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Biomolecules Jan 2021Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester... (Review)
Review
Propolis, a product of the honey bee, has been used in traditional medicine for many years. A hydrophobic bioactive polyphenolic ester, caffeic acid phenethyl ester (CAPE), is one of the most extensively investigated active components of propolis. Several studies have indicated that CAPE has a broad spectrum of pharmacological activities as anti-oxidant, anti-inflammatory, anti-viral, anti-fungal, anti-proliferative, and anti-neoplastic properties. This review largely describes CAPE neuroprotective effects in many different conditions and summarizes its molecular mechanisms of action. CAPE was found to have a neuroprotective effect on different neurodegenerative disorders. At the basis of these effects, CAPE has the ability to protect neurons from several underlying causes of various human neurologic diseases, such as oxidative stress, apoptosis dysregulation, and brain inflammation. CAPE can also protect the nervous system from some diseases which negatively affect it, such as diabetes, septic shock, and hepatic encephalopathy, while numerous studies have demonstrated the neuroprotective effects of CAPE against adverse reactions induced by different neurotoxic substances. The potential role of CAPE in protecting the central nervous system (CNS) from secondary injury following various CNS ischemic conditions and CAPE anti-cancer activity in CNS is also reviewed. The structure-activity relationship of CAPE synthetic derivatives is discussed as well.
Topics: Alzheimer Disease; Animals; Anti-Inflammatory Agents; Antifungal Agents; Antioxidants; Antiviral Agents; Apoptosis; Brain; Caffeic Acids; Humans; Inflammation; Ischemia; Neurodegenerative Diseases; Parkinson Disease; Phenylethyl Alcohol; Propolis; Psychotic Disorders; Seizures
PubMed: 33525407
DOI: 10.3390/biom11020176 -
Naunyn-Schmiedeberg's Archives of... May 2024Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or... (Review)
Review
Trauma and toxic substances are connected in several aspects. On the one hand, toxic substances can be the reason for traumatic injuries in the context of accidental or violent and criminal circumstances. Examples for the first scenario is the release of toxic gases, chemicals, and particles during house fires, and for the second scenario, the use of chemical or biological weapons in the context of terroristic activities. Toxic substances can cause or enhance severe, life-threatening trauma, as described in this review for various chemical warfare, by inducing a tissue trauma accompanied by break down of important barriers in the body, such as the blood-air or the blood-gut barriers. This in turn initiates a "vicious circle" as the contribution of inflammatory responses to the traumatic damage enhances the macro- and micro-barrier breakdown and often results in fatal outcome. The development of sophisticated methods for detection and identification of toxic substances as well as the special treatment of the intoxicated trauma patient is summarized in this review. Moreover, some highly toxic substances, such as the protein toxins from the pathogenic bacterium Clostridioides (C.) difficile, cause severe post-traumatic complications which significantly worsens the outcome of hospitalized patients, in particular in multiply injured trauma patients. Therefore, novel pharmacological options for the treatment of such patients are necessarily needed and one promising strategy might be the neutralization of the toxins that cause the disease. This review summarizes recent findings on the molecular and cellular mechanisms of toxic chemicals and bacterial toxins that contribute to barrier breakdown in the human body as wells pharmacological options for treatment, in particular in the context of intoxicated trauma patients. "trauma-toxicology" comprises concepts regrading basic research, development of novel pharmacological/therapeutic options and clinical aspects in the complex interplay and "vicious circle" of severe tissue trauma, barrier breakdown, pathogen and toxin exposure, tissue damage, and subsequent clinical complications.
Topics: Humans; Animals; Wounds and Injuries
PubMed: 37999755
DOI: 10.1007/s00210-023-02845-3 -
Therapeutic Drug Monitoring Aug 2023Although designer benzodiazepines (DBZDs) constitute a minor part of new psychoactive substances, they deserve the greatest attention because of their popularity among... (Review)
Review
PURPOSE
Although designer benzodiazepines (DBZDs) constitute a minor part of new psychoactive substances, they deserve the greatest attention because of their popularity among drug users and increasing number and availability. This review covers the effects of different DBZDs, available pharmacological evaluation tools, and their reported toxicity and potential pharmacodynamic and pharmacokinetic interactions with other drugs commonly co-abused with DBZDs.
METHODS
For this narrative review, a nonsystematic search was performed on PubMed, EMBASE, Google Scholar, and PubMed Central databases between June and July 2021.
RESULTS
The current consensus hypothesis suggests that DBZDs mediate their effects through interactions with the GABA A receptor, producing similar effects to benzodiazepines used in therapy, including sedation, hypnosis, anxiolysis, muscle relaxation, euphoria, amnesia, and addiction. Owing to the complexity of their action mechanism and the numerous GABA A subtype receptors, the pharmacodynamic metrics of DBZDs are very difficult to establish. The pharmacological effects of DBZD are related to their structure, influencing their binding to GABA A receptor subunits. Quantitative structure-activity relationship studies successfully predicted the biological activity and relative potency of DBZD but could not predict the main pharmacological effect of a given DBZD. Exploring the effects by netnographic studies is one of the available alternatives, despite its limitations. DBZDs are usually identified in the context of polysubstance use. Pharmacodynamic interactions between DBZDS and other CNS depressants, such as opioids, have been extensively reported. However, pharmacokinetic interactions between DBZDs and opioids are considered less important, and contradictory conclusions about their clinical significance have been reported.
CONCLUSIONS
Understanding the mechanism of action and other pharmacological metrics is highly important in the clinical management of DBZDs.
Topics: Humans; Receptors, GABA-A; Analgesics, Opioid; Benzodiazepines; Substance-Related Disorders
PubMed: 36750450
DOI: 10.1097/FTD.0000000000001071 -
Current Neuropharmacology 2023The use of psychostimulant drugs can modify brain function by inducing changes in the reward system, mainly due to alterations in dopaminergic and glutamatergic... (Review)
Review
The use of psychostimulant drugs can modify brain function by inducing changes in the reward system, mainly due to alterations in dopaminergic and glutamatergic transmissions in the mesocorticolimbic pathway. However, the etiopathogenesis of addiction is a much more complex process. Previous data have suggested that microglia and other immune cells are involved in events associated with neuroplasticity and memory, which are phenomena that also occur in addiction. Nevertheless, how dependent is the development of addiction on the activity of these cells? Although the mechanisms are not known, some pathways may be involved. Recent data have shown psychoactive substances may act directly on immune cells, alter their functions and induce various inflammatory mediators that modulate synaptic activity. These could, in turn, be involved in the pathological alterations that occur in substance use disorder. Here, we extensively review the studies demonstrating how cocaine and amphetamines modulate microglial number, morphology, and function. We also describe the effect of these substances in the production of inflammatory mediators and a possible involvement of some molecular signaling pathways, such as the toll-like receptor 4. Although the literature in this field is scarce, this review compiles the knowledge on the neuroimmune axis that is involved in the pathogenesis of addiction, and suggests some pharmacological targets for the development of pharmacotherapy.
Topics: Humans; Microglia; Central Nervous System Stimulants; Cocaine; Amphetamines; Substance-Related Disorders
PubMed: 36503452
DOI: 10.2174/1570159X21666221208142151 -
American Family Physician Apr 2020Most frequent headaches are typically migraine or tension-type headaches and are often exacerbated by medication overuse. Repeated headaches can induce central...
Most frequent headaches are typically migraine or tension-type headaches and are often exacerbated by medication overuse. Repeated headaches can induce central sensitization and transformation to chronic headaches that are intractable, are difficult to treat, and cause significant morbidity and costs. A complete history is essential to identify the most likely headache type, indications of serious secondary headaches, and significant comorbidities. A headache diary can document headache frequency, symptoms, initiating and exacerbating conditions, and treatment response over time. Neurologic assessment and physical examination focused on the head and neck are indicated in all patients. Although rare, serious underlying conditions must be excluded by the patient history, screening tools such as SNNOOP10, neurologic and physical examinations, and targeted imaging and other assessments. Medication overuse headache should be suspected in patients with frequent headaches. Medication history should include nonprescription analgesics and substances, including opiates, that may be obtained from others. Patients who overuse opiates, barbiturates, or benzodiazepines require slow tapering and possibly inpatient treatment to prevent acute withdrawal. Patients who overuse other agents can usually withdraw more quickly. Evidence is mixed on the role of medications such as topiramate for patients with medication overuse headache. For the underlying headache, an individualized evidence-based management plan incorporating pharmacologic and nonpharmacologic strategies is necessary. Patients with frequent migraine, tension-type, and cluster headaches should be offered prophylactic therapy. A complete management plan includes addressing risk factors, headache triggers, and common comorbid conditions such as depression, anxiety, substance abuse, and chronic musculoskeletal pain syndromes that can impair treatment effectiveness. Regular scheduled follow-up is important to monitor progress.
Topics: Analgesics; Anxiety; Depression; Family Practice; Fibromyalgia; Headache Disorders; Humans; Migraine Disorders; Musculoskeletal Pain; Neurologic Examination; Substance-Related Disorders
PubMed: 32227826
DOI: No ID Found -
New Therapeutic Approaches Involving Psychopharmacology, Digital Technology, and fMRI Neurofeedback.The American Journal of Psychiatry Dec 2022
Topics: Humans; Neurofeedback; Psychopharmacology; Magnetic Resonance Imaging; Digital Technology
PubMed: 36453034
DOI: 10.1176/appi.ajp.20220866 -
Transcultural Psychiatry Oct 2022Following decades of prohibition and widespread concern about their mind-altering properties, there is increasing public, scholarly, and clinical interest in the...
Following decades of prohibition and widespread concern about their mind-altering properties, there is increasing public, scholarly, and clinical interest in the therapeutic potential of psychedelic substances. Serotonergic substances in particular (DMT, psilocybin, and LSD) are now being tested as treatments for such ailments as depression, anxiety, and substance use disorder. This thematic issue of presents articles that investigate the cultural assumptions, political dimensions, and clinical and ethical implications that arise from this renewed interest. After reviewing ongoing debates on therapeutic mechanisms of action and the importance of context, we argue that psychedelics can be conceptualized as "active super-placebos"-that is, substances that enhance ritual, symbolic, and interpersonal therapeutic processes by increasing suggestibility and the influence of extra-pharmacological, "non-specific" factors. Rather than simply freeing up habitual constraints on perception, the articles in this issue support the claim that psychedelic encounters typically entail processes of sense-making, crystallization of meaning, and enculturation into contextually mediated assumptive worlds (or ideologies) and behaviours that necessarily install novel constraints with potentially maladaptive consequences. We highlight the importance of clinical and epistemic integrity in the framing of psychedelic therapies. The importance of structuring and providing oversight for the therapeutic context raises difficult questions about the search for appropriate forms of epistemic authority that are at once respectful of the plural cultural origins of psychedelic rituals and mindful of best practices and standards in clinical care.
Topics: Humans; Hallucinogens; Psychotherapy; Anxiety; Substance-Related Disorders; Anxiety Disorders
PubMed: 36263513
DOI: 10.1177/13634615221131465 -
International Journal of Molecular... Sep 2023The growing popularity of the use of nutraceuticals in the prevention and alleviation of symptoms of many diseases in humans and dogs means that they are increasingly... (Review)
Review
The growing popularity of the use of nutraceuticals in the prevention and alleviation of symptoms of many diseases in humans and dogs means that they are increasingly the subject of research. A representative of the nutraceutical that deserves special attention is turmeric. Turmeric belongs to the family and is grown extensively in Asia. It is a plant used as a spice and food coloring, and it is also used in traditional medicine. The biologically active factors that give turmeric its unusual properties and color are curcuminoids. It is a group of substances that includes curcumin, de-methoxycurcumin, and bis-demethoxycurcumin. Curcumin is used as a yellow-orange food coloring. The most important pro-health effects observed after taking curcuminoids include anti-inflammatory, anticancer, and antioxidant effects. The aim of this study was to characterize turmeric and its main substance, curcumin, in terms of their properties, advantages, and disadvantages, based on literature data.
Topics: Humans; Dogs; Animals; Curcumin; Curcuma; Food Coloring Agents; Diarylheptanoids; Anti-Inflammatory Agents; Plant Extracts
PubMed: 37834009
DOI: 10.3390/ijms241914561 -
Drug Delivery Dec 2023Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to... (Review)
Review
Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.
Topics: Peptides; Lipids
PubMed: 38010881
DOI: 10.1080/10717544.2023.2284685