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Pharmacognosy Magazine Jul 2017Coumarins exert many biological effects in humans, animals, and plants, which make the evaluation of their biological activities and study of their role in ethnomedicine...
INTRODUCTION
Coumarins exert many biological effects in humans, animals, and plants, which make the evaluation of their biological activities and study of their role in ethnomedicine highly valued.
OBJECTIVES
Here, we selected seven plants which have ethnopharmacological use as antimicrobial in Iraq and the aims were to quantify the two structural isomers bergapten and methoxsalen in their seeds, to evaluate the antibacterial activities against several clinical isolates, and to isolate bergapten and methoxsalen from .
MATERIALS AND METHODS
Seven plants were extracted by petroleum ether (PE) and ethanol (EtOH). Bergapten and methoxsalen were separated and purified by preparative thin-layer chromatography. Quantification of the furanocoumarins has been conducted by high-performance liquid chromatography, and all the plant extracts and pure compounds were checked for antibacterial activities utilizing alamar blue microplate assay.
RESULTS
was deprived of bergapten and methoxsalen and methoxsalen was not detected from . Bergapten was abundant in PE more than in EtOH; on the other hand, EtOH was rich in methoxsalen. The separation of the two structural isomers was performed using normal phase chromatography and ultraviolet light as an indicator. All extracts showed weak to moderate antibacterial activities against Gram-positive isolates which were more sensitive than the negative ones. extract was least active, uncover the antibacterial role of bergapten and methoxsalen.
CONCLUSION
These findings support the medicinal use of seeds of seven plants from family and quantify the two pharmacologically important furanocoumarins (bergapten and methoxsalen).
SUMMARY
This study was conducted to evaluate the antibacterial activities of seven plants seeds used in local medicine in Iraq. High-performance liquid chromatography was used to quantify bergapten and xanthotoxin in non-polar and polar extracts of these seeds. This study supports the medicinal use of these plants and clarifies the role of bergapten and xanthotoxin in antibacterial activities of these plants. EtOH: Ethanol; MIC: Minimum inhibitory concentration; PE: Petroleum ether; Rf: Retardation factor; Rt: Retention time.
PubMed: 28808379
DOI: 10.4103/pm.pm_503_16 -
Cell Journal 2014Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with...
OBJECTIVE
Methoxsalen is a natural photoactive compound which is found in many seed plants. A number of epidermal proliferative disorders can be treated by methoxsalen along with long wave ultraviolet A (UVA).
MATERIALS AND METHODS
In an experimental study, we aimed to demonstrate the effect of methoxsalen, UVA and their combination on oogenesis Balb/C mice. There were two experimental groups and a control group. The experimental groups were composed of i. a short term group with treatment duration of 15 days and ii. a long term group with treatment duration of 5 weeks. Both the long term and short term experimental groups were further subdivided into a UVA group, a methoxsalen group and a methoxsalen plus UVA group. After treatment, mature females in prosterus phase of ovarian cycle were scarified with ether, while their ovaries were removed and prepared for histological studies.
RESULTS
Both macro and microscopic studies showed significant anomalies (p<0.05) among experimental group ovaries as compared to control group. The obtained results showed a significant decrease in the following factors: number and diameter of corpus lutei, Graafian follicles, diameter of granulosa cell layer and oocytes, number of primordial and primary and growing follicles, while we observed an increase in number of atretic follicle. Furthermore, our findings confirmed an increase in theca diameter only through UVA treatment. Methoxsalen also reduced circulating estrogen levels in blood serum, significantly. Other cases of teratogenecity, such as follicles with three oocytes and disorganization in corpus luteum cells were observed.
CONCLUSION
The result suggests that UVA, methoxsalen and their combination cause health problems and cell injuries.
PubMed: 24381860
DOI: No ID Found -
Bioorganic Chemistry Aug 2019Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine...
Seventy-one 7-oxycoumarins, 66 synthesized and 5 commercially sourced, were tested for their ability to inhibit growth in murine PAM212 keratinocytes. Forty-nine compounds from the library demonstrated light-induced lethality. None was toxic in the absence of UVA light. Structure-activity correlations indicate that the ability of the compounds to inhibit cell growth was dependent not only on their physiochemical characteristics, but also on their ability to absorb UVA light. Relative lipophilicity was an important factor as was electron density in the pyrone ring. Coumarins with electron withdrawing moieties - cyano and fluoro at C - were considerably less active while those with bromines or iodine at that location displayed enhanced activity. Coumarins that were found to inhibit keratinocyte growth were also tested for photo-induced DNA plasmid nicking. A concentration-dependent alteration in migration on neutral gels caused by nicking was observed.
Topics: Animals; Cell Proliferation; Cells, Cultured; Coumarins; Dose-Response Relationship, Drug; Keratinocytes; Mice; Molecular Structure; Photochemical Processes; Photosensitizing Agents; Structure-Activity Relationship
PubMed: 31170642
DOI: 10.1016/j.bioorg.2019.103014 -
Molecules (Basel, Switzerland) Apr 2014Gerbera anandria (Compositae) was extracted with 75% ethanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of...
Gerbera anandria (Compositae) was extracted with 75% ethanol and the residue was fractionated using light petroleum, chloroform and ethyl acetate. The constituents of the extracts were separated by column chromatography employing solvents of different polarity. Column chromatography of the light petroleum fraction resulted in the isolation of methyl hexadecanoate, while the chloroform fraction afforded xanthotoxin, 2-hydroxy-6-methylbenzoic acid, 7-hydroxy-1(3H)-isobenzofuranone, a mixture of β-sitosterol and stigmasterol, and 8-methoxysmyrindiol and the ethyl acetate fraction gave gerberinside, apigenin-7-O-β-d-glucopyranoside and quercetin. A new coumarin, 8-methoxysmyrindiol, was found. The chemical structures of the isolated compounds were established by MS and NMR (HSQC, HMBC). Free radical scavenging and cytotoxic activities of crude extracts and 8-methoxysmyrindiol were further investigated. The ethyl acetate phase exerted the strongest DPPH free radical scavenging activity in comparison to the other fractions. The coumarin 8-methoxysmyrindiol demonstrated cytotoxicity against multiple human cancer cell lines, with the highest potency in HepG2 cells.
Topics: Antineoplastic Agents, Phytogenic; Asteraceae; Benzoates; Benzofurans; Biphenyl Compounds; Cell Line, Tumor; Cell Survival; Decanoates; Flavonoids; Free Radical Scavengers; Humans; Methoxsalen; Phytosterols; Picrates; Plant Extracts; Solvents
PubMed: 24699147
DOI: 10.3390/molecules19044046 -
The Cochrane Database of Systematic... Jun 2022Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the... (Review)
Review
Extracorporeal photopheresis versus alternative treatment for chronic graft-versus-host disease after haematopoietic stem cell transplantation in children and adolescents.
BACKGROUND
Chronic graft-versus-host disease (cGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation, occurring in 6% to 65% of the paediatric recipients. Currently, the therapeutic mainstay for cGvHD is treatment with corticosteroids, frequently combined with other immunosuppressive agents in people with steroid-refractory manifestations. There is no established standard treatment for steroid-refractory cGvHD. The therapeutic options for these patients include extracorporeal photopheresis (ECP), an immunomodulatory treatment that involves ex vivo collection of mononuclear cells from peripheral blood, exposure to the photoactive agent 8-methoxypsoralen, ultraviolet radiation and re-infusion of the processed cell product. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and first updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of cGvHD in children and adolescents after haematopoietic stem cell transplantation.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL) (2021), MEDLINE (PubMed) and Embase databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We aimed to include randomised controlled trials (RCTs) comparing ECP with or without alternative treatment versus alternative treatment alone in children and adolescents with cGvHD after haematopoietic stem cell transplantation.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreements in the selection of trials by consultation with a third review author.
MAIN RESULTS
We found no studies meeting the criteria for inclusion in this 2021 review update.
AUTHORS' CONCLUSIONS
We could not evaluate the efficacy of ECP in the treatment of cGvHD in children and adolescents after haematopoietic stem cell transplantation since the second review update again found no RCTs. Current recommendations are based on retrospective or observational studies only. Thus, ideally, ECP should be applied in the context of controlled trials only. However, performing RCTs in this population will be challenging due to the limited number of eligible participants, variable disease presentation and the lack of well-defined response criteria. International collaboration, multicentre trials and appropriate funding for such trials will be needed. If treatment decisions based on clinical data are made in favour of ECP, recipients should be carefully monitored for beneficial and harmful effects. In addition, efforts should be made to share this information with other clinicians, for example by setting up registries for children and adolescents treated with ECP.
Topics: Adolescent; Child; Chronic Disease; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 35679154
DOI: 10.1002/14651858.CD009898.pub4 -
Investigational New Drugs Apr 2021Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative...
Background Androgen deprivation therapy (ADT) is a standard treatment for high-risk biochemically-recurrent, non-metastatic prostate cancer (BRPC) but is not curative and associated with toxicity. Racemetyrosine (SM-88) is an amino-acid analogue used with methoxsalen, phenytoin, and sirolimus (MPS) to enhance SM-88 activity. Method A phase 1b/2, open-label trial in BRPC and rising PSA. Patients were given daily SM-88 (230 mg BID), methoxsalen (10 mg), phenytoin (50 mg), and sirolimus (0.5 mg)). Outcome measures included changes in PSA, circulating tumor cells (CTCs) and imaging. Results 34 subjects were screened, 23 treated and 21 remained on study for ≥12 weeks. The median PSA was 6.4 ng/ml (range 1.7-80.1); doubling-time 6.2 months (range 1.4-36.6) and baseline testosterone 319.1 ng/ml (range 2.5-913.7). Median duration of therapy was 6.5 months (2.6-14.0). CTCs (median 48.5 cells/4 ml (range 15-268) at baseline) decreased a median of 65.3% in 18 of 19 patients. For patients who achieved an absolute CTC nadir count of <10 cells/4 ml (n = 10), disease control was 100% i.e. no metastases or PSA progression, while on trial (p = 0.005). PSA fell by ≥50% in 4.3% (1 subject). No patients developed metastatic disease while on treatment (metastases free survival =100%). There were no treatment-related adverse events (AEs) and quality of life was unchanged from baseline on the EORTC QLQ-C30 and QLQ-PR25. Testosterone levels rose slightly on SM-88 and were unrelated to efficacy or toxicity. Conclusions Use of SM-88 was associated with disease control while maintaining QOL. SM-88 may delay the need for ADT and the associated hormonal side effects. Larger trials are planned.Trial registration number, date of registration - NCT02796898, June 13, 2016.
Topics: Aged; Aged, 80 and over; Androgen Antagonists; Humans; Kaplan-Meier Estimate; Male; Methoxsalen; Middle Aged; Neoplasm Recurrence, Local; Phenytoin; Prostate-Specific Antigen; Prostatic Neoplasms; Quality of Life; Sirolimus; Tyrosine
PubMed: 32924093
DOI: 10.1007/s10637-020-00993-4 -
Transplantation and Cellular Therapy May 2022Therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) involves intensive immunosuppression, which is associated with significant risk of infection....
Therapy for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) involves intensive immunosuppression, which is associated with significant risk of infection. Extracorporeal photopheresis (ECP) is used to treat SR-aGVHD and is considered more immunomodulatory than immunosuppressive. However, pediatric data are mostly retrospective and often involve multistep ECP that includes apheresis followed by separate photosensitizing/reinfusion on another device. This study aimed to prospectively evaluate the efficacy and safety of a single-device ECP system in children with SR-aGVHD. In this open-label multicenter phase 3 study of the Therakos CellEx Photopheresis System in children/young adults age 1 to 21 years with SR-aGVHD. Patients were treated 3 times per week for 4 weeks, then twice weekly through week 12 while maintaining standard aGVHD prophylaxis. The primary efficacy endpoint was the proportion of patients achieving an overall response (OR) at day +28 without the addition of next-line systemic treatment. Secondary endpoints included the proportion of patients achieving OR at weeks 8 and 12; the mean weekly steroid dose at weeks 4, 8, and 12; and treatment-emergent adverse events (TEAEs). Twenty-nine children (median age, 8 years) were enrolled. OR was 55% by day 28, 74% by week 8, and 79% by week 12. Progressive improvements were observed in the skin and the gastrointestinal tract. The mean steroid dose was decreased from 1.54 mg/kg/day at baseline to 0.90 mg/kg/day at week 4; 35% of patients achieved a >50% steroid dose reduction by week 4, and 75% achieved a >50% steroid dose reduction by week 12. Of the 168 TEAEs reported among 25 patients (86%), 28 events (17%) were infections and 14 events (8%) were considered likely treatment related (all nonserious). Of 627 ECP treatments administered in children and young adults, 68% required blood priming. TEAEs related to Uvadex or ECP were rare, hypocalcemia was the most common (3 events total). Three deaths occurred and were deemed unrelated to ECP by the investigators. Use of the Therakos CellEx Photopheresis System was effective in children with SR-aGVHD, with more than one-half experiencing improvement by day 28 and further responses observed over 12 weeks. Very few TEAEs were attributable to ECP, and no new safety signals were observed.
Topics: Adolescent; Adult; Child; Child, Preschool; Graft vs Host Disease; Humans; Infant; Photopheresis; Prospective Studies; Retrospective Studies; Steroids; Young Adult
PubMed: 35124293
DOI: 10.1016/j.jtct.2022.01.025 -
The Cochrane Database of Systematic... Sep 2022Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of... (Review)
Review
BACKGROUND
Acute graft-versus-host disease (aGvHD) is a major cause of morbidity and mortality after haematopoietic stem cell transplantation (HSCT), occurring in 8% to 85% of paediatric recipients. Currently, the therapeutic mainstay for aGvHD is treatment with corticosteroids. However, there is no established standard treatment for steroid-refractory aGvHD. Extracorporeal photopheresis (ECP) is a type of immunomodulatory method amongst different therapeutic options that involves ex vivo collection of peripheral mononuclear cells, exposure to the photoactive agent 8-methoxypsoralen and ultraviolet-A radiation, and reinfusion of these treated blood cells to the patient. The mechanisms of action of ECP are not completely understood. This is the second update of a Cochrane Review first published in 2014 and updated in 2015.
OBJECTIVES
To evaluate the effectiveness and safety of ECP for the management of aGvHD in children and adolescents after HSCT.
SEARCH METHODS
We searched the Cochrane Register of Controlled Trials (CENTRAL), MEDLINE (PubMed) and Embase (Ovid) databases from their inception to 25 January 2021. We searched the reference lists of potentially relevant studies without any language restrictions. We searched five conference proceedings and nine clinical trial registries on 9 November 2020 and 12 November 2020, respectively.
SELECTION CRITERIA
We sought to include randomised controlled trials (RCTs) comparing ECP with or without standard treatment versus standard treatment alone in children and adolescents with aGvHD after HSCT.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the study selection. We resolved disagreement in the selection of trials by consultation with a third review author.
MAIN RESULTS
We identified no additional studies in the 2021 review update, so there are still no studies that meet the criteria for inclusion in this review.
AUTHORS' CONCLUSIONS
The efficacy of ECP in the treatment of aGvHD in children and adolescents after HSCT is unknown, and its use should be restricted to within the context of RCTs. Such studies should address a comparison of ECP alone or in combination with standard treatment versus standard treatment alone. The 2021 review update brought about no additions to these conclusions.
Topics: Adolescent; Adrenal Cortex Hormones; Child; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Methoxsalen; Photopheresis; Steroids
PubMed: 36166494
DOI: 10.1002/14651858.CD009759.pub4 -
Molecules (Basel, Switzerland) Mar 2020Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis...
Osteopenia or osteoporosis occurs frequently in alcoholics and patients with alcoholic fatty liver disease. Methoxsalen (MTS), 8-methoxypsoralen, improved osteoporosis in ovariectomized and diabetic mouse models; however, its effects on alcohol-induced osteopenia and steatosis have not been reported. This study examined the effects of MTS on alcohol-induced bone loss and steatosis. Rats in the alcohol groups were fed a Liber-DeCarli liquid diet containing 36% of its calories as alcohol. MTS was at 0.005% in their diet, while alendronate (positive control; 500 μg/kg BW/day) was administered orally for eight weeks. The pair-fed group received the same volume of isocaloric liquid diet containing dextrin-maltose instead of alcohol as the alcohol control group consumed the previous day. In the alcohol-fed rats, the MTS and alendronate increased the bone volume density, bone surface density and trabecular number, while the bone specific surface, trabecular separation and structure model index were decreased in the tibia. MTS down-regulated tibial tartrate-resistant acid phosphatase 5 (TRAP) expression compared to the alcohol control group. MTS or alendronate prevented chronic alcohol-induced hepatic lipid accumulation and the triglyceride level in the alcohol-fed rats by decreasing the lipogenic enzyme activities and increasing the fatty acid oxidation enzyme activities. MTS reduced significantly the serum levels of alcohol, TRAP and tumor necrosis factor-α compared to the alcohol control group. Overall, these results suggest that MTS is likely to be an alternative agent for alcoholic osteopenia and hepatosteatosis.
Topics: Alcoholism; Animals; Biomarkers; Bone Diseases, Metabolic; Bone and Bones; Cytokines; Dietary Supplements; Disease Models, Animal; Fatty Liver; Inflammation Mediators; Methoxsalen; Protective Agents; Rats
PubMed: 32151025
DOI: 10.3390/molecules25051177 -
International Journal of Molecular... Jan 2021(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and...
(1) Cisplatin (CDDP) is used in melanoma chemotherapy, but it has many side effects. Hence, the search for natural substances that can reduce the dose of CDDP, and CDDP-related toxicity, is highly desired. Coumarins have many biological properties, including anticancer and antiproliferative effects. (2) An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay on two human melanoma cell lines (FM55P and FM55M2) examined the antitumor properties of CDDP and five naturally occurring coumarins (osthole, xanthotoxin, xanthotoxol, isopimpinellin, and imperatorin). The antiproliferative effects produced by combinations of CDDP with the coumarins were assessed using type I isobolographic analysis. (3) The most potent anticancer properties of coumarins were presented by osthole and xanthotoxol. These compounds were characterized by the lowest median inhibitory concentration (IC) values relative to the FM55P and FM55M2 melanoma cells. Isobolographic analysis showed that for both melanoma cell lines, the combination of CDDP and osthole exerted synergistic and additive interactions, while the combination of CDDP and xanthotoxol exerted additive interactions. Combinations of CDDP with xanthotoxin, isopimpinellin, and imperatorin showed antagonistic and additive interactions in two melanoma cell lines. (4) The combination of CDDP and osthole was characterized by the most desirable synergistic interaction. Isobolographic analysis allows the selection of potential candidates for cancer drugs among natural substances.
Topics: Apoptosis; Cell Line, Tumor; Cell Proliferation; Cisplatin; Coumarins; Drug Synergism; Furocoumarins; Humans; Melanoma; Methoxsalen
PubMed: 33430369
DOI: 10.3390/ijms22020537