Chemical composition of Boenninghausenia sessilicarpa / 中国药科大学学报

@#The petroleum ether fraction of ethanol extracts from Boenninghausenia sessilicarpawas isolated by combination of several chromatographic methods including silica gel, ODS, and Sephadex LH-20 column chromatography, and finally purified by preparative HPLC. The structures of the isolated compounds were identified based on the spectral data. As a result, 15 coumarin compounds were isolated and identified from the petroleum ether extraction. Their structures were determined as osthenon (1), murrangatin (2), 3-(1,1-dimethylallyl)-8-hydroxy-7-methoxycoumarin (3), xanthotoxin (4), isopimpinellin (5), chalepensin (6), isodemethylfuropinarine (7), imperatorin (8), phellopterin (9), heraclenol (10), byakangelicin (11), neobyakangelicol (12), chalepin (13), luvangetin (14), 3-(1, 1-dimethylallyl)-xanthyletin (15). Among them, compounds 1 - 3, 6 - 10 and 14 -15 were firstly isolated from B. sessilicarpa.

Seven new 3,4-dihydro-furanocoumarin derivatives from Angelica dahurica / 中草药·英文版

OBJECTIVE@#To study the chemical constituents of the roots of Angelica dahurica, a well-known Chinese herbal medicine named Baizhi in Chinese.@*METHODS@#Compounds were separated by various chromatographies, and the structures of new compounds were elucidated based on the analysis of their spectroscopic and spectrometric data (1D, 2D NMR, HRESI MS, IR, and UV). The absolute configurations of new compounds were determined by the calculated electronic circular dichroism and chemical derivatization. The inhibitory activities of all isolates against nitric oxide (NO) production were evaluated using lipopolysaccharide-activated RAW 264.7 macrophage cells.@*RESULTS@#Seven new 3,4-dihydro-furanocoumarin derivatives ( 1a/ 1b, 2a/ 2b, 3a/ 3b, 4) together with a known furanocoumarin ( 5) were isolated from the roots of A. dahurica. The new compounds included three pairs of enantiomers, (4S, 2''R)-angelicadin A ( 1a)/(4R, 2''S)-angelicadin A ( 1b), (4S, 2''S)-angelicadin A ( 2a)/(4R, 2''R)-angelicadin A ( 2b), and (4S, 2''S)-secoangelicadin A ( 3a)/(4R, 2''R)-secoangelicadin A ( 3b), together with (4R, 2''R)-secoangelicadin A methyl ester ( 4). The known xanthotoxol ( 5) inhibited the NO production with the half-maximal inhibitory concentration (IC50) value of (32.8 ± 0.8) µmol/L, but all the new compounds showed no inhibitory activities at the concentration of 100 µmol/L.@*CONCLUSION@#This is the first report of the discovery of 3,4-dihydro-furanocoumarins from A. dahurica. The results are not only meaningful for the understanding of the chemical constituents of A. dahurica, but also enrich the reservoir of natural products.

Effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier in vitro and in vivo / 药学学报

A BBB co-culture cell model consisting of rat brain microvascular endothelial cells (BMEC) and astrocytes (AS) was established to study the effect of Angelica dahurica coumarins on the transport behavior of puerarin across blood-brain barrier (BBB) in vitro and in vivo. The barrier function of this model was evaluated by measuring the transendothelial resistance, phenol red permeability and BBB related protein expression. The permeability assay and western blot methods were performed to study the effects of Angelica dahurica coumarins on the BBB permeability and the expression of BBB related protein. The animal experiment protocols in this study were approved by the Animal Ethics Committee of Xi'an Jiaotong University (Animal Ethics No.: 2021-1329). The results showed that the established BMEC/AS co-culture model could be used to evaluate drug transport across BBB in vitro. After combined with Angelica dahurica coumarins, the transport capacity of puerarin was significantly increased in vitro and in vivo. Additionally, Angelica dahurica coumarins enhanced BBB permeability and inhibited the protein expression of P-glycoprotein (P-gp), zonula occludens-1 (ZO-1) and occludin. Angelica dahurica coumarins might increase BBB permeability by inhibiting the expression of P-gp and tight junction protein, thereby increasing the content of puerarin in brain tissue.

Differential analysis of coumarins in Angelica dahurica from different origins / 中国药房

OBJECTIVE To screen the differential components of coumarins in Angelica dahurica from two origins （A. dahurica cv.‘ Hangbaizhi’； A. dahurica cv.‘ Qibaizhi’）. METHODS Non-targeted metabolomics technique of UPLC-Q-Exactive- MS/MS was used to analyze the coumarins in 6 batches of A. dahurica cv. ‘Hangbaizhi’ and 12 batches of A. dahurica cv. ‘Qibaizhi’. The differential components were screened by principal component analysis， partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. Cluster analysis was performed on differential components. RESULTS A total of 41 coumarins were identified in 18 batches of samples， in which 23 coumarins were differential components. Therein， 6 differential components were higher in content in A. dahurica cv.‘ Hangbaizhi’， while 17 differential components were higher in content in A. dahurica cv.‘ Qibaizhi’. The content of marmesin galactoside in A. dahurica cv.‘ Hangbaizhi’ was significantly higher than that in A. dahurica cv.‘ Qibaizhi’. Based on 23 differential components， A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv. ‘Qibaizhi’ could be grouped into one category， respectively. CONCLUSIONS The screened differential components of coumarins can be used to distinguish A. dahurica cv. ‘Hangbaizhi’ from A. dahurica cv. ‘Qibaizhi’， especially marmesin galactoside contributed the most， which can be used to identify A. dahurica cv.‘ Hangbaizhi’ and A. dahurica cv.‘ Qibaizhi’.

Establishment of Cryosectioning Method and Histochemical Localization Analysis of Volatile Oil and Coumarin Components of Ferula ferulaeoides / 中国实验方剂学杂志

ObjectiveTo establish the frozen section method of Ferula ferulaeoides， and to study the histochemical localization of volatile oil and coumarins in different organs of F. ferulaeoides. MethodThe roots， stems， petioles and leaves of F. ferulaeoides were used as materials to investigate the concentration of sucrose protectant， liquid nitrogen flash-freezing time， embedding conditions， section thickness， freezing temperature and time and post-treatment methods， the most suitable section conditions were screened by comparing the integrity， microscopic effect， elongation and clarity of frozen sections. Sudan Ⅳ staining method and fluorescence microscopy were used to locate the volatile oil and coumarins of F. ferulaeoides. ResultThe optimal conditions for frozen sections of the roots， stems， petioles and leaves of F. ferulaeoides were as follows：10%， 15% and 20% gradient sucrose as the protectant for roots， 10%， 20% and 30% gradient sucrose as the protectant for stems and petioles， 20%， 25% and 30% gradient sucrose as the protectant for leaves， glue-water （2∶1） as the embedding agent， quick-freeze in liquid nitrogen for 20 s， warmed up at -25 ℃ for 30 min， sliced at -20 ℃ with the thickness of 25 μm， rinsed with the same concentration of sucrose solution （gradient sucrose solution selected the last concentration）， and the slices placed on the ice pack for a period of time and stored at room temperature. Among them， the concentration of sucrose protectant was the most important factor. The results of histochemical localization showed that volatile oil and coumarins in four organs of F. ferulaeoides were mainly distributed in resin canal. ConclusionFrozen section of F. ferulaeoides is established for the first time with high rate of slicing and simplified steps， its volatile oil and coumarins are mainly accumulated in resin canal.

Coumarin (2H-1-Benzopyran-2-one) act against planktonic and biofilm forms of Staphylococcus aureus, Klebsiellapneumoniae and Pseudomonas aeruginosa

SUMMARY Introduction: biofilm-related infections caused by Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa are difficult to treat and few effective pharmacological options are currently available for this purpose. In this context, coumarin (2H-1-Benzopyran-2-one) has been reported to have antibacterial and antibiofilm activity, but this potential remains poorly understood. Aim: to investigate the action of coumarin on planktonic and biofilm forms of S. aureus, K. pneumoniae and P. aeruginosa. Results: a minimum inhibitory concentration (MIC) of coumarin ranging from 256 to 1024 fig/mL was observed, with a remarkable ability to inhibit the formation of biofilms and to act on mature biofilms in concentrations close to MIC. Conclusion: coumarin has strong activity against planktonic and biofilm forms on the three species of great relevance in the clinical scenario. These results are interesting to enable a pharmacological alternative for the treatment of these infections.

Introducción: las infecciones relacionadas con la biopelícula causadas por Staphylococcus aureus, Klebsiella pneumoniae y Pseudomonas aeruginosa son difíciles de tratar y actualmente existen pocas opciones farmacológicas eficaces para este propósito. En este contexto, se ha informado que la cumarina (2H-1-Benzopiran-2-ona) tiene actividad antibacteriana y antibiofilm, pero este potencial sigue siendo poco conocido. Objetivo: investigar la acción de la cumarina sobre formas planctónicas y de biopelículas de S. aureus, K. pneumoniae y P. aeruginosa. Resultados: se observó una concentración inhibitoria mínima (CMI) de cumarina en el rango de 256 a 1024 µg/mL, con una notable capacidad para inhibir la formación de biofilms y actuar sobre biofilms maduros en concentraciones cercanas a la CMI. Conclusión: la cumarina tiene una fuerte actividad contra las formas planctónicas y biofilm sobre las tres especies de gran relevancia en el escenario clínico. Estos resultados son interesantes para habilitar una alternativa farmacológica para el tratamiento de estas infecciones.

Introdução: as infecções relacionadas ao biofilme causadas por Staphylococcus aureus, Klebsiella pneumoniae e Pseudomonas aeruginosa são difíceis de tratar e poucas opções farmacológicas eficazes estão disponíveis atualmente para esse propósito. Nesse contexto, foi relatado que a cumarina (2H-1-benzopirano-2-ona) tem atividade antibacteriana e antibiofilme, mas esse potencial permanece pouco conhecido. Objetivo: investigar a ação da cumarina sobre as formas planctónicas e de biofilme de S. aureus, K. pneumoniae e P. aeruginosa. Resultados: observou-se uma concentração inibitória mínima (CIM) de cumarina variando de 256 a 1024 µg/mL, com notável capacidade de inibir a formação de biofilmes e de atuar sobre biofilmes maduros em concentrações próximas à CIM. Conclusão: a cumarina possui forte atividade contra as formas planctónicas e de biofilme sobre as três espécies de grande relevância no cenário clínico. Esses resultados são interessantes para possibilitar uma alternativa farmacológica para o tratamento dessas infecções.

Three new coumarins and a new coumarin glycoside from Micromelum integerrimum / 中国天然药物

Three new coumarins, integmarins A-C (1-3), and a new coumarin glycoside, integmaside A (4) were isolated from the leaves and stems of Micromelum integerrimum. Their structures were elucidated on the basis of 1D and 2D NMR and MS data, and their absolute configurations were assigned according to the ECD data of the in situ formed transition metal complexes and comparison of experimental and calculated ECD data. Compounds 1 and 2 are two rare coumarins with butyl and propyl moieties at the C-6 position; compound 3 is a novel coumarin with a highly oxidized prenyl group, and compound 4 is a rare bisdihydrofuranocoumarin glycoside.

Chemical constituents from Clausena excavata and their inhibitory activities against proliferation of synoviocytes / 中国中药杂志

The chemical constituents from the stems and leaves of Clausena excavata were isolated and purified by column chromatography with silica gel, ODS, Sephadex LH-20 and RP-HPLC. The chemical structures of the isolated compounds were identified on the basis of physicochemical properties, spectroscopic analysis, as well as the comparisons with the data reported in literature. Nineteen compounds were isolated from the 90% ethanol extract of the stems and leaves of C. excavata, which were identified as methyl orsellinate(1), syringaresinol(2), lenisin A(3), scopoletin(4), osthenol(5), N-benzoyltyrarnine methyl ether(6), N-p-coumaroyltyramine(7), aurantiamide acetate(8), 1H-indole-3-carboxaldehyde(9), furostifoline(10), clausenalansine E(11), 3-formylcarbazole(12), clausine L(13), clausine E(14), methyl carbazole-3-carboxylate(15), glycosinin(16), murrayafoline A(17), clausine H(18) and 2,7-dihydroxy-3-formyl-1-(3'-methyl-2'-butenyl)carbazole(19). Among these isolated compounds, compounds 1-11 were isolated from C. excavata for the first time, and compounds 1, 2 and 10 were isolated from the genus Clausena for the first time. In addition, this study evaluated the anti-rheumatoid arthritis activities of compounds 1-19 by measuring their anti-proliferative effects on synoviocytes in vitro according to MTS method. Compounds 10-19 displayed remarkable anti-rheumatoid arthritis activities, which exhibited the inhibitory effects on the proliferation of MH7 A synovial fibroblast cells with the IC_(50) values ranging from(27.63±0.18) to(235.67±2.16) μmol·L~(-1).

Effect of Chuanxiong Rhizoma on the absorption and clearance of four coumarins in Angelicae Dahuricae Radix / 药学学报

To study the changes in the pharmacokinetic behavior of four coumarins (bergapten, oxypeucedanin, imperatorin and isoimperatorin) in rats before and after combinating Angelicae Dahuricae Radix with Chuanxiong Rhizoma. The plasma concentrations of the drugs were determined by ultra performance liquid chromatography-fluorescence detection (UPLC-FLD) for dose response and time dependent curves. The pharmacokinetic parameters were calculated by DAS 3.2.8, and SPSS 20.0 was used to analyze the differences of main pharmacokinetic parameters between the two groups. The result showed: comparing with Angelicae Dahuricae Radix group, the area under drug time curve (AUC0-24 h) of bergapten, oxypeucedanin and imperatorin increased by 177.2%, 97.14% and 54.43% respectively, AUC0-∞ increased by 282.3%, 104.2%, and 75.40% respectively, and clearance rate (CLZ/F) decreased by 68.26%, 51.08% and 43.98% respectively; the peak drug concentration (Cmax) of four coumarins was significantly increased; the distribution volume (VZ/F) of bergapten was significantly decreased. These data indicated that Chuanxiong Rhizoma can promote the absorption of coumarins in Angelicae Dahuricae Radix, slow down the elimination of coumarins, and increase their bioavailability in vivo. The animal experiment scheme in this study has been approved by the Experimental Animal Ethics Committee of Beijing University of Chinese Medicine (approval number: BUCM-4-2020083105-3072).

One new coumarin from seeds of Herpetospermum pedunculosum / 中国中药杂志

This paper aims to investigate the chemical constituents of the seeds of Herpetospermum pedunculosum. One new coumarin and two known lignans were isolated from the ethanolic extract of the seeds of H. pedunculosum with thin layer chromatography(TLC), silica gel column chromatography, Sephedax LH-20 chromatography, Semi-preparative high performance liquid chromatography and recrystallization, etc. Their structures were elucidated as herpetolide H(1), phyllanglaucin B(2), and buddlenol E(3) by analysis of their physicochemical properties and spectral data. Among them, compound 1 was a new compound, and compounds 2 and 3 were isolated from this genus for the first time. In vitro anti-inflammatory activity test showed that herpetolide H had certain NO inhibitory activity for LPS-induced RAW 264.7 cells, with its IC_(50) value of(46.57±3.28) μmol·L~(-1).

Study on fragmentation patterns of coumarins in Notopterygium inchum with ultrahigh performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry / 中国中药杂志

To demonstrate the fragmentation patterns of simple coumarins furanocourmarin(C_7-C_8), furanocourmarin(C_6-C_7) and dihydrofuran coumarin by mass spectrometry, with fraxin, scopoletin, isopsoralen, pimpinellin, isoimperatorin, notopterol and noda-kenin as study subjects, so as to provide a basis for rapid identification of compounds in different subtypes of coumarins. Ultrahigh performance liquid chromatography combined with quardrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was implemented in both positive and negative ion modes. Masslynx software was employed to provide the elemental constituents of each detected ion based on its accurate molecular weight. Chemdraw 2014 was used to cultivate mass number of each inferred structure. The fragment pattern of each compound was determined based on the structures inferred from all the relevant ions. And the patterns were drawn by Chemdraw 2014. The deviation between the calculated molecular weight of the inferred structure and the detected value of the ions was used to assess the correctness of the inferred structures in the fragmentation patterns. The results showed that with UPLC-Q-TOF, neutral loss of CO_2 and CO was reflected in lactone and furan skeletons from the courmarin structure. An even mass was attributed to the loss of an odd number of methyl radicals from compounds with a methoxy substituent. Furanocourmarin(C_7-C_8) produced a protonated molecular ion([M+H]~+), while the other courmarin subtypes produced either a sodium adduct of the molecular ion([M+Na]~+) or a sodium adduct of the molecular ion([M+Na]~+) with a protonated molecular ion([M+H]~+). The m/z 203.03 was a diagnostic ion for furanocourmarin(C_6-C_7), and the m/z 147.04 was supplementary evidence for furanocourmarin(C_6-C_7) identification. The characteristic ion of furanocourmarin(C_7-C_8) was m/z 131.05, while m/z 187.04 was the characteristic ion of dihydrofuran coumarin. The m/z 203.03 ion for furanocourmarin(C_7-C_8) was pretty weak. In negative ion mode, furanocourmarin(C_7-C_8) did not have any signals that were different from the other subtypes of courmarins. The fragmentation patterns in negative ion mode for the other subtypes of courmarins were similar to those in positive ion mode. Four types of fragmentation patterns were identified as forcourmarins from Notopterygium inchum. This study provides the basis for the rapid identification of courmarin subtypes by mass spectrometry.

Analysis of Chemical Constituents in Violae Herba and Investigation of Its Antioxidant Activity in Vitro / 中国实验方剂学杂志

Objective:To investigate the chemical constituents and antioxidant activities of Violae Herba from the Violaceae. Method:The 5 kg of Violae Herba was refluxing extracted with 3 times the amount of 95% ethanol for three times， then the extracting solution was combined， filtrated， concentrated under vacuum to get the total extract. Seven corresponding fractions were eluted with petroleum ether， dichloromethane， dichloromethane-methanol （50∶1， 10∶1， 5∶1， 2∶1） and methanol by silica gel column chromatography （60-100 mesh） on the total extract. Each fraction was isolated and purified by normal phase silica gel column chromatography， octadecylsilane chemically bonded silica （ODS） column chromatography， Sephadex LH-20 column chromatography and preparative high performance liquid chromatography （HPLC）， respectively. The structures of the obtained compounds were identified by spectroscopic methods of nuclear magnetic resonance （NMR）， mass spectroscopy （MS） and infrared spectroscopy （IR）. Meanwhile， some of these compounds isolated from Violae Herba were carried on the 1，1-diphenyl-2-picrylhydrazyl （DPPH） free radical scavenging experiment. Result:Fourteen compounds were isolated from the 95% ethanol extract of Violae Herba， including <italic>N</italic>-acetyl-1-ethyl ester glutamic acid （<bold>1</bold>）， <italic>N</italic>-acetyl glutamic acid-1-ethyl-5-methyl ester （<bold>2</bold>）， aurantiamide （<bold>3</bold>）， <italic>rel</italic>-（2<italic>α</italic>，3<italic>β</italic>）-7-<italic>O</italic>-methylcedrusin （<bold>4</bold>）， oleanolic acid （<bold>5</bold>）， <italic>α</italic>-tocopherol-quinone （<bold>6</bold>）， tectochrysin （<bold>7</bold>）， isoscopoletin （<bold>8</bold>）， esculetin （<bold>9</bold>）， 24-ethylcholesta-4，24（28）<italic>Z</italic>-dien-3-one （<bold>10</bold>）， stigmasta-4，25-dien-3-one （<bold>11</bold>）， <italic>β</italic>-sitostenone （<bold>12</bold>）， <italic>β</italic>-sitosterol （<bold>13</bold>）， （24<italic>R</italic>）-3<italic>β</italic>-hydroxy-ethylcholest-5-en-7-one （<bold>14</bold>）. Conclusion:Compound <bold>2</bold> is a new natural product， compounds <bold>1</bold>， <bold>4</bold>， <bold>6</bold>， <bold>7</bold>， <bold>10</bold>-<bold>12 </bold>are isolated from the genus <italic>Viola</italic> for the first time. Compound <bold>9</bold> has significant antioxidant activity， while compounds <bold>2</bold>， <bold>6 </bold>and<bold> 8</bold> have certain DPPH free radical scavenging activity.

Effects of polyethylene glycol length on oral absorption of coumarin 6-loaded nanostructured lipid carrier / 中国药科大学学报

@#Polyethylene glycol (PEG) of different lengths were prepared to investigate their effects on oral absorption of nanostructured lipid carrier (NLCs).Three kinds of PEG-modified NLCs with different chain lengths, including polyethylene glycol (100) monostearate (S100), polyethylene glycol (55) monostearate (S55), polyethylene glycol (40) monostearate (S40), were prepared by film dispersion method.Coumarin 6 was chosen as a fluorescent probe to characterize the physicochemical properties of NLCs with different lengths.Meanwhile, the stability of NLCs in simulate buffer, the release behavior, cytotoxicity of NLCs, the uptake kinetics and cellular uptake mechanisms were evaluated. This work demonstrated that the thickness of the hydrated layer increased with the increase of PEG length. Of note, S100-modified NLCs (pNLC-EG100) exhibited higher cellular uptake efficiency compared with other formulations. Thus, S100 was optimized as the best molecular weight for PEG-modified NLCs on oral drug delivery system.

Layered dissolving microneedles as a need-based delivery system to simultaneously alleviate skin and joint lesions in psoriatic arthritis

Psoriatic arthritis (PsA) is a complicated psoriasis comorbidity with manifestations of psoriatic skin and arthritic joints, and tailoring specific treatment strategies for simultaneously delivering different drugs to different action sites in PsA remains challenging. We developed a need-based layered dissolving microneedle (MN) system loading immunosuppressant tacrolimus (TAC) and anti-inflammatory diclofenac (DIC) in different layers of MNs,

Designing, molecular docking, and dynamics simulations studies of 1,2,3-triazole clamped Uracil-Coumarin hybrids against EGFR tyrosine kinase

Since the last decade, hybrid drug strategies have attracted many researchers for their improved anti-cancer potential incomparison to single drug components. Complying to this approach, 28 novel Uracil–Coumarin hybrids with differentsized linkers (2–5 carbon atoms) and substituents were designed to occupy the active site of protein epidermal growthfactor receptor (EGFR) tyrosine kinase (Protein Data Bank ID: 1M17). Molecular docking studies were performedfor all ligands (A1-D7) to identify the potential candidate using Schrödinger software. The relative binding affinity ofhybrids toward EGFR was compared with standard Erlotinib on the basis of gScore and Emodel score. Positively, allthe hybrids docked inside the cavity and showed significant interactions, compounds A6, A2, and A7 with short-chainlinker (two carbon atoms) and halogen substituents were found to have more interactions and better docking score thanstandard Erlotinib. The visualization results depicted that compound A6 showed the highest affinity and formed thebest binding pose to the target EGFR with gScore = −8.891 kcal/mol and Emodel score = −100.744 in comparison tostandard Erlotinib (gScore of −8.538 kcal/mol and Emodel score = −80.588). Moreover, a molecular dynamics studyalso reveals that ligand A6 forms a stable complex with root mean square deviation (RMSD) of 0.3 nm and the plateauphase started just after 10 ns (time). Hence, the present research provides computational insights of Uracil–Coumarinhybrids as potential ligands against EGFR tyrosine kinase and in future in vitro investigations of these hybrids mayprove their therapeutic potential against cancer.

Antiproliferative and photoprotective activities of the extracts and compounds from Calea fruticosa

In this paper, we complement our previous study on the antiproliferative activity of Calea fruticosa (Asteraceae) by isolating the compounds apigenin-4',7-dimethyl ether (1), budlein A (2), quercetin (3), and cichoriin (4) from the plant's aerial parts. The antiproliferative activity of these compounds was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method against human tumor cell lines. Compound 3 displayed moderate antiproliferative activity in three cell lines (HCT-116, PC-3, and SF-295, with cell growth inhibition values of 72.97, 74.55, and 68.94%) and high antiproliferative activity (90.86%) in the HL-60 cell line. The in vitro sun protection factor (SPF) of the extracts and compound 4, with and without sunscreen, was determined by a spectrophotometric method. The ethanol extract exhibited the highest SPF (9.67) at a concentration of 0.100 mg/mL, while compound 4, isolated from this extract, showed a SPF of 13.79 at the same concentration. A relative increased efficacy of SPF was observed for the extracts and compound 4 when sunscreen was also used. Compound 4 has not been reported previously from any species within the genus Calea. Compounds 1-4 were obtained from this species for the first time.

Stability of hydroalcoholic extracts of two species of guaco; Mikania glomerata SPRENG. and Mikania laevigata SCHULTZ. (Asteraceae), by UHPLC-MS

It is important to study the stability of plant extracts used as active ingredients in phytotherapic medicine, as degradation of the active principles directly affects the efficacy and safety of these products. Therefore, a stability study of the hydroalcoholic extract of the species: Mikania glomerata and Mikania laevigata was conducted in order to determine the speed of degradation and shelf life of these extracts, which are incorporated in cough syrup in Brazil. Leaves of both species were dried in an oven or by lyophilization (freeze-dried). Hydroalcoholic extracts underwent both accelerated stability study of six months and long-term stability study for 12 months. Samples were stored at different temperatures and every three months were analysed by ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) to monitor their chemical profile, quantifying coumarin and chlorogenic acid. For all conditions of the study, a reduction of the content of the chemical marker of this species, coumarin, greater than 5% was observed, so a shelf life of two years cannot be assigned to the hydroalcoholic extracts of these species as observed in commercial extracts.

8-Propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one: A new coumarin with monoamine oxidase B inhibitory activity and possible anti-parkinsonian effects

Parkinson's disease is a common neurodegenerative disorder. In this study, the monoamine oxidase inhibitory activity and potential anti-parkinsonian effects of 8-propyl-6H-[1,3]dioxolo[4,5-g]chromen-6-one (FCS303), a new synthetic coumarin, were evaluated. To do this, we used the reserpine model of Parkinson's disease, an assay of levodopa/carbidopa potentiation, the catalepsy model of haloperidol, and an in vitro assay against monoamine oxidase (MAO) activity. Additionally, lipid peroxidation and protein carbonyl group quantification was performed in mice brain homogenates previously treated with haloperidol. FCS303 inhibited monoamine oxidase B (MAO-B) with an IC50 of 5.46 ± 0.36 µM; however, there was no effect on monoamine oxidase A (MAO-A). The oral administration of FCS303 led to a significant reversal of hypokinesia in the reserpine model (at 24 h, doses of 100 and 200 mg/kg) and in the levodopa/carbidopa potentiation assay (at 2 and 24 h, dose of 200 mg/kg). In addition, FCS303 (100 mg/kg) showed anti-cataleptic activity against haloperidol. FCS303 (50 mg/kg) significantly decreased lipid peroxidation and protein carbonyl quantification. These results suggest that FCS303 could present anti-parkinsonian activity related to MAO-B inhibitory activity.

Synthesis and Anti-NSCLC Activity of Coumarin-anilinopyrimidine Combined Compounds / 中国药学杂志

OBJECTIVE: To design and synthesize a series of combined compounds of coumarins and anilinopyrimidines (7a-7j) investigate their anti-NSCLC activities in vitro. METHODS: The target compounds were obtained by condensation of anilinopyrimidines and coumarin derivatives via the combination principle, then the anti-NSCLC activity of these compounds was studied by MTT. Molecular docking studies were performed to afford the binding mode of the compound and EGFR. RESULTS: The structures of the target compounds were confirmed by MS, 1H-NMR and 13C-NMR. Compounds 7a-7j displayed different degrees of inhibitory activities on the proliferation of NSCLC cell line H1975 (IC50=2.70-17.59 μmol•L-1). Six compounds showed higher anti-proliferative activity on H1975 cells than gefitinib (IC50=9.18 μmol•L-1). CONCLUSION: Compound 7j (IC50=2.70 μmol•L-1) has the best inhibitory effect on H1975 cells, suggesting that 7j may be a potential anti-NSCLC agent for further investigation.

HPLC fingerprint of Cnidii Fructus formula granule and determination of six main coumarin components / 中草药

Objective: To establish an HPLC fingerprint of Cnidii Fructus formula granule analysis method for simultaneous determination of six main coumarin components, including osthol, xanthotoxin, xanthotol, bergapten, imperatorin and isopimpinellin, in order to provide reference for the study of the material basis of Cnidii Fructus formula granule. Methods: The method was performed by high performance liquid chromatography with a Waters XBridge C18 (250 mm × 4.6 mm, 5 μm) column and methanol (A)-0.1% acetic acid (B) as the mobile phase for gradient elution. The flow rate was 0.5 mL/min, the injection volume was 10 μL and the column temperature was 40 ℃. The detection wavelength was set at 320 nm. The chromatographic fingerprint evaluation system published by the State Pharmacopoeia Commission (2012 Edition) was used to establish the fingerprint of Cnidii Fructus formula granule, and the content of six main coumarin components was simultaneously determined. Results: The research on the 18 batches of Cnidii Fructus formula granule showed that the fingerprint similarity was greater than 0.992 and 19 common peaks were calibrated with satisfied peak resolution. The content determination results showed that the content of both xanthotoxin and osthol were the main coumarin components in Cnidii Fructus formula granule. According to the methodological investigation, the precision RSD values were all less than 1.6%. The sample was stable within 48 h and this method had good repeatability. The average recovery rates of xanthotol, xanthotoxin, imperatorin, isopimpinellin, bergapten and osthol were 100.69%, 101.03%, 99.48%, 100.88%, 101.27% and 100.35%, respectively. All of these coumarin components’ RSD were less than 2.5%. The six components showed a good linear relationship within a certain concentration range. The results of the content determination of xanthotol, xanthotoxin, isopimpinellin, bergapten, imperatorin and osthol respectively were 8.01-8.29, 2.37-2.63, 4.30-4.61, 4.04-4.40, 3.45-3.90 and 6.02-6.80 mg/g among the 18 batches of the Cnidii Fructus formula granule. Conclusion: The fingerprint method and the determination method of six main coumarin components in the Cnidii Fructus formula granule established in this study are simple, stable, accurate and reliable. This method can be used for the quality control of the Cnidii Fructus formula granule.