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International Journal of Molecular... Dec 2021Aqueous-ethanol extracts (70%) from the leaves of Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography...
Aqueous-ethanol extracts (70%) from the leaves of Regel. (Ranunculaceae Juss.)-collected from natural populations of Kyrgyzstan-were studied by liquid chromatography with high-resolution mass spectrometry (LC-HRMS). There was no variation of the metabolic profiles among plants that were collected from different populations. More than 160 compounds were found in the leaves, of which 72 were identified to the class level and 58 to the individual-compound level. The class of flavonoids proved to be the most widely represented (19 compounds), including six aglycones [quercetin, kaempferol, aromadendrin, 6-methoxytaxifolin, phloretin, and (+)-catechin] and mono- and diglycosides (the other 13 compounds). In the analyzed samples of , 14 fatty acid-related compounds were identified, but coumarins and furochromones that were found in were the most interesting result; furochromones khelloside, khellin, visnagin, and cimifugin were found in for the first time. Coumarins 5,7-dihydroxy-4-methylcoumarin, scoparone, fraxetin, and luvangetin and furochromones methoxsalen, 5--methylvisammioside, and visamminol-3'-O-glucoside were detected for the first time in the genus Salisb. For all the above compounds, the structural formulas are given. Furthermore, detailed information (with structural formulas) is provided on the diversity of chromones and furochromones in other representatives of . The presence of chromones in plants of the genus confirms its closeness to the genus L. because chromones are synthesized by normal physiological processes only in these members of the Ranunculaceae family.
Topics: Chromatography, Liquid; Chromones; Coumarins; Mass Spectrometry; Phytochemicals; Ranunculaceae
PubMed: 35008829
DOI: 10.3390/ijms23010406 -
PloS One 2012Two classes of F(420)-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium...
Two classes of F(420)-dependent reductases (FDR-A and FDR-B) that can reduce aflatoxins and thereby degrade them have previously been isolated from Mycobacterium smegmatis. One class, the FDR-A enzymes, has up to 100 times more activity than the other. F(420) is a cofactor with a low reduction potential that is largely confined to the Actinomycetales and some Archaea and Proteobacteria. We have heterologously expressed ten FDR-A enzymes from diverse Actinomycetales, finding that nine can also use F(420)H(2) to reduce aflatoxin. Thus FDR-As may be responsible for the previously observed degradation of aflatoxin in other Actinomycetales. The one FDR-A enzyme that we found not to reduce aflatoxin belonged to a distinct clade (herein denoted FDR-AA), and our subsequent expression and analysis of seven other FDR-AAs from M. smegmatis found that none could reduce aflatoxin. Certain FDR-A and FDR-B enzymes that could reduce aflatoxin also showed activity with coumarin and three furanocoumarins (angelicin, 8-methoxysporalen and imperatorin), but none of the FDR-AAs tested showed any of these activities. The shared feature of the compounds that were substrates was an α,β-unsaturated lactone moiety. This moiety occurs in a wide variety of otherwise recalcitrant xenobiotics and antibiotics, so the FDR-As and FDR-Bs may have evolved to harness the reducing power of F(420) to metabolise such compounds. Mass spectrometry on the products of the FDR-catalyzed reduction of coumarin and the other furanocoumarins shows their spontaneous hydrolysis to multiple products.
Topics: Aflatoxins; Anti-Bacterial Agents; Bacterial Proteins; Coumarins; Flavins; Furocoumarins; Gene Expression Regulation; Hydrolysis; Khellin; Mass Spectrometry; Methoxsalen; Mycobacterium smegmatis; Oxidoreductases; Phylogeny; Species Specificity; Xenobiotics
PubMed: 22383957
DOI: 10.1371/journal.pone.0030114 -
Experimental Dermatology Mar 2016Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in...
Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEV(P) (rp19/) (PSO) (4) is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro. In this study, we used heterozygous SNEV(+/-) mice (SNEV-knockout results in early embryonic lethality) and wild-type littermate controls as a model to elucidate the role of SNEV(P) (rp19/) (PSO) (4) in DNA damage repair and senescence in vivo. We performed PUVA treatment as model system for potently inducing cellular senescence, consisting of 8-methoxypsoralen in combination with UVA on mouse skin to induce DNA damage and premature skin ageing. We show that SNEV(P) (rp19/) (PSO) (4) expression decreases during organismal ageing, while p16, a marker of ageing in vivo, increases. In response to PUVA treatment, we observed in the skin of both SNEV(P) (rp19/) (PSO) (4) and wild-type mice an increase in γ-H2AX levels, a DNA damage marker. In old SNEV(P) (rp19/) (PSO) (4) mice, this increase is accompanied by reduced epidermis thickening and increase in p16 and collagenase levels. Thus, the DNA damage response occurring in the mouse skin upon PUVA treatment is dependent on SNEV(P) (rp19/) (PSO) (4) expression and lower levels of SNEV(P) (rp19/) (PSO) (4) , as in old SNEV(+/-) mice, result in increase in cellular senescence and acceleration of premature skin ageing.
Topics: Aging, Premature; Animals; Cellular Senescence; Collagen; Collagenases; Cyclin-Dependent Kinase Inhibitor p16; DNA Damage; Epidermis; Female; Genotype; Heterozygote; Histones; Male; Methoxsalen; Mice; Mice, Inbred C57BL; Mice, Knockout; PUVA Therapy; RNA Splicing Factors; Skin; Skin Aging
PubMed: 26663487
DOI: 10.1111/exd.12910 -
Molecules (Basel, Switzerland) Oct 2018Eight alkaloids (⁻) were isolated from , and their herbicide activities were evaluated through in vitro, semivivo, and in vivo assays. The most relevant results were...
Eight alkaloids (⁻) were isolated from , and their herbicide activities were evaluated through in vitro, semivivo, and in vivo assays. The most relevant results were observed for Compounds and ⁻ at 150 μM, which decreased dry biomass by 20% and 23%, respectively. These are significant results since they presented similar values with the positive control, commercial herbicide 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Based on the performed assays, Compound (graveoline) is classified as an electron-transport inhibitor during the light phase of photosynthesis, as well as a plant-growth regulator. On the other hand, Compounds ⁻ inhibited electron and energy transfers, and are also plant-growth inhibitors. These phytotoxic behaviors based on acridone and quinolone alkaloids may serve as a valuable tool in the further development of a new class of herbicides since natural products represent an interesting alternative to replace commercial herbicides, potentially due their low toxicity.
Topics: Alkaloids; Biomass; Diuron; Electron Transport; Herbicides; Methoxsalen; Photosynthesis; Ruta
PubMed: 30347671
DOI: 10.3390/molecules23102693 -
Journal of Food Protection Jun 2023In this research, we evaluated the aphicidal effect of the ethanolic extract of stems and bark of Ficus petiolaris Kunth (Moraceae), in laboratory bioassays in an...
In this research, we evaluated the aphicidal effect of the ethanolic extract of stems and bark of Ficus petiolaris Kunth (Moraceae), in laboratory bioassays in an artificial diet against apterous adult females of Melanaphis sacchari Zehntner (Hemiptera: Aphididae). The extract was evaluated at different concentrations (500, 1,000, 1,500, 2,000, and 2,500 ppm), and the highest percentage of mortality (82%) was found at 2,500 ppm after 72 h. The positive control imidacloprid (Confial®) at 1% eliminated 100% of the aphids, and the negative control (artificial diet) only presented mortality of 4%. The chemical fractionation of the stem and bark extract of F. petiolaris yielded five fractions of FpR1-5, which were each evaluated at 250, 500, 750, and 1,000 ppm. FpR2 had the strongest aphicidal effect, with 89% mortality at 72 h at 1,000 ppm. The pure xanthotoxin compound extracted from this fraction was even more effective, with 91% aphid mortality after 72 h at 100 ppm. The lethal concentration (LC) of xanthotoxin was 58.7 ppm (72 h). Our results indicate that the extract of F. petiolaris showed toxic activity against this aphid, and its xanthotoxin compound showed strong aphicidal activity at low concentrations.
Topics: Animals; Female; Aphids; Ficus; Methoxsalen; Sorghum; Plant Extracts
PubMed: 37019182
DOI: 10.1016/j.jfp.2023.100084 -
In Vivo (Athens, Greece) 2005It has been shown that cytochrome P450 enzymes (CYPs) and acetyltransferase can be used as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility.... (Comparative Study)
Comparative Study
BACKGROUND
It has been shown that cytochrome P450 enzymes (CYPs) and acetyltransferase can be used as biomarkers of carcinogen-DNA adduct levels and human cancer susceptibility. The gastrointestinal tract is the portal of entry of foreign compounds and presents xenobiotic metabolizing N-acetyltransferase (NAT) and CYPs activities. 5-Methoxypsoralen (5-MOP) has been used in combination with UV radiation in skin photochemotherapy for decades. A number of studies have demonstrated that 5-MOP is inhibitory towards mouse and human CYP isoforms, but investigations on the direct effects on NAT activity in laboratory animals and human cancer cells are limited. The main objective of this study was to document the effects of 5-MOP on the modulation of NAT activities in the stomach and colon of rats and human stomach and colon tumor cell lines.
MATERIALS AND METHODS
N-Acetylation of 2-aminofluorene (AF) to 2-acetylaminofluorene (AAF) by NAT in the stomach and colon of Sprague-Dawley (SD) rats and in human stomach (SC-M1) and colon (COLO 205) tumor cell lines was investigated.
RESULTS
The data show that the metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the further metabolism of AAF was slower in the stomach than in the colon. 5-MOP increased the activity of NATand also increased the further metabolism of AAF at 24 h in the rat stomach. In the rat colon, no statistically significant changes caused by 5-MOP were observed in NAT activity, but 5-MOP increased the further metabolism of AAF at 24 to 72 h. 5-MOP decreased the activity of NAT only at 72-h incubation in SC-M1 cells. In COLO 205 cells, however, 5-MOP decreased the activity of NAT between 24 h and 72 h. The optimal concentrations of 5-MOP to induce decreased NAT activity in SC-M1 cells were 0.05 mM to 25 mM. In COLO 205 cells, the data indicate that the higher the concentrations of 5-MOP, the higher the acetylation of AF; a promotion effect of NAT activity occured at a higher dose (50 mM) of 5-MOP and an inhibition effect occured at lower doses (0.05-0.5 mM) of 5-MOP, while concentrations of 5-25 mM of 5-MOP showed no significant difference compared with the control regimen.
CONCLUSION
The metabolic activity of NAT in the rat colon was higher than that in the rat stomach, and the results also showed a high degree of correspondence with SC-M1 cells and COLO 205 cells. 5-MOP more efficiently inhibited NAT activity in human stomach and colon tumor cell lines than in the stomach and colon of rats.
Topics: 2-Acetylaminofluorene; 5-Methoxypsoralen; Acetylation; Adenocarcinoma; Animals; Arylamine N-Acetyltransferase; Cell Line, Tumor; Colon; Colonic Neoplasms; Cytosol; Dose-Response Relationship, Drug; Enzyme Inhibitors; Fluorenes; Humans; Kinetics; Male; Methoxsalen; Rats; Rats, Sprague-Dawley; Stomach; Stomach Neoplasms
PubMed: 16277023
DOI: No ID Found -
Molecules (Basel, Switzerland) Apr 2022The objectives of this study were to investigate the melanogenetic potential of the psoralen derivatives 5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen,...
The objectives of this study were to investigate the melanogenetic potential of the psoralen derivatives 5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen in B16F10 melanoma cells. The results indicated that melanin production is significantly stimulated in B16F10 melanoma cells with 5-methoxypsoralen, 8-methoxypsoralen, and 5,8-dimethoxypsoralen, especially for 5-methoxypsoralen (bergapten), as reported previously. In addition, Western blot results showed that the protein levels of microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein-1 (TRP-1), and tyrosinase-related protein-2 (TRP-2) increase after bergapten treatment for the first time. The results also showed that bergapten promotes the phosphorylation of Akt at Ser 473 and glycogen synthase kinase-3β at Ser 9. Moreover, bergapten increased the content of β-catenin in the cell cytoplasm and nucleus by reducing the phosphorylated β-catenin (p-β-catenin) content. The results also indicated that bergapten regulates melanogenesis by upregulating the phosphorylation of p38 and JNK-mitogen-activated protein kinase. Taken together, these findings suggest that the regulation of melanogenesis by bergapten may be mediated by the β-catenin and MAPK signaling pathways and that bergapten might provide new insights into the pathogenesis of pigmented diseases.
Topics: 5-Methoxypsoralen; Animals; Cell Line, Tumor; Ficusin; Furocoumarins; Melanins; Melanoma; Melanoma, Experimental; Methoxsalen; Monophenol Monooxygenase; beta Catenin
PubMed: 35565964
DOI: 10.3390/molecules27092613 -
International Journal of Nanomedicine 20198-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and...
BACKGROUND
8-methoxypsoralen (8-MOP) is one of the most commonly utilized drugs in psoralen-ultraviolet A therapy for treatment of vitiligo. However, poor skin retention and systemic side effects limit the clinical application of 8-MOP.
METHODS
Microemulsions (MEs) and chitosan derivative-coated 8-MOP MEs were developed and compared for dermal delivery of 8-MOP. Ex vivo skin retention/permeation study was performed to select the ME formulation with the highest retention:permeation ratio. Four different chitosan-coated MEs were prepared and compared with the ME formulation for their ability to distribute 8-MOP in the skin.
RESULTS
Among various ME formulations developed, a formulation containing 2.9% ethyl oleate, 17.2% Cromophor EL35, 8.6% ethanol and 71.3% water showed the highest ex vivo skin retention:permeation ratio (1.98). Of four chitosan-coated MEs prepared, carboxymethyl chitosan-coated MEs (CC-MEs) and hydroxypropyl chitosan-coated MEs (HC-MEs) showed higher ex vivo skin retention:permeation ratio (1.46 and 1.84). and were selected for in vivo pharmacokinetic study. AUC (0-12 h) for 8-MOP MEs (4578.56 h·ng·mL) was higher than HC-MEs (3422.47 h·ng·mL), CC-MEs (2808.51 h·ng·mL) and tincture (1500.16 h·ng·mL). Also, AUCplasma (0-12 h) for MEs (39.35±13.90 h·ng·mL) was significantly lower than HC-MEs (66.32 h·ng·mL), CC-MEs (59.70 h·ng·mL) and tincture (73.02 h·ng·mL).
CONCLUSION
These combined results suggested that the MEs developed could be a promising and safe alternative for targeted skin delivery of 8-MOP.
Topics: Administration, Cutaneous; Animals; Chitosan; Drug Delivery Systems; Emulsions; Humans; Male; Methoxsalen; Microdialysis; Permeability; Rats, Sprague-Dawley; Skin; Skin Absorption; Swine
PubMed: 31015760
DOI: 10.2147/IJN.S191940 -
Toxicology and Applied Pharmacology Dec 2017Furanocoumarins derived from herbal and citrus extracts can act as antibacterial, antioxidant, immunomodulator, apoptotic, and selective anticancer agents, prompting a...
Furanocoumarins derived from herbal and citrus extracts can act as antibacterial, antioxidant, immunomodulator, apoptotic, and selective anticancer agents, prompting a biological investigation to determine and predict their clinical therapeutic significance. Here, the cell cytotoxic effects of bergapten and xanthotoxin were analyzed alone and in combination with standard chemotherapeutics on three multidrug resistant cells and their nonresistant parental counterparts. The furanocoumarins modulatory effects on MDR1, BCRP, and MRP pump expression and function were investigated. Although quantitative real time PCR demonstrated that the MDR transcript level changes in a time dependent manner, flow cytometric analyses using fluorescent-labeled antibodies have indicated that bergapten and xanthotoxin had no significant effect on the protein levels. FACS analyses indicated that these prominent anticancer agents significantly blocked MDR1, BCRP, and MRP transporter function. Maximum furanocoumarin-mediated pump activity blockage in the MDR-resistant cells was quantified as 87% of normal and consequently, chemotherapeutic accumulation increased up to 2.7-fold and cytotoxicity tension increased 104-fold. MDR1 efflux kinetics also revealed that the maximum velocity and the pump affinity to daunorubicin were uncompetitively decreased. We conclude that bergapten and xanthotoxin are cytotoxic agents capable of preventing daunorubicin, mitoxantrone, and cisplatin binding to ABC-transporters and subsequently inhibiting their efflux out of cells and they may be a potential combination therapy for malignant cancers.
Topics: 5-Methoxypsoralen; ATP Binding Cassette Transporter, Subfamily B; ATP Binding Cassette Transporter, Subfamily G, Member 2; ATP-Binding Cassette Transporters; Antineoplastic Agents, Phytogenic; Cell Proliferation; Cell Survival; Cisplatin; Daunorubicin; Dose-Response Relationship, Drug; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Humans; Kinetics; MCF-7 Cells; Methoxsalen; Mitoxantrone; Multidrug Resistance-Associated Protein 2; Multidrug Resistance-Associated Proteins; Neoplasm Proteins; Neoplasms
PubMed: 29079042
DOI: 10.1016/j.taap.2017.10.018 -
The Journal of Investigative Dermatology Sep 1961
Topics: Dermatitis, Phototoxic; Methoxsalen; Photosensitivity Disorders
PubMed: 13693837
DOI: No ID Found