Metabolites in Conocarpus erectus leaves attenuate α-amylase activity by modulating amino acid residues of α-amylase: an in vitro and docking study / Los metabolitos en las hojas de Conocarpus erectus atenúan la actividad de la α-amilasa al modular los residuos de aminoácidos de la α-amilasa: un estudio in vitro y de acoplamiento

The antioxidant activity and the inhibitory potential of α-amylase of lyophilized hydroethanolic extracts of Conocarpus erectus leaves obtained by ultrasonication were determined. The most potent extract was subjected to ultra-high performance liquid chromatography system equipped with mass spectrometer for metabolite identification. The identified metabolites were docked in α-glucosidase to assess their binding mode. The results revealed that 60% ethanolic extract exhibited highest ferric reducing antioxidant power (4.08 ± 0.187 mg TE/g DE) and α-amylase inhibition (IC50 58.20 ± 1.25 µg/mL. The metabolites like ellagic acid, 3-O-methyl ellagic acid, ferujol, 5, 2 ́-dihydroxy-6,7,8-trimethyl flavone and kaempferol glucoside were identified in the extract and subjected to molecular docking studies regarding α-amylase inhibition. The comparison of binding affinities revealed 3-O-methyl ellagic acid as most effective inhibitor of α-amylase with binding energy of -14.5911 kcal/mol comparable to that of acarbose (-15.7815 kcal/mol). The secondary metabolites identified in the study may be extended further for functional food development with antidiabetic properties.

Se determinó la actividad antioxidante y el potencial inhibidor de la α-amilasa de extractos hidroetanólicos liofilizados de hojas de Conocarpus erectus obtenidos por ultrasónicación. El extracto más potente se sometió a un sistema de cromatografía líquida de ultra alto rendimiento equipado con un espectrómetro de masas para la identificación de metabolitos. Los metabolitos identificados se acoplaron en α-glucosidasa para evaluar su modo de unión. Los resultados revelaron que el extracto etanólico al 60% exhibió el mayor poder antioxidante reductor férrico (4.08 ± 0.187 mg TE/g DE) e inhibición de la α-amilasa (IC50 58.20 ± 1.25 µg/mL. Los metabolitos como el ácido elágico, 3-O-metil elágico ácido, ferujol, 5, 2 ́-dihidroxi-6,7,8-trimetil flavona y kaempferol glucósido se identificaron en el extracto y se sometieron a estudios de acoplamiento molecular con respecto a la inhibición de la α-amilasa. La comparación de las afinidades de unión reveló 3-O-metil El ácido elágico como inhibidor más eficaz de la α-amilasa con una energía de unión de -14,5911 kcal/mol comparable a la de la acarbosa (-15,7815 kcal/mol). Los metabolitos secundarios identificados en el estudio pueden ampliarse aún más para el desarrollo funcional de alimentos con propiedades antidiabéticas.

Study on secondary metabolites of endophytic fungus Cladosporium sp. JJM22 hosted in Ceriops tagal / 中国中药杂志

Nine secondary metabolites(S)-5-hydroxy-4-methylchroman-2-one(1), 4-methoxynaphthalene-1,5-diol(2), 8-methoxynaphthalene-1,7-diol(3), 1,8-dimethoxynaphthalene(4),(2R,4S)-2,3-dihydro-2-methyl-benzopyran-4,5-diol(5),(2R,4R)-3,4-dihydro-4-methoxy-2-methyl-2H-1-benzopyran-5-ol(6), 7-O-α-D-ribosyl-2,3-dihydro-5-hydroxy-2-methyl-chromen-4-one(7),(R)-3-methoxyl-1-(2,6-dihydroxyphenyl)-butan-1-one(8) and helicascolide A(9) were isolated from endophytic fungus Cladosporium sp. JJM22 by using column chromatographies of silica gel and ODS, and semi-preparative HPLC. Their structures were analyzed on the basis of spectroscopic and chemical data, especially NMR and MS. All isolated compounds were evaluated for their anti-inflammatory activities by examining the inhibitory activities on nitric oxide(NO) production induced by lipopolysaccharide in mouse macrophage RAW264.7 cells in vitro. Compounds 2-4 showed inhibitory activities.

Phytochemistry and Biological Activities of Werneria and Xenophyllum species / Fitoquímica y actividades biológicas de especies de Werneria y Xenophyllum

Plants of the genera Werneria (Asteraceae) and Xenophyllum (genus extracted from Werneria) are used in traditional medicine of Latin America for the treatment of mountain sickness, hypertension and gastrointestinal disorders. Only a small number of species of these genera have been studied, leading to the isolation of compounds belonging to the classes of benzofurans, chromenes, acetophenones, coumarates, diterpenes and pyrrolizidine alkaloids. Some of the plant extracts and/or compounds have shown antimicrobial, anti-HIV, hypotensive and photoprotective activities.

Las plantas de los géneros Werneria (Asteraceae) y Xenophyllum (género extraido de Werneria) son usadas en la medicina tradicional de América Latina para el tratamiento del mal de montaña, hipertensión y desórdenes gastrointestinales. Solo un pequeño número de especies de estos géneros ha sido investigado, lográndose aislar compuestos que pertenecen a las clases de benzofuranos, cromenos, acetofenonas, cumaratos, diterpenos y alcaloides pirrolizidínicos. Algunos de los extractos y/o compuestos de dichas plantas han mostrado actividades antimicrobianas, anti-HIV, hipotensoras y fotoprotectoras.

Overexpression of autophagy-related gene 3 promotes autophagy and inhibits salinomycin-induced apoptosis in breast cancer MCF-7 cells / 南方医科大学学报

OBJECTIVE@#To study the effects of the overexpression of autophagy-related gene 3 (ATG3) on autophagy and salinomycin-induced apoptosis in breast cancer cells and explore the underlying mechanisms.@*METHODS@#We used the lentivirus approach to establish a breast cancer cell line with stable overexpression of ATG3. Western blotting, immunofluorescence staining and transmission electron microscopy were used to analyze the effect of ATG3 overexpression on autophagy in breast cancer MCF-7 cells. Using the AKT/mTOR agonists SC79 and MHY1485, we analyzed the effect of AKT/mTOR signal pathway activation on ATG3 overexpression-induced autophagy. Western blotting and flow cytometry were used to analyze the effect of autophagy on apoptosis of the ATG3-overexpressing cells treated with salinomycin and 3-MA (an autophagy inhibitor).@*RESULTS@#In ATG3-overexpressing MCF-7 cells, ATG3 overexpression obviously promoted autophagy, inhibited the AKT/mTOR signaling pathway, significantly weakened salinomycin-induced apoptosis ( < 0.01), caused significant reduction of the levels of the pro-apoptotic proteins cleaved-caspase 3 ( < 0.01) and Bax ( < 0.05), and enhanced the expression of the anti-apoptotic protein Bcl-2 ( < 0.05). The inhibition of autophagy obviously weakened the inhibitory effect of ATG3 overexpression on salinomycin-induced apoptosis.@*CONCLUSIONS@#ATG3 overexpression promotes autophagy possibly by inhibiting the AKT/mTOR signaling pathway to decrease salinomycin-induced apoptosis in MCF-7 cells, suggesting that autophagy induction might be one of the mechanisms of drug resistance in breast cancer cells.

Effect of brazilin on apoptosis and autophagy of tongue cancer Tca8113 cells and its molecular mechanism / 南方医科大学学报

OBJECTIVE@#To investigate the effects of brazilin on the proliferation, apoptosis and autophagy of human tongue squamous cell carcinoma Tca8113 cells in vitro and explore its molecular mechanism.@*METHODS@#The changes in the proliferation, morphology and apoptosis of Tca8113 cells in response to brazilin treatment were detected using MTT assay, Hoechst33342 staining, and Annexin V/PI double staining, respectively. The expressions of apoptosis-related protein Bax, Bcl-2, cleaved caspase-3 and autophagy-related proteins p-AMPK, p-mTOR, LC3B, and p62 in the treated cells were detected using Western blotting. The effect of treatment with both the AMPK pathway inhibitor and brazilin on the expressions of the pathway-related proteins p-AMPK, p-mTOR, and LC3B was assessed.@*RESULTS@#MTT assay showed that brazilin significantly inhibited the proliferation of Tca8113 cells with an IC50 of 31.17 μmol/L at 24 h. Hoechst33342 staining showed that brazilin induced apoptotic morphological changes in Tca8113 cells in a concentration-dependent manner. Treatment with different concentrations of brazilin resulted in increased apoptosis in the cells. Brazilin obviously inhibited the expression of Bcl-2, p62 and p-mTOR and enhanced the expressions of Bax, cleaved caspase-3, LC3B and p-AMPK. The AMPK pathway inhibitor significantly inhibited the increase in p-AMPK and LC3B expressions and the decrease in p-mTOR expression induced by brazilin.@*CONCLUSIONS@#Brazilin can inhibit the proliferation and promote apoptosis in Tca8113 cells and at the same time induces autophagy in the cells through the AMPK/mTOR pathway.

Brazilin and Caesalpinia sappan L. extract protect epidermal keratinocytes from oxidative stress by inducing the expression of GPX7 / 中国天然药物

Caesalpinia sappan L., belonging to the family Leguminosae, is a medicinal plant that is distributed in Southeast Asia. The dried heartwood of this plant is used as a traditional ingredient of food, red dyes, and folk medicines in the treatment of diarrhea, dysentery, tuberculosis, skin infections, and inflammation. Brazilin is the major active compound, which has exhibited various pharmacological effects, including anti-platelet activity, anti-hepatotoxicity, induction of immunological tolerance, and anti-inflammatory and antioxidant activities. The present study aimed to evaluate the antioxidant activity and expression of antioxidant enzymes of C. sappan L. extract and its major compound, brazilin, in human epidermal keratinocytes exposed to UVA irradiation. Our results indicated that C. sappan L. extract reduced UVA-induced HO production via GPX7 activation. Moreover, brazilin exhibited antioxidant effects that were similar to those of C. sappan L. via glutathione peroxidase 7 (GPX7), suggesting that C. sappan L. extract and its natural compound represent potential treatments for oxidative stress-induced photoaging of skin.

Brazilin and Caesalpinia sappan L. extract protect epidermal keratinocytes from oxidative stress by inducing the expression of GPX7 / 中国天然药物

Caesalpinia sappan L., belonging to the family Leguminosae, is a medicinal plant that is distributed in Southeast Asia. The dried heartwood of this plant is used as a traditional ingredient of food, red dyes, and folk medicines in the treatment of diarrhea, dysentery, tuberculosis, skin infections, and inflammation. Brazilin is the major active compound, which has exhibited various pharmacological effects, including anti-platelet activity, anti-hepatotoxicity, induction of immunological tolerance, and anti-inflammatory and antioxidant activities. The present study aimed to evaluate the antioxidant activity and expression of antioxidant enzymes of C. sappan L. extract and its major compound, brazilin, in human epidermal keratinocytes exposed to UVA irradiation. Our results indicated that C. sappan L. extract reduced UVA-induced HO production via GPX7 activation. Moreover, brazilin exhibited antioxidant effects that were similar to those of C. sappan L. via glutathione peroxidase 7 (GPX7), suggesting that C. sappan L. extract and its natural compound represent potential treatments for oxidative stress-induced photoaging of skin.

Antifungal activity against colletotrichum acutatum and colletotrichum gloeosporioides of the major constituents from wood sawdust of platymiscium gracile benth / Actividad antifúngica contra colletotrichum acutatum y colletotrichum gloeosporioides de los constituyentes mayoritarios del aserrín de madera de platymiscium gracile benth

The tree tomato (Solanum betaceum Cav., Solanaceae) anthracnose, caused by the fungi Colletotrichum acutatum and Colletotrichum gloeosporioides, is the most important disease of this crop in Colombia for its wide distribution and the losses it causes. In the present work, the in vitro antifungal activity of the soluble fractions in n-hexane, dichloromethane, and ethyl acetate, and their major constituents from the sawdust of timber specie Platymiscium gracile Benth. (Fabaceae) against both fungi was evaluated. The n-hexane-soluble fraction exhibited the greatest inhibitory effect. The metabolites homopterocarpin (a pterocarpan, 0.39 percent dry weight), calycosin (an isoflavone, 2.01 percent) and scoparone (a coumarin, 1.48 percent) were isolated for the first time from wood sawdust of P. gracile. The structure of these compounds was determined by 1H and 13C NMR analyses. The three compounds tested showed significant antifungal activity.

La antracnosis del tomate de árbol (Solanum betaceum Cav., Solanaceae), ocasionada por los hongos Colletotrichum acutatum y Colletotrichum gloeosporioides, es la enfermedad más importante de este cultivo en Colombia por su amplia distribución y las pérdidas que ocasiona. En el presente trabajo se evaluó la actividad antifúngica in vitro de las fracciones solubles en n-hexano, diclorometano y acetato de etilo, y sus componentes mayoritarios, del aserrín de la especie maderable Platymiscium gracile Benth. (Fabaceae), contra ambos hongos. La fracción en n-hexano exhibió el mayor efecto inhibitorio. Los metabolitos homopterocarpina (un pterocarpano; 0.39 por ciento del peso seco de aserrín), calicosin (una isoflavona; 2.01 por ciento) y escoparona (una cumarina; 1.48 por ciento) se aislaron por primera vez desde el aserrín de madera de P. gracile empleando técnicas cromatográficas. La estructura de los compuestos se determinó por análisis de RMN de 1H y 13C. Los tres metabolitos mostraron una actividad antifúngica significativa contra ambos hongos.

Reproductive toxicity of brazilein in ICR mice / 中国天然药物

Brazilein is an active small molecular compound extracted from Caesalpinia sappan L. with favorable pharmacological properties on immune system, cardiovascular system, and nervous system. C. sappan has been used as a traditional medicine in China for hundreds of years for various diseases. However, the general reproductive toxicity of brazilein is still unknown. The purpose of the present study was to thoroughly evaluate the general reproductive toxicity of brazilein in ICR mice to support the future drug development and modernization of this potent traditional Chinese medicine. The results showed that, although no apparent toxicity on the reproducibility of the male was observed, brazilein might cause considerable risks to the fetuses and females as indicated by the ratios of dead fetuses and reabsorptions. In conclusion, our results from the present study provided some useful insights about the safety profile of brazilein, suggesting that brazilein should be used with caution in pregnant women.

Brazilein inhibits neuronal inflammation induced by cerebral ischemia and oxygen-glucose deprivation through targeting NOD2 expression / 中国天然药物

Brazilein is reported to have immunosuppressive effect on cardiovascular and cerebral-vascular diseases. The essential roles of innate immunity in cerebral ischemia are increasingly identified, but no studies concerning the influence of brazilein on the innate immunity receptors have been reported. The present study was designed to investigate the regulation of NOD2 (Nucleotide-binding oligomerization domain-containing protein 2) by brazilein for its protection of neuron in cerebral ischemia in vivo and oxygen-glucose deprivation in vitro. The results showed that brazilein could reverse the elevated expression of NOD2 and TNFα (tumor necrosis factor alpha) elicited by cerebral ischemia and reperfusion. This reduction could also be detected in normal mice and C17.2 cells, indicating that this suppressive effect of brazilein was correlated with NOD2. The results from GFP reporter plasmid assay suggested brazilein inhibited NOD2 gene transcription. In conclusion, brazilein could attenuate NOD2 and TNFα expression in cerebral ischemia and NOD2 may be one possible target of brazilein for its immune suppressive effect in neuro-inflammation.

Comparative pharmacokinetics of bergenin, a main active constituent of Saxifraga stolonifera Curt., in normal and hepatic injury rats after oral administration / 中国天然药物

Bergenin, isolated from the herb of Saxifrage stolonifera Curt. (Hu-Er-Cao) has hepatoprotective, anti-inflammatory, antitussive, and neuroprotective activities. The aim of the present study was to establish a simple, rapid, and sensitive RP-HPLC method for determination of bergenin in rat plasma and compare its oral pharmacokinetic behaviors in normal and CCl-induced hepatic injury rats. With norisoboldine as an internal standard, chromatographic separation was performed on a C analytical column with acetonitrile and water (11 : 89, V/V) containing 0.1% formic acid as the mobile phase. A good linearity was obtained over the range of 100-10 000 ng·mL. The lower limit of quantification was 50 ng·mL. The developed method was successfully applied to a study of the pharmacokinetic difference of bergenin (100 mg·kg) between normal and hepatic injury rats after oral administration. Marked alterations of pharmacokinetic parameters in hepatic injury rats were observed. Compared to normal rats, the AUC of bergenin in hepatic injury rats was elevated to 2.11-fold and C was increased by 130%, whereas CL value was only 55% of the normal rats, suggesting that the systemic exposure of bergenin was significantly increased under hepatic injury status.

Sclerotiorin is non-mutagenic and inhibits human PMNL 5-lipoxygenase and platelet aggregation.

Sclerotiorin, isolated from the fermented broth of Penicillium frequentans, exhibited potent inhibition against human polymorphonuclear leukocytes 5-lipoxygenase and human platelet aggregation with a half maximal value 36 µM and 250 µM, respectively. Further, the Ames test has demonstrated the sclerotiorin to be non-mutagenic.

Effects of karanjin on cell cycle arrest and apoptosis in human A549, HepG2 and HL-60 cancer cells

BACKGROUND: We have investigated the potential anticancer effects of karanjin, a principal furanoflavonol constituent of the Chinese medicine Fordia cauliflora, using cytotoxic assay, cell cycle arrest, and induction of apoptosis in three human cancer cell lines (A549, HepG2 and HL-60 cells). RESULTS: MTT cytotoxic assay showed that karanjin could inhibit the proliferation and viability of all three cancer cells. The induction of cell cycle arrest was observed via a PI (propidium iodide)/RNase Staining Buffer detection kit and analyzed by flow cytometry: karanjin could dose-dependently induce cell cycle arrest at G2/M phase in the three cell lines. Cell apoptosis was assessed by Annexin V-FITC/PI staining: all three cancer cells treated with karanjin exhibited significantly increased apoptotic rates, especially in the percentage of late apoptosis cells. CONCLUSION: Karanjin can induce cancer cell death through cell cycle arrest and enhance apoptosis. This compound may be effective clinically for cancer pharmacotherapy.

Cancer Therapy with Phytochemicals: Present and Future Perspectives / 生物医学与环境科学（英文）

Recently, a wide range of food-derived phytochemical compounds and their synthetic derivatives have been proposed for cancer treatment. Unfortunately, data available in related literature focus on the anti-cancer properties of compounds derived from edible plants, while very little is known about those derived from non-edible plants. And thus, the underlying mechanisms of their anti-cancer effects are yet to be elucidated. This review collates the available data on the anti-cancer activities of six phytochemical-derived compounds from edible and non-edible plants, i.e. rottlerin, berbamine, sparstolonin B, sulforaphane, plumbagin and 6-shogaol. These compounds are used as bioactive markers for cytotoxicity against tumors. As such, understanding their mode of action will provide the rationale for the combination strategies of these compounds with other drugs in the battle against cancer.

A novel chromene with anti-tumor activities from fungus Phomopsis sp / 中国中药杂志

A new chromene (1) and six known compounds identified as 6-hydroxymellein (2), 6-hydroxy-5-methylmellein (3) nectriapyrone (4), chermesinone A(5), chermesinone B(6), and pomopxanthone A(7), were isolated in our investigation of the cytotoxic constituents from the fermented rice substrate of endophytic fungus Phomopsis sp. HCCB03519. The structures of these com pounds were elucidated through spectroscopic data analysis. All compounds exhibited inhibitory activities against cancer cell lines. Compound 7 showed stronger inhibition against cancer cells than the positive control 5-Fu.

The Toxicity of Nonsteroidal Anti-inflammatory Eye Drops against Human Corneal Epithelial Cells in Vitro

This study investigated the toxicity of commercial non-steroid anti-inflammatory drug (NSAID) eye solutions against corneal epithelial cells in vitro. The biologic effects of 1/100-, 1/50-, and 1/10-diluted bromfenac sodium, pranoprofen, diclofenac sodium, and the fluorometholone on corneal epithelial cells were evaluated after 1-, 4-, 12-, and 24-hr of exposure compared to corneal epithelial cell treated with balanced salt solution as control. Cellular metabolic activity, cellular damage, and morphology were assessed. Corneal epithelial cell migration was quantified by the scratch-wound assay. Compared to bromfenac and pranoprofen, the cellular metabolic activity of diclofenac and fluorometholone significantly decreased after 12-hr exposure, which was maintained for 24-hr compared to control. Especially, at 1/10-diluted eye solution for 24-hr exposure, the LDH titers of fluorometholone and diclofenac sodium markedly increased more than those of bromfenac and pranoprofen. In diclofenac sodium, the Na+ concentration was lower and amount of preservatives was higher than other NSAIDs eye solutions tested. However, the K+ and Cl- concentration, pH, and osmolarity were similar for all NSAIDs eye solutions. Bromfenac and pranoprofen significantly promoted cell migration, and restored wound gap after 48-hr exposure, compared with that of diclofenac or fluorometholone. At 1/50-diluted eye solution for 48-hr exposure, the corneal epithelial cellular morphology of diclofenac and fluorometholone induced more damage than that of bromfenac or pranoprofen. Overall, the corneal epithelial cells in bromfenac and pranoprofen NSAID eye solutions are less damaged compared to those in diclofenac, included fluorometholone as steroid eye solution.

Nebivolol in preventing atrial fibrillation following coronary surgery in patients over 60 years of age / Nebivolol na prevenção da fibrilação atrial após a cirurgia coronária em pacientes acima de 60 anos de idade

Objective: Postoperative atrial fibrillation is a common complication after cardiac surgery, with an incidence as high as 20-50%. Increased age is associated with a significant increase in postoperative atrial fibrillation risk. This common complication is associated with higher morbidity and mortality rates. The aim of this study was to assess the efficacy of nebivolol in preventing atrial fibrillation following coronary artery bypass surgery in patients over 60 years of age. Methods: In this prospective randomized study, 200 patients who were candidates for elective coronary artery bypass surgery were divided into two groups. The first group was administered with nebivolol and the second group was administered with metoprolol. Treatment was initiated four days prior to surgery, and patients were monitored for atrial fibrillation until discharge. Forty-one patients recieved 50 mg metoprolol succinate daily, which was initiated minimum 4 days before surgery. Results: Demographic data were similar in both groups. The incidence of postoperative atrial fibrillation in both groups was similar, with no significant difference being identified [n=20 (20%); n=18 (18%), P=0.718; respectively]. There were not any mortality at both groups during study. Inotropic agent requirement at ICU was similar for both groups [n=12 (12%), n=18 (18%), P=0.32]. Conclusion: We compared the effectiveness of nebivolol and metoprolol in decreasing the incidence of postoperative atrial fibrillation, and determined that nebivolol was as effective as metoprolol in preventing postoperative atrial fibrillation at patients. Nebivolol may be the drug of choice due to its effects, especially after elective coronary artery bypass surgery. .

Objetivo: Pós-operatório fibrilação atrial é uma complicação comum após a cirurgia cardíaca, com uma incidência tão elevada quanto 20-50%. O aumento da idade está associado com elevação significativa no risco de pós-operatório da fibrilação atrial. Esta complicação comum é associada com taxas de morbidade e mortalidade. O objetivo deste estudo foi avaliar a eficácia do nebivolol na prevenção da fibrilação atrial após cirurgia de revascularização do miocárdio de pacientes acima de 60 anos de idade. Métodos: Neste estudo prospectivo e randomizado, duzentos pacientes candidatos à cirurgia de revascularização do miocárdio foram divididos em dois grupos. O primeiro grupo foi administrado com nebivolol e o segundo grupo, com metoprolol. O tratamento foi iniciado quatro dias antes da cirurgia, e os pacientes foram monitorados para fibrilação atrial até a alta. Quarenta e um pacientes receberam 50 mg de sucinato de metoprolol diário, que foi iniciado, no mínimo, 4 dias antes da cirurgia. Resultados: Os dados demográficos foram semelhantes nos dois grupos. A incidência de fibrilação atrial pós-operatória em ambos os grupos foi semelhante, com nenhuma diferença significativa sendo identificado [n=20 (20%); n=18 (18%), P=0,718; respectivamente]. Não houve mortalidade em ambos os grupos durante o estudo. A necessidade de agente inotrópico em UTI foi semelhante nos dois grupos [n=12 pessoas (12%), n=18 (18%), P=0,32]. Conclusão: Nós comparamos a eficácia do nebivolol e metoprolol na diminuição da incidência de fibrilação atrial no pós-operatório, e verificamos que nebivolol foi tão eficaz como metoprolol na prevenção de fibrilação atrial no pós-operatório em pacientes. Nebivolol pode ser a droga de escolha devido aos seus efeitos, especialmente depois da cirurgia revascularização do miocárdio. .

Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study / Nebivolol reduz pressão arterial central em pacientes hipertensos estágio I: estudo experimental de coorte única

CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP) has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients. DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital. METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR), central BP and augmentation index) before and after 3 months of using nebivolol. RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2) with large abdominal waist (102.1 ± 7.2 cm). There were significant decreases in peripheral systolic BP (P = 0.0020), diastolic BP (P = 0.0049), HR (P < 0.0001) and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083) after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment. CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP. .

CONTEXTO E OBJETIVOS: A avaliação da pressão arterial central (PAc) tem crescido substancialmente nos últimos anos porque as evidências mostraram que PAc central é mais relevante para os desfechos cardiovasculares do que pressão arterial (PA) periférica. Assim, diferentes classes de anti-hipertensivos têm efeitos diferentes sobre PAc apesar de reduções semelhantes na PA braquial. O objetivo foi investigar o efeito do nebivolol, β-bloqueador com propriedades vasodilatadoras, nos parâmetros bioquímicos e hemodinâmicos de pacientes hipertensos. TIPO DE ESTUDO E LOCAL: Estudo de coorte única experimental realizado em ambulatório de hospital universitário. MÉTODOS: Todos os 26 pacientes recrutados foram submetidos à avaliação bioquímica e hemodinâmica (PA, frequência cardíaca, FC, PAc, augmentation index) antes e após três meses usando nebivolol. RESULTADOS: 88,5% dos indivíduos eram do sexo masculino, com média de idade de 49,7 ± 9,3 anos, predominância de sobrepeso (29,6 ± 3,1 kg/m2) e aumento da cintura abdominal (102,1 ± 7,2 cm). Houve diminuição significativa da PA sistólica periférica (P = 0,0020) e diastólica (P = 0,0049), da FC (P < 0,0001) e da PAc (129,9 ± 12,3 x 122,3 ± 10,3 mmHg, P = 0,0083) após o tratamento em comparação aos valores basais. Não houve diferença no augmentation index, nem nos parâmetros bioquímicos antes e após o período de tratamento. CONCLUSÕES: O uso de nebivolol parece estar associado à redução significativa da PAc em hipertensos estágio 1, além da redução da pressão sistólica e diastólica braquial. .

Inhibitory activities of Lignum Sappan extractives on growth and growth-related signaling of tumor cells / 中国天然药物

AIM@#To investigate the active constituents of Lignum Sappan (Caesalpinia sappan L.) on growth-related signaling and cell mitosis.@*METHOD@#The influence of the ethyl acetate (EtOAc) extract of Lignum Sappan and its constituents on growth-related signaling were evaluated by a luciferase assay in cells stably-transfected with NF-κB, STAT1, or STAT3 responsive luciferase reporter plasmid. The inhibitory effect on the cell cycle was determined by flow cytometric analysis. The anti-tumor activities were assessed in vitro and in vivo.@*RESULTS@#The EtOAc extract of Lignum Sappan had inhibitory activities on growth-related signaling and cell mitosis. Three major active compounds were sappanchalcone, brazilin, and butein. Sappanchalcone blocked cell cycle progression in the G2/M phase, brazilin inhibited TNFα/NF-κB signaling, while butein inhibited IL-6/STAT3 signaling, as well as TNFα/NF-κB signaling. The three compounds all demonstrated cytotoxic activities against human tumor cells in vitro. In a S180 tumor cell-bearing mice model, the anti-tumor efficacy of the EtOAc extract was better than the individual compounds acting alone.@*CONCLUSION@#These results indicate that Lignum Sappan contains multiple active compounds with different antitumor activities, which act synergistically to enhance their anti-tumor effects. The EtOAc extract of Lignum Sappan may be better than individual active constituent as a novel medicine for the treatment of cancer.

Synthesis and cytotoxic activity of 3, 4, 11-trihydroxyl modified derivatives of bergenin / 中国天然药物

To synthesize a series of 3-, 4-, and/or 11-trihydroxy modified bergenin derivatives and evaluated their cytotoxic activity in vitro. The phenolic hydroxyl groups of bergenin were protected by benzyl groups with benzyl bromide. Treatment of dibenzyl bergenin with the corresponding acid in the presence of EDC·HCl and DMAP in CH2Cl2, followed by hydrogenation over Pd/C catalysts, afforded derivatives of bergenin esters. All of the target compounds were identified by IR, MS, and (1)H NMR. Twenty-six novel and three known derivatives of bergenin esters were synthesized. Their cytotoxicity values were evaluated by the MTT assay on the inhibition of DU-145 and BGC-823 cells in vitro. Several triply-substituted (3a, 4a, 5a, 6a, 7a) and doubly-substituted (8b, 9b) bergenin derivatives exhibited higher cytotoxic activity than bergenin. The result showed that the size of substituents and the lipophilicity of the bergenin esters displayed an important role on their cytotoxic activity.