Topic Review
κ-Opioid Receptor Agonists
The κ-opioid receptor (KOR) belongs to the class of inhibitory G protein-coupled receptors (GPCRs), widely expressed throughout the central nervous system and peripheral tissues. Due to the implications of KOR activation, KOR agonists have attracted recent attention for their ability to produce analgesia without the harmful side effects typically associated with MOR activation. In addition, KOR agonists show the potential for the treatment of pruritis, multiple sclerosis, Alzheimer’s disease, immune mediated diseases such as osteoarthritis, atopic dermatitis, food allergy, gastrointestinal diseases, cancer, hypoxia and ischemia.
  • 375
  • 20 Feb 2023
Topic Review
β-Naphthoflavone, Ethanol Reverse Mitochondrial Dysfunction
The 1-methyl-4-phenylpyridinium (MPP+) is a parkinsonian-inducing toxin that promotes neurodegeneration of dopaminergic cells by directly targeting complex I of mitochondria. Recently, it was reported that some Cytochrome P450 (CYP) isoforms, such as CYP 2D6 or 2E1, may be involved in the development of this neurodegenerative disease. In order to study a possible role for CYP induction in neurorepair, we designed an in vitro model where undifferentiated neuroblastoma SH-SY5Y cells were treated with the CYP inducers β-naphthoflavone (βNF) and ethanol (EtOH) before and during exposure to the parkinsonian neurotoxin, MPP+. The toxic effect of MPP+ in cell viability was rescued with both βNF and EtOH treatments. We also report that this was due to a decrease in reactive oxygen species (ROS) production, restoration of mitochondrial fusion kinetics, and mitochondrial membrane potential. These treatments also protected complex I activity against the inhibitory effects caused by MPP+, suggesting a possible neuroprotective role for CYP inducers. These results bring new insights into the possible role of CYP isoenzymes in xenobiotic clearance and central nervous system homeostasis.
  • 661
  • 02 Nov 2020
Topic Review
β-Lactamase Inhibitors
The inhibitors of β-lactamases (BLI) have gained a prominent role in the safeguard of beta-lactams. In the last years, new β-lactam–BLI combinations have been registered or are still under clinical evaluation, demonstrating their effectiveness to treat complicated infections. It is also noteworthy that the pharmacokinetics of BLIs partly matches that of β-lactams companions, meaning that some clinical situations, as well as renal impairment and renal replacement therapies, may alter the disposition of both drugs. Common pharmacokinetic characteristics, linear pharmacokinetics across a wide range of doses, and known pharmacokinetic/pharmacodynamic parameters may guide modifications of dosing regimens for both β-lactams and BLIs. However, comorbidities (i.e., burns, diabetes, cancer) and severe changes in individual pathological conditions (i.e., acute renal impairment, sepsis) could make dose adaptation difficult, because the impact of those factors on BLI pharmacokinetics is partly known. Therapeutic drug monitoring protocols may overcome those issues and offer strategies to personalize drug doses in the intensive care setting. Further prospective clinical trials are warranted to improve the use of BLIs and their β-lactam companions in severe and complicated infections. 
  • 610
  • 11 Jul 2021
Topic Review
β-Caryophyllene
β-caryophyllene (BCP) is a cannabinoid receptor 2 (CB2) agonist that tempers inflammation. An interaction between the CB2 receptor and peroxisome proliferator-activated receptor gamma (PPAR-γ) has been suggested and PPAR-γ activation exerts anti-arthritic effects. The aim of this study was to characterize the therapeutic activity of BCP and to investigate PPAR-γ involvement in a collagen antibody induced arthritis (CAIA) experimental model. CAIA was induced through intraperitoneal injection of a monoclonal antibody cocktail and lipopolysaccharide (LPS; 50 µg/100 µL/ip). CAIA animals were then randomized to orally receive either BCP (10 mg/kg/100 µL) or its vehicle (100 µL of corn oil). BCP significantly hampered the severity of the disease, reduced relevant pro-inflammatory cytokines, and increased the anti-inflammatory cytokine IL-13. BCP also decreased joint expression of matrix metalloproteinases 3 and 9. Arthritic joints showed increased COX2 and NF-kB mRNA expression and reduced expression of the PPARγ coactivator-1 alpha, PGC-1α, and PPAR-γ. These conditions were reverted following BCP treatment. Finally, BCP reduced NF-kB activation and increased PGC-1α and PPAR-γ expression in human articular chondrocytes stimulated with LPS. These effects were reverted by AM630, a CB2 receptor antagonist. These results suggest that BCP ameliorates arthritis through a cross-talk between CB2 and PPAR-γ.
  • 708
  • 01 Nov 2020
Topic Review
α-Synuclein Phosphorylation and Its Kinases
α-Synuclein is a protein with a molecular weight of 14.5 kDa and consists of 140 amino acids encoded by the SNCA gene. Missense mutations and gene duplications in the SNCA gene cause hereditary Parkinson’s disease. Highly phosphorylated and abnormally aggregated α-synuclein is a major component of Lewy bodies found in neuronal cells of patients with sporadic Parkinson’s disease, dementia with Lewy bodies, and glial cytoplasmic inclusion bodies in oligodendrocytes with multiple system atrophy. Aggregated α-synuclein is cytotoxic and plays a central role in the pathogenesis of the above-mentioned synucleinopathies. In a healthy brain, most α-synuclein is unphosphorylated; however, more than 90% of abnormally aggregated α-synuclein in Lewy bodies of patients with Parkinson’s disease is phosphorylated at Ser129, which is presumed to be of pathological significance. Several kinases catalyze Ser129 phosphorylation, but the role of phosphorylation enzymes in disease pathogenesis and their relationship to cellular toxicity from phosphorylation are not fully understood in α-synucleinopathy. G-protein-coupled receptor kinases, casein kinase II, and polo-like kinase possess the ability to phosphorylate α-synuclein protein. On this point, inhibition of these kinases is able to prevent α-synuclein phosphorylation, which indicates the potential therapeutic targets and availability of drug development for α-synucleinopathies. α-Synuclein phosphorylation can clinically be an accompanying event in the brains of patients with Parkinson’s disease rather than the critical factor for α-synuclein aggregation and toxicity. Nevertheless, increasing phosphorylated α-synuclein and the accumulation with disease progression is useful as a therapeutic target and biomarker.
  • 404
  • 08 Jun 2022
Topic Review
α-Melanocytic Hormone
The melanocortin system encompasses melanocortin peptides, five receptors, and two endogenous antagonists. Besides pigmentary effects generated by α-Melanocytic Hormone (α-MSH), new physiologic roles in sexual activity, exocrine secretion, energy homeostasis, as well as immunomodulatory actions, exerted by melanocortins, have been described recently. 
  • 526
  • 02 Feb 2021
Topic Review
Zoopharmacology
Zoopharmacognosy is the multidisciplinary approach of the self-medication behavior of many kinds of animals. Recent studies showed the presence of antitumoral secondary metabolites in some of the plants employed by animals and their use for the same therapeutic purposes in humans. Other related and sometimes confused term is Zootherapy, which consists on the employment of animal parts and/or their by-products such as toxins, venoms, etc., to treat different human ailments. Therefore, the aim of this work is to provide a brief insight for the use of Zoopharmacology (comprising Zoopharmacognosy and Zootherapy) as new paths to discover drugs studying animal behavior and/or using compounds derived from animals.
  • 664
  • 28 Jun 2021
Topic Review
Zeolite/Pharmaceuticals System
Zeolites belong to aluminosilicate microporous solids, with strong and diverse catalytic activity, which makes them applicable in almost every kind of industrial process, particularly thanks to their eco-friendly profile. Another crucial characteristic of zeolites is their tremendous adsorption capability. Therefore, it is self-evident that the widespread use of zeolites is in environmental protection, based primarily on the adsorption capacity of substances potentially harmful to the environment, such as pharmaceuticals, pesticides, or other industry pollutants. On the other hand, zeolites are also recognized as drug delivery systems (DDS) carriers for numerous pharmacologically active agents. The enhanced bioactive ability of DDS zeolite as a drug carrying nanoplatform is confirmed, making this system more specific and efficient, compared to the drug itself. These two applications of zeolite, in fact, illustrate the importance of (ir)reversibility of the adsorption process. 
  • 898
  • 11 Aug 2022
Topic Review
Zebrafish Motile Cilia
Zebrafish is a vertebrate teleost widely used in many areas of research. As embryos, they develop quickly and provide unique opportunities for research studies owing to their transparency for at least 48 h post fertilization. Zebrafish have many ciliated organs that include primary cilia as well as motile cilia. Using zebrafish as an animal model helps to better understand human diseases such as Primary Ciliary Dyskinesia (PCD), an autosomal recessive disorder that affects cilia motility, currently associated with more than 50 genes. 
  • 664
  • 22 Sep 2021
Topic Review
Xenobiotics Modulating Aryl Hydrocarbon Receptor in Energy Homeostasis
There are fundamental sex differences in the regulation of energy homeostasis. Better understanding of the underlying mechanisms of energy balance that account for this asymmetry will assist in developing sex-specific therapies for sexually dimorphic diseases such as obesity. Multiple organs, including the hypothalamus and adipose tissue, play vital roles in the regulation of energy homeostasis, which are regulated differently in males and females. Various neuronal populations, particularly within the hypothalamus, such as arcuate nucleus (ARC), can sense nutrient content of the body by the help of peripheral hormones such leptin, derived from adipocytes, to regulate energy homeostasis. Substances from diet and environmental contaminants can exert insidious effects on energy metabolism, acting peripherally through the aryl hydrocarbon receptor (AhR). Developmental AhR activation can impart permanent alterations of neuronal development that can manifest a number of sex-specific physiological changes, which sometimes become evident only in adulthood. AhR is being investigated as a potential target for treating obesity. The consensus is that impaired function of the receptor protects from obesity in mice. AhR also modulates sex steroid receptors.
  • 255
  • 01 Aug 2022
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