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Indian Journal of Ophthalmology Nov 2017Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA) radiation exposure as photochemotherapy (Psoralens and...
Psoralen compounds such as methoxsalen are photosensitizer agents used in conjunction with ultraviolet A (UVA) radiation exposure as photochemotherapy (Psoralens and ultraviolet-A therapy [PUVA therapy]) for certain epidermal skin disorders such as psoriasis and vitiligo. Methoxsalen has been shown to be associated with premature cataract formation by forming adducts with lens proteins following oral administration and subsequent UVA exposure. Hence, the use of UV-filtering glasses is recommended during PUVA therapy sessions. Ocular tissues can be exposed to its photosensitizing effect with subsequent UV radiation exposure through sunlight if the patient was to be without protective eye glasses, potentially causing macular toxicity. Till date, there have been no reports in the literature of any posterior segment ocular toxicity arising from methoxsalen use. Here, we describe a case of a bilateral macular toxicity in a middle-aged male treated with methoxsalen for vitiligo.
Topics: Electrooculography; Electroretinography; Humans; Macula Lutea; Male; Methoxsalen; Middle Aged; Photosensitizing Agents; Retinal Diseases; Retinal Pigment Epithelium; Visual Acuity; Vitiligo
PubMed: 29133667
DOI: 10.4103/ijo.IJO_413_17 -
Biomedicine & Pharmacotherapy =... Feb 2022Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and... (Review)
Review
Acetylcholinesterase (AChE) inhibitor is the first choice for the treatment of Alzheimer's disease (AD), but it has some defects, such as dose limitation and unsatisfactory long-term treatment effect. Recent studies have shown that butyrylcholinesterase (BuChE) inhibitors or double acetyl and butyryl cholinesterase inhibitors have better curative effects on AD, and the side effects are lower than those of specific AChE inhibitors. Dual target cholinesterase inhibitors have become a new hotspot in the research of anti-AD drugs. Herein, the synthesis and bioactivities of BuChE inhibitors were reviewed.
Topics: Acridines; Alzheimer Disease; Butyrylcholinesterase; Cholinesterase Inhibitors; Humans; Methoxsalen; Structure-Activity Relationship
PubMed: 34953393
DOI: 10.1016/j.biopha.2021.112556 -
BioRxiv : the Preprint Server For... Jun 2023Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine...
Cigarette smoking remains the leading preventable cause of disease and death. Nicotine is the primary reinforcing ingredient in cigarettes sustaining addiction. Cotinine is the major metabolite of nicotine that produces a myriad of neurobehavioral effects. Cotinine supported self-administration and rats with a history of intravenous self-administration of cotinine exhibited relapse-like drug-seeking behavior, suggesting cotinine may also be reinforcing. To date, a potential contribution of cotinine to nicotine reinforcement remains unknown. Nicotine metabolism is mainly catalyzed by hepatic CYP2B1 enzyme in the rat and methoxsalen is a potent CYP2B1 inhibitor. The study tested the hypothesis that methoxsalen inbibits nicotine metabolism and self-administration, and that cotinine replacement attenuates the inhibitory effects of methoxsalen. Acute methoxsalen decreased plasma cotinine levels and increased nicotine levels following subcutaneous nicotine injection. Repeated methoxsalen reduced the acquisition of nicotine self-administration, leading to fewer nicotine infusions, disruption of lever differentiation, smaller total nicotine intake, and lower plasma cotinine levels. On the other hand, methoxsalen did not alter nicotine self-administration during the maintenance phase despite great reduction of plasma cotinine levels. Cotinine replacement by mixing cotinine with nicotine for self-administration dose-dependently increased plasma cotinine levels, counteracted effects of methoxsalen, and enhanced the acquisition of self-administration. Neither basal nor nicotine-induced locomotor activity was altered by methoxsalen. These results indicate that methoxsalen depressed cotinine formation from nicotine and the acquisition of nicotine self-administration, and that replacement of plasma cotinine attenuated the inhibitory effects of methoxsalen, suggesting that cotinine may contribute to the development of nicotine reinforcement.
PubMed: 37333320
DOI: 10.1101/2023.06.04.543614 -
Oxidative Medicine and Cellular... 2022Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit... (Review)
Review
Bergapten (BP) or 5-methoxypsoralen (5-MOP) is a furocoumarin compound mainly found in bergamot essential oil but also in other citrus essential oils and grapefruit juice. This compound presents antibacterial, anti-inflammatory, hypolipemic, and anticancer effects and is successfully used as a photosensitizing agent. The present review focuses on the research evidence related to the therapeutic properties of bergapten collected in recent years. Many preclinical and studies have been evidenced the therapeutic action of BP; however, few clinical trials have been carried out to evaluate its efficacy. These clinical trials with BP are mainly focused on patients suffering from skin disorders such as psoriasis or vitiligo. In these trials, the administration of BP (oral or topical) combined with UV irradiation induces relevant lesion clearance rates. In addition, beneficial effects of bergamot extract were also observed in patients with altered serum lipid profiles and in people with nonalcoholic fatty liver. On the contrary, there are no clinical trials that investigate the possible effects on cancer. Although the bioavailability of BP is lower than that of its 8-methoxypsoralen (8-MOP) isomer, it has fewer side effects allowing higher concentrations to be administered. In conclusion, although the use of BP has therapeutic applications on skin disorders as a sensitizing agent and as components of bergamot extract as hypolipemic therapy, more trials are necessary to define the doses and treatment guidelines and its usefulness against other pathologies such as cancer or bacterial infections.
Topics: 5-Methoxypsoralen; Humans; Methoxsalen; Oils, Volatile; Photosensitizing Agents; Plant Extracts; Ultraviolet Rays
PubMed: 35509838
DOI: 10.1155/2022/8615242 -
Journal of Clinical Apheresis Aug 2015Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency,... (Review)
Review
Systemic autoimmune diseases (AID) have multiorgan, heterogeneous clinical presentations and are characterized by dysregulation of the immune system, immunodeficiency, irreversible organ damage and increased morbidity and mortality. Preventing or decreasing flares of AID correlate with durable disease control, significant reduction of inflammation and prevention of disability or therapy-related toxicity. There is an urgent need for better treatment of severe, therapy-refractory AID. Extracorporeal photopheresis (ECP) is a cell-based immunomodulatory treatment which has been extensively used in variety of autoimmune disorders for the last two decades. ECP treatment is FDA approved for the treatment of cutaneous T-cell lymphoma (CTCL) with particularly promising results seen in graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HCT). Prolonged therapy is safe, well tolerated and allows reduction of systemic immunosuppression in therapy-refractory patients. Both clinical and experimental evidence suggest that ECP mechanism of action is characterized by apoptosis and phagocytosis of activated cells by antigen-presenting cells (APC), secretion of anti-inflammatory cytokines and stimulation of regulatory T cells (Tregs). The focus of this paper is to review the current evidence of ECP use in the treatment of AID. Here, we summarize the experience of nine major AID from 65 published reports. The key findings demonstrate substantial evidence of ECP feasibility, safety and in some AID also promising efficacy. However, the role of ECP in AID therapy is not established as most published studies are retrospective with limited number of patients and the trials are small or poorly standardized. The available data support future investigations of ECP as a therapeutic modality for the treatment of AID in well-designed prospective clinical studies. J
Topics: Apoptosis; Autoimmune Diseases; Blood Component Removal; Clinical Trials as Topic; Humans; Immune Tolerance; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Methoxsalen; Phagocytosis; Photopheresis; Photosensitizing Agents; Research Design; Retrospective Studies; Ultraviolet Rays
PubMed: 25546289
DOI: 10.1002/jca.21367 -
Biomedicine & Pharmacotherapy =... Jul 2023Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment...
BACKGROUND
Thrombocytopenia is a common hematological disease caused by many factors. It usually complicates critical diseases and increases morbidity and mortality. The treatment of thrombocytopenia remains a great challenge in clinical practice, however, its treatment options are limited. In this study, the active monomer xanthotoxin (XAT) was screened out to explore its medicinal value and provide novel therapeutic strategies for the clinical treatment of thrombocytopenia.
METHODS
The effects of XAT on megakaryocyte differentiation and maturation were detected by flow cytometry, Giemsa and phalloidin staining. RNA-seq identified differentially expressed genes and enriched pathways. The signaling pathway and transcription factors were verified through WB and immunofluorescence staining. Tg (cd41: eGFP) transgenic zebrafish and mice with thrombocytopenia were used to evaluate the biological activity of XAT on platelet formation and the related hematopoietic organ index in vivo.
RESULTS
XAT promoted the differentiation and maturation of Meg-01 cells in vitro. Meanwhile, XAT could stimulate platelet formation in transgenic zebrafish and recover platelet production and function in irradiation-induced thrombocytopenia mice. Further RNA-seq prediction and WB verification revealed that XAT activates the IL-1R1 target and MEK/ERK signaling pathway, and upregulates the expression of transcription factors related to the hematopoietic lineage to promote megakaryocyte differentiation and platelet formation.
CONCLUSION
XAT accelerates megakaryocyte differentiation and maturation to promote platelet production and recovery through triggering IL-1R1 and activating the MEK/ERK signaling pathway, providing a new pharmacotherapy strategy for thrombocytopenia.
Topics: Mice; Animals; Thrombopoiesis; Blood Platelets; Megakaryocytes; Methoxsalen; Zebrafish; Thrombocytopenia; Transcription Factors; Signal Transduction; Mitogen-Activated Protein Kinase Kinases
PubMed: 37156117
DOI: 10.1016/j.biopha.2023.114811 -
International Journal of Molecular... Mar 2019This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen...
This study evaluated whether bergapten and methoxsalen could prevent diabetes-induced osteoporosis and its underlying mechanism. For 10 weeks, bergapten or methoxsalen (0.02%, /) was applied to diabetic mice that were provided with a high-fat diet and streptozotocin. Bone mineral density (BMD) and microarchitecture quality were significantly reduced in the diabetic control group; however, both bergapten and methoxsalen reversed serum osteocalcin, bone-alkaline phosphatase and femur BMD. These coumarin derivatives significantly increased bone volume density and trabecular number, whereas they decreased the structure model index of femur tissue in diabetic mice. Conversely, tartrate-resistant acid phosphatase 5 (TRAP) staining revealed that these derivatives reduced osteoclast numbers and formation in diabetic bone tissue. Additionally, both bergapten and methoxsalen tended to downregulate the expression of osteoclast-related genes such as receptor activator of nuclear factor kappa-B ligand (), nuclear of activated T-cells, cytoplasmic 1 () and in diabetic femurs, with and expression showing significant reductions. Our data suggest that both bergapten and methoxsalen prevent diabetic osteoporosis by suppressing bone resorption.
Topics: 5-Methoxypsoralen; Alkaline Phosphatase; Animals; Bone Density; Diabetes Mellitus, Experimental; Diet, High-Fat; Disease Models, Animal; Gene Expression Regulation; Humans; Male; Methoxsalen; Mice; NFATC Transcription Factors; Osteocalcin; Osteogenesis; Osteoporosis; RANK Ligand; Streptozocin; Tartrate-Resistant Acid Phosphatase
PubMed: 30875838
DOI: 10.3390/ijms20061298