RESUMEN

Citrus sinensis and Citrus limonia were obtained by germination from seeds, and isotopic-labeling experiments using d-[1-13C]glucose were performed with the seedlings. After 60 days, the seedlings were analyzed by high-performance liquid chromatography-ultraviolet-solid-phase extraction-nuclear magnetic resonance, data and the 13C enrichment patterns of xanthyletin and seselin indicated that the pyran ring was formed by the methylerythritol phosphate pathway and that the coumarin moiety was derived from the shikimate pathway in both compounds. This information regarding the biosynthetic pathway can be used to increase resistance against phytopathogens, because xanthyletin and seselin are reported to have antimicrobial activity on the growth of Xylella fastidiosa, which causes citrus variegated chlorosis in orange.

Asunto(s)

Marcaje Isotópico/métodos , Piranocumarinas/metabolismo , Isótopos de Carbono , Cromatografía Líquida de Alta Presión , Citrus/metabolismo , Citrus sinensis/metabolismo , Espectroscopía de Resonancia Magnética , Estructura Molecular , Enfermedades de las Plantas/microbiología , Piranocumarinas/química , Piranocumarinas/aislamiento & purificación , Ácido Shikímico/metabolismo , Extracción en Fase Sólida , Espectrofotometría Ultravioleta , Xylella/efectos de los fármacos

RESUMEN

Dihydropyranocoumarins (DPCs) were isolated from Peucedanum japonicum Thunb as anti-obesity compounds in 3T3-L1 adipocytes assay; however, it is uncertain whether DPC exerts anti-obesity activity in vivo. Therefore, this study evaluated the oral intake of pure DPCs in mice fed a high-fat diet, and also attempted to enhance its activity by nanoparticulation. Increases in body weight gain and fat accumulation in white adipose tissues were significantly suppressed by the dietary intake of DPCs (1.943 mg/mouse/day). DPCs intake also significantly decreased the mean size of adipocytes and upregulated mRNA levels of thermogenesis-related genes. Nanoparticulation of DPCs with polylactic-co-glycolic acid (PLGA) dramatically increased its activity almost 100-fold over that of a non-nanoparticulated form. Thus, our findings clearly demonstrated the anti-obesity activity of DPCs in vivo and suggested that PLGA nanoparticle encapsulation was useful to enhance the anti-obesity activity of DPCs with the aim to develop natural and safe anti-obesity agents.

Asunto(s)

Fármacos Antiobesidad/farmacología , Dieta Alta en Grasa , Nanopartículas/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Piranocumarinas/farmacología , Adipocitos , Animales , Fármacos Antiobesidad/química , Fármacos Antiobesidad/aislamiento & purificación , Apiaceae/química , Peso Corporal/efectos de los fármacos , Células Cultivadas , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Extractos Vegetales/química , Piranocumarinas/química , Piranocumarinas/aislamiento & purificación

RESUMEN

BACKGROUND: Qianhu is a traditional Chinese medicine. It is thought that Qianhu roots will harden after bolting and not be suitable for medicinal purposes. Bolting Qianhu and unbolting Qianhu are referred to as "Xiong Qianhu" and "Ci Qianhu," respectively. In this study, the properties, microscopic and chemical characteristics of Ci Qianhu and Xiong Qianhu roots were compared using fluorescence microscopy, laser microdissection coupled with ultra-high-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry, and high-performance liquid chromatography with diode-array detection. RESULTS: Microscopy results showed that the area of secondary xylem in the root increased after bolting, with the cork and secretory canals showing strong fluorescence intensity. A total of 34 peaks, mostly pyranocoumarins, were identified in the tissues of Ci Qianhu and Xiong Qianhu. The secretory canals contained the highest variability of coumarins, whereas the secondary xylem contained the least coumarins. Moreover, seven coumarins, especially the pyran- coumarin, decreased after bolting. Generally, both before and after bolting, coumarin level was the highest in the bark, followed by the middle part, and the lowest in the inner part. CONCLUSION: Thus, it was indicated that the area of secondary xylem increased after bolting, however the coumarin variant and content decreased in the secondary xylem of Qianhu. The result shows that the quality of Qianhu decreases after bolting, which supports the viewpoint that Xiong Qianhu is not suitable for medicinal use.

Asunto(s)

Apiaceae/química , Cumarinas/química , Medicina Tradicional China , Piranocumarinas/química , Cromatografía Líquida de Alta Presión , Cumarinas/aislamiento & purificación , Humanos , Espectrometría de Masas , Especificidad de Órganos , Raíces de Plantas/química , Piranocumarinas/aislamiento & purificación , Xilema/química

RESUMEN

Angelica gigas Nakai (AGN) is a crucial oriental medicinal herb that grows especially in Korea and the Far-East countries. It contains chemically active compounds like pyranocoumarins, polyacetylenes and essential oils, which might be useful for treatment of several chronic diseases. It has been used for centuries as a traditional medicine in Southeast Asia, but in Western countries is used as a functional food and a major ingredient of several herbal products. The genus Angelica is also known as 'female ginseng' due to its critical therapeutic role in female afflictions, such as gynecological problems. However, it is well-documented that the AGN pyranocoumarins may play vital beneficial roles against cancer, neurodisorders, inflammation, osteoporosis, amnesia, allergies, depression, fungi, diabetes, ischemia, dermatitis, reactive oxygen species (ROS) and androgen. Though numerous studies revealed the role of AGN pyranocoumarins as therapeutic agents, none of the reviews have published their molecular mechanism of action. To the best of our knowledge, this would be the first review that aims to appraise the biosynthesis of AGN's major active pyranocoumarins, discuss effective extraction and formulation methods, and detail the molecular action mechanism of decursin (D), decursinol angelate (DA) and decursinol (DOH) in chronic diseases, which would further help extension of research in this area.

Asunto(s)

Angelica/química , Antineoplásicos Fitogénicos/farmacología , Medicamentos Herbarios Chinos/farmacología , Neoplasias/tratamiento farmacológico , Fitoterapia/métodos , Piranocumarinas/farmacología , Angelica sinensis , Animales , Antineoplásicos Fitogénicos/biosíntesis , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacocinética , Benzopiranos/aislamiento & purificación , Benzopiranos/metabolismo , Benzopiranos/farmacocinética , Benzopiranos/farmacología , Butiratos/aislamiento & purificación , Butiratos/metabolismo , Butiratos/farmacocinética , Butiratos/farmacología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Humanos , Extracción Líquido-Líquido/métodos , Medicina Tradicional Coreana , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/patología , Extractos Vegetales/química , Raíces de Plantas/química , Plantas Medicinales , Piranocumarinas/aislamiento & purificación , Piranocumarinas/metabolismo , Piranocumarinas/farmacocinética , Roedores

RESUMEN

We have previously shown that the ethanol extract of dried Angelica gigas Nakai (AGN) root exerts anticancer activity against androgen receptor (AR)-negative human DU145 and PC-3 prostate cancer xenografts and primary carcinogenesis in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. The major pyranocoumarin isomers decursin (D) and decursinol angelate (DA), when provided at equi-molar intake to that provided by AGN extract, accounted for the inhibitory efficacy against precancerous epithelial lesions in TRAMP mice. Since we and others have shown in rodents and humans that D and DA rapidly and extensively convert to decursinol, here we tested whether decursinol might be an in vivo active compound for suppressing xenograft growth of human prostate cancer cells expressing AR. In SCID-NSG mice carrying subcutaneously inoculated human LNCaP/AR-Luc cells overexpressing the wild type AR, we compared the efficacy of 4.5[Formula: see text]mg decursinol per mouse with equi-molar dose of 6[Formula: see text]mg D/DA per mouse. The result showed that decursinol decreased xenograft tumor growth by 75% and the lung metastasis, whereas D/DA exerted a much less effect. Measurement of plasma decursinol concentration, at 3[Formula: see text]h after the last dose of respective dosing regimen, showed higher circulating level in the decursinol-treated NSG mice than in the D/DA-treated mice. In a subsequent single-dose pharmacokinetic experiment, decursinol dosing led to 3.7-fold area under curve (AUC) of plasma decursinol over that achieved by equi-molar D/DA dosing. PK advantage notwithstanding, decursinol represents an active compound to exert in vivo prostate cancer growth and metastasis inhibitory activity in the preclinical model.

Asunto(s)

Adenocarcinoma/patología , Angelica/química , Antineoplásicos Fitogénicos , Benzopiranos/farmacología , Benzopiranos/farmacocinética , Butiratos/farmacología , Butiratos/farmacocinética , Xenoinjertos , Trasplante de Neoplasias , Fitoterapia , Neoplasias de la Próstata/patología , Piranocumarinas/metabolismo , Animales , Benzopiranos/uso terapéutico , Butiratos/uso terapéutico , Línea Celular , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Humanos , Masculino , Ratones SCID , Ratones Transgénicos , Raíces de Plantas/química , Neoplasias de la Próstata/tratamiento farmacológico , Piranocumarinas/aislamiento & purificación

RESUMEN

Seven pyranocoumarins, clauemarmarins A-G, along with 6 known analogues were isolated from the stems of Clausena emarginata. Their structures were elucidated by extensive spectroscopic analyses, and the absolute stereochemistries at C-6″ of clauemarmarin B, C and D and the absolute configurations of clauemarmarin E, F and G were determined by ECD experiments. Compounds clauemarmarin C, D and two known analogues exhibited hepatoprotective activities against DL-galactosamine-induced damage in WB-F344 cells at the concentration of 10 µM.

Asunto(s)

Clausena/química , Hígado/efectos de los fármacos , Tallos de la Planta/química , Piranocumarinas/aislamiento & purificación , Piranocumarinas/farmacología , Alcaloides/química , Galactosamina/farmacología , Piranocumarinas/química

RESUMEN

For the first time, the separation of coumarin derivatives from the petroleum ether extract of the fruits of Mutellina purpurea through high-performance countercurrent chromatography (HPCCC) is described. Four compounds, pteryxin (1; 2.72 mg), hyuganin C (2; 7.94 mg), osthol (3; 4.30 mg), and hyuganin A (4; 3.09 mg), were obtained in a single run following the injection of crude extract (300 mg). Additionally, auraptenol (5) and hyuganin D (6) were identified using LC-ESI-(Q)TOF-MS. The structures of the isolated compounds were elucidated through spectroscopic (NMR and MS) methods. This is apparently the first report of the identification of dihydropyranocoumarins in this plant, and the first time that HPCCC was used to separate them.

Asunto(s)

Apiaceae/química , Cumarinas/aislamiento & purificación , Piranocumarinas/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Cumarinas/química , Distribución en Contracorriente/métodos , Estructura Molecular , Extractos Vegetales/química , Polonia , Piranocumarinas/química

RESUMEN

A carbazole-pyranocoumarin conjugate, carbazomarin B (1), and two carbazole alkaloids, 6-methoxymukonidine (2) and 2-hydroxy-3-methoxycarbazole (3), together with 27 known compounds (4-30), were isolated from the stems of Clausena excavata. Their structures have been elucidated by spectroscopic analyses. Compound 2 showed moderate cytotoxicity to HuCCA-1, MOLT-3 and HepG2 cancer cell lines with IC50 values of 15.09-28.50 µg/mL, but none to A549 cell line. Heptaphylline (6) and nordentatin (23) were found to show moderate cytotoxic activity against HepG2 cell line with IC50 values of 12.33 and 11.33, respectively, while clausine K (27) exhibited strong cytotoxicity with IC50 value of 1.05 µg/mL, better than a standard drug (etoposide, IC50 13.40 µg/mL).

Asunto(s)

Antibacterianos/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Carbazoles/aislamiento & purificación , Clausena/química , Piranocumarinas/aislamiento & purificación , Antibacterianos/química , Antibacterianos/farmacología , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Carbazoles/química , Carbazoles/farmacología , Células Hep G2 , Humanos , Espectroscopía de Resonancia Magnética , Tallos de la Planta/química , Piranocumarinas/química , Piranocumarinas/farmacología

RESUMEN

This study investigated the anti-inflammatory activity of corymbocoumarin, an angular-type pyranocoumarin isolated from Seseli gummiferum subsp. corymbosum in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. Corymbocoumarin not only inhibited the production of nitric oxide (NO) and prostaglandin E2 (PGE2), but also inhibited the protein and mRNA expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Corymbocoumarin also attenuated pro-inflammatory cytokine tumor necrosis factor-α (TNF-α). Investigation of the effect on nuclear factor κB (NF-κB) signaling pathway showed that corymbocoumarin inhibited the phosphorylation of Akt and inhibitory κB (IκB)-α and decreased the subsequent translocation of the p65 and p50 NF-κB subunits to the nucleus. A further study revealed that corymbocoumarin exerted anti-inflammatory activity through induction of heme oxygenase (HO)-1 expression. The in vivo study showed that corymbocoumarin (20mg/kg, i.p.) reduced paw swelling in carrageenan-induced acute inflammation model. Taken together, these results suggest that corymbocoumarin exerts its anti-inflammatory effect in LPS-stimulated RAW 264.7 cells by suppressing NF-κB activation and inducing HO-1 expression. Corymbocoumarin may provide a useful therapeutic approach for inflammation-associated diseases.

Asunto(s)

Antiinflamatorios/uso terapéutico , Apiaceae/inmunología , Edema/tratamiento farmacológico , Macrófagos/efectos de los fármacos , FN-kappa B/metabolismo , Piranocumarinas/uso terapéutico , Animales , Antiinflamatorios/aislamiento & purificación , Dinoprostona/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Lipopolisacáridos/inmunología , Macrófagos/inmunología , Masculino , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Ratones Endogámicos ICR , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Piranocumarinas/aislamiento & purificación , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos

RESUMEN

A simple, rapid and robust liquid chromatography-tandem mass spectrometry was established and validated for simultaneous quantifications of three pyranocoumarins (praeruptorin A-C) in rat plasma. Following a single-step liquid-liquid extraction, the analytes were separated on a reversed-phase C18 column with a mobile phase consisting of methanol and 10 mM ammonium acetate solution (70 : 30, v/v) at a constant flow rate of 0.3 mL/min. The linear calibration curves were obtained over the concentration ranges 2.93-1470 ng/mL for praeruptorin A, 1.47-734 ng/mL for praeruptorin B and 2.00-1000 ng/mL for praeruptorin C. The within-batch accuracy was -8.6 to 7.5% for praeruptorin A, -9.5 to 12.0% for praeruptorin B and -10.5 to 12.5% for praeruptorin C, respectively. The between-batch accuracy was -3.5 to 1.4% for praeruptorin A, -8.7 to 3.4% for praeruptorin B and -6.0 to 4.3% for praeruptorin C, respectively. The within-batch and between-batch precisions were ≤13.1 and ≤8.2%, respectively. This method is suitable to simultaneously determine the three pyranocoumarins in plasma and thus to investigate the pharmacokinetics of the pyranocoumarins of Peucedanum praeruptorum in rats.

Asunto(s)

Apiaceae/química , Cromatografía Líquida de Alta Presión/métodos , Piranocumarinas/sangre , Piranocumarinas/farmacocinética , Espectrometría de Masas en Tándem/métodos , Animales , Estabilidad de Medicamentos , Modelos Lineales , Masculino , Extractos Vegetales/química , Raíces de Plantas/química , Piranocumarinas/química , Piranocumarinas/aislamiento & purificación , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

A new dihydropyranocoumarin, (+)-cis-(3'S,4'S)-diisobutyrylkhellactone (1), together with five known compounds, 3'-senecioyl-4'-acetylkhellactone (2), 3'-isovaleryl-4'-acetylkhellactone (3), 3',4'-disenecioylkhellactone (4), 3'-isovaleryl-4'-senecioylkhellactone (5), and 3',4'-diisovalerylkhellactone (6), was isolated from Glehnia littoralis. Their chemical structures were elucidated based on the spectroscopic data interpretation, particularly 1D and 2D NMR data including HMQC and HMBC. All the isolated compounds showed the potential to inhibit LPS-induced nitric oxide production in RAW 264.7 cells with IC50 values ranging from 7.4 to 44.3µM.

Asunto(s)

Apiaceae/química , Macrófagos/efectos de los fármacos , Óxido Nítrico/antagonistas & inhibidores , Extractos Vegetales/farmacología , Piranocumarinas/química , Piranocumarinas/farmacología , Animales , Línea Celular , Concentración 50 Inhibidora , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Piranocumarinas/aislamiento & purificación

RESUMEN

Angular-type pyranocoumarins (APs), the derivatives of khellactone, are widely documented as the main active constituents in Peucedani Radix (Chinese name: Qian-hu). Owing to the natural occurrence of chiral centers, enantiomers of APs are extensively distributed in the original plant, and enantioselective performances have been definitely demonstrated for these enantiomers. In current study, the chemical characterization of the major and minor APs in Peucedani Radix was performed using ultra high performance liquid chromatography coupled with diode array detector and hybrid ion trap-orbitrap mass spectrometry. On the other hand, a heart-cut two-dimensional achiral-chiral liquid chromatography combining triple quadropole-linear ion trap mass spectrometry system (2D LC-MS/MS) was developed for simultaneous enantiospecific quantification of eighteen coumarins, including seven pairs of enantiomers. Eleven APs (1-11) were recruited to propose UV absorption characteristics and electrospray ionization fragmentation patterns of APs. A total of 42 components were categorized into APs based on their UV spectral properties and identified according to the proposed mass fragmentation pathways, while two linear-type furanocoumarins (12-13) were unambiguously assigned by further purification. A Capcell core RP-C18 column was employed in the primary LC dimension to achieve efficient racemic separation for the main chemical constituents (1-9 and 12-13) in Peucedani Radix, while a Chiralpak AD-RH column was utilized in the secondary dimension to contribute enantioselective separation for seven enantiomerically enriched components (1, 3 and 5-9). Collectively, the results provided the chemical evidences for revealing the material basis of the therapeutic effects of Peucedani Radix, and the developed 2D LC-MS/MS system in the present study is expected to be an ideal tool for the quality control of Peucedani Radix as well as a reliable technique for complex matrices containing both achiral and chiral components.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/química , Piranocumarinas/análisis , Espectrometría de Masas en Tándem/métodos , Piranocumarinas/aislamiento & purificación , Estereoisomerismo

RESUMEN

Enantiomers and diastereoisomers of angular-type pyranocoumarins (APs) are abundant in Peucedani Radix (Chinese name: Qian-hu), eliciting distinct activities in vitro and in vivo. Our ongoing investigation on APs yielded eight pairs of enantiomers (1a and 1b, 2a and 2b, 3a and 3b, 4a and 4b, 5a and 5b, 6a and 6b, 7a and 7b and 8a and 8b) via enantiomeric separation of trans-3'-angeloylkhellactone (1), trans-3'-acetyl-4'-isobutyrylkhellactone (2), trans-3'-acetyl-4'-angeloyl-khellactone (3), 3'-angeloyloxy-4'-oxo-3',4'-dihydroseselin (4), cis-3'-acetyl-4'-angeloylkhellactone (5), cis-3'-isovaleryl-4'-acetylkhellactone (6), cis-3'-angeloyl-4'-isovalerylkhellactone (7) and cis-3',4'-diisovalerylkhellactone (8), respectively, using semi-preparative AD-RH chiral column. All the compounds (1-8) were enantioseparated for the first time, while the absolute configurations of 2a, 2b, 6a and 8b were reported first.

Asunto(s)

Apiaceae/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Piranocumarinas/aislamiento & purificación , Algoritmos , Cumarinas , Medicamentos Herbarios Chinos/química , Resonancia Magnética Nuclear Biomolecular , Raíces de Plantas , Piranocumarinas/química , Estereoisomerismo

RESUMEN

From the stem bark of a Madagascan endemic plant, Millettia richardiana Baill., lonchocarpenin and betulinic acid were isolated and their structures established by spectroscopic methods. The analysis of dichloromethane fractions suggested the presence of beta-amyrin, lupeol, palmitic acid, linoleic acid and stearic acid. Except for beta-amyrin and lupeol, these compounds are described for the first time for the Millettia genus.

Asunto(s)

Millettia/química , Piranocumarinas/aislamiento & purificación , Triterpenos/aislamiento & purificación , Triterpenos Pentacíclicos , Ácido Betulínico

RESUMEN

The aim of this study is to investigate and compare the metabolic rate and profiles of pyranocoumarin isomers decursin and decursinol angelate using liver microsomes from humans and rodents, and to characterize the major metabolites of decursin and decursinol angelate in human liver microsomal incubations using LC-MS/MS. First, we conducted liver microsomal incubations of decursin and decursinol angelate in the presence or absence of NADPH. We found that in the absence of NADPH, decursin was efficiently hydrolyzed to decursinol by hepatic esterase(s), but decursinol angelate was not. In contrast, formation of decursinol from decursinol angelate was mediated mainly by cytochrome P450(s). Second, we measured the metabolic rate of decursin and decursinol angelate in liver S9 fractions from mice and humans. We found that human liver S9 fractions metabolized both decursin and decursinol angelate more slowly than those of the mouse. Third, we characterized the major metabolites of decursin and decursinol angelate from human liver microsomes incubations using HPLC-UV and LC-MS/MS methods and assessed the in vivo metabolites in mouse plasma from a one-dose PK study. Decursin and decursinol angelate have different metabolite profiles. Nine metabolites of decursin and nine metabolites of decursinol angelate were identified in human liver microsome incubations besides decursinol using a hybrid triple quadruple linear ion trap LC-MS/MS system, and many of them were later verified to be also present in plasma samples from rodent PK studies.

Asunto(s)

Benzopiranos/metabolismo , Butiratos/metabolismo , Microsomas Hepáticos/metabolismo , Piranocumarinas/metabolismo , Animales , Apiaceae/química , Benzopiranos/aislamiento & purificación , Butiratos/aislamiento & purificación , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Endogámicos , Piranocumarinas/aislamiento & purificación , Ratas , Ratas Sprague-Dawley

RESUMEN

Zosima absinthifolia (Vent) Link (Apiaceae) is a perennial herb indigenous to Iran. It has been used as a medicinal plant from ancient time in Iran, Turkey and Pakistan. In the present work, air-dried and powdered plant roots were extracted with n-hexane, dichloromethane and methanol, respectively, using Soxhlet apparatus. The dichloromethane extract was subjected to vacuum liquid chromatography (VLC) and preparative thin layer chromatography (P-TLC) to yield two pyranocoumarins, aegelinol and agasyllin. The antimicrobial assay was performed using agar dilution method. The results showed that purified compounds have modest to weak antibacterial and antifungal activity.

Asunto(s)

Antifúngicos/farmacología , Bacterias/efectos de los fármacos , Cumarinas/farmacología , Extractos Vegetales/farmacología , Piranocumarinas/farmacología , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Apiaceae/química , Cromatografía en Capa Delgada , Cumarinas/química , Hexanos/química , Humanos , Extractos Vegetales/química , Raíces de Plantas/química , Plantas Medicinales/química , Piranocumarinas/química , Piranocumarinas/aislamiento & purificación

RESUMEN

Antifungal activity of petroleum ether extract of Psoralea corylifolia L. seed, tested against Fusarium sp. namely, Fusarium oxysporum, Fusarium moniliforme, and Fusarium graminearum, was evaluated by agar well diffusion assay. The chromatographic fractionation of the extract yielded a new phenyl derivative of pyranocoumarin (PDP). The structure of the PDP was confirmed using spectroscopic characterization (GC-MS, IR, and NMR), and a molecular mass of m/z 414 [M-2H](+) with molecular formula C(27)H(28)O(4) was obtained. The PDP had a potent antifungal activity with a minimum inhibitory concentration of 1 mg/mL against Fusarium sp. Molecular docking using Grid-Based Ligand Docking with Energetics (GLIDE, Schrodinger) was carried out with the Tri101, trichothecene 3-O-acetyltransferase, as target protein to propose a mechanism for the antifungal activity. The ligand PDP showed bifurcated hydrogen bond interaction with active site residues at TYR 413 and a single hydrogen bond interaction at ARG 402 with a docking score -7.19 and glide energy of -45.78 kcal/mol. This indicated a strong binding of the ligand with the trichothecene 3-O-acetyltransferase, preventing as a result the acetylation of the trichothecene mycotoxin and destruction of the "self-defense mechanism" of the Fusarium sp.

Asunto(s)

Acetiltransferasas/antagonistas & inhibidores , Antifúngicos/farmacología , Enfermedades de las Plantas/prevención & control , Psoralea/química , Piranocumarinas/farmacología , Acetilación/efectos de los fármacos , Acetiltransferasas/química , Acetiltransferasas/metabolismo , Alcanos , Antifúngicos/química , Antifúngicos/aislamiento & purificación , Antifúngicos/metabolismo , Fraccionamiento Químico , Fusarium/efectos de los fármacos , Fusarium/enzimología , Pruebas de Sensibilidad Microbiana , Modelos Moleculares , Extractos Vegetales/química , Unión Proteica , Piranocumarinas/química , Piranocumarinas/aislamiento & purificación , Piranocumarinas/metabolismo , Semillas/química , Análisis Espectral , Termodinámica

RESUMEN

Korean Angelica gigas Nakai (AGN) is a major medicinal herb used in Asian countries such as Korea and China. Traditionally, its dried root has been used to treat anemia, pain, infection and articular rheumatism in Korea, most often through boiling in water to prepare the dosage forms. The pyranocoumarin compound decursin and its isomer decursinol angelate (DA) are the major chemical components in the alcoholic extracts of the root of AGN. The in vitro anti-tumor activities of decursin and/or DA against prostate cancer, lung cancer, breast cancer, colon cancer, bladder cancer, sarcoma, myeloma and leukemia have been increasingly reported in the past decade whereas the in vivo efficacy in mouse models was established only for a few organ sites. Preliminary pharmacokinetic studies by us and others in rodent models indicated that decursinol (DOH), which has much less in vitro direct anticancer activities by itself, is the major and rapid in vivo hydrolysis metabolite of both decursin and DA. Besides decursin, DA and DOH, other chemical components in AGN such as polysaccharides and polyacetylenes have been reported to exert anti-cancer and anti-inflammation activities as well. We systematically reviewed the published literature on the anti-cancer and other bio-activities effects of AGN extract and decursin, DA and DOH, as well as other chemicals identified from AGN. Although a number of areas are identified that merit further investigation, one critical need is first-in-human studies of the pharmacokinetics of decursin/DA to determine whether humans differ from rodents in absorption and metabolism of these compounds.

Asunto(s)

Angelica/química , Anticarcinógenos/farmacología , Neoplasias/prevención & control , Extractos Vegetales/farmacología , Piranocumarinas/farmacología , Animales , Anticarcinógenos/aislamiento & purificación , Anticarcinógenos/farmacocinética , Anticarcinógenos/uso terapéutico , Humanos , Medicina Tradicional Coreana , Estructura Molecular , Neoplasias/irrigación sanguínea , Neoplasias/inmunología , Neoplasias/patología , Neovascularización Patológica/prevención & control , Extractos Vegetales/aislamiento & purificación , Extractos Vegetales/farmacocinética , Extractos Vegetales/uso terapéutico , Raíces de Plantas/química , Piranocumarinas/aislamiento & purificación , Piranocumarinas/farmacocinética , Piranocumarinas/uso terapéutico , República de Corea

RESUMEN

In this study, the decursin derivative dihydropyranocoumarin D2 (1) was selected for its effects on melanogenesis using a spontaneously immortalized mouse melanocyte cell line (Mel-Ab). The results showed that 1 effectively inhibited melanin synthesis in a concentration-dependent manner, but that it did not inhibit tyrosinase in a cell-free system. In addition, the changes in ERK, Akt, and microphthalmia-associated transcription factor (MITF) in response to treatment with 1 were assessed. The results revealed that ERK was dramatically up-regulated and MITF was down-regulated in response to treatment with 1, but that Akt was unchanged. Therefore, the effects of 1 on melanogenesis were examined in the absence or presence of PD98059 (a specific inhibitor of the ERK pathway). PD98059 restored hypopigmentation and the down-regulation of MITF induced by 1. Finally, MITF down-regulation by 1 was clearly restored by both chloroquine, a lysosomal proteolysis inhibitor, and MG132, a proteasome inhibitor.

Asunto(s)

Flavonoides/farmacología , Hipopigmentación/inducido químicamente , Melaninas/biosíntesis , Melanocitos/efectos de los fármacos , Factor de Transcripción Asociado a Microftalmía/efectos de los fármacos , Monofenol Monooxigenasa/metabolismo , Piranocumarinas/aislamiento & purificación , Piranocumarinas/farmacología , Animales , Benzopiranos/química , Butiratos/química , Relación Dosis-Respuesta a Droga , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/efectos de los fármacos , Leupeptinas/farmacología , Lisosomas/efectos de los fármacos , Lisosomas/metabolismo , Melanocitos/metabolismo , Ratones , Estructura Molecular , Inhibidores de Proteasoma , Piranocumarinas/química

RESUMEN

Two new dihydropyranocoumarins, scuteflorins A (1) and B (2), together with the known compounds decursin (3), chrysin (4), oroxylin A (5), wogonin (6), 5,7-dihydroxy-8,2'-dimethoxyflavone, dihydrochrysin, dihydrooroxylin A, lupenol, scutellaric acid, pomolic acid, ursolic acid, beta-sitosterol, daucosterol, and palmitic acid, were isolated from the aerial parts of Scutellaria lateriflora, commonly used as a dietary supplement. The structures of 1 and 2 were established by means of 1D and 2D NMR spectra as well as HRMS data. The absolute configuration of coumarins 1 and 2 was determined by comparison of experimental and theoretical calculated CD spectra. The cytotoxicity and antioxidant effects of the methanol extract of this plant and some of the constituent flavonoids were evaluated in vitro.

Asunto(s)

Piranocumarinas/aislamiento & purificación , Algoritmos , Animales , Chlorocebus aethiops , Ensayos de Selección de Medicamentos Antitumorales , Flavanonas/química , Flavanonas/aislamiento & purificación , Flavonoides/química , Flavonoides/aislamiento & purificación , Células HL-60 , Humanos , Resonancia Magnética Nuclear Biomolecular , Piranocumarinas/química , Piranocumarinas/farmacología , Células Vero