arrhythmias ◽

Antiarrhythmic Drugs ◽

Mechanisms Of Action ◽

Current Evidence ◽

Clinical Effects ◽

Trigger Activity ◽

Impulse Formation ◽

Indications For Use

The lecture is devoted to one of the most difficult problems of modern cardiology – the use of antiarrhythmic therapy in clinical practice. The basic mechanisms of arrhythmias, aspects of their onset, maintenance and termination are briefly described. The current evidence on the electrophysiological mechanisms of cardiac arrhythmias – re-entry, abnormal impulse formation, and trigger activity – is presented. The article contains information about the remodeling of ion channels properties. The Sicilian gambit is analyzed, in which the mechanisms of arrhythmias are compared to the mechanisms of anti-arrhythmic action of drugs. Classification of anti-arrhythmic drugs, their mechanisms of action, indications and contraindications, side effects, and interaction with other drugs are presented.

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Acupuncture for Gastrointestinal Disorders

Integrative Gastroenterology ◽

10.1093/med/9780190933043.003.0011 ◽

2019 ◽

pp. 229-254

Author(s):

Malcolm B. Taw ◽

Andrew Shubov

Keyword(s):

Gastric Emptying ◽

Chinese Medicine ◽

Vagal Tone ◽

Evidence Base ◽

Mechanisms Of Action ◽

Current Evidence ◽

Gastrointestinal Disorders ◽

Current Evidence Base ◽

The Brain ◽

East West

This chapter provides an introduction to acupuncture, elucidates known neurobiological mechanisms of action, and summarizes the current evidence base for the use of acupuncture in the treatment of various gastrointestinal (GI) disorders. It reviews how acupuncture can increase esophageal and GI motility, reduce transient lower esophageal sphincter relaxations, stimulate gastric emptying, accelerate antral contractions, regulate neurohormonal mediators, promote autonomic and vagal tone, and modulate different regions of the brain-gut-microbiota axis. The therapeutic rationale for acupuncture as well as basic theories and concepts from a traditional Chinese medicine (TCM) perspective are also described. This chapter concludes with a discussion about the potential therapeutic combination of integrative East-West medicine to treat GI disorders.

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Probiotics and constipation: mechanisms of action, evidence for effectiveness and utilisation by patients and healthcare professionals

Proceedings of The Nutrition Society ◽

10.1017/s0029665119000934 ◽

2019 ◽

Vol 79 (1) ◽

pp. 147-157 ◽

Cited By ~ 1

Author(s):

Eirini Dimidi ◽

S. Mark Scott ◽

Kevin Whelan

Keyword(s):

Public Health ◽

Chronic Constipation ◽

Healthcare Professionals ◽

Mechanisms Of Action ◽

Current Evidence ◽

Present Evidence ◽

The Public ◽

Considerable Impact ◽

Public Health Strategies

The aim of this narrative review is to assess and present evidence on the mechanisms of action of probiotics in constipation, their effectiveness and their utilisation by patients and healthcare professionals. Chronic constipation is a common bothersome disorder that has a considerable impact on patients' quality of life. Probiotics have been increasingly investigated for their effectiveness in various disorders, including chronic constipation. Probiotics may affect gut motility and constipation through their impact on the gut microbiota and fermentation, the central and enteric nervous system and the immune system. However, evidence for the effectiveness of probiotics in the management of constipation remains varied, with some strains demonstrating improvements, while others show no effect. Despite the uncertainty in evidence and the fact that the majority of healthcare professionals do not recommend probiotics for constipation, an increased prevalence of probiotic use by people with constipation has been shown. Therefore, there is a need for public health strategies to inform the public about where strong evidence of probiotic effectiveness exist, and where evidence is still weak. Education of healthcare professionals on the increased utilisation of probiotics for constipation by the public and on current evidence for the effectiveness of specific strains is also required.

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The Neuroprotective Effects of Astaxanthin: Therapeutic Targets and Clinical Perspective

Molecules ◽

10.3390/molecules24142640 ◽

2019 ◽

Vol 24 (14) ◽

pp. 2640 ◽

Cited By ~ 20

Author(s):

Fakhri ◽

Aneva ◽

Farzaei ◽

Sobarzo-Sánchez

Keyword(s):

Oxidative Stress ◽

Neurodegenerative Disorders ◽

Neurological Disorders ◽

Spinal Cord Injuries ◽

Neurological Diseases ◽

Mechanisms Of Action ◽

Clinical Perspective ◽

Neuroprotective Effects ◽

Brain And Spinal Cord ◽

Neuronal Disorders

As the leading causes of human disability and mortality, neurological diseases affect millions of people worldwide and are on the rise. Although the general roles of several signaling pathways in the pathogenesis of neurodegenerative disorders have so far been identified, the exact pathophysiology of neuronal disorders and their effective treatments have not yet been precisely elucidated. This requires multi-target treatments, which should simultaneously attenuate neuronal inflammation, oxidative stress, and apoptosis. In this regard, astaxanthin (AST) has gained growing interest as a multi-target pharmacological agent against neurological disorders including Parkinson’s disease (PD), Alzheimer’s disease (AD), brain and spinal cord injuries, neuropathic pain (NP), aging, depression, and autism. The present review highlights the neuroprotective effects of AST mainly based on its anti-inflammatory, antioxidative, and anti-apoptotic properties that underlies its pharmacological mechanisms of action to tackle neurodegeneration. The need to develop novel AST delivery systems, including nanoformulations, targeted therapy, and beyond, is also considered.

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Pharmacological Modulators of Tau Aggregation and Spreading

Brain Sciences ◽

10.3390/brainsci10110858 ◽

2020 ◽

Vol 10 (11) ◽

pp. 858

Author(s):

Antonio Dominguez-Meijide ◽

Eftychia Vasili ◽

Tiago Fleming Outeiro

Keyword(s):

Tau Protein ◽

Neurodegenerative Disorders ◽

Molecular Mechanisms ◽

Mechanisms Of Action ◽

Tau Aggregation ◽

The Brain ◽

Pharmacological Modulators

Tauopathies are neurodegenerative disorders characterized by the deposition of aggregates composed of abnormal tau protein in the brain. Additionally, misfolded forms of tau can propagate from cell to cell and throughout the brain. This process is thought to lead to the templated misfolding of the native forms of tau, and thereby, to the formation of newer toxic aggregates, thereby propagating the disease. Therefore, modulation of the processes that lead to tau aggregation and spreading is of utmost importance in the fight against tauopathies. In recent years, several molecules have been developed for the modulation of tau aggregation and spreading. In this review, we discuss the processes of tau aggregation and spreading and highlight selected chemicals developed for the modulation of these processes, their usefulness, and putative mechanisms of action. Ultimately, a stronger understanding of the molecular mechanisms involved, and the properties of the substances developed to modulate them, will lead to the development of safer and better strategies for the treatment of tauopathies.

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Viewpoint: Mechanisms of Action and Therapeutic Potential of Neurohormetic Phytochemicals

Dose-Response ◽

10.2203/dose-response.07-004.mattson ◽

2007 ◽

Vol 5 (3) ◽

pp. dose-response.0 ◽

Cited By ~ 66

Author(s):

Mark. P. Mattson ◽

Tae Gen Son ◽

Simonetta Camandola

Keyword(s):

Animal Models ◽

Neurodegenerative Disorders ◽

Histone Deacetylases ◽

Therapeutic Potential ◽

Antioxidant Properties ◽

Disease Process ◽

Antioxidant Response ◽

Mechanisms Of Action ◽

Cellular Stress Response ◽

Vegetables And Fruits

The nervous system is of fundamental importance in the adaptive (hormesis) responses of organisms to all types of stress, including environmental “toxins”. Phytochemicals present in vegetables and fruits are believed to reduce the risk of several major diseases including cardiovascular disease, cancers and neurodegenerative disorders. Although antioxidant properties have been suggested as the basis of health benefits of phytochemicals, emerging findings suggest a quite different mechanism of action. Many phytochemicals normally function as toxins that protect the plants against insects and other damaging organisms. However, at the relatively low doses consumed by humans and other mammals these same “toxic” phytochemicals activate adaptive cellular stress response pathways that can protect the cells against a variety of adverse conditions. Recent findings have elucidated hormetic mechanisms of action of phytochemicals (e.g., resveratrol, curcumin, sulforaphanes and catechins) using cell culture and animal models of neurological disorders. Examples of hormesis pathways activated by phytochemicals include the transcription factor Nrf-2 which activates genes controlled by the antioxidant response element, and histone deacetylases of the sirtuin family and FOXO transcription factors. Such hormetic pathways stimulate the production of antioxidant enzymes, protein chaperones and neurotrophic factors. In several cases neurohormetic phytochemicals have been shown to suppress the disease process in animal models relevant to neurodegenerative disorders such as Alzheimer's and Parkinson's diseaess, and can also improve outcome following a stroke. We are currently screening a panel of biopesticides in order to establish hormetic doses, neuroprotective efficacy, mechanisms of action and therapeutic potential as dietary supplements.

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Hydroxychloroquine in COVID-19 Patients: Pros and Cons

Frontiers in Pharmacology ◽

10.3389/fphar.2020.597985 ◽

2020 ◽

Vol 11 ◽

Author(s):

Nour K. Younis ◽

Rana O. Zareef ◽

Sally N. Al Hassan ◽

Fadi Bitar ◽

Ali H. Eid ◽

...

Keyword(s):

Molecular Mechanisms ◽

Mechanisms Of Action ◽

Current Evidence ◽

Therapeutic Effects ◽

Medical Centers ◽

Life Threatening ◽

Pros And Cons ◽

Neurological Effects

The pandemic of COVID-19, caused by SARS-CoV-2, has recently overwhelmed medical centers and paralyzed economies. The unparalleled public distress caused by this pandemic mandated an urgent quest for an effective approach to manage or treat this disease. Due to their well-established anti-infectious and anti-inflammatory properties, quinine derivatives have been sought as potential therapies for COVID-19. Indeed, these molecules were originally employed in the treatment and prophylaxis of malaria, and later in the management of various autoimmune rheumatic and dermatologic diseases. Initially, some promising results for the use of hydroxychloroquine (HCQ) in treating COVID-19 patients were reported by a few in vitro and in vivo studies. However, current evidence is not yet sufficiently solid to warrant its use as a therapy for this disease. Additionally, the therapeutic effects of HCQ are not without many side effects, which range from mild gastrointestinal effects to life-threatening cardiovascular and neurological effects. In this review, we explore the controversy associated with the repurposing of HCQ to manage or treat COVID-19, and we discuss the cellular and molecular mechanisms of action of HCQ.

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