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International Journal of Molecular... Jan 2021Phloridzin is an important phytochemical which was first isolated from the bark of apple trees. It is a member of the dihydrochalcones and mainly distributed in the... (Review)
Review
Phloridzin is an important phytochemical which was first isolated from the bark of apple trees. It is a member of the dihydrochalcones and mainly distributed in the plants of the genus, therefore, the extraction method of phloridzin was similar to those of other phenolic substances. High-speed countercurrent chromatography (HSCCC), resin adsorption technology and preparative high-performance liquid chromatography (HPLC) were used to separate and purify phloridzin. Many studies showed that phloridzin had multiple pharmacological effects, such as antidiabetic, anti-inflammatory, antihyperglycaemic, anticancer and antibacterial activities. Besides, the physiological activities of phloridzin are cardioprotective, neuroprotective, hepatoprotective, immunomodulatory, antiobesity, antioxidant and so on. The present review summarizes the biosynthesis, distribution, extraction and bioavailability of the natural compound phloridzin and discusses its applications in food and medicine.
Topics: Animals; Biological Availability; Biological Products; Chalcones; Chemical Fractionation; Chromatography, High Pressure Liquid; Countercurrent Distribution; Humans; Malus; Phlorhizin; Plant Extracts; Structure-Activity Relationship
PubMed: 33478062
DOI: 10.3390/ijms22020962 -
Cells Apr 2022Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of... (Review)
Review
Two-pore channels (TPCs) are ligand-gated cation-selective ion channels that are preserved in plant and animal cells. In the latter, TPCs are located in membranes of acidic organelles, such as endosomes, lysosomes, and endolysosomes. Here, we focus on the function of these unique ion channels in mast cells, which are leukocytes that mature from myeloid hematopoietic stem cells. The cytoplasm of these innate immune cells contains a large number of granules that comprise messenger substances, such as histamine and heparin. Mast cells, along with basophil granulocytes, play an essential role in anaphylaxis and allergic reactions by releasing inflammatory mediators. Signaling in mast cells is mainly regulated via the release of Ca from the endoplasmic reticulum as well as from acidic compartments, such as endolysosomes. For the crosstalk of these organelles TPCs seem essential. Allergic reactions and anaphylaxis were previously shown to be associated with the endolysosomal two-pore channel TPC1. The release of histamine, controlled by intracellular Ca signals, was increased upon genetic or pharmacologic TPC1 inhibition. Conversely, stimulation of TPC channel activity by one of its endogenous ligands, namely nicotinic adenine dinucleotide phosphate (NAADP) or phosphatidylinositol 3,5-bisphosphate (PI(3,5)P), were found to trigger the release of Ca from the endolysosomes; thereby improving the effect of TPC1 on regulated mast cell degranulation. In this review we discuss the importance of TPC1 for regulating Ca homeostasis in mast cells and the overall potential of TPC1 as a pharmacological target in anti-inflammatory therapy.
Topics: Anaphylaxis; Animals; Calcium; Calcium Channels; Endosomes; Histamine; Homeostasis; NADP
PubMed: 35563771
DOI: 10.3390/cells11091465 -
Frontiers in Pharmacology 2022Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of... (Review)
Review
Classical psychedelics represent a family of psychoactive substances with structural similarities to serotonin and affinity for serotonin receptors. A growing number of studies have found that psychedelics can be effective in treating various psychiatric conditions, including post-traumatic stress disorder, major depressive disorder, anxiety, and substance use disorders. Mental health disorders are extremely prevalent in the general population constituting a major problem for the public health. There are a wide variety of interventions for mental health disorders, including pharmacological therapies and psychotherapies, however, treatment resistance still remains a particular challenge in this field, and relapse rates are also quite high. In recent years, psychedelics have become one of the promising new tools for the treatment of mental health disorders. In this review, we will discuss the three classic serotonergic naturally occurring psychedelics, psilocybin, ibogaine, and N, N-dimethyltryptamine, focusing on their pharmacological properties and clinical potential. The purpose of this article is to provide a focused review of the most relevant research into the therapeutic potential of these substances and their possible integration as alternative or adjuvant options to existing pharmacological and psychological therapies.
PubMed: 35837277
DOI: 10.3389/fphar.2022.927984 -
Neurotoxicology and Teratology 2021Discussions about non-pharmacologic interventions for Neonatal Abstinence Syndrome and Neonatal Opioid Withdrawal Syndrome (NAS/NOWS) have been minor compared with wider... (Review)
Review
Reconceptualizing non-pharmacologic approaches to Neonatal Abstinence Syndrome (NAS) and Neonatal Opioid Withdrawal Syndrome (NOWS): A theoretical and evidence-based approach.
Discussions about non-pharmacologic interventions for Neonatal Abstinence Syndrome and Neonatal Opioid Withdrawal Syndrome (NAS/NOWS) have been minor compared with wider attention to pharmacologic treatments. Although historically under-recognized, non-pharmacologic interventions are of paramount importance for all substance-exposed infants and remain as a first line therapy for the care of infants affected by NAS. Here we examine the role of non-pharmacologic interventions for NAS/NOWS by incorporating theoretical perspectives from different disciplines that inform the importance of individualized assessment of the mother-caregiver/infant dyad and interventions that involve both individuals. NAS/NOWS is a complex, highly individualized constellation of signs/symptoms that vary widely in onset, duration, severity, expression, responses to treatment and influence on long-term outcomes. NAS/NOWS often occurs in infants with multiple prenatal/postnatal factors that can compromise neurobiological self-regulatory functioning. We propose to rethink some of the long-held assumptions, beliefs, and paradigms about non-pharmacologic care of the infant with NAS/NOWS, which is provided as non-specific or as "bundled" in current approaches. This paper is Part I of a two-part series on re-conceptualizing non-pharmacologic care for NAS/NOWS as individualized treatment of the dyad. Here, we set the foundation for a new treatment approach grounded in developmental theory and evidence-based observations of infant neurobiology and neurodevelopment. In Part II, we provide actionable, individually tailored evaluations and approaches to non-pharmacologic NAS/NOWS treatment based on measurable domains of infant neurobehavioral functioning.
Topics: Analgesics, Opioid; Evaluation Studies as Topic; Evidence-Based Medicine; Female; Humans; Infant; Mothers; Neonatal Abstinence Syndrome; Pregnancy; Substance Withdrawal Syndrome
PubMed: 34419619
DOI: 10.1016/j.ntt.2021.107020 -
The AAPS Journal Jan 2022The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the... (Review)
Review
The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here. Graphical Abstract.
Topics: Animals; Biological Availability; Biopharmaceutics; Drug Compounding; Drug Development; Drug and Narcotic Control; Excipients; Humans; Permeability; Pharmaceutical Preparations; Therapeutic Equivalency
PubMed: 34988701
DOI: 10.1208/s12248-021-00670-1 -
Current Topics in Behavioral... 2022Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need,...
Substance use disorders (SUD) represent a significant public health issue with a high need for novel and efficacious treatment options. In light of this high unmet need, recent results reporting beneficial outcomes of psychedelic-assisted therapy in SUD are particularly relevant. However, several questions remain with regard to this treatment approach. The clinical mechanisms of action of psychedelic substances in the treatment of SUD are not well understood. Closing this knowledge gap is critical to inform and optimize the psychotherapeutic embedding of the acute substance administration. In this chapter, we discuss potential mechanisms that have implications on psychotherapeutic approaches including induced neuroplasticity, alterations in brain network connectivity, reward and emotion processing, social connectedness, insight, and mystical experiences. Furthermore, we outline considerations and approaches that leverage these mechanisms in order to optimize the therapeutic embedding by maximizing synergy between substance effects and psychotherapy. Understanding the mechanisms of action, developing psychotherapeutic approaches accordingly, and evaluating their synergistic efficacy in scientific studies will be critical to advance the framework of psychedelic-assisted therapy for addiction, create evidence-based approaches, and achieve the best treatment outcome for patients with SUD.
Topics: Emotions; Hallucinogens; Humans; Psychotherapy; Psychotropic Drugs; Substance-Related Disorders
PubMed: 34910289
DOI: 10.1007/7854_2021_284 -
Frontiers in Pharmacology 2023
PubMed: 36817121
DOI: 10.3389/fphar.2023.1146426 -
Pharmacological Research Jun 2024Substance use disorders (SUD), also named addiction when it is severe, is a chronic brain disorder with serious impact on individual who suffer, the public health and... (Review)
Review
Substance use disorders (SUD), also named addiction when it is severe, is a chronic brain disorder with serious impact on individual who suffer, the public health and with high burden of disease. They are multitude of mechanisms/factors involved in addiction: from individual characteristics of the person (from genetic to impacts of stress, sex, and age) to social and environmental situation (availability and accessibility of substances, cultural and legal aspects, socio-economical situation) and type of substance of use (pharmacological characteristics) Then, research on Addiction must include different, complementary, and translational perspectives. In this review, we explore the neurobiological, psychosocial, and epidemiological knowledge of substance addiction, and the main role played by pharmacology in the research in this field. In Spain, since 2002, collaborative networks have emerged for comprehensive research on addictions, with the creation of the Addictive Disorders Network (RTA), currently redefined as the Research Network for Primary Care in Addictions (RIAPAd) with the support of the Carlos III Health Institute (Instituto de Salud Carlos III). Basic (including neuropharmacology and behavioral pharmacology), clinical and epidemiological research groups stand out, combining efforts to address prevention, early detection and treatment through interdisciplinary cooperation and the subsequent dissemination of results.
PubMed: 38834163
DOI: 10.1016/j.phrs.2024.107233 -
Drug and Alcohol Dependence Reports Mar 2022Pregnant and parenting women who use substances report high rates of comorbid depression and anxiety. Due to the significant impact of this comorbidity on treatment... (Review)
Review
Pregnant and parenting women who use substances report high rates of comorbid depression and anxiety. Due to the significant impact of this comorbidity on treatment adherence and maternal/child outcomes, effective psychosocial and behavioral interventions to address depression and anxiety in this population are necessary. A directed search of PubMed, PsycINFO, and CINAHL databases produced 22 articles from 20 distinct studies examining non-pharmacologic interventions with an effect on depression and anxiety among pregnant or parenting women using substances. Of the 20 studies reviewed, 8 were randomized controlled trials, 7 were quasi-experimental studies, and 5 were cohort studies. Results revealed a wide array of interventions targeting intrapersonal, interpersonal, and/or structural factors within these women's lives. Parenting therapy and psychosocially enhanced treatment programs had the strongest evidence for positive treatment effect in improving symptoms of depression and anxiety. The use of contingency-management, case-managed care, patient or wellness navigators, mindfulness-based therapy, maternal-child relationship-focused therapy, family therapy, peer support, and therapeutic community-based interventions show promise but warrant further experimental exploration. Comprehensive and gender-specific residential treatment was observationally associated with improvements in depression and anxiety; however, the specific modality of efficacy is unclear. Future research should focus on identifying which modalities are most cost-effective, feasible, and acceptable among this uniquely vulnerable population.
PubMed: 36845894
DOI: 10.1016/j.dadr.2021.100017 -
Molecules (Basel, Switzerland) Jun 2021In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where... (Review)
Review
In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB); cannabinoid receptor 2 (CB), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer-both in vivo and in vitro clinical trials-has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.
Topics: Animals; Autoimmune Diseases of the Nervous System; Cytokines; Endocannabinoids; Humans; Immunosuppressive Agents; Leukocytes; Receptors, Cannabinoid; T-Lymphocytes
PubMed: 34205169
DOI: 10.3390/molecules26113389