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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 -
Bulletin of Experimental Biology and... Mar 2021A single intraperitoneal administration of cisplatin in the MTD to outbred female mice disturbed hemostasis and formed the procoagulant phenotype of hemostatic potential...
A single intraperitoneal administration of cisplatin in the MTD to outbred female mice disturbed hemostasis and formed the procoagulant phenotype of hemostatic potential on days 7-10 culminating in a pronounced hypocoagulation on day 15. Hemostasis was corrected with warfarin and an extract containing furocoumarins composed of isopimpinellin (42.97%), bergapten (35.18%), and xanthotoxin (15.41%). The extract was standardized with gas chromatography-mass spectrometry, thin-layer chromatography, and HPLC. Furocoumarins and reference drug warfarin were administered intragastrically during 4 days starting on day 6 after the administration of cisplatin. Both furocoumarins and warfarin corrected hypercoagulation on days 7-10. On day 10, furocoumarins normalized coagulation, whereas warfarin resulted in hypocoagulation. On days 15-30, no effects of warfarin were observed. furocoumarins corrected hypocoagulation on days 15-20 with prolongation of this effect up to experimental day 30.
Topics: 5-Methoxypsoralen; Animals; Chromatography, High Pressure Liquid; Chromatography, Thin Layer; Cisplatin; Female; Furocoumarins; Gas Chromatography-Mass Spectrometry; Hemostatic Disorders; Methoxsalen; Mice; Rats; Warfarin
PubMed: 33788113
DOI: 10.1007/s10517-021-05119-1 -
Assay and Drug Development Technologies Jan 2022This study focuses on the development of topical formulation of methoxsalen using Babchi oil as formulation component that can be applied at body surfaces providing...
This study focuses on the development of topical formulation of methoxsalen using Babchi oil as formulation component that can be applied at body surfaces providing sustained delivery and enhanced penetration of methoxsalen leading to significant epidermal localization and better anti-psoriatic activity. The combination of psoralens, that is, methoxsalen (synthetic) and Babchi oil (natural) has been developed into nanoemulgel formulations. A total of four nanoemulsion formulations was developed using Babchi oil as oil phase and Tween 80 as surfactant by high-pressure homogenization method. The prepared nanoemulsions were characterized for entrapment efficiency, mean droplet size, and zeta potential. Based on characterization results, the optimized nanoemulsion formulation(s) were incorporated into the carbopol gel base to make a nanoemulgel. The prepared nanoemulgel formulations were analyzed for pH, drug content determination, spreadability, viscosity, skin permeation, and studies. The nanoemulsions showed droplet size between 51.3 and 146.7 nm, entrapment efficiency of 92.76%-98.10%, and zeta potential of -28.1 to -54.89 mev. The nanoemulsions showed varied in vitro drug release. In skin permeation, nanoemulgel (NG2) showed increased penetration and localized accumulation of methoxsalen across the skin compared with plain gel. results were substantiated by results showing significant amelioration of hyperproliferative skin symptoms. The promising results suggested that nanoemulgel system is a suitable carrier for the topical delivery of methoxsalen-Babchi oil.
Topics: Drug Liberation; Emulsions; Humans; Psoriasis; Skin; Skin Absorption
PubMed: 34883035
DOI: 10.1089/adt.2021.112 -
Photochemical & Photobiological... Aug 2020Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy for various diseases. Autologous leukocytes are collected, photoactivated with a...
BACKGROUND
Extracorporeal photopheresis (ECP) is an effective immunomodulatory therapy for various diseases. Autologous leukocytes are collected, photoactivated with a photosensitizer (8-methoxypsoralen, 8-MOP) and UVA light, and subsequently reinfused back to the patient. Leukapheresis and UVA irradiation systems can be integrated into one device (inline) or handled by two separate devices (offline). ECP works via intercalation of 8-MOP into DNA helices and UVA-based interactions to inhibit DNA replication. 8-MOP is known to adhere to plastic materials, which might reduce its availability for intercalation. In the present study we examined the bioavailability of 8-MOP when different plastic materials and solvents are used as matrices.
METHODS
Varying amounts of shredded ethylene vinyl acetate (EVA) and polyvinylchloride (PVC) from the MacoGenic irradiation bag (EVA1), UVA PIT irradiation bag (EVA2), UVA PIT recirculation bag (PVC A) and UVA PIT tubing (PVC B) by MacoPharma and PIT Medical Systems, respectively, were incubated with 200 ng mL 8-MOP dissolved in diisopropyl ether (DIPE) plus toluene 90/10 vol%, deionized water or plasma. After 2 h 8-MOP concentrations were determined by GC-MS.
RESULTS
After incubation, 8-MOP concentrations varied depending on the amount and type of plastic (PVC > EVA) and solvent (water > plasma > DIPE/toluene). Absorption to 200 mg EVA1 or EVA2 resulted in 8-MOP concentrations of 57% or 32% in water, 91% or 80% in plasma, and 93% or 92% in DIPE/toluene, while 200 mg PVC A and PVC B yielded recovery rates of 26% and 10% in water, 76% and 75% in plasma, and 55% and 30% in DIPE/toluene, respectively. Remaining 8-MOP differed significantly between container materials (EVA vs. PVC; p < 0.022) but not manufacturers (MacoPharma vs. PIT Medical Systems).
CONCLUSION
Absorption loss of 8-MOP depends on the type of plastic and solvent and is more pronounced with water than with plasma. As the DNA binding effect of 8-MOP is dose-dependent, ECP starting doses should be adjusted to ensure that a sufficient concentration of free bioavailable 8-MOP is present during UV irradiation.
Topics: Ethers; Gas Chromatography-Mass Spectrometry; Humans; Methoxsalen; Photopheresis; Photosensitizing Agents; Polyvinyl Chloride; Polyvinyls; Toluene; Ultraviolet Rays
PubMed: 32638713
DOI: 10.1039/c9pp00378a -
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 -
Xenobiotica; the Fate of Foreign... Feb 2019The objective is to evaluate methoxsalen as an in vitro phenotyping tool in comparison to ABT as a nonspecific inactivator of P450 mediated metabolism. The reversible...
The objective is to evaluate methoxsalen as an in vitro phenotyping tool in comparison to ABT as a nonspecific inactivator of P450 mediated metabolism. The reversible inhibition of methoxsalen and ABT against the P450, FMO, AO, MAO-A and -B, enzymes were evaluated using standard marker probe reactions. The time-dependent inhibition of P450 enzymes was evaluated in human liver microsomes. CES1 activities were determined by monitoring the depletion of known substrate, the clopidogrel. The metabolism of P450 substrates in the presence and absence of methoxsalen or ABT was evaluated in human liver microsomes. Methoxsalen is a direct inhibitor and inhibited the activities (>90%) of all enzymes at a concentration of 300 µM except for CYP2C9. Methoxsalen is also a potent time-dependent inhibitor of all P450 enzymes except for CYP2C19 (moderate) at a concentration of 300 µM. Methoxsalen inhibited the metabolism of P450 substrates in the pre-incubation mode. ABT is a potent TDI of several P450 except for CYP2C19 (47%) and CYP2C9 (27%). The results indicate that methoxsalen is a potent pan P450 inhibitor than ABT and can be a better tool in distinguishing P450 mediated metabolism form non-P450 metabolism in human liver microsomes.
Topics: Clopidogrel; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Humans; Methoxsalen; Microsomes, Liver; Phenotype; Protein Isoforms; Triazoles
PubMed: 29382249
DOI: 10.1080/00498254.2018.1434913 -
Cutis Feb 2022
Topics: Dermatitis, Phototoxic; Humans; Methoxsalen; Photosensitizing Agents; Ultraviolet Rays
PubMed: 35659812
DOI: 10.12788/cutis.0462 -
Combinatorial Chemistry & High... 2020Monoamine oxidases (MAOs) play a crucial role during the development of various neurodegenerative disorders. There are two MAO isozymes, MAO-A and MAO-B. MAO-A is a... (Review)
Review
BACKGROUND
Monoamine oxidases (MAOs) play a crucial role during the development of various neurodegenerative disorders. There are two MAO isozymes, MAO-A and MAO-B. MAO-A is a flavoenzyme, which binds to the outer mitochondrial membrane and catalyzes the oxidative transformations of neurotransmitters like serotonin, norepinephrine, and dopamine.
MATERIALS AND METHODS
Focus on synthetic studies has culminated in the preparation of many MAOA inhibitors, and advancements in combinatorial and parallel synthesis have accelerated the developments of synthetic schemes. Here, we provided an overview of the synthetic protocols employed to prepare different classes of MAO-A inhibitors. We classified these inhibitors according to their molecular scaffolds and the synthetic methods used.
RESULTS
Various synthetic and natural derivatives from a different class of MAO-A inhibitors were reported.
CONCLUSION
The review provides a valuable tool for the development of a new class of various selective MAO-A inhibitors for the treatment of depression and other anxiety disorders.
Topics: Animals; Antidepressive Agents; Biological Products; Coumarins; Dopamine; Drug Evaluation, Preclinical; Humans; Methoxsalen; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neurodegenerative Diseases; Structure-Activity Relationship; Umbelliferones
PubMed: 32342809
DOI: 10.2174/1386207323666200428091306 -
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