Proliferation Inhibitory Activity of Quinones from Blaps rynchopetera Defense Secretion on Colorectal Tumor Cells / 中国结合医学杂志

OBJECTIVE@#To explore the proliferation inhibitory effect of quinones from Blaps rynchopetera defense secretion on colorectal tumor cell lines.@*METHODS@#Human colorectal cancer cell HT-29, human colorectal adenocarcinoma cell Caco-2 and normal human colon epithelial cell CCD841 were chosen for the evaluation of inhibitory activity of the main quinones of B. rynchopetera defense secretion, including methyl p-benzoquinone (MBQ), ethyl p-benzoquinone (EBQ), and methyl hydroquinone (MHQ), through methyl thiazolyl tetrazolium assay. The tumor-related factors, cell cycles, related gene expressions and protein levels were detected by enzyme-linked immunosorbent assy, flow cytometry, RT-polymerase chain reaction and Western blot, respectively.@*RESULTS@#MBQ, EBQ, and MHQ could significantly inhibit the proliferation of Caco-2, with half maximal inhibitory concentration (IC50) values of 7.04 ± 0.88, 10.92 ± 0.32, 9.35 ± 0.83, HT-29, with IC50 values of 14.90 ± 2.71, 20.50 ± 6.37, 13.90 ± 1.30, and CCD841, with IC50 values of 11.40 ± 0.68, 7.02 ± 0.44 and 7.83 ± 0.05 µg/mL, respectively. Tested quinones can reduce the expression of tumor-related factors tumor necrosis factor α, interleukin (IL)-10, and IL-6 in HT-29 cells, selectively promote apoptosis, and regulate the cell cycle which can reduce the proportion of cells in the G1 phase and increase the proportion of the S phase. Meanwhile, tested quinones could up-regulate mRNA and protein expression of GSK-3β and APC, while down-regulate that of β-catenin, Frizzled1, c-Myc, and CyclinD1 in the Wnt/β-catenin pathway of HT-29 cells.@*CONCLUSION@#Quinones from B. rynchopetera defense secretion could inhibit the proliferation of colorectal tumor cells and reduce the expression of related factors, which would be functioned by regulating cell cycle, selectively promoting apoptosis, and affecting Wnt/β-catenin pathway-related mRNA and protein expressions.

Dysideanones F-G and dysiherbols D-E, unusual sesquiterpene quinones with rearranged skeletons from the marine sponge Dysidea avara / 中国天然药物

Four new sesquiterpene quinone meroterpenoids, dysideanones F-G (1-2) and dysiherbols D-E (3-4), were isolated from the marine sponge Dysidea avara collected from the South China Sea. The new structures were elucidated by extensive analysis of spectroscopic data including HR-MS and 1D and 2D NMR spectra, and their absolute configurations were assigned by single-crystal X-ray diffraction and ECD calculations. Anti-inflammatory evaluation showed that dysiherbols D-E (3-4) exhibited moderate inhibitory activity on TNF-α-induced NF-κB activation in human HEK-293T cells with IC50 values of 10.2 and 8.6 μmol·L-1, respectively.

Constituent analysis of Jingzhi Guanxin Soft Capsule based on UHPLC-Q-Orbitrap HRMS / 中草药

Objective: In order to establish a rapid and efficient analysis method for identification of the complex components in Jingzhi Guanxin Soft Capsule, and provide the basic research data for the systematic elaboration of its chemical constituents. Methods: An ultra-high performance liquid chromatography-quadrupole/Orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used for the identification analysis of the components in Jingzhi Guanxin Soft Capsule, and the multistage fragments ions data was compared with the standard substance and literature consulting. Results: Forty-three compounds were identified in this study, including flavones, phthalides, organic acids, quinones and other categories. Conclusion: The chemical constituents of Jingzhi Guanxin Soft Capsule are identified systematically, accurately and efficiently, which provide the theory basis for the further research of its pharmacodynamic material basis and quality control.

Research progress on active components of fungi transforming Chinese materia medica / 中草药

Active components of Chinese materia medica (CMM) are the material basis of its efficacy and the keys to realize modernization of CMM. How to improve the content of active ingredients of CMM has become a research hotspot, and microbial transformation is one of its key technologies. The practice has proved that the strains are different, the types of CMM are different, and the transformation effects are different. Therefore, the research on fungal transformation of CMM active ingredients such as terpenes, alkaloids, phenylpropanoids, quinones, steroids, organic acids, etc. is reviewed in this study.

An overview of odoriferous marine seaweeds of the Dictyopteris genus: insights into their chemical diversity, biological potential and ecological roles

ABSTRACT Since the middle of the twentieth century the marine algae have attracted attention as a source of new drugs. Dictyopteris is an important group of marine seaweeds and is widely distributed in tropical, subtropical and temperate regions. This genus is known by its characteristic "ocean smell". Some species show a distinct phytochemistry, with specific secondary metabolites, including C11-hydrocarbons, sulfur compounds and quinone derivatives, not usually found in marine seaweeds and described for the first time in the literature. Furthermore, several terpenes, steroids and halogenated compounds have been described. This chemical diversity gives it interesting biological properties, including cytotoxic, antimicrobial, antioxidant, anti-inflammatory and anti-herbivory activities. These findings highlight the importance to continue investigations on this genus and the need to compile the data available so far, since the species are quite heterogeneous, notably in relation to the chemical constitution. This paper reviews the literature on the Dictyopteris genus, focusing on its secondary metabolites and biological activities, in order to build the base for further studies.

Research progress on chemical constituents and biological activities of Wikstroemia indica / 中草药

Wikstroemia indica as a Chinese herbal medicine, belonging to family Thymelaeaceae, was the root and root bark of the plant. Studies found that W. indica had acids, alcohols or esters, quinones, steroids, coumarins, lignans, flavonoids, terpenes, diarylheptanes, and fat-soluble ingredients, and has the effects of antibacterial, anti-virus, cytotoxic, and anti-inflammatory activities etc. The contents of coumarins, flavonoids, quinines, and lignans were measured and applied quality evaluation. In addition, as a toxic Chinese herbal medicine, the toxicity of W. indica could be reduced by processing methods, so further research is needed to confirm the relationship between the compound and its pharmacological activity. In this paper, the researches from 2010 to 2017 on chemical constituents, biological activities, and components detection of W. indica were collected and summarized, aiming to provide reference for further research and development on W. indica.

Main chemical constituents research of Qishen Yiqi Dropping Pills based on UHPLC-Q-Orbitrap HRMS / 中草药

Objective To recognize the chemical profile of Qishen Yiqi Dropping Pills (QYDP) comprehensively, systematically and rapidly; ultra high performance liquid chromatography-quadrupole/orbitrap high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was employed to identify the main chemical composition of this preparation. Methods A gradient elution for separation was achieved through ACQUITY UPLC® BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with acetonitrile-water (containing 0.1% formic acid) as the mobile phase. Then, the novel Q-Orbitrap MS technology was employed to detect the information of accurate mass and multistage fragment ions. Chemical constituents were characterized by comparing their relative retention time and mass data with that of the reference substance, meanwhile the reference literature, Mass Bank database, and Chemical Book network database were also consulted. Results A total of 53 ingredients were finally identified in this study, including 14 organic acids, 10 flavones, 10 authraquinones, 2 saponins, 7 amino acids, and 10 others. Conclusion An efficient method was established in this work to identify the main chemical ingredients of QYDP rapidly and accurately; Meanwhile, this research will lay a scientific foundation for the further research on pharmacodynamic material basis, quality control, and clinical application of this medicine.

Chemical constituents from roots and rhizomes of Rubia oncotricha and their cytotoxic activities / 中国中药杂志

Fourteen compounds, including rubiprasin D (1), rubiprasin B (2), rubiprasin C (3), oleanolic acid (4), methyl-5-hydroxy-dinaphtho[1, 2-2'3']furan-7, 12-dione-6-carboxylate (5), rubioncolin C (6), mollugin (7), furomollugin (8), 3-amino-2-methoxycarbonyl-1, 4-naphthoquinone (9), 1-hydroxy-2-methyl-9, 10-anthraquinone (10), 2-hydroxy-6-methyl-9, 10-anthraquinone (11), 1, 4-dihydroxy-2-hydroxymethyl-9, 10-anthraquinone (12), 2-hydroxy-1-methoxy-9, 10-anthraquinone (13), and 1-hydroxy-2-methoxy-6-methyl-9, 10-anthraquinone(14), were isolated from the methanol extract of the roots and rhizomes of Rubia oncotricha using various column chromatographies. Their structures were mainly determined on basis of NMR and MS spectroscopic data analyses. Among them, 1 is a new oleanane triterpene, and compounds 2-5, 9 and 11-13 were obtained from this plant for the first time. Cytotoxic and nematicidal activities of all these compounds were evaluated, and the results showed that only 4, 6, 11 and 12 exhibited cytotoxicities against A549, SGC-7901 and HeLa cancer cell lines. The IC₅₀ of 6 were 19.42, 2.74, 8.07 μmol·L⁻¹, respectively.

Citotoxicidad in vitro y potencialidades de los compuestos quinoides como agentes antitumorales / Cytotoxicity in vitro and potential of quinoid compounds as antitumor agents

La búsqueda e identificación de nuevos compuestos activos para la terapéutica del cáncer se ha centrado esencialmente en la investigación de productos naturales y de sus análogos sintéticos. El presente trabajo pretende sistematizar los conocimientos sobre las bases moleculares de la actividad citotóxica de los compuestos quinoides y su uso como agente antitumoral. Se realizó una revisión de artículos originales, de corte experimental, publicados en la década 2004-2014 en algunas bases de datos de la Biblioteca Virtual de Salud (BVS). Se constató que numerosos estudios han avalado la capacidad de los productos quinoides de inhibir el crecimiento celular, sustentado en sus posibilidades de dañar al ADN por estrés oxidativo y de interactuar de modo biorreductivo con otras biomoléculas. Además, que la potencia de la citotoxicidad de los compuestos quinoides se incrementa ante cadenas laterales alquiladas y anillos aromatizados unidos al motivo quinona. Las evidencias experimentales sugieren un promisorio futuro de estas moléculas como agentes antitumorales, en base a su citotoxicidad y elevada selectividad ante líneas celulares neoplásicas(AU)

The search and identification of new active compounds for cancer therapy has focused mainly on research of natural products and their synthetic analogs. This paper aims to systematize the knowledge of the molecular basis of the cytotoxic activity of the quinoid compounds and their use as an antitumor agent. A review was performed on original articles, experimental section, published in the 2004-2014 decade in some databases of the Virtual Health Library (VHL). Numerous studies have supported the ability of quinoid products inhibiting cell growth, based on their ability to damage DNA by oxidative stress and thus have a biorreductive interaction with other biomolecules. Furthermore, the power of cytotoxicity increases quinoid compounds alkylated with side chains attached to rings and quinone flavored motif. Experimental evidence suggests a promising future of these molecules as antitumor agents, based on their high selectivity and cytotoxicity against neoplastic cell lines(AU)

ANTHELMINTIC ACTIVITY OF LAPACHOL, β-LAPACHONE AND ITS DERIVATIVES AGAINST Toxocara canis LARVAE / Atividade anti-helmíntica do lapachol, β-lapachona e derivados contra larvas de Toxocara canis

Anthelmintics used for intestinal helminthiasis treatment are generally effective; however, their effectiveness in tissue parasitosis (i.e. visceral toxocariasis) is moderate. The aim of this study was to evaluate the in vitro activity of lapachol, β-lapachone and phenazines in relation to the viability of Toxocara canis larvae. A concentration of 2 mg/mL (in duplicate) of the compounds was tested using microculture plates containing Toxocara canis larvae in an RPMI-1640 environment, incubated at 37 °C in 5% CO2 tension for 48 hours. In the 2 mg/mL concentration, four phenazines, lapachol and three of its derivatives presented a larvicide/larvistatic activity of 100%. Then, the minimum larvicide/larvistatic concentration (MLC) test was conducted. The compounds that presented the best results were nor-lapachol (MLC, 1 mg/mL), lapachol (MLC 0.5 mg/mL), β-lapachone, and β-C-allyl-lawsone (MLC, 0.25 mg/mL). The larvae exposed to the compounds, at best MLC with 100% in vitro activity larvicide, were inoculated into healthy BALB/c mice and were not capable of causing infection, confirming the larvicide potential in vitro of these compounds.

Os anti-helmínticos empregados no tratamento das helmintoses intestinais, de modo geral, são eficazes, porém nas parasitoses teciduais, como é o caso da toxocaríase visceral, a eficácia é moderada. Este estudo teve como objetivo avaliar in vitro a atividade do lapachol, β-lapachona e fenazinas derivadas da β-lapachona sobre a viabilidade de larvas de Toxocara canis. Os compostos foram testados na concentração de 2 mg/mL (em duplicata) em placas de microcultivo, contendo larvas de T. canis em meio RPMI-1640, sendo incubados, a 37 °C, em tensão de CO2 de 5%, por 48 horas. Na concentração de 2 mg/mL, quatro fenazinas, o lapachol e três derivados, apresentaram atividade larvicida/larvostática de 100%. A seguir, foi realizado o teste de concentração larvicida/larvostártica mínima (CLM). Os compostos que apresentaram os melhores resultados foram o nor-lapachol (CLM, 1 mg/mL), lapachol (CLM, 0,5 mg/mL), a β-lapachona e a β-C-alil-lausona (CLM, 0,25 mg/mL). As larvas expostas aos compostos, na melhor CLM 100% in vitro foram inoculadas em camundongos BALB/c saudáveis não sendo capazes de causar infecção, confirmando o potencial larvicida in vitro desses compostos.

Optimization of Protein Extraction for Lichen Thalli

Lichen-forming fungal proteins have been seldom searched due to many difficulties in their extraction. Phenols, quinones, proteases, and other components released during cell disruption have been known to be the greatest challenges related to protein extraction from lichens. To overcome these problems and maintain good electrophoretic resolution and high protein concentration, an extraction buffer containing polyvinylpolypyrrolidone, ascorbic acid, Triton X-100, polyethylene glycol, proteinase, and oxidase inhibitors in sodium phosphate buffer was developed. This extraction buffer showed high efficiency for all lichen species tested in the study.

Survey of active components in commonly-used Chinese materia medica injections and related Chinese materia medica for cardiovascular disease / 中草药

To summarize the active components in commonly-used Chinese materia medica (CMM) injections and related CMM for cardiovascular disease, and provide the reference for the effective treatment of cardiovascular disease. We searched CNKI, Wanfang Data, PubMedand, and the reference lists of identified articles (from initial to September 1, 2014), and reviewed the literature. The commonly-used CMM injections for cardiovascular disease involve 15 kinds of injection, including Shenfu Injection, Shenmai Injection, Ciwujia Injection, Danhong Injection, etc. Three prescriptions originated from classical prescriptions but others were from the result of clinical and research. The CMMs in these prescriptions were all less in number, single flavor accounted for 60%, the maximum was three herbs. These injections mainly aimed at heart blood stasis syndrome, with many pharmacological effects of protection on cerebral ischemia-reperfusion damage, anti-thrombosis, anti-oxidants, and expansion of coronary artery. The most commonly-used CMMs were Salvia Miltiorrhiza Radix, Ginseng Radix et Rhizoma Rubra, and Carthami Flos. The kinds of active components included flavonoid, saponin, quinones, etc. This article provides a basis for the effective treatment of cardiovascular disease.

Synthesis and antiproliferative evaluation of new isomeric ellipticine quinones / Síntesis y evaluación de la actividad antiproliferativa de nuevas elipticinquinonas isomericas

The synthesis of new isomeric ellipticine quinones 3a-c and their in vitro antiproliferative activities on cancer cell lines is reported. The designed N-heterocyclic quinones 3a-c were synthesized through a three step sequence which involves: a) one-pot preparation of 4-methoxycarbonyl-3,4-dimethylisoquinoline-5,8-quinone 1 from 2,5-dihydroxyacetophenone, methyl aminocrotonate and silver (II) oxide; b) regioselective amination of 1 with arylamines to give aminoquinones 2a-c and c) palladium-catalyzed intramolecular oxidative coupling of 7-aminoisoquinoline-5,8-quinones 2a-c. The in vitro antiproliferative activity of the new angular quinones was evaluated againts one normal cell line (lung fibroblasts) and gastric, lung and bladder cancer cell lines in 72-h drug exposure assays. The new compounds displayed similar or higher antiproliferative activity with respect to their quinone precursors 2a-c. The isomeric ellipticine quinone 2b appears as the more active member on bladder cancer cell line (IC50: 2.4 uM), comparable to etoposide used as anticancer reference drug...

Se describe la síntesis de las nuevas quinonas 3a-c, isoméricas de elipticina, y sus actividades antiproliferativas in vitro en líneas de células de cáncer. Las quinonas N-heterocíclicas 3a-c se sintetizaron a través de una secuencia que involucra: a) preparación de 4- metoxicarbonil-3,4-dimetlisoquinolin-5,8-quinone 1 a partir de 2,5-dihidroxiacetofenona, aminocrotonato de metilo y óxido de plata (I); b) aminación regioselectiva de 1 con arilaminas para producir las aminoquinonas 2a-c y c) acoplamiento oxidante intramolecular de 7- aminoisoquinolin-5,8-quinonas 2a-c catalizado con paladio. La actividad antiproliferative in vitro de los nuevos compuestos fue evaluada en una línea celular normal (fibroblastos de pulmón) y líneas de células de cáncer gástrico, pulmón y vejiga en ensayos de exposición de 72 horas a la droga. Las quinonas 3a-c exhiben interesantes propiedades antiproliferativas destacando la elipticinquinona isomérica 2b en células de cáncer de vejiga (IC50: 2.4 uM) comparado con etopósido usada como droga anticancer de referencia. Los nuevos compuestos mostraron actividades antiproliferativa similar o mayor respecto de las correspondientes quinonas precursoras 2a-c. La elipticin quinona isomérica 2b corresponde al miembro más activo en células de câncer de vejiga (IC50: 2.4 uM), comparable a la del etopósido, usada como droga anticáncer de referencia...

Blood shizonticidal activities of phenazines and naphthoquinoidal compounds against Plasmodium falciparum in vitro and in mice malaria studies

Due to the recent advances of atovaquone, a naphthoquinone, through clinical trials as treatment for malarial infection, 19 quinone derivatives with previously reported structures were also evaluated for blood schizonticide activity against the malaria parasite Plasmodium falciparum. These compounds include 2-hydroxy-3-methylamino naphthoquinones (2-9), lapachol (10), nor-lapachol (11), iso-lapachol (12), phthiocol (13) and phenazines (12-20). Their cytotoxicities were also evaluated against human hepatoma and normal monkey kidney cell lines. Compounds 2 and 5 showed the highest activity against P. falciparum chloroquine-resistant blood-stage parasites (clone W2), indicated by their low inhibitory concentration for 50% (IC50) of parasite growth. The therapeutic potential of the active compounds was evaluated according to the selectivity index, which is a ratio of the cytotoxicity minimum lethal dose which eliminates 50% of cells and the in vitro IC50. Naphthoquinones 2 and 5, with activities similar to the reference antimalarial chloroquine, were also active against malaria in mice and suppressed parasitaemia by more than 60% in contrast to compound 11 which was inactive. Based on their in vitro and in vivo activities, compounds 2 and 5 are considered promising molecules for antimalarial treatment and warrant further study.

Phytochemical screening and hypoglycemic activity of Carica papaya leaf in streptozotocin-induced diabetic rats

The extraction of plant constituents is essential to isolate biologically active compounds, aimed to understand their role on the treatment of diabetes. This study was designed to explore the preliminary phytochemical and physicochemical analysis of Carica papaya L., Caricaceae, leaf, and further evaluation of its hypoglycemic effect on diabetic rats. C. papaya leaves were extracted using chloroform, n-hexane or ethanol. For each extract a phytochemical screening was performed. The tests were conducted in triplicate and the qualitative and quantitative determination of the various metabolites was done using analytical standards proposed by Mexican Herbal Pharmacopoeia. The chloroform extract, containing steroids and quinones as major components, was chosen to study C. papaya biological effects. The chloroform extract was evaporated to dryness, and doses 0, 31, 62, 125 mg/kg were orally administered in 300 µl polyethylene glycol to diabetic rats; and 0 and 62 mg/kg to non-diabetic rats. After a 20-day treatment with the chloroform extract, the animals were sacrificed and blood was obtained for biochemical studies. The main effect observed was a decrease in serum glucose, triglycerides and transaminases in diabetic rats after the administration of C. papaya chloroform extract. These results confirm the potential beneficial action of C. papaya to treat the symptoms of diabetic patients.

Búsqueda en bases de datos de actividad biológica de moléculas quinoides / Database search on biological activity of quinoid molecules

Introducción: las quinonas son moléculas biológicas ampliamente distribuidas en la naturaleza. Recientemente el grupo de investigación de productos naturales, de la Universidad de Cartagena; obtuvo por extracción de plantas del género tabebuia y por síntesis química un número importante de estos compuestos. Sin embargo, con el fin de seguir profundizando en los estudios de sus actividades y su relación con el tipo de estructura lineal o angular se realizó una revisión en varias bases de datos. Objetivo: buscar información que permitiera conocer si los compuestos obtenidos se encontraban reportados; así como también la actividad biológica y los bioensayos realizados a estas moléculas in vivo, in vitro e in silico. Métodos: esta investigación fue desarrollada con el uso de un diseño que aplicó la edición de moléculas, mediante la interfaz gráfica de servidores (PUBCHEM CHEMIDPLUS ADVANCE, CHEBI) y una búsqueda de datos complementarios en la base de datos PUBMED. Los datos de la actividad biológica más relevantes fueron relacionados con la estructura química de los compuestos sintetizados y de los análogos suministrados por PUBMED. Resultados: de los compuestos hallados en las bases de datos, 24 presentaron código en la base de datos PUBCHEM, 12 mostraron reportes de actividad biológica en las bases de datos, y se encontró que el mayor número de bioensayos fue reportado con furanonaftoquinonas, seguido por naftoquinonas. Conclusiones: la actividad citotóxica y anticancerígena en diferentes líneas celulares, representa el mayor número de bioensayos realizados a estos compuestos.

Introduction: quinones are biological molecules widely distributed on the nature. Recently the group of natural products of the University of Cartagena (Colombia) obtained by extraction of plants of genus tabebuia and by chemistry synthesis an important number of these compounds. However with the purpose of made more detailed studies about the biological activity and structural type reported for these compounds, (naphtoquinone and furanonaphtoquinone linear o angular) reviewed in several database. Objective: search information that allows us to know 1) The compounds were already registered 2) Biological activity and bioassay performed to these molecules, in vivo, in vitro and in silico. Methods: this research was developed using a design of review than involved the edition of molecules by a graphic interface of server (PUBCHEM CHEMIDPLUS ADVANCE, CHEBI) and supplementary data search in PUBMED database. The most relevant data about biological activity was related with chemical structure of the synthesized compounds and their analogues obtained from databases. Results: the compounds tested on the database, 24 were already on PUBCHEM database, 12 molecules show reports of biological activity on the databases. Founding that bigger number of bioassays was reported with furanonaphtoquinones, followed by naphtoquinones. Conclusion: the cytotoxic and anticancer activity in cell lines of different type, represent the most of performed bioassay.

Pharmacokinetics of main components in Salvia Miltiorrhizae Radix et Rhizoma diterpene quinones composition and its solid dispersion micro-pellets in rats in vivo / 中草药

Objective: To establish a UPLC-MS/MS method for determining the plasma concentration of dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinone IIA in rats, and to study the pharmacokinetics of Salvia miltiorrhiza diterpene quinones composition (SMDQC) and its solid dispersion micro-pellets (SDMP). Methods: Sprague-Dawley rats were ig administered with SMDQC and its SDMP, respectively. Then the blood samples were obtained at different time points. Electrospray ionization (ESI) source was applied and operated in the positive ion mode. The plasma concentration of dihydrotanshinone I, tanshinone I, cryptotanshinone, and tanshinone IIA was then detected by UPLC-MS/MS, and the pharmcoknetic parameters were calculated by DAS 2.1.1 program. Results: The RSDs of intra- and inter-day precisions of all analytes were less than 14.6%, and the average recoveries of the four active constituents were more than 74.49%. The pharmacokinetic results showed that after ig administration of SDMP, Cmax and AUC0-∞ of the four active constituents increased significantly compared with those of SMDQC. Conclusion: The method has the high sensitivity and selectivity, and proves to be suitable for the pharmacokinetic study of SMDQC and its SDMP. The results show that the SDMP could enhance the solubility of SMDQC to improve its absorption. The relative bioavailability of the four representative constituents is 138%-204% of the crude drug.

Influences of plumbagin on phosphatidylinositol 3-kinase/protein kinase B signaling pathway in rats with hepatic fibrosis / 中华传染病杂志

Objective To explore the influences of plumbagin on phosphatidylinositol 3-kinase (PI3K)/ protein kinase B (Akt) signaling pathway in rats with carbon tetrachloride induced liver fibrosis.Methods Forty male SD rats were assigned to control group,model group,2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group,with 10 rats in each group.Rats of the control group were injected with 0.9％ NaCl solution (2 mL/kg) intraperitoneally,while rats of the other three groups were injected with 60％ carbon tetrachloride/peanut oil (2 mL/kg,3 times a week for 6 weeks) intraperitoneally.Since the third week after modeling,rats of plumbagin treated groups were treated with intraperitoneal injection of plumbagin at a dose of 2 mg/kg and 3 mg/kg (twice a week for 4 weeks),respectively.Serum levels of alanine aminotransferase (ALT),aspartate aminotransferase (AST),albumin (Alb) were monitored routinely.Hyaluronic acid (HA) and laminin (LN) were measured by radioimmunoassay after 6 weeks; protein expression of liver PI3K,Akt and phosphorylated Akt (p-Akt) were evaluated by Western blotting and immunohistochemistry,respectively.Comparison of means among groups was performed by univariate analysis of variance.Results The hepatic fibrosis model was successfully established after 6 weeks.Serum levels of ALT,AST,HA and LN of model group were significantly higher than those of control group (all P＜0.05).Serum levels of ALT,AST,HA and LN of 2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group were significantly lower than those of model group,and the differences were statistically significant (all P＜0.05).The protein expressions of PI3K and Akt in each group were comparable (all P＞0.05).The p-Akt protein was mainly expressed in nucleus of hepatocytes.The levels of p-Akt protein in control group,model group,2 mg/kg plumbagin treated group and 3 mg/kg plumbagin treated group were 0.0821±0.0003,0.7374±0.0037,0.3679 ±0.0332 and 0.1327±0.0561,respectively,and that in model group was significantly higher than control group (t =851.302,P＜0.05),but those in plumbagin treated groups were both lower than model group (t=71.858 and 28.363,all P＜0.05).Conclusions Plumbagin presents anti-fibrotic effects in the liver,by down-regulating the expression of p-Akt during the development of fibrosis,which might be one of the antifibrotic mechanisms.

Avances en los mecanismos moleculares del cáncer / Advances in the molecular mechanisms of cancer

In this review, epidemiological, physiological, pathophysiological and pharmacological themes of cancer are dealt. So far, there are over 200types of cancers, which are linked to six key events that collectively lead to the formation of a malignance: self-sufficiency in growth signals, insensitivity to growth inhibitory signals, evasion of apoptosis, unlimited replication potential, sustained angiogenesis and invasion and metastasis. These six capabilities are possibly shared by most human tumors. In2000, there were 10 million new cancer cases and 6 million cancer deaths worldwide. According to estimates by the American Cancer Society, the disease produced approximately 556,000 deaths in 2003, corresponding to 1,500 deaths from cancer every day in America. Annually, in Chile, cancer is responsible for 23 percent of all deaths, constituting the second leading cause of death after cardiovascular diseases. They have identified several risk factors for cancer such as smoking, chronic infections, alcohol consumption, reproductive factors, hormone replacement therapy, dietary habits, sunlight, among others. These factors may cause multiple genetic alterations that involve activation of several oncogenes and the loss of two or more suppressor genes, but not a single change will lead to the formation of a neoplasm. The Knowledge of the molecular differences between normal and malignant cells could be used to target specific pathways and receptors of the latter, thus preventing normal cell death.

Anticonvulsant activity of thymoquinone and its structural analogues

It has been widely reported that the crude oil of Nigella sativa L., Ranunculaceae, seeds and its major chemical component thymoquinone present anticonvulsant activity. These facts led us to verify the pharmacological potential of five structurally related para-benzoquinones on the pentylenotetrazol-induced seizures model, and establish the structural characteristics that influence the anticonvulsant activity of thymoquinone. The unsubstituted para-benzoquinone was the compound that exhibited the highest potency, while 2-methyl-p-benzoquinone was inactive. It was found that the presence of alkyl groups attached to the ring influence the pharmacological activity of the para-benzoquinones. In addition, the number, position, and size of these groups change the anticonvulsant potency of the compounds.