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This article explores the synthesis of methyl-substituted psoralen derivatives and their potential for DNA photocrosslinking. Psoralen is a natural compound used in skin disease treatment, but it can have toxic and mutagenic effects. The researchers aimed to enhance the reactivity of psoralen and control crosslinked product formation by adding methyl substituents at specific positions. They developed a synthetic method for creating psoralen derivatives and tested their photocrosslinking abilities with DNA. The results showed that the presence of methyl substituents reduced the formation of harmful diadducts. The article suggests further research to explore different psoralen derivatives and investigate their photocrosslinking properties. [Extracted from the article]

Background. System pharmacological approaches play important roles in drug discovery and development and in biomolecular exploration to investigate the multitarget therapeutic effects of phytochemicals for the treatment of acute and chronic ailments. Objectives. The aim of the study was to apply a system pharmacological approach to investigate the multitarget therapeutic effects of furocoumarins of Apium graveolens L. for the treatment of kidney disease. Methods. Several furocoumarins of Apium graveolens were screened from online databases. Network biology and poly-pharmacology analyses were performed to investigate the multitarget therapeutic effect of furocoumarins. The potential metabolites that showed significant interactions with various genes were selected for in silico docking analysis with CASP-3 and SOD proteins. In silico ADME analysis was also performed to investigate the pharmacokinetic behavior of targeted furocoumarins. Results. Out of thirteen furocoumarins selected for analysis, six showed partial or significant interaction with SOD and CASP-3 proteins. These metabolites may alleviate kidney dysfunction by reducing oxidative and inflammatory stress, regulating apoptosis, slowing down the progression of diabetic nephropathy, and reducing hypertension and glomerular vascular rigidity. In silico docking analysis revealed bergapten as a potential therapeutic agent for kidney disease treatment. In silico docking analysis showed anglicine, imperatorin, and sphondin exhibited strong interaction with CASP-3 and SOD with binding energy −6.5, −7.2, −6.5 and −6.8, −6.2 −5.7 kcal/mol, respectively. These components exhibited greater conventional hydrogen bonding with CASP-3 and SOD than other furocoumarins. Furthermore, in silico ADME analysis of metabolites showed that all furocoumarins have a highly lipophilic nature, good skin permeability, and GI absorption, as well as good blood-brain permeability (BBB). Conclusion. Furocoumarins reduce kidney dysfunction and associated pathophysiological complications via the reduction of glomerular vascular rigidity, diabetic nephropathy, and oxidative and inflammatory stress. However, further biomolecular and clinical examinations are necessary to validate and enhance the credibility of present findings. [ABSTRACT FROM AUTHOR]

Psoralens are eponymous for PUVA (psoralen plus UV-A radiation) therapy, which inter alia can be used to treat various skin diseases. Based on the same underlying mechanism of action, the synthetic psoralen amotosalen (AMO) is utilized in the pathogen reduction technology of the INTERCEPT® Blood System to inactivate pathogens in plasma and platelet components. The photophysical behavior of AMO in the absence of DNA is remarkably similar to that of the recently studied psoralen 4′-aminomethyl-4,5′,8-trimethylpsoralen (AMT). By means of steady-state and time-resolved spectroscopy, intercalation and photochemistry of AMO and synthetic DNA were studied. AMO intercalates with a higher affinity into A,T-only DNA (KD = 8.9 × 10−5 M) than into G,C-only DNA (KD = 6.9 × 10−4 M). AMO covalently photobinds to A,T-only DNA with a reaction quantum yield of ΦR = 0.11. Like AMT, it does not photoreact following intercalation into G,C-only DNA. Femto- and nanosecond transient absorption spectroscopy reveals the characteristic pattern of photobinding to A,T-only DNA. For AMO and G,C-only DNA, signatures of a photoinduced electron transfer are recorded. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is a common opportunistic pathogen with growing resistance and presents heightened treatment challenges. Quorum sensing (QS) is a cell-to-cell communication system that contributes to the production of a variety of virulence factors and is also related to biofilm formation of P. aeruginosa. Compared to traditional antibiotics which kill bacteria directly, the anti-virulence strategy by targeting QS is a promising strategy for combating pseudomonal infections. In this study, the QS inhibition potential of the compounds derived from the Traditional Chinese Medicines was evaluated by using in silico, in vitro, and in vivo analyses. The results showed that psoralen, a natural furocoumarin compound derived from Psoralea corylifolia L., was capable of simultaneously inhibiting the three main QS regulators, LasR, RhlR, and PqsR of P. aeruginosa. Psoralen had no bactericidal activity but could widely inhibit the production of extracellular proteases, pyocyanin, and biofilm, and the cell motilities of the model and clinical P. aeruginosa strains. RNA-sequencing and quantitative PCR analyses further demonstrated that a majority of QS-activated genes in P. aeruginosa were suppressed by psoralen. The supplementation of psoralen could protect Caenorhabditis elegans from P. aeruginosa challenge, especially for the hypervirulent strain PA14. Moreover, psoralen showed synergistic antibacterial effects with polymyxin B, levofloxacin, and kanamycin. In conclusions, this study identifies the anti-QS and antibiofilm effects of psoralen against P. aeruginosa strains and sheds light on the discovery of anti-pseudomonal drugs among Traditional Chinese Medicines. Key points: • Psoralen derived from Psoralea corylifolia L. inhibits the virulence-related phenotypes of P. aeruginosa. • Psoralen simultaneously targets the three core regulators of P. aeruginosa QS system and inhibits the expression of a large part of downstream genes. • Psoralen protects C. elegans from P. aeruginosa challenge and enhances the susceptibility of P. aeruginosa to antibiotics. [ABSTRACT FROM AUTHOR]

Being an important constituent of naturally occurring heterocyclic compounds with a myriad of interesting biological activities, the furocoumarin motif has claimed vast interest in synthetic and medicinal research. Designing organic synthesis following a green and sustainable approach finds special importance in terms of energy efficiency, and cost‐effectiveness and hence becoming an important domain of research in the recent past. The methodologies for the sustainable synthesis of furocoumarin presented here particularly include the strategies developed under microwave irradiation, solvent‐free conditions or uses of green solvent, metal‐free routes, room temperature mediated and following one‐pot MCR reactions. This review article attempts to highlight the recent advances in the sustainable synthesis of furocoumarins along with general aspects like natural occurrence, and biological activities of this particular heterocyclic scaffold. [ABSTRACT FROM AUTHOR]

Citrus essential oils (EOs) contain a variety of secondary metabolites, including coumarins (Cs), furocoumarins (FCs) and polymethoxyflavones (PMFs), all with different biological activities. While Regulation (EC) No 1334/2008 strictly regulates the use of coumarins, undesirable side effects of consuming furocoumarins remain without established maximum toxicity limits for human dietary intake. This study is based on an in‐silico approach aimed at determining these toxicity limits for the oxygenated heterocyclic compounds of citrus EOs approved for use in food. In addition, an innovative quantitative structure‐property relationship (QSPR) using the linear retention index system was explored to characterize the oxygenated heterocyclic compounds (COHs) present in these essential oils. Molecular docking of the studied compounds provided crucial insights into the structure‐odor relationships, offering insights into their mechanisms of action. In addition, an analysis of the pharmacokinetic and pharmacodynamic properties through ADME‐Tox deconstruction provides insight into the potential side effects of their consumption. The results are consolidated by dynamic simulations, providing crucial data for the development of regulations on the maximum toxicity limits of citrus EOs, given the health implications of the various compounds such as coumarins, furocoumarins and polymethoxyflavones present in these essential oils. [ABSTRACT FROM AUTHOR]

Bergaptol (5-hydroxypsoralen or 5-hydroxyfuranocoumarin) is a naturally occurring furanocoumarin widely found in citrus fruits, which has multiple health benefits. Nonetheless, no specific review articles on bergaptol have been published. Compiling updated information on bergaptol is crucial in guiding future research direction and application. The present review focuses on the research evidence related to the pharmacological properties and toxicity of bergaptol. Bergaptol has anti-inflammatory, antioxidant, anti-cancer, anti-osteoporosis, anti-microbial, and anti-lipidemic effects. It can inhibit the activities of cytochrome P450s (CYP), especially CYP2C9 and CYP3A4, thereby affecting the metabolism and concentrations of some drugs and toxins. Compared with other coumarins, bergaptol has the least potency to inhibit CYP3A4 in cancer cells. Instead, it can suppress drug efflux transporters, such as P-glycoprotein, thereby overcoming chemotherapeutic drug resistance. Furthermore, bergaptol has antimicrobial effects with a high potential for inhibition of quorum sensing. In vivo, bergaptol can be retained in plasma for longer than other coumarins. Nevertheless, its toxicity has not been clearly reported. In vitro study suggests that, unlike most furocoumarins, bergaptol is not phototoxic or photomutagenic. Existing research on bergaptol has mostly been conducted in vitro. Further in vivo and clinical studies are warranted to identify the safe and effective doses of bergaptol for its multimodal application. [ABSTRACT FROM AUTHOR]

The data on the structure, photochemical and photophysical properties of furocoumarins (psoralens) and their analogs are collected and systemized in this review. Current points of view about the role of triplet states and reactions of [2+2]-photocycloaddition in the coupling of these compounds with biomacromolecules (DNA, proteins, lipids) upon photoexcitation by the light of the UV-A range (320‒400 nm), as well as electron transfer and reactions of the furocoumarin triplets with oxygen to afford active oxygen structures, are presented. The interaction of furocoumarin triplets with biomacromolecules is a basis of photochemotherapy (PUVA therapy). The use of furocoumarins of natural origin in the PUVA therapy has revealed a series of unwanted side effects. Therefore, in recent years, attempts have been made to synthesize new compounds for photochemotherapy. The current state of the art in these studies is considered in the review: these are modified psoralens, derivatives of angular furocoumarins, angelicine and allopsoralen, and nitrogen-containing psoralen isosteres, furoquinolinones and furodihydroquinolines. [ABSTRACT FROM AUTHOR]

[Objectives] To explore the effect of psoralen combined with paclitaxel on the apoptosis of MCF-7 cells. [Methods] The effects of different concentrations of psoralen, paclitaxel, or the combination of psoralen and paclitaxel on cell viability were detected using CCK-8 as- say kit. Cell cycle distribution and apoptosis after 24 h of psoralen (0.16, 0.32, 0.64 mmol/L), paclitaxel (0.1 µmol/L), combined action of psoralen (0.32 mmol/L) and paclitaxel (0.1 µmol/L) were detected using flow cytometry. [Results] Lower concentration of psoralen (0.04-0.32 mmol/L) showed no significant inhibitory effect on cells. After combined with paclitaxel, the inhibitory effect on MCF-7 cell proliferation was significantly higher than that of the group treated alone. Compared with the paclitaxel group, the cell apoptosis rate in the drug combination group was significantly increased. Different low concentrations of psoralen can block the cell cycle of MCF-7 at Go/G, phase, while paclitaxel can block the cell cycle at G₂/M phase. After combined action, the number of cells blocked at G₂/M phase decreased. [Conclusions] Overall, the combined effect of psoralen and paclitaxel can enhance anti-tumor ability by inhibiting cell proliferation, inducing apoptosis, and blocking cell cycle. [ABSTRACT FROM AUTHOR]

Citrus essential oils, thanks to their pleasant aroma, are certainly the most used ingredients in the formulation of hydroalcoholic fragrances. The non-volatile fraction of Citrus essential oil is composed for 10–20% of coumarins, furocoumarins and polymethoxyflavones. It is well known that furocoumarins induce photosensitization and have potential carcinogenic and mutagenic effects. It follows that furocoumarins levels in cosmetics product are constantly monitored by opinions and regulations issued by the International Fragrance Association. The aim of this research article was to quantify coumarins, furocoumarins and polymethoxyflavones in thirty commercial hydroalcoholic fragrances using supercritical fluid chromatography in combination with triple quadrupole mass spectrometry technique (SFC-QqQ-MS). According to author's knowledge, this is the first report on the determination of oxygen heterocyclic compounds in hydroalcoholic fragrances by means of SFC-QqQ-MS technique. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to provide data for the type and content of linear furocoumarins (FCs) in Angelica dahurica (AD) in order to assess their cumulative risks and provide a scientific basis for the rational use and quality evaluation of the medicinal AD to improve public health. Methods: A UPLC method was developed for the simultaneous determination of nine FCs initially by using imperatorin (Im) as the internal standard substance, including Im, phellopterin (Ph), isoimperatorin (Is), oxypeucedanin hydrate (Oh), byakangelicin (Bn), xanthotoxin (8-MOP), bergapten (5-MOP), byakangelicol (Bl), and oxypeucedanin (Op) in two species of Angelica dahurica (AD). And, the risk assessment for the total FCs in AD was explored using the hazard index combined with the toxic equivalency factor (TEF-HI) strategy for the first time. Results: The established method revealed acceptable applicability, and there were no significant differences compared with the external standard method (ESM). The quantitative results demonstrated that the total content of FCs in Angelica dahurica (BZ) were higher than that in Angelica dahurica var. formosana (HBZ), and there was a great difference between the Bl and Op. Moreover, the risk assessment data revealed that the risk of total FCs in AD to human health was low. Conclusions: The established UPLC method that determined nine FCs in AD using a single marker could solve the problem of difficulty in obtaining a chemical reference substance with high purity and requiring a long determination time. And, the TEF-HI risk assessment approach associated with FCs in ADs could guide the rational utilization of toxic FCs in ADs in the progress of improving public health safety. In short, the whole systematic strategy provides a scientific basis for rational quality evaluation and the healthy use of related herbal medicines. [ABSTRACT FROM AUTHOR]

The role of psoralen (PS), a major active component extracted from Psoralea corylifolia L. seed, in renal fibrosis is still unclear. Thus, the objective of this study was to evaluate the effects of PS on the development and progression of renal fibrosis induced by unilateral ureteral obstruction (UUO) in a mouse model. Mice were divided into four groups: PS (20 mg/kg, i.g., n = 5), PS + sham (n = 5), UUO (n = 10), and PS + UUO (n = 10). PS was intragastrically administered 24 h before UUO and continued afterwards for 7 days. All mice were killed 7 days post UUO. Severe tubular atrophy, tubular injury, and tubulointerstitial fibrosis (TIF) were significantly developed in UUO mice. A higher expression of transforming growth factor-β1 (TGF-β1) was accompanied by elevated levels of α-smooth muscle actin (α-SMA) and phosphorylated Smad2/3 (pSmad2/3) at 7 days post UUO. However, PS treatment reduced tubular injury, interstitial fibrosis, and the expression levels of TGF-β1, α-SMA, and pSmad2/3. Furthermore, the levels of macrophages (represented by F4/80 positive cells) and the inflammasome, reflected by inflammasome markers such as nucleotide-binding and oligomerization domain-like receptors protein 3 (NLRP3) and cleaved caspase1 (cCASP-1), were significantly decreased by PS treatment. These results suggest that PS merits further exploration as a therapeutic agent in the management of chronic kidney disease (CKD). [ABSTRACT FROM AUTHOR]

The treatment of periodontitis focuses on controlling the progression of inflammation, reducing plaque accumulation, and promoting bone tissue reconstruction. Among them, the reconstruction of irregular bone resorption caused by periodontitis is a long‐standing challenge. At present, the local drug treatment of periodontitis is mainly anti‐inflammatory and antibacterial drugs. In this study, psoralen (Pso), a Chinese herbal medicine with anti‐inflammatory, antibacterial, and osteogenic effects, was selected for the local treatment of periodontitis. Meanwhile, an injectable methacrylate gelatin (GelMA) platform loading with Pso was constructed. Pso‐GelMA had the properties of fluidity, light cohesion, self‐healing, and slow release, which could be better used in the deep and narrow structure of the periodontal pocket, and greatly increased the effectiveness of local drug delivery. The pore size of Gelma hydrogel did not change after loading Pso by SEM. In vitro, Pso‐GelMA effectively upregulated the expression of osteogenic genes and proteins, increased alkaline phosphatase activity, promoted the mineralisation of rat bone marrow mesenchymal stem cells (BMSCs) extracellular matrix, and had significant antibacterial effects on Staphylococcus aureus and Fusobacterium nucleatum. Therefore, Pso‐GelMA has immense promise in the adjuvant treatment of periodontitis. [ABSTRACT FROM AUTHOR]

H atoms on C atoms were fixed geometrically and refined using a rider model with fixed isotropic shift parameters I U i SB I iso i sb = n I U i SB I eq i sb , where n = 1.5 for methyls and 1.2 for others ( I U i SB I eq i sb is the equivalent isotropic shift parameter of the corresponding C atoms). The other planar prenyl fragment of the molecule was situated practically perpendicular to the tricyclic coumarin plane as indicated by torsion angles C2'-C1'-O4-C1" (177°) and C1'-O4-C1"-C2" (178°). The crystal of B 5 b had intermolecular H-bonds between the hydroxyl H atom and the carbonyl O atom (O4-H...O1) of molecules transformed by a center of symmetry. Unit-cell constants of crystals of B 3 b and B 5 b were determined and refined on an HPC XtaLAB Synergy diffractometer (Rigaku, Japan) using Cu K I i -radiation (T = 293 K) [[17]]; I a i = 6.7474(1), I b i = 7.2728(2), I c i = 17.8720(4) Å; I i = 100.390(2)°; V = 862.64(3) Å SP 3 sp ; I P i 2 SB 1 sb ; I Z i = 2 for B 3 b and I a i = 6.8403(3), I b i = 7.9425(5), I c i = 8.3065(4) Å; I i = 84.995(4), I i = 82.508(4), I i = 76.093(5)°; V = 433.58(4) Å SP 3 sp ; P-1, I Z i = 2 for B 5 b . [Extracted from the article]

Anti-neoplastic effect of DNA cross-linking agents such as cisplatin, mitomycin C, and psoralen is attributed to their ability to induce DNA interstrand cross-links (ICLs), which block replication, transcription, and linear repair pathways by preventing DNA strand separation and trigger apoptosis. It is generally agreed that the Fanconi anemia (FA) pathway orchestrates the removal of ICLs by the combined actions of various DNA repair pathways. Recently, attention has been focused on the ability of the NEIL3-initiated base excision repair pathway to resolve psoralen- and abasic site-induced ICLs in an FA-independent manner. Intriguingly, overexpression of NEIL3 is associated with chemo-resistance and poor prognosis in many solid tumors. Here, using loss- and gain-of-function approaches, we demonstrate that NEIL3 confers resistance to cisplatin and participates in the removal of cisplatin–DNA adducts. Proteomic studies reveal that the NEIL3 protein interacts with the 26S proteasome in a cisplatin-dependent manner. NEIL3 mediates proteasomal degradation of WRNIP1, a protein involved in the early step of ICL repair. We propose that NEIL3 participates in the repair of ICL-stalled replication fork by recruitment of the proteasome to ensure a timely transition from lesion recognition to repair via the degradation of early-step vanguard proteins. [ABSTRACT FROM AUTHOR]

Background: Bituminaria bituminosa is a long-day plant. The plant has a high pastoral value and palatability. It is grazed by cattle, goats and sheep. Leaves and stems contain four furanocoumarins' psoralen, angelicin, xanthotoxin and bergapten. The seed is covered by the fruit. Germination was not observed in beaked fruits. A cut with a scalpel can increase the germination rate. According to the literature there are not enough studies about the culture media and convenient conditions. Methods: In our study, we tried six medium for callus production with different hormone concentrations including 2,4-D, BAP and kinetin. In this study, a protocol for callus induction and analysis of isoflavonoids and terpenes of Bituminaria bituminosa has been developed. Result: Maximum callus induction frequency was observed on Murashige and Skoog (MS) medium supplemented with 0.75 mg/L 2,4-D + 2.5 mg/L kinetin in young primary leaves. 0.75 mg/L 2,4-D+2.5 mg/L kinetin medium is more successful in the production ofses of flavonoids that can be produced in vitro and is more successful in producing phenols. In terpene production, it is seen that 1.25 mg/L 2,4-D+3.5 mg/L BAP, which is the best callus producing medium containing BAP, is the most successful medium among all tested mediums. [ABSTRACT FROM AUTHOR]

Possible enhancements of DNA damage with light of different wavelengths and ionizing radiation (Rhenium-188—a high energy beta emitter (Re-188)) on plasmid DNA and FaDu cells via psoralen were investigated. The biophysical experimental setup could also be used to investigate additional DNA damage due to photodynamic effects, resulting from Cherenkov light. Conformational changes of plasmid DNA due to DNA damage were detected and quantified by gel electrophoresis and fluorescent staining. The clonogene survival of the FaDu cells was analyzed with colony formation assays. Dimethyl sulfoxide was chosen as a chemical modulator, and Re-188 was used to evaluate the radiotoxicity and light (UVC: λ = 254 nm and UVA: λ = 366 nm) to determine the phototoxicity. Psoralen did not show chemotoxic effects on the plasmid DNA or FaDu cells. After additional treatment with light (only 366 nm—not seen with 254 nm), a concentration-dependent increase in single strand breaks (SSBs) was visible, resulting in a decrease in the survival fraction due to the photochemical activation of psoralen. Whilst UVC light was phototoxic, UVA light did not conclude in DNA strand breaks. Re-188 showed typical radiotoxic effects with SSBs, double strand breaks, and an overall reduced cell survival for both the plasmid DNA and FaDu cells. While psoralen and UVA light showed an increased toxicity on plasmid DNA and human cancer cells, Re-188, in combination with psoralen, did not provoke additional DNA damage via Cherenkov light. [ABSTRACT FROM AUTHOR]

Patients with early stage cutaneous T cell lymphoma (CTCL) usually have a benign and chronic disease course, characterized by temporally response to conventional skin directed therapies and intrinsic possibility to evolve. Using the combination of psoralen plus ultraviolet A irradiation (PUVA) and low‐dose interferon‐α (INF), the principal treatment goal is to keep confined the disease to the skin, preventing disease progression. Among 87 patients with early stage IA to IIA MF treated with low‐dose IFN‐α2b and PUVA in our center, complete remission (CR) were reported in 70 patients (80.5%) and the overall response rate (ORR) was 97.8% (n = 85), with a median time to best response to therapy of 5 months (range, 1–30). Among the responders, only the 8% of patients had a relapse with major event. The median follow‐up was 207 months (range, 6–295). Survival data showed a median overall survival (OS) not reached (95% CI; 235‐NR months), a disease free survival (DFS) of 210 months (95% CI; 200–226 months) and a median time to next treatment (TTNT) of 38.5 months (95% CI, 33–46 months). The long follow up of this study verifies our preliminary results already published in 2006 and confirms the efficacy of INF‐PUVA combination therapy in a real world setting, according conventional (OS and DFS) and emerging (TTNT) clinical endpoint of treatment efficacy. [ABSTRACT FROM AUTHOR]

High biological activity of natural furocoumarins is often linked to a series of adverse side effects, e.g., genotoxicity. This makes it desirable to develop semi-synthetic derivatives with reduced negative activity while retaining or even enhancing the positive properties. Previously, we have studied the genotoxic activity of a library of twenty-one 1,2,3-triazolyl-modified furocoumarins and 2,3-dihydrofurocoumarins and identified modifications that minimize the negative properties. In the current article, we report on an investigation into the cytotoxic activity of the same library. We have aimed to rank the substances in order of the severity of their cytotoxicity and therefore to predict, with the use of statistical processing, the most promising substituents for the furocoumarin scaffold. [ABSTRACT FROM AUTHOR]

Psoralen derivatives are well known for their unique phototoxicity and also exhibits promising anti-breast cancer activity both in the presence and the absence of UVA irradiation. However, the structure–activity relationship on this scaffold remains lacking. Herein, a series of psoralen derivatives with various C-5 substituents were synthesized and evaluated for their in vitro dark and light-activated cytotoxicity against three breast cancer cell lines: MDA-MB-231, T47-D, and SK-BR-3. The type of substituents dramatically impacted the activity, with the 4-bromobenzyl amide derivative (3c) exhibiting the highest dark cytotoxicity against T47-D (IC50 = 10.14 µM), with the activity comparable to those of the reference drugs (doxorubicin, 1.46 µM; tamoxifen citrate, 20.86 µM; lapatinib 9.78 µM). On the other hand, the furanylamide 3g exhibits the highest phototoxicity against SK-BR-3 cells with the IC50 of 2.71 µM, which is almost tenfold increase compared to the parent compound, methoxsalen. Moreover, these derivatives showed exceptional selectivity towards HER2+ (SK-BR-3) over the HER2− (MDA-MB-231) breast cancer cell lines, which correlates well with the results from the molecular docking study, revealing that 3g formed favorable interactions within the active site of the HER2. Additionally, the cell morphology of SK-BR-3 cells suggested that the significant phototoxicity was related to induction of cell apoptosis. Most of the synthesized psoralen derivatives possess acceptable physicochemical properties and are suitable for being further developed as a novel anti-breast cancer agent in the future. [ABSTRACT FROM AUTHOR]

The level of bioactive metabolites is the most critical factor to become a functional food material. This study offered the practical method to enhance furanocoumarins (FCs) content in Angelica acutiloba which is an herbal vegetable and functional food ingredient. FCs content in root part was significantly increased by the treatment of the signaling molecule, ethylene. Newly increased FC derivatives were annotated as xanthotoxin (XAT), psoralen (PSR), isopimpinellin (IPP), and bergapten (BGT). The contents of FCs continued to increase until they reached the level where XAT (54-fold, 64.9 μg/g → 3499 μg/g), PSR (7-fold, 31.9 μg/g → 214 μg/g), IPP (23-fold, 16.2 μg/g → 375 μg/g), and BGT (51-fold, 29.5 μg/g → 1512 μg/g). Hereby, the content of FC derivatives increased selectively, and other metabolites were not affected by ethylene. The metabolite changes were systematically investigated using UPLC-ESI-Q-TOF/MS analysis to obtain a clear difference in the PLS-DA score, S-plot, and heatmap to explain the gradual fluctuation in the metabolite levels over the treatment time (96 h). Additionally, FCs enriched roots showed a distinctive inhibitory activity against monoamine oxidase (MAO-A and B) compared to control roots because of the increased FCs content. A. acutiloba with greatly enhanced FCs content is applicable as functional food material for new purposes. [Display omitted] • Furanocoumarins enriched Angelica acutiloba roots. • Monoamine oxidase inhibition of Angelica acutiloba roots. • Selective induction of furanocoumarins by ethylene. • Systematic investigation of the changes in metabolites of A. acutiloba roots. [ABSTRACT FROM AUTHOR]

Bo-Feng Yin, Zhi-Ling Li, Zi-Qiao Yan, Zheng Guo, Jia-Wu Liang have contributed equally to this work Correction to: Stem Cell Research & Therapy (2022) 13:241 https://doi.org/10.1186/s13287-... Following publication of the original article [[1]], the authors have identified that the incorrect image of micro-CT scanning for normal group in Fig. Psoralen alleviates radiation-induced bone injury by rescuing skeletal stem cell stemness through AKT-mediated upregulation of GSK-3 and NRF2. Correction to: Psoralen alleviates radiation-induced bone injury by rescuing skeletal stem cell stemness through AKT mediated up-regulation of GSK-3 and NRF2. [Extracted from the article]

Background: Repairing radiation-induced bone injuries remains a significant challenge in the clinic, and few effective medicines are currently available. Psoralen is a principal bioactive component of Cullen corylifolium (L.) Medik and has been reported to have antitumor, anti-inflammatory, and pro-osteogenesis activities. However, less information is available regarding the role of psoralen in the treatment of radiation-induced bone injury. In this study, we explored the modulatory effects of psoralen on skeletal stem cells and their protective effects on radiation-induced bone injuries. Methods: The protective effects of psoralen on radiation-induced osteoporosis and irradiated bone defects were evaluated by microCT and pathological analysis. In addition, the cell proliferation, osteogenesis, and self-renewal of SSCs were explored. Further, the underlying mechanisms of the protective of psoralen were investigated by using RNA sequencing and functional gain and loss experiments in vitro and in vivo. Statistical significance was analyzed using Student's t test. The one-way ANOVA was used in multiple group data analysis. Results: Here, we demonstrated that psoralen, a natural herbal extract, mitigated radiation-induced bone injury (irradiation-induced osteoporosis and irradiated bone defects) in mice partially by rescuing the stemness of irradiated skeletal stem cells. Mechanistically, psoralen restored the stemness of skeletal stem cells by alleviating the radiation-induced suppression of AKT/GSK-3β and elevating NRF2 expression in skeletal stem cells. Furthermore, the expression of KEAP1 in skeletal stem cells did not significantly change in the presence of psoralen. Moreover, blockade of NRF2 in vivo partially abolished the promising effects of psoralen in a murine model of irradiation-induced osteoporosis and irradiated bone regeneration. Conclusions: In summary, our findings identified psoralen as a potential medicine to mitigate bone radiation injury. In addition, skeletal stem cells and AKT-GSK-3β and NRF2 may thus represent therapeutic targets for treating radiation-induced bone injury. [ABSTRACT FROM AUTHOR]

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-β-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-β-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-β-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-β-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-β-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo. [ABSTRACT FROM AUTHOR]

Psoralen is the main coumarin component of Fructus psoraleae. Previously, we have found that psoralen induced hepatocytes apoptosis via PERK and ATF6 related ER stress pathways in vitro. In this study, we investigated the toxicity and ER stress induced by psoralen in female C57 mice. Mice were fed with 80 mg/kg of psoralen intra-gastrically for either 3, 7, or 21 days. Liver and kidney were weighed and their coefficients were calculated. The serum was isolated to examine the biochemical parameters including alanine aminotransferase (ALT) activity, aspartate aminotransferase (AST) activity, alkaline phosphatase (ALP) activity, blood urea nitrogen (BUN), total bile acid (TBA), total bilirubin (TBIL), and creatinine (CRE). The transcription and expression of ER stress-related markers were determined by Wes-automated Protein Simple system, Western blot and RT-PCR. Psoralen administration for 3 days significantly increased liver coefficients but decreased kidney coefficients of mice. Histopathological examination showed minimal inflammatory cell foci and vacuolar degeneration in the liver. Besides, serum levels of ALT, TBA, BUN, and CRE were markedly altered by psoralen. Moreover, psoralen significantly increased expression and transcription levels of ER stress related markers, including Grp78, PERK, eIF2α, ATF4, IRE1α, ATF6, and XBP1. These results illustrated that psoralen induced liver injuries through ER stress signaling in female mice. [ABSTRACT FROM AUTHOR]

Background: Repairing radiation-induced bone injuries remains a significant challenge in the clinic, and few effective medicines are currently available. Psoralen is a principal bioactive component of Cullen corylifolium (L.) Medik and has been reported to have antitumor, anti-inflammatory, and pro-osteogenesis activities. However, less information is available regarding the role of psoralen in the treatment of radiation-induced bone injury. In this study, we explored the modulatory effects of psoralen on skeletal stem cells and their protective effects on radiation-induced bone injuries. Methods: The protective effects of psoralen on radiation-induced osteoporosis and irradiated bone defects were evaluated by microCT and pathological analysis. In addition, the cell proliferation, osteogenesis, and self-renewal of SSCs were explored. Further, the underlying mechanisms of the protective of psoralen were investigated by using RNA sequencing and functional gain and loss experiments in vitro and in vivo. Statistical significance was analyzed using Student's t test. The one-way ANOVA was used in multiple group data analysis. Results: Here, we demonstrated that psoralen, a natural herbal extract, mitigated radiation-induced bone injury (irradiation-induced osteoporosis and irradiated bone defects) in mice partially by rescuing the stemness of irradiated skeletal stem cells. Mechanistically, psoralen restored the stemness of skeletal stem cells by alleviating the radiation-induced suppression of AKT/GSK-3β and elevating NRF2 expression in skeletal stem cells. Furthermore, the expression of KEAP1 in skeletal stem cells did not significantly change in the presence of psoralen. Moreover, blockade of NRF2 in vivo partially abolished the promising effects of psoralen in a murine model of irradiation-induced osteoporosis and irradiated bone regeneration. Conclusions: In summary, our findings identified psoralen as a potential medicine to mitigate bone radiation injury. In addition, skeletal stem cells and AKT-GSK-3β and NRF2 may thus represent therapeutic targets for treating radiation-induced bone injury. [ABSTRACT FROM AUTHOR]

Using repositioning to find new indications for existing functional substances has become a global target of research. The objective of this study is to investigate the anti-inflammatory potential of psoralen derivatives (5-hydroxypsoralen, 5-methoxypsoralen, 8-hydroxypsoralen, and 8-methoxypsoralen) in macrophages cells. The results indicated that most psoralen derivatives exhibited significantly inhibited prostaglandin E2 (PGE2) production, particularly for 8-hydroxypsoralen (xanthotoxol) in lipopolysaccharide (LPS)-stimulated macrophage RAW 264.7 cells. In addition, xanthotoxol treatment decreased the PGE2, IL-6, and IL-1β production caused by LPS stimulation in a concentration-dependent manner. Moreover, Western blot results showed that the protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), which activated with LPS treatment, were decreased by xanthotoxol treatment. Mechanistic studies revealed that xanthotoxol also suppressed LPS-stimulated phosphorylation of the inhibitor of κBα (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in RAW 264.7 cells. The Western blot assay results show that xanthotoxol suppresses LPS-induced p65 translocation from cytosol to the nucleus in RAW 264.7 cells. Moreover, we tested the potential application of xanthotoxol as a cosmetic material by performing human skin patch tests. In these tests, xanthotoxol did not induce any adverse reactions at a 100 μΜ concentration. These results demonstrate that xanthotoxol is a potential therapeutic agent for topical application that inhibits inflammation via the MAPK and NF-κB pathways. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The impact of naturally occurring furocoumarins on essential agrumen oils, namely bergamot, lime and, lemon, was investigated upon exposure to UV-A light. For this purpose, the oils were initially freed from furocoumarins and coumarins by precipitation in cold hexane. Such pretreated oils, as well as samples of these oils spiked with separated furocoumarins were irradiated for up to 10 days. All essential oils devoid of furocoumarins showed a massive degradation of the predominant terpenes R-(+)-limonene and γ-terpinene. For lime and lemon essential oils 10% and 7.5% of the initial R-(+)-limonene amount was degraded within 10 days, respectively. In addition, a noticeable hydroperoxide formation was observed. For γ-terpinene, this effect was even more pronounced and in both, lime and lemon essential oil samples, the terpene was entirely converted into p-cymene after 6 days. In comparison, addition of 5% furocoumarins to the essential oils decelerated the photo degradation of R-(+)-limonene and γ-terpinene by up to one order of magnitude. The protective effect of furocoumarins, presumably due to bathochromic shifts of emitted light to less harmful longer wavelengths, also improved the olfactory quality. The results demonstrate that blends of non-volatile furocoumarins and volatile terpenes extend the shelf-life of light-sensitive agrumen oils. [ABSTRACT FROM AUTHOR]

In our previous report (J. Phys. Org. Chem., 2019), we discussed novel silicon photosensitizers (PSs) in psoralen ultraviolet A (PUVA) therapy. Continuing this quest, we have scrutinized a new brand of PSs, via density functional theory (DFT) and time‐dependent density functional theory (TD‐DFT) methods. These PSs show intense narrow absorption peaks in the therapeutic window with very high molar absorption coefficients (ε). Calculated vertical ionization potential (VIP) and vertical electron affinity (VEA) values indicate that our PSs can produce reactive oxygen species (ROS) through type I mechanism. Also, energies of the first triplet excited states (T1) and spin–orbit coupling (SOC) constants verify the possibility and efficiency of type II mechanism for the generation of the singlet excited state of molecular oxygen (1O2). The results introduce new potential PSs in PDT and PUVA therapy. [ABSTRACT FROM AUTHOR]

Background: The aim of this retrospective study was to compare the efficacy and safety of different phototherapeutic modalities in the treatment of cutaneous lichen planus (LP). Methods: We retrospectively analyzed the chart data of 53 patients with generalized LP who had been subjected to narrowband UVB (NB‐UVB) or photochemotherapy (PUVA) between January 1997 and April 2020. Of these, 30 patients had received NB‐UVB, 18 patients oral PUVA and 5 patients bath PUVA. Results: Fifty patients completed a full treatment course. The percentage of patients with a complete (>90% clearing) or good (51%‐90% clearing) response was similar for NB‐UVB versus PUVA (86.2% vs. 90.5%; P = 1.00). The number of exposures required for obtaining a complete or good response was also comparable for both treatment groups (NB‐UVB: 28.9 ± 12.3 vs. PUVA: 25.4 ± 10.1; P =.209). Adverse events, in particular gastrointestinal upsets, were recorded in 26.1% of patients treated with oral PUVA while none were observed with NB‐UVB. Conclusion: The therapeutic outcome and the number of treatments required for achieving a complete or good response were comparable for NB‐UVB and PUVA; however, PUVA therapy was associated with a substantially higher rate of moderate adverse events. [ABSTRACT FROM AUTHOR]

Objective To establish an ultra-high performance liquid chromatography (UPLC) method for simultaneous determination of umbelliferonel, nodakenin, psoralen, xanthotoxin and bergapten contents in Peucedanum decursivum Radix. Methods The analysis was achieved on a Symmetry®C18 column (4.6 mm × 250 mm, 5 μm), with acetonitrile and water as the mobile phase in gradient elution mode. The column temperature was maintained at 30°C, with flow rate 1.0 mL·min−1. The injection volume of sample was 10 μL. The ultraviolet detection wavelength was set at the maximum absorption wavelength 325 nm for umbelliferonel and nodakenin, 259 nm for psoralen, xanthotoxin and bergapten, respectively. Results The five kinds of coumarins in Peucedanum decursivum Radix were separated well and the linear relation was obtained (R 2 ≥ 0.9998). The average recoveries were 101.31, 105.27, 90.85, 106.42 and 90.19%, respectively, with Relative standard deviation (RSD) 3.07, 3.17, 1.62, 2.53 and 4.54%, respectively. Conclusions The established method was accurate and feasible, which could be used as the basis of quality control of Peucedanum decursivum Radix. [ABSTRACT FROM AUTHOR]

[Display omitted] • A new method for efficient extraction of psoralen from fig leaves was developed. • The application of resin as catalyst in the field of chemical engineering was proposed. • Extraction yield of psoralen catalyzed by D072 resin was 1.91-fold than before. • The content of psoralen enriched by X-5 resin was 24.8-fold than before. In this study, using fig leaves as materials, strong acidic cation exchange resin of D072 with –SO 3 H functional group was selected as catalyst to promote the conversion of psoralen-glucoside (PO) to psoralen (PSO), and the strong acidic cation exchange resin transformation method (SACERTM) was developed for efficient extraction of PSO from fig leaves. Under the optimized extraction conditions, the yield of PSO was 36.74 mg/g. The transformation efficiency of PO to PSO reached 70.41% using 2 g of D072 resin as catalyst. Then, PSO in fig extract was enriched efficiently by X-5 macroporous adsorption resin (MAR). After eluting with 14-fold of column volume of 70% ethanol at 0.64 BV/h of elution flow rate, the purity of PSO was 24.8-fold higher than before enrichment. The results show that SACERTM combined with MAR purification is an efficient method for extracting and enriching PSO from fig leaves. [ABSTRACT FROM AUTHOR]

Endothelins and -melanocyte-stimulating hormone are increased in plasma of patients treated with UVA1 and psoralen plus UVA GLO:HYQ/01nov22:phpp12789-fig-0001.jpg PHOTO (COLOR): 1 Plasma endothelins (ET) (1-3) were significantly increased as early as 3 h after UVA1 at day 1 and day 14 (*ap < .05 and **abp < .01) and at day 1 under cream PUVA therapy (*ap < .05) (paired t-test). Keywords: endothelins; human skin; irradiation; ultraviolet A light; -MSH EN endothelins human skin irradiation ultraviolet A light -MSH 611 613 3 11/17/22 20221101 NES 221101 Dear Sir, Ultraviolet light (UV) and/or UVA plus psoralen (PUVA) may have a systemic effect on melanocytes of shielded skin. [Extracted from the article]

Furocoumarins are the useful derivatives of coumarin, and they act as skin photosensitizing material due to their exciting exciplex states. Dendrimers also form exciplexes when they contain coumarin as core and used for light harvesting. A number of ingredients in human nutrition contain coumarins. The apiaceae family is the most common example of this class that contains carrots, celery and parsley etc. Rutaceae family is also an important food source that contains coumarins and provides citrus food. Besides fruits and vegetables, beverages like coffee, wine, black and green tea also incorporates coumarin derivatives. Few coumarin dyes show absorption and one emission peak but it can show a double amplified spontaneous emission band due to the generation of super exciplexes in coumarins. Exciplex formation of different coumarin derivatives including 7−methoxy coumarin, 7−hydroxy coumarin show wide application in synthesis of various other derivatives and they can be used as dye due to their prominent fluorescence properties. Exciplexes and excimers of coumarin are widely used in lasers. Both singlet and triplet state exciplexes are considered. Thus a comprehensive review of excited state complexes of coumarin derivatives is discussed here with emphases on the interaction and overlap of the energy levels. [ABSTRACT FROM AUTHOR]

A small library of coumarin and their psoralen analogues EMAC10157a-b-d-g and EMAC10160a-b-d-g has been designed and synthesised to investigate the effect of structural modifications on their inhibition ability and selectivity profile towards carbonic anhydrase isoforms I, II, IX, and XII. None of the new compounds exhibited activity towards hCA I and II isozymes. Conversely, both coumarin and psoralen derivatives were active against tumour associated isoforms IX and XII in the low micromolar or nanomolar range of concentration. These data further corroborate our previous findings on analogous derivatives, confirming that both coumarins and psoralens are interesting scaffolds for the design of isozyme selective hCA inhibitors. [ABSTRACT FROM AUTHOR]

8‐Methoxypsoralen (8‐MOP) serves as a PUVA (psoralen + UV‐A) agent in the treatment of certain skin diseases. Derivatives of 8‐MOP with cationic aromatic substituents at the five positions were synthesized and characterized by steady‐state, femtosecond and nanosecond spectroscopy as well as cyclic voltammetry. The aromatic substituents' positive charge increases the water solubility and the affinity toward intercalation into DNA. The aromatic substituents were supposed to lower the psoralen S1 energy and thereby suppress a photo‐induced electron transfer (PET) with guanine‐bearing DNA. Such a suppression of this PET is expected to increase the propensity of psoralens to photo‐addition to DNA. For derivatives bearing methylpyridinium residues, femtosecond spectroscopy revealed an intramolecular PET occurring on the picosecond time scale. This PET precludes the population of the triplet state. As triplet states are the precursor state for the photo‐addition to DNA, their intermolecular PET renders these derivatives ineffective in terms of PUVA. For two derivatives bearing trimethylphenylammonium moieties, such an intramolecular PET does not occur and the triplet state is populated. Surprisingly, these compounds also exhibit no PUVA activity. Based on these findings, implications for further optimization of PUVA agents are discussed. [ABSTRACT FROM AUTHOR]

In addition to the antiflatulent, emollient, antifungal, antihemorrhoidal, antioxidant, anthelmintic effects, Prangos species have been used to stop bleeding and for the treatment of wounds and scars in central Asia and Turkey. In the present study, the compounds were isolated using chromatographic methods, and their structures were identified by 1H NMR and direct comparison with the reference compounds where available. Fifteen known coumarins were isolated from the dichloromethane extract as osthol, murraol, auraptenol, peroxyauraptenol, 4'-senecioiloxyosthol, meranzin hydrate, scopoletin, umbelliferone, isoimperatorin, oxypeucedanin, oxypeucedanin hydrate, oxypeucedanin methanolate, gosferol, psoralen, and marmesin. The cytotoxic activities of all isolated compounds from dichloromethane extract of P. turcica roots were evaluated using MTT assay on human adenocarcinoma (prostate PC-3) cells. 4'-senecioiloxyosthol, oxypeucedanin methanolate, gosferol, psoralen, peroxyauraptenol and marmesin were tested for the first time on the PC-3 cell line. Osthol and peroxyauraptenol showed the highest cytotoxic activity with IC50 values of 65 and 72 µg/mL, respectively. Additionally, auraptenol, scopoletin, gosferol, psoralen, 4'-senecioiloxyosthol and dichloromethane extract of root part (Pt/R/DCM) demonstrated moderate to low cytotoxic activity. Consequently, the most potent compounds, osthol and peroxyauraptenol, may be used as a lead compound to develop effective drug substances to treat prostate cancer. [ABSTRACT FROM AUTHOR]

To study the effects of psoralen on the intestinal barrier and alveolar bone loss (ABL) in rats with chronic periodontitis. Fifty-two 8-week-old specific pathogen-free (SPF) male Sprague-Dawley (SD) rats were randomly divided into the following four groups: Control group (Control), psoralen group of healthy rats (Pso), periodontitis model group (Model), and psoralen group of periodontitis rats (Peri+Pso). The alveolar bone resorption of maxillary molars was observed via haematoxylin-eosin staining and micro-computed tomography. The expression level of receptor activator of nuclear factor-κB ligand (RANKL) and osteoprotegerin (OPG) in periodontal tissues was evaluated by immunofluorescence staining. The changes in serum tumour necrosis factor (TNF)-α, interleukin (IL)-10, IL-6, intestinal mucosal occludin, and claudin-5 were detected using enzyme-linked immunosorbent assay (ELISA). The level of intestinal mucosal NOD2 was detected using immunohistochemical methods. DNA was extracted from the intestinal contents and the 16s rRNA gene was sequenced using an Illumina MiSeq platform. The expression of NOD2 protein in the intestinal tract of periodontitis rats decreased after intragastric psoralen administration. Psoralen increased the intestinal microbiota diversity of rats. The level of serum pro-inflammatory factor TNF-α decreased and the level of anti-inflammatory factor IL-10 increased. ABL was observed to be significantly decreased in rats treated with psoralen. Psoralen decreased the RANKL/OPG ratio of periodontitis rats. Psoralen may affect the intestinal immune barrier and ecological barrier, mediate immune response, promote the secretion of anti-inflammatory factor IL-10, and reduce the secretion of the pro-inflammatory factor TNF-α, thus reducing ABL in experimental periodontitis in rats. [ABSTRACT FROM AUTHOR]

Fructus Psoraleae (FP), widely used in traditional medicine, is increasingly reported to cause serious hepatotoxicity in recent years. However, the main toxic constituents responsible for hepatotoxicity and the underlying mechanisms are poorly understood. In the present study, psoralen, a main and quality-control constituent of FP, was intragastrically administered to Sprague-Dawley rats at a dose of 60 mg/kg for 1, 3 and 7 days. Blood and selected tissue samples were collected and analyzed for biochemistry and histopathology to evaluate hepatotoxicity. The results showed that psoralen could induce hepatotoxicity by enhanced liver-to-body weight ratio and alterations of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total cholesterol after administration for 3 days. In addition, histopathological examinations also indicated the hepatotoxicity induced by psoralen. Furthermore, the mRNA and protein levels of hepatic bile acid transporters were significantly changed, in which MRP4, ABCG5 and ABCG8 were repressed, while the protein level of NTCP tended to increase in the rat liver. Taken together, psoralen caused liver injury possibly through affecting bile acid transporters, leading to the disorder of bile acid transport and accumulation in hepatocytes. [ABSTRACT FROM AUTHOR]

Cold-pressed Citrus essential oils namely lemon, bergamot, lime, grapefruit, mandarin, sweet and bitter orange are obtained from the peel of Citrus fruits. They were normally used in food, cosmetic, and pharmaceutical industries as ingredients. Essential oils extraction processes produce oils with different sensory qualities, and often these processes are expensive and have a low yield. For such a reason adulteration process are frequent, so careful attention must be paid to ensure the oils' genuineness and authenticity. Moreover, psoralen levels are continuously monitored by opinions and regulations released from International Fragrance Association and the European Parliament due to their photoactivity. This review aims to browse the scientific literature of the past 30 years on the characterization of the non-volatile fraction of cold-pressed Citrus essential oils to discuss results achieved so far and highlight future prospect. [ABSTRACT FROM AUTHOR]

A concise, one‐pot route for the synthesis of furo[3,2‐c]‐coumarins under the catalysis of Zn(OTf)2 is reported. Utilizing this synthetic strategy, libraries of furocoumarin analogues can be easily obtained by multicomponent tandem reactions with different nucleophile in the presence of 4‐hydroxycoumarin and arylglyoxal monohydrate system, This transformation exhibited highly atom economical and good functional group compatibility. [ABSTRACT FROM AUTHOR]

Psoralen is one of the most effective ingredients extracted from the Chinese herb, Psoralea corylifolia L. Studies have found that psoralen has anti-inflammatory and estrogen-like effects; however, little research has been conducted to elucidate the mechanisms underlying these effects. Through the molecule docking assay, psoralen was found to have a better combination with ERα than ERβ. In human periodontal ligament cells, psoralen was found to upregulate the estrogen target genes (e.g., CTSD, PGR, TFF1) and down-regulate the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) stimulated by P. gingivalis LPS, as well as TLR4-IRAK4-NF-κb signaling pathway proteins. These effects were reversed by the ER antagonist ICI 182780. These results indicated that psoralen may exert anti-inflammatory effects as an agonist to ER, which could provide a theoretical basis for the use of psoralen for adjuvant therapy and prevention of periodontitis. [ABSTRACT FROM AUTHOR]

In view of the complicated pathophysiological process of vascular dementia (VD), drugs for the clinical treatment of VD mainly target related risk factors, while drugs with excellent efficacy in cognitive function are still relatively lacking. Imperatorin (IMP), an active constituent extracted from angelica dahuricae and notopterygium Notopterygii, which has anti-inflammatory, vasodilator, anticoagulant, block calcium channel, anticonvulsant, and anti oxygen free radical injury properties. Therefore,the present study examined its effects on VD rats and the underlying molecular mechanisms, in order to provide promising therapeutic methods. VD was established by modified ligation of perpetual two-vessel occlusion (2VO). After 2VO surgery, IMP (2.5, 5, and 10 mg/kg) was administered by intraperitoneal injection for 12 consecutive weeks to evaluate therapeutic effects. Cognitive function was verified by the Morris water maze. The neuronal morphological changes were examined via Hematoxylin–Eosin staining. Real-Time PCR and Western blot were used for detecting pro- and antiapoptotic biomarkers, and the hippocampus synaptic damage was examined by Transmission electron microscope. We revealed that 2VO-induced cognitive impairment, hippocampus CA1 neuron damage, apoptosis and synaptic damage. IMP-treatment significantly improved 2VO-induced cognitive deficits and hippocampus neuron damage. Molecular analysis revealed that IMP inhibited apoptosis through the down regulation of Bax, Caspase-3 and upregulation of Bcl-2. Meanwhile, IMP-treatment markedly improved synaptic ultrastructure morphology, increased the SAZ length, PSD thickness and up-regulated PSD-95 expression. Collectively, our findings demonstrated that IMP was effective in the treatment of 2VO-induced VD via inhibiting apoptosis of hippocampus neurons and reducing the synaptic plasticity destroy. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Psoralen (PSO), a natural product in Ficus carica L., exhibits remarkable pharmacological activity and clinical efficacy. However, achieving selective recognition and effective recovery in PSO separation process remains a challenge. In this study, an intelligent solvent-responsive surface molecularly imprinted membranes (SR-SMIMs) with switchable adsorption/desorption behavior was developed and applied to separate PSO. Cellulose membranes were modified with chitosan and polydopamine in sequence, followed by the construction of a surface molecularly imprinting layer using bi-functional monomers (AM and 4-VPBA) and solvent-responsive cross-linking agent (TEGDMA). The TEGDMA drives the swelling or shrinking of polymer chains, resulting in a switch in the adsorption/desorption behavior of SR-SMIMs. Hence, SR-SMIMs exhibited remarkable adsorption capacity of 40.69 mg·g-1 towards PSO in 25% methanol and can be efficiently desorbed with satisfactory efficiency in methanol. The molecular simulation and NMR analysis demonstrated that the recognition mechanism of SR-SMIMs was a synergistic effect of hydrogen bonding, π-π stacking and Van der Waals forces. Furthermore, the SR-SMIMs were effectively employed for the separation of PSO from Ficus carica L. leaves, exhibiting an impressive adsorption capacity of 20.51 mg·g-1 and a high elution recovery rate of 92.54%. This efficient and sustainable SR-SMIMs possessed promising potential for specific separation of target compound from complex natural plants extracts. [Display omitted] • Integrated strategy of high-affinity bifunctional monomer and solvent-responsive crosslinker. • Psoralen in Ficus carica L. leaves was efficiently separated by well-oriented SR-SMIMs. • Efficient elution was achieved by switchable adsorption/release behavior of SR-SMIMs. • A new insight of membrane recognition mechanism by molecular simulations and NMR. • The application of SR-SMIMs in natural product separation was pioneered. [ABSTRACT FROM AUTHOR]

Epidemiological studies have found that high citrus fruit consumption was associated with higher risk of skin cancer. Citrus fruits and some vegetables contain furocoumarins, which may interact with ultraviolet radiation to induce skin cancer. We aimed to determine the effects of two furocoumarins, including 8-methoxypsoralen (8-MOP) and 6′,7′-dihydroxybergamottin (DHB), on UVA-induced DNA damage in human epidermal melanocytes, the origin of melanoma. Our hypothesis was that these dietary furocoumarins increase UVA-induced DNA damage in melanocytes, compared to cells exposed to UV alone. We incubated melanocytes with 8-MOP or DHB, followed by exposure to physiological doses of UVA radiation. We used Western blots to quantify the UVA-induced DNA damage measured by the fraction of phosphorylated histone variant H2AX (γH2AX), which is a marker of DNA damage, relative to total H2AX (γH2AX/H2AX) in the presence or absence of furocoumarins. To quantify the UVA-induced change in γH2AX/H2AX, we calculated the UVA:Control ratio as the ratio of γH2AX/H2AX in UVA-exposed cells to that in cells without UVA (control). The mean UVA:Control ratios were borderline significantly higher for cells treated with 8-MOP and significantly higher for cells treated with DHB, compared to that of untreated cells. This study suggests that furocoumarins (particularly 8-MOP and DHB) enhance UVA-induced DNA damage in melanocytes, which is a potential novel mechanism for citrus and furocoumarins to elevate the risk of skin cancer. [Display omitted] • Two dietary furocoumarins enhanced UVA-induced DNA damage in skin melanocytes. • 8-methoxypsoralen & 6′,7′-dihydroxybergamottin interacted with UVA to affect cells. • Dietary furocoumarins may increase the risk of skin cancer in combination with UVA. • This suggests a novel link between dietary compounds and the risk of skin cancer. [ABSTRACT FROM AUTHOR]

Aim of the study is to compare efficacy of targeted broad‐band UVB phototherapy and topical psoralen with targeted UVA phototherapy treatments in localized vitiligo for 3 months prospectively. The cases with symmetrical vitiligo lesions were included in the study. Broad‐band targeted UVB was applied on one side and targeted UVA phototherapy with topical psoralen on the other side. Twenty‐two patients who were diagnosed with localized vitiligo were enrolled in this study. These cases consisted of 6 (27.3%) females and 16 (72.7%) males aging between 17 and 69 (34.22 ± 14.15). Fifty‐four lesions (27 left, 27 right) were compared for treatments. After the first month of the treatments, the sides of the lesions were compared in order to evaluate improvement. Percentages of success were 25% for targeted broad‐band UVB microphototherapy and 75% for topical psoralen with targeted UVA microphototherapy. When the two treatment methods were compared with each other, a significant difference was found in terms of treatment response (P =.017). At the end of the third month, the success rates were 37.5% for targeted broad‐band UVB microphototherapy and 62.5% for topical psoralen with targeted UVA microphototherapy, however a statistically significant difference was not determined between the two treatments (P >.05). Both targeted broad‐band UVB phototherapy and topical psoralen with targeted UVA phototherapy provided repigmentation for localized vitiligo at the end of the third month. Our investigation shows that both treatments are safe and they provide repigmentation with a limited response. [ABSTRACT FROM AUTHOR]

The investigation of the DNA‐histone interactions and factors that affect such interactions in the nucleosome is essential for understanding the role of chromatin organization in all cellular processes involved in the repair, transcription, and replication of the eukaryotic genome. As a kind of photosensitive molecule, psoralen (PSO) is used in the treatment of skin disease with ultraviolet light (PSO and ultra violet light, type A). The effect of treatment is remarkable, but the side effect is also obvious. PSO can be embedded in a 5′ TA sequence in double‐stranded DNA (dsDNA), and dsDNA is mainly wrapped around a histone octamer to form a nucleosome structure in human cells. Therefore, it is very necessary to explore the influence of PSO on DNA‐histone interactions. To this end, the binding specificity and mode of DNA and histone in the presence or absence of PSO are investigated systematically. The results show that the presence of PSO (no matter if there is ultra violet light treatment) can increase the overall probability of histone binding to dsDNA while lowering the selectivity of histone binding to the specific DNA sequence in vitro. In addition, the increase of solution ionic strength can lower the ratio of histone binding to nonspecific DNA. [ABSTRACT FROM AUTHOR]