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Endocrinology and Metabolism (Seoul,... Jun 2022Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion... (Review)
Review
Vitamin D has received considerable optimistic attention as a potentially important factor in many pathological states over the past few decades. However, the proportion of the active form of vitamin D metabolites responsible for biological activity is highly questionable in disease states due to flexible alterations in the enzymes responsible for their metabolism. For instance, CYP3A4 plays a crucial role in the biotransformation of vitamin D and other drug substances. Food-drug and/or drug-drug interactions, the disease state, genetic polymorphism, age, sex, diet, and environmental factors all influence CYP3A4 activity. Genetic polymorphisms in CYP450-encoding genes have received considerable attention in the past few decades due to their extensive impact on the pharmacokinetic and dynamic properties of drugs and endogenous substances. In this review, we focused on CYP3A4 polymorphisms and their interplay with vitamin D metabolism and summarized the role of vitamin D in calcium homeostasis, bone diseases, diabetes, cancer, other diseases, and drug substances. We also reviewed clinical observations pertaining to CYP3A4 polymorphisms among the aforementioned disease conditions. In addition, we highlighted the future perspectives of studying the pharmacogenetics of CYP3A4, which may have potential clinical significance for developing novel diagnostic genetic markers that will ascertain disease risk and progression.
Topics: Cytochrome P-450 CYP3A; Endocrine System Diseases; Humans; Neoplasms; Pharmacogenetics; Polymorphism, Genetic; Vitamin D
PubMed: 35654576
DOI: 10.3803/EnM.2021.1349 -
International Journal of Nanomedicine 2014The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport... (Review)
Review
The protective properties of the blood-brain barrier (BBB) are conferred by the intricate architecture of its endothelium coupled with multiple specific transport systems expressed on the surface of endothelial cells (ECs) in the brain's vasculature. When the stringent control of the BBB is disrupted, such as following EC damage, substances that are safe for peripheral tissues but toxic to neurons have easier access to the central nervous system (CNS). As a consequence, CNS disorders, including degenerative diseases, can occur independently of an individual's age. Although the BBB is crucial in regulating the biochemical environment that is essential for maintaining neuronal integrity, it limits drug delivery to the CNS. This makes it difficult to deliver beneficial drugs across the BBB while preventing the passage of potential neurotoxins. Available options include transport of drugs across the ECs through traversing occludins and claudins in the tight junctions or by attaching drugs to one of the existing transport systems. Either way, access must specifically allow only the passage of a particular drug. In general, the BBB allows small molecules to enter the CNS; however, most drugs with the potential to treat neurological disorders other than infections have large structures. Several mechanisms, such as modifications of the built-in pumping-out system of drugs and utilization of nanocarriers and liposomes, are among the drug-delivery systems that have been tested; however, each has its limitations and constraints. This review comprehensively discusses the functional morphology of the BBB and the challenges that must be overcome by drug-delivery systems and elaborates on the potential targets, mechanisms, and formulations to improve drug delivery to the CNS.
Topics: Animals; Biological Transport, Active; Blood-Brain Barrier; Chemistry, Pharmaceutical; Colloids; Drug Delivery Systems; Humans; Liposomes; Nanomedicine; Nanoparticles; Nanotechnology
PubMed: 24550672
DOI: 10.2147/IJN.S52236 -
SLAS Discovery : Advancing Life... Apr 2019Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new... (Review)
Review
Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new scaffolds have emerged. The effectiveness of antibiotics, however, is in sharp decline because of the emergence of drug-resistant microorganisms. The prevalence of drug resistance, both in clinical and community settings, is a consequence of bacterial ingenuity in altering pathways and/or cell morphology, making it a persistent threat to human health. The fundamental ability of pathogens to survive in a multitude of habitats can be triggered by recognition of chemical signals that warn organisms of exposure to a potentially harmful environment. Host immune defenses, including reactive oxygen intermediates and antibacterial substances, are among the multitude of chemical signals that can subsequently trigger expression of phenotypes better adapted for survival in that hostile environment. Thus, resistance development appears to be unavoidable, which leads to the conclusion that developing an alternative perspective for treatment options is vital. This review will discuss emerging medicinal chemistry approaches for addressing the global multidrug resistance in the 21st century.
Topics: Anti-Bacterial Agents; Chemistry, Pharmaceutical; Drug Resistance, Microbial; Humans; Reactive Oxygen Species; Structure-Activity Relationship
PubMed: 30523713
DOI: 10.1177/2472555218812657 -
Current Topics in Behavioral... 20173,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this... (Review)
Review
3,4-Methylenedioxypyrovalerone (MDPV) is a psychoactive component of so-called bath salts products that has caused serious medical consequences in humans. In this chapter, we review the neuropharmacology of MDPV and related analogs, and supplement the discussion with new results from our preclinical experiments. MDPV acts as a potent uptake inhibitor at plasma membrane transporters for dopamine (DAT) and norepinephrine (NET) in nervous tissue. The MDPV formulation in bath salts is a racemic mixture, and the S isomer is much more potent than the R isomer at blocking DAT and producing abuse-related effects. Elevations in brain extracellular dopamine produced by MDPV are likely to underlie its locomotor stimulant and addictive properties. MDPV displays rapid pharmacokinetics when injected into rats (0.5-2.0 mg/kg), with peak plasma concentrations achieved by 10-20 min and declining quickly thereafter. MDPV is metabolized to 3,4-dihydroxypyrovalerone (3,4-catechol-PV) and 4-hydroxy-3-methoxypyrovalerone (4-OH-3-MeO-PV) in vivo, but motor activation produced by the drug is positively correlated with plasma concentrations of parent drug and not its metabolites. 3,4-Catechol-PV is a potent uptake blocker at DAT in vitro but has little activity after administration in vivo. 4-OH-3-MeO-PV is the main MDPV metabolite but is weak at DAT and NET. MDPV analogs, such as α-pyrrolidinovalerophenone (α-PVP), display similar ability to inhibit DAT and increase extracellular dopamine concentrations. Taken together, these findings demonstrate that MDPV and its analogs represent a unique class of transporter inhibitors with a high propensity for abuse and addiction.
Topics: Adrenergic Uptake Inhibitors; Animals; Behavior, Animal; Benzodioxoles; Brain; Dopamine Plasma Membrane Transport Proteins; Dopamine Uptake Inhibitors; Humans; Neuropharmacology; Norepinephrine Plasma Membrane Transport Proteins; Psychotropic Drugs; Pyrrolidines; Substance-Related Disorders; Synthetic Cathinone
PubMed: 27830575
DOI: 10.1007/7854_2016_53 -
Planta Medica Oct 2017For centuries, pharmacognosy was essential for the identification, quality, purity, and, until the end of the 18th century, even for the efficacy of medicinal plants.... (Review)
Review
For centuries, pharmacognosy was essential for the identification, quality, purity, and, until the end of the 18th century, even for the efficacy of medicinal plants. Since the 19th century, it concentrated on authenticity, purity, quality and the analysis of active substances, and was established as an academic branch discipline within pharmacy and continuously developed into a modern, highly sophisticated science. Even though the paradigm in pharmacy changed in the 19th century with the discovery of morphine and concentrated on single substances that could be synthesized fast by the upcoming industry, medicinal plants always remained an important element of the Materia medica, and during the last decades, medicinal plants continue to be a source of remedies, and natural products are an inspiration for new medicine. In this research, pharmacognostic skills remain an essential element, both with regards to identity, quality assurance of botanicals (both herbal medicines and supplements), and the discovery and development of new medicines. Over the years, the specific pharmacognostical tools have changed dramatically, and most recently, DNA-based techniques have become another element of our spectrum of scientific methods.
Topics: Biological Products; DNA Barcoding, Taxonomic; DNA, Plant; Dietary Supplements; Europe; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; Humans; Materia Medica; Pharmacognosy; Plants, Medicinal; Quality Control
PubMed: 28486742
DOI: 10.1055/s-0043-108999 -
Molecules (Basel, Switzerland) Mar 2019In this work, we explore the current knowledge about the phytochemistry and in vitro and in vivo evaluations of the extracts and, where appropriate, the main active... (Review)
Review
In this work, we explore the current knowledge about the phytochemistry and in vitro and in vivo evaluations of the extracts and, where appropriate, the main active components characterized and isolated from the . Of the 15 species, most phytochemical, pharmacological, and toxicological studies have focused on . These plants are used for the treatment of various health disorders. Numerous phytochemical investigations of plants from the have shown the presence of hydrocarbons, alcohols, esters, ethers, aldehydes, ketones, fatty acids, phospholipids, volatile compounds, phenolic compounds, flavonoids, alkaloids, steroids, terpenes, lactones, and carbohydrates. Various studies have confirmed that extracts and active substances isolated from the have multiple pharmacological activities. The species has emerged as a source of traditional medicine used for human health. Further studies on the phytochemical, pharmacological, and toxicological properties and their mechanisms of action, safety, and efficacy in the species of is recommended.
Topics: Apocynaceae; Biotechnology; Ethnopharmacology; Medicine, Traditional; Molecular Structure; Phytochemicals; Plant Extracts; Plants, Medicinal; Toxicology
PubMed: 30934947
DOI: 10.3390/molecules24071238 -
Life Sciences Mar 2013Uncontrolled recreational drugs are proliferating in number and variety. Effects of long-term use are unknown, and regulation is problematic, as efforts to control one... (Review)
Review
Uncontrolled recreational drugs are proliferating in number and variety. Effects of long-term use are unknown, and regulation is problematic, as efforts to control one chemical often lead to several other structural analogs. Advanced analytical instrumentation and methods are continuing to be developed to identify drugs, chemical constituents of products, and drug substances and metabolites in biological fluids. Several mass spectrometry based approaches appear promising, particularly those that involve high resolution chromatographic and mass spectrometric methods that allow unbiased data acquisition and sophisticated data interrogation. Several of these techniques are shown to facilitate both targeted and broad spectrum analyses, the latter of which are often of particular benefit when dealing with misleadingly labeled products or assessing a biological matrix for illicit drugs and metabolites. The development and application of novel analytical approaches such as these will help to assess the nature and degree of exposure and risk and, where necessary, inform forensics and facilitate implementation of specific regulation and control measures.
Topics: Cannabinoids; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Humans; Illicit Drugs; Mass Spectrometry; Solid Phase Microextraction; Spectrometry, Mass, Electrospray Ionization; Substance-Related Disorders
PubMed: 23154240
DOI: 10.1016/j.lfs.2012.10.031 -
Journal of Ethnopharmacology Jan 2021Due to the outbreaks such as SARS, bird flu and swine flu, which we frequently encounter in our century, we need fast solutions with no side effects today more than... (Review)
Review
ETHNOPHARMACOLOGICAL RELEVANCE
Due to the outbreaks such as SARS, bird flu and swine flu, which we frequently encounter in our century, we need fast solutions with no side effects today more than ever. Due to having vast ethnomedical experience and the richest flora (34% endemic) of Europe and the Middle East, Turkey has a high potential for research on this topic. Plants that locals have been using for centuries for the prevention and treatment of influenza can offer effective alternatives to combat this problem. In this context, 224 herbal taxa belonging to 45 families were identified among the selected 81 studies conducted in the seven regions of Turkey. However, only 35 (15.6%) of them were found to be subjected to worldwide in vitro and in vivo research conducted on anti-influenza activity. Quercetin and chlorogenic acid, the effectiveness of which has been proven many times in this context, have been recorded as the most common (7.1%) active ingredients among the other 56 active substances identified.
AIM OF THE STUDY
This study has been carried out to reveal the inventory of plant species that have been used in flu treatment for centuries in Turkish folk medicine, which could be used in the treatment of flu or flu-like pandemics, such as COVID 19, that humanity has been suffering with, and also compare them with experimental studies in the literature.
MATERIALS AND METHODS
The investigation was conducted in two stages on the subject above by using electronic databases, such as Web of Science, Scopus, ScienceDirect, ProQuest, Medline, Cochrane Library, EBSCO, HighWire Press, PubMed and Google Scholar. The results of both scans are presented in separate tables, together with their regional comparative analysis.
RESULTS
Data obtained on taxa are presented in a table, including anti-influenza mechanism of actions and the active substances. Rosa canina (58.7%) and Mentha x piperita (22.2%) were identified as the most common plants used in Turkey. Also, Sambucus nigra (11.6%), Olea europaea (9.3%), Eucalyptus spp., Melissa officinalis, and Origanum vulgare (7.0%) emerged as the most investigated taxa.
CONCLUSION
This is the first nationwide ethnomedical screening work conducted on flu treatment with plants in Turkey. Thirty-nine plants have been confirmed in the recent experimental anti-influenza research, which strongly shows that these plants are a rich pharmacological source. Also, with 189 (84.4%) taxa, detections that have not been investigated yet, they are an essential resource for both national and international pharmacological researchers in terms of new natural medicine searches. Considering that the production of antimalarial drugs and their successful use against COVID-19 has begun, this correlation was actually a positive and remarkable piece of data, since there are 15 plants, including Centaurea drabifolia subsp. Phlocosa (an endemic taxon), that were found to be used in the treatment of both flu and malaria.
Topics: Antiviral Agents; Betacoronavirus; COVID-19; Coronavirus Infections; Ethnopharmacology; Humans; Influenza, Human; Medicine, Traditional; Pandemics; Phytotherapy; Plants, Medicinal; Pneumonia, Viral; SARS-CoV-2; Turkey
PubMed: 32882361
DOI: 10.1016/j.jep.2020.113319 -
Medicinal Research Reviews Jan 2016Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic... (Review)
Review
Natural products have made significant contribution to cancer chemotherapy over the past decades and remain an indispensable source of molecular and mechanistic diversity for anticancer drug discovery. More often than not, natural products may serve as leads for further drug development rather than as effective anticancer drugs by themselves. Generally, optimization of natural leads into anticancer drugs or drug candidates should not only address drug efficacy, but also improve absorption, distribution, metabolism, excretion, and toxicity (ADMET) profiles and chemical accessibility associated with the natural leads. Optimization strategies involve direct chemical manipulation of functional groups, structure-activity relationship directed optimization and pharmacophore-oriented molecular design based on the natural templates. Both fundamental medicinal chemistry principles (e.g., bioisosterism) and state-of-the-art computer-aided drug design techniques (e.g., structure-based design) can be applied to facilitate optimization efforts. In this review, the strategies to optimize natural leads to anticancer drugs or drug candidates are illustrated with examples and described according to their purposes. Furthermore, successful case studies on lead optimization of bioactive compounds performed in the Natural Products Research Laboratories at UNC are highlighted.
Topics: Animals; Antineoplastic Agents; Biological Products; Chemistry, Pharmaceutical; Drug Design; Drug Discovery; Drug Stability; Humans; Mice; Molecular Structure; Neoplasms; Solubility; Structure-Activity Relationship
PubMed: 26359649
DOI: 10.1002/med.21377 -
Neural Plasticity 2021Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different... (Review)
Review
Recent pharmacoepidemiologic studies suggest that pharmacological neuroenhancement (pNE) and mood enhancement are globally expanding phenomena with distinctly different regional characteristics. Sociocultural and regulatory aspects, as well as health policies, play a central role in addition to medical care and prescription practices. The users mainly display self-involved motivations related to cognitive enhancement, emotional stability, and adaptivity. Natural stimulants, as well as drugs, represent substance abuse groups. The latter comprise purines, methylxanthines, phenylethylamines, modafinil, nootropics, antidepressants but also benzodiazepines, -adrenoceptor antagonists, and cannabis. Predominant pharmacodynamic target structures of these substances are the noradrenergic/dopaminergic and cholinergic receptor/transporter systems. Further targets comprise adenosine, serotonin, and glutamate receptors. Meta-analyses of randomized-controlled studies in healthy individuals show no or very limited verifiability of positive effects of pNE on attention, vigilance, learning, and memory. Only some members of the substance abuse groups, i.e., phenylethylamines and modafinil, display positive effects on attention and vigilance that are comparable to caffeinated drinks. However, the development of new antidementia drugs will increase the availability and the potential abuse of pNE. Social education, restrictive regulatory measures, and consistent medical prescription practices are essential to restrict the phenomenon of neuroenhancement with its social, medical, and ethical implications. This review provides a comprehensive overview of the highly dynamic field of pharmacological neuroenhancement and elaborates the dramatic challenges for the medical, sociocultural, and ethical fundaments of society.
Topics: Affect; Central Nervous System Stimulants; Drug Development; Ethics; Forecasting; Humans; Motivation; Nootropic Agents; Pharmacoepidemiology
PubMed: 33519929
DOI: 10.1155/2021/8823383