Three-dimensional multi-component analysis of Aurantii Fructus quality and research on influencing factors / 中国中药杂志

The present study explored the consistency of the content proportions of active components of Aurantii Fructus and analyzed the influencing factors based on three-dimensional multi-component analysis. A total of 839 Aurantii Fructus samples in 65 research articles were analyzed using the three-dimensional multi-component analysis mode. The content data of flavonoid components(naringin, hesperidin, neohesperidin, narirutin, and nobiletin), coumarin components(meranzin and gluconolactone), and alkaloid(synephrine) in 386 samples which met the criteria of 2020 edition of the Chinese Pharmacopoeia were extracted and adjusted to percentages, and the content ratios between components were calculated. The influencing factors of Aurantii Fructus quality were analyzed. The results showed content ratios of components as follows: neohesperidin∶naringin in the range of 0.4-1.2; narirutin∶naringin in the range of 0.02-0.16; hesperidin∶naringin in the range of 0.01-0.3; nobiletin∶naringin in the range of 0.000 588 3-0.069 68; synephrine∶naringin in the range of 0.02-0.042; gluconolactone∶naringin in the range of 0.001-0.01; meranzin∶naringin in the range of 0.000 4-0.035. The quality of Aurantii Fructus was closely related to the origin, variety, harvesting time, and processing method of medicinal materials. Harvesting time had a greater impact on the quality of Aurantii Fructus, and the origin and variety had a certain impact on the quality of Aurantii Fructus. The findings of this study indicated that the ratios between flavonoid components, flavonoids and coumarin components, and flavonoids and alkaloids fluctuated. The production base should optimize the varieties, harvesting period, and processing methods of Aurantii Fructus to provide a scientific basis for the production of high-quality Aurantii Fructus.

Synthesis of some novel pyrimidine, thiophene, coumarin, pyridine and pyrrole derivatives and their biological evaluation as analgesic, antipyretic and anti-inflammatory agents

Pyrimidine derivative 3 was afforded through the reaction of compound (1) with 5-ureidohydantion (2). Product 3 underwent a cyclization to produce fused pyrimidine derivative 7, although the latter product 7 was synthesized through one step via the reaction of compound (1) with 5-ureidohydantion (2) using another catalyst. Compound 3 was oriented to react with cyclic ketones 8a,b in the presence of elemental sulfur, salicylaldehyde (10), aryldiazonium chlorides 12a,b and ω-bromo-4-methoxy- acetophenone (14), which afforded, fused thiophene derivatives 9a,b, coumarin derivative 11, arylhdrazono derivatives 13a,b and 4-methoxyphenyl butenyl derivative 15, respectively. The latter product 15 was reacted with either potassium cyanide (16a) or potassium thiocyanide (16b) to form cyano and thiocyano derivatives 17a,b, respectively. Compound 17a underwent further cyclization to afford pyridopyrimidine derivative 19. Compound 15 was reacted with either hydrazine (20a) or phenylhydrazine (20b) to produce hydrazo derivatives 21a,b and these products were cyclize to produce pyrrole derivatives 23a,b. Finally, 5-ureidohydantion (2) was reacted with compounds 24a,b,c to afford pyrimidine derivatives 25a,b,c. The structures of the synthesized compounds were confirmed using IR, 1H NMR, 13C NMR and mass spectrometry techniques. Compounds 11 and 19 have promising as analgesic and antipyretic activities

In vitro intestinal permeability studies, pharmacokinetics and tissue distribution of 6-methylcoumarin after oral and intraperitoneal administration in Wistar rats

ABSTRACT 6-Methylcoumarin (6MC) is a semisynthetic coumarin with important in vitro and in vivo anti-inflammatory activity. In order to continue the pre-clinical characterization of this molecule, in vitro intestinal permeability, plasma profile and tissue distribution after oral administration in rats were studied. The permeability of 6MC was evaluated by the Caco-2 cellular model in both the apical-basal (A-B) and basal-apical (B-A) directions. The pharmacokinetics and biodistribution were evaluated in rats after oral and intraperitoneal administration at doses of 200 mg/kg. Transport experiments with Caco-2 cells showed that 6MC presented high permeability at all concentrations evaluated. This finding suggested that 6MC could be transported across the gut wall by passive diffusion. The plasma concentration-time curve showed that the maximum concentration (Cmax) was 17.13 ± 2.90 µg/mL at maximum time (Tmax) of 30 min for the oral route and Cmax 26.18 ± 2.47 µg/mL at 6.0 min for the intraperitoneal administration, with elimination constant of (Ke ) 0.0070 min-1 and a short life half time of (T1/2 ) lower that 120 min. The distribution study showed that 6MC has high accumulation in the liver, and widespread distribution in all the organs evaluated.

Mecanismos moleculares da interação entre betalaínas cumarínicas fluorescentes e células de glioma humano / Molecular mechanisms of interaction between fluorescent coumarinic betalains and human glioma cells

Moléculas orgânicas fluorescentes são uma importante ferramenta para biologia celular. Compostos ideais para esta aplicação devem ter alto brilho (produto do coeficiente de atenuação molar e do rendimento quântico de fluorescência), ser fotoestáveis e internalizáveis, não comprometer a viabilidade celular e interagir com biomoléculas com algum grau de especificidade. Nesta Tese de Doutorado é apresentado o estudo do uso de cBeet120, uma betalaína cumarínica artificial, e células de glioma humano da linhagem U87-MG. Betalaínas são pigmentos de plantas que apresentam alta biocompatibilidade que servem como material de partida para o desenvolvimento de derivados funcionais. A sonda se acumula principalmente no núcleo das células U87- MG e marca principalmente nucléolos via interação com proteínas. A presença de DNAse ou RNAase elimina a marcação nuclear, sem afetar a fraca marcação citoplasmática de fundo. Estudos de inibição de transporte sugerem que cBeet120 é internalizada por transportadores de L-glutamato da família de transportadores de amino ácidos excitatórios (EAAT). O uso de artemisinina para inibição Ca2+-ATPases aumenta a velocidade de internalização de cBeet120 em células U87-MG. Quando irradiada com luz de cor ciano, cBeet120 no interior do núcleo de células vivas é fotoativada, resultando em um aumento da intensidade de fluorescência com o tempo (monitorado por 90 min) e o deslocamento hipsocrômico do máximo de emissão. Em células fixadas com paraformaldeído, o padrão de marcação da célula se torna mais difuso e a sonda emite fluorescência sem fotoativação. Medidas de tempo de vida de fluorescência em solução e imageamento por microscopia de tempo de vida de fluorescência permitem inferir a ocorrência da formação de um complexo proteína-cBeet120 ou um produto de transiminação que pode estar sujeito a isomerização cis/trans

Fluorescent organic molecules are an important tool for cell biology. Ideal compounds for this application must have high brightness (product of the molar attenuation coefficient and fluorescence quantum yield), be photostable and internalizable by cells, do not compromise cellular viability and interact with biomolecules with some degree of specificity. In this Doctorate Thesis, we describe the interaction of cBeet120, an artificial coumarinic betalain, and human glioma cells of line U87-MG. Betalains are plant pigments that exhibit high biocompatibility that serve as starting material for the development of functional derivatives. The probe accumulates mainly in the nucleus of the U87-MG cells and mainly marks nucleoli via interaction with proteins. The presence of DNAse or RNAase eliminates nuclear labeling, without affecting the poor background cytoplasmic labeling. Transport inhibition studies suggest that cBeet120 is internalized by L-glutamate transporters from the excitatory amino acid transporter (EAAT) family. The use of artemisinin for inhibition Ca2+-ATPases increases the rate of cBeet120 internalization in U87-MG cells. When irradiated with cyan colored light, cBeet120 within the nucleus of living cells is photoactivated, resulting in an increase in fluorescence intensity over time (monitored for 90 min) and the hypochromic shift of the emission maximum. In cells fixed with paraformaldehyde, the labeling pattern of the cell becomes more diffuse and the probe emits fluorescence without photoactivation. Fluorescence life-time measurements in solution and fluorescence life-time imaging microscopy allows to infer the occurrence of the formation of a protein-cBeet120 complex or the formation of a transimination product that may be subject to cis/trans isomerization

Validação de um método analítico rápido por CLAE-UV para determinação de cumarina em guaco (Mikania glomerata Sprengel) confirmado com espectrometria de massas / Validation of a rapid analytical method by HPLC for determining coumarin in guaco (Mikania glomerata Sprengel) confirmed with mass spectrometry

RESUMO A espécie Mikania glomerata Sprengel, popularmente conhecida no Brasil como guaco, é amplamente utilizada como expectorante para tratar doenças respiratórias e tem a sua atividade farmacológica atribuída principalmente a cumarina. Os resultados mostraram que o método apresenta linearidade de 0,05 a 0,8 mg mL-1. Ele foi considerado seletivo, exato e preciso. A proposta de um método rápido para determinação de cumarina em extratos de guaco torna-se interessante para a rotina de controle de qualidade industrial, visando à obtenção de medicamentos fitoterápicos padronizados.

ABSTRACT The species Mikania glomerata Sprengel, popularly known in Brazil as “guaco”, is widely used as an expectorant to treat respiratory diseases. Its pharmacological activity is mainly attributed to coumarin. The results showed that the method for determining coumarin presented linearity from 0.05 to 0.8 mg mL-1. It was considered selective, accurate, and precise according to the specific resolution from ANVISA, the Brazilian regulatory agency. The proposal of a rapid method for the determining coumarin in extracts of guaco is interesting for routine industrial quality control in order to obtain standardized, efficient, and safe phytotherapic medicines.

Stability of Tilo ® tablets formulation obtained from dry extract of Justice pectoralis Jacq

Justicia pectoralis Jacq., Acanthaceae, is a herb known popularly in Cuba as Tilo and used traditionally as sedative. The development in a solid pharmaceutical (Tablets 100 mg) using dry extract of Justicia pectolaris aqueous extract is of interest for the development of phytomedicines, which uses this active raw material. The aim of the present study was to carry out chemical and biological stability studies to the formulation. A method of coumarin determination by High Performance Liquid Chromatography (HPLC) was used and validated. The stability studies during different periods of time (24 months) showed a stability of the product stored at 32 ± 2 °C, and protected of the light.

Justicia pectoralis Jacq., Acanthaceae é uma erva conhecida popularmente em Cuba como Tilo e utilizada tradicionalmente como sedativo. O desenvolvimento de formas farmacêuticas sólidas (comprimido 100 mg) usando extrato aquoso seco de J. pectoralis é de interesse no desenvolvimento de fitoterápicos que empreguem esse princípio ativo. O objetivo do presente estudo foi realizar estudos de estabilidade químicos e biológicos da formulação. Um método de determinação de cumarinas por Cromatografia Líquida de Alta Eficiência (CLAE) foi usado e devidamente validado. Os estudos de estabilidade durante diferentes períodos de tempo (24 meses) mostraram a estabilidade do produto preservado a 32 ± 2 °C e protegido da luz.

Rendimento extrativo de cumarina de folhas de guaco (Mikania glomerata Sprengel) submetidas a diferentes temperaturas de secagem / Extraction yield of coumarin from guaco (Mikania glomerata Sprengel) leaves subjected to different drying temperatures

O objetivo deste trabalho foi avaliar o efeito da temperatura do ar de secagem no rendimento extrativo da cumarina de folhas de guaco. Foram empregados 6 tratamentos de secagem, sendo ar ambiente, ar aquecido a 40, 50, 60, 70 e 80ºC. Utilizou-se secador de bandejas, tendo como fonte de aquecimento o gás liquefeito de petróleo (GLP). Os rendimentos extrativos da cumarina, depois de realizada a secagem, foram comparados com os valores obtidos da planta fresca (tratamento testemunha). A extração da cumarina foi realizada pelo método a quente, em banho-maria a 65ºC, sendo a identificação e quantificação realizada por cromatografia líquida de alta eficiência (CLAE). Em função dos resultados obtidos, pôde-se concluir que a temperatura do ar de secagem a 50ºC possibilitou o melhor resultado para o rendimento extrativo de cumarina em folhas de guaco.

The aim of this study was to evaluate the effect of drying on the extraction yield of coumarin from guaco leaves. Six drying treatments were used, being room air, heated air at 40, 50, 60, 70 and 80ºC. A tray dryer was used with liquefied petroleum gas (LPG) as heating source. The extraction yield of coumarin, after drying, was compared to the values obtained from the fresh plant (control treatment). Coumarin extraction was carried out by using the heat method, in water bath at 65ºC, and identification and quantification were done by means of high performance liquid chromatography (HPLC). Considering the obtained results, the temperature of the drying air at 50ºC led to the best result for the extraction yield of coumarin in guaco leaves.

Chemical constituents from the stem of Brosimum potabile (Moraceae) / Constituintes químicos do cerne de Brosimum potabile (Moraceae)

Three coumarins, 5-methoxypsoralene, xanthyletin, and (-)-marmesin, have been isolated from the ethanolic extract of the stem of the Amazonian plant Brosimum potabile. The structures were determined on the basis of NMR analyses and by comparison with spectroscopic data in the literature. The analysis of the hexane fractions by GC-MS in EIMS mode suggested the presence of (1-methylpentyl)-benzene; α,α-dimethyl-4-(1-methylethyl)-benzenemethanol; 1-methyl-3,5-bis(1-methylethyl)-benzene; urs-12-ene; chola-5,22-dien-3ß-ol; cholesta-4,6-dien-3ß-ol; sitosteryl 9(Z)-octadecenoate; cholesta-5,22-dien-3ß-ol; cholesta-4,6,22-trien-3-one; and cholesta-4,22-dien-3-one. NMR data of other hexane fractions indicated the presence of 3ß-acetoxy-lup-12,20(29)-diene; 3ß-acetoxy-olean-12-ene; 3ß-acetoxy-urs-12-ene; and adian-5-ene. All these compounds are first described in B. potabile.

Três cumarinas, 5-metoxipsoraleno, xantiletina e (-)-marmesina, foram isoladas no extrato etanólico do cerne da planta amazônica Brosimum potabile. Suas estruturas foram determinadas a partir das análises por RMN e por comparação com dados espectroscópicos da literatura. As análises das frações hexânicas por CG/EM sugeriram a presença de (1-metilpentil)-benzeno; α,α-dimetil-4-(1-metiletil)-benzenometanol; 1-metil-3,5-bis(1-metiletil)-benzeno; urs-12-eno; cola-5,22-dien-3ß-ol; colesta-4,6-dien-3ß-ol; (9Z)-octadecenoato de sitosterila; colesta-5,22-dien-3ß-ol; colesta-4,6,22-trien-3-ona e colesta-4,22-dien-3-ona. Dados de RMN de outras frações hexânicas indicaram a presença de 3ß-acetóxi-lup-12,20(29)-dieno; 3ß-acetóxi-olean-12-eno; 3ß-acetóxi-urs-12-eno e adian-5-eno. Todos esses compostos foram identificados pela primeira vez em B. potabile.

Estudo fitoquímico da espécie Pterocaulon interruptum DC. (Asteraceae) / Phytochemical study of Pterocaulon interruptum Dc., Asteraceae

A análise fitoquímica das partes aéreas de Pterocaulon interruptum DC. (Asteraceae) resultou no isolamento de cinco compostos: uma cumarina, sabandinol, dois esteróides, estigmasterol e 3-O-acetil-taraxasterol e dois flavonóides, quercetina e taxifolina 7-O-prenilada. As estruturas destas substâncias foram estabelecidas por análises espectroscópicas, sendo que este é o primeiro trabalho sobre o isolamento destes compostos em Pterocaulon interruptum DC.

Chemical investigation of the aerial parts of Pterocaulon interruptum DC., Asteraceae, resulted in the isolation of five compounds: one coumarin, sabandinol, two steroids, stigmasterol and 3-O-acetyl taraxasterol and two flavonoids, quercetin (flavonol) and 7-O-prenyl taxifolin (dihydroxyflavonol). The structures of these compounds were established by spectroscopic analysis. This paper deals with the first report of these compounds in Pterocaulon interruptum DC.

Spectrophotometric studies on some hydroxy nitrosocoumarins

The UV and visible absorption spectra of some hydroxy nitrosocoumarins have been studied in organic solvents of varying polarities. The dependence of the band shift on the nature of substituent, dielectric effect and specific solvation was studied. The acid dissociation constants of the different ionizable groups were determined using the half- height and the modified limiting absorbance methods. The observed transition energy and oscillator strengths were correlated with those calculated from the SCF PPP CI method for molecular orbitals

Perfil fluorimetrico de algumas tinturas-mae de origem vegetal / Fluorimetric spectres of some vegetal mother-tinctures

Numerosas especies vegetais apresentam compostos fluorescentes em sua composicao. Tais compostos sao farmacologica e toxicologicamente ativos. As cumarinas sao um desses grupos de compostos, absorvendo luz no ultravioleta proximo. Doze tinturas-mae que apresentam cumarinas como compostos secundarios foram examinadas quanto a essa propriedade fisica