Anti-tumor mechanism of sesquiterpenoids from Cryptoporus volvatus based on molecular docking / 南方医科大学学报

OBJECTIVE@#To identify the target genes mediating anti-tumor effect of sesquiterpenoids from Cryptoporus volvatus and explore the possible mechanism using molecular docking and molecular dynamics simulation.@*METHODS@#Based on the chemical structure of sesquiterpenes from C. volvatus, we explored the online reverse target finding websites PharmMapper, SEA, Target Hunter and related literature for preliminary prediction of possible anti-tumor targets. Discovery Studio 4.0 (Libdock function) and Maestro 12.3 were used to connect sesquiterpenes with the possible targets, and the potential targets were selected according to the scores. The interaction between the sesquiterpenes and the targets were analyzed using 2D interaction diagram, and the influence of different sesquiterpene skeletons on their activity was inferred based on their activity measurements in experiment. Kinetic simulation was performed for front-end protein sequence (1UNQ) of the Akt (protein kinase B) and for the complex formed by 1UNQ and compound 4 (which had the best cytotoxic activity in vitro) in its optimal conformation, and the root mean square deviation (RMSD) value and root mean square float (RMSF) value of the complex and 1UNQ were measured to evaluate the stability of the binding of compound 4 to the target.@*RESULTS@#The sesquiterpenes showed optimal binding with 1UNQ. Analysis of 2D interaction diagram suggested that the hydrogen bonding and electrostatic force were the most important forces mediating the interaction between the sesquiterpenes and 1UNQ. Analysis of the optimal 3D conformation showed that for different sesquiterpenes, a slight change of the molecular framework produced a steric hindrance effect and caused changes in their bioactivity. Kinetic simulation showed that the complex formed by compound 4 and1UNQ had a lower RMSD than the target pure protein sequence, indicating that compound 4 could stably bind to 1UNQ. The anti-tumor effect of the sesquiterpenoids from C. volvatus was associated with their ability to cause Lys-144 acetylation, which blocks Akt binding to the downstream PIP3 and thus affects the proliferation of tumor cells.@*CONCLUSION@#1UNQ is the target of sesquiterpenoids from C. volvatus, which affects the proliferation of tumor cells by acetylating Lys-14.

Polyhydroxylated eudesmane sesquiterpenoids and sesquiterpenoid glucoside from the flower buds of Tussilago farfara / 中国天然药物

Chemical fractionation of the n-BuOH partition, which was generated from the EtOH extract of the flower buds of Tussilago farfara, afforded a series of polar constituents including four new sesquiterpenoids (1-4), one new sesquiterpenoid glucoside (5) and one known analogue (6) of the eudesmane type, as well as five known quinic acid derivatives (7-11). Structures of the new compounds were unambiguously characterized by detailed spectroscopic analyses, with their absolute configurations being established by X-ray crystallography, electronic circular dichroism (ECD) calculation and induced ECD experiments. The inhibitory effect of all the isolates against LPS-induced NO production in murine RAW264.7 macrophages was evaluated, with isochlorogenic acid A (7) showing significant inhibitory activity.

Sesquiterpenoids from the leaves of Sarcandra glabra / 中国天然药物

Sarglanoids A-F, six new sesquiterpenoids belonging to eudesmane (1-5) and eremophilane (6) types, were isolated from the leaves of Sarcandra glabra, a famous traditional Chinese medicine (TCM). Their structures including absolute configurations were elucidated through extensive spectroscopic analysis and electronic circular dichroism (ECD) calculations. Compounds 1-2 were rare N-containing eudesmane-type sesquiterpenoids. Compound 3 exhibited inhibitory activity against nitric oxide (NO) production in lipopolysaccharides (LPS)-induced RAW 264.7 cells with IC50 values at 20.00 ± 1.30 μmol·L-1. These findings provide scientific evidence for sesquiterpenoids as the material foundation of S. glabra.

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.

Atractylenolide III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein

ABSTRACT Purpose: To evaluate the influence of atractylenolide (Atr) III on sepsis-induced lung damage. Methods: We constructed a mouse sepsis model through cecal ligation and puncture. These mice were allocated to the normal, sepsis, sepsis + Atr III-L (2 mg/kg), as well as Atr III-H (8 mg/kg) group. Lung injury and pulmonary fibrosis were accessed via hematoxylin-eosin (HE) and Masson's staining. We used terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and flow cytometry for detecting sepsis-induced lung cell apoptosis. The contents of the inflammatory cytokines in lung tissue were measured via enzyme-linked immunosorbent assay (ELISA). Results: Atr III-H did not only reduce sepsis-induced lung injury and apoptosis level, but also curbed the secretion of inflammatory factors. Atr III-H substantially ameliorated lung function and raised Bcl-2 expression. Atr III-H eased the pulmonary fibrosis damage and Bax, caspase-3, Vanin-1 (VNN1), as well as Forkhead Box Protein O1 (FoxO1) expression. Conclusions: Atr III alleviates sepsis-mediated lung injury via inhibition of FoxO1 and VNN1 protein.

Sesquiterpenes and polyphenols with glucose-uptake stimulatory and antioxidant activities from the medicinal mushroom Sanghuangporus sanghuang / 中国天然药物

A chemical investigation on the fermentation products of Sanghuangporus sanghuang led to the isolation and identification of fourteen secondary metabolites (1-14) including eight sesquiterpenoids (1-8) and six polyphenols (9-14). Compounds 1-3 were sesquiterpenes with new structures which were elucidated based on NMR spectroscopy, high resolution mass spectrometry (HRMS) and electronic circular dichroism (ECD) data. All the isolates were tested for their stimulation effects on glucose uptake in insulin-resistant HepG2 cells, and cellular antioxidant activity. Compounds 9-12 were subjected to molecular docking experiment to primarily evaluate their anti-coronavirus (SARS-CoV-2) activity. As a result, compounds 9-12 were found to increase the glucose uptake of insulin-resistant HepG2 cells by 18.1%, 62.7%, 33.7% and 21.4% at the dose of 50 μmol·L

Research progress on chemical constituents from Chloranthus plants and their biological activities / 中国中药杂志

The genus Chloranthus has 13 species and 5 varieties in China, which can be found in the southwest and northeast regions. Phytochemical studies on Chloranthus plants have reported a large amount of terpenoids, such as diterpenoids, sesquiterpenoids, and sesquiterpenoid dimers. Their anti-inflammation, anti-tumor, antifungal, antivirus, and neuroprotection activities have been confirmed by previous pharmacological research. Herein, research on the chemical constituents from Chloranthus plants and their biological activities over the five years was summarized to provide scientific basis for the further development and utilization of Chloranthus plants.

Lapiferin protects against H1N1 virus-induced pulmonary inflammation by negatively regulating NF-kB signaling

H1N1 virus-induced excessive inflammatory response contributes to severe disease and high mortality rates. There is currently no effective strategy against virus infection in lung. The present study evaluated the protective roles of a natural compound, lapiferin, in H1N1 virus-induced pulmonary inflammation in mice and in cultured human bronchial epithelial cells. Initially, Balb/C mice were grouped as Control, H1N1 infection (intranasally infected with 500 plaque-forming units of H1N1 virus), lapiferin (10 mg/kg), and H1N1+lapiferin (n=10/group). Lung histology, expression of inflammatory factors, and survival rates were assessed after 14 days of exposure. Administration of lapiferin significantly alleviated the virus-induced inflammatory infiltrate in lung tissues. Major pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were decreased at both mRNA and protein levels by lapiferin administration in the lung homogenate. Lapiferin also reduced inflammatory cell numbers in bronchoalveolar fluid. Mechanistically, lapiferin suppressed the transcriptional activity and protein expression of NF-κB p65, causing inhibition on NF-κB signaling. Pre-incubation of human bronchial epithelial cells with an NF-κB signaling specific activator, ceruletide, significantly blunted lapiferin-mediated inhibition of pro-inflammatory cytokines secretion in an air-liquid-interface cell culture experiment. Activation of NF-κB signaling also blunted lapiferin-ameliorated inflammatory infiltrate in lungs. These results suggested that lapiferin was a potent natural compound that served as a therapeutic agent for virus infection in the lung.

Antibacterial and antiproliferative activities of the fresh leaf essential oil of Psidium guajava L. (Myrtaceae) / Atividades antibacteriana e antiproliferativa do óleo essencial das folhas frescas de Psidium guajava L. (Myrtaceae)

Abstract This study evaluated the antibacterial and antiproliferative activities of the essential oil of Psidium guajava leaves (PG-EO), traditionally used in folk medicine. The essential oil was obtained from fresh leaves by hydrodistillation, using a modified Clevenger apparatus. The major PG-EO chemical constituents were identified by GC-MS and GC-FID as being β-caryophyllene (16.1%), α-humulene (11.9%), aromadendrene oxide (14.7%), δ-selinene (13.6%), and selin-11-en-4α-ol (12.5%). The antibacterial activity of the essential oil of P. guajava leaves was determined in terms of its minimum inhibitory concentrations (MIC) using the broth microdilution method in 96-well microplates. PG-EO had moderate activity against Streptococcus mutans (MIC = 200 µg/mL), S. mitis (MIC = 200 µg/mL), S. sanguinis (MIC = 400 µg/mL), S. sobrinus (MIC = 100 µg/mL), and S. salivarius (MIC = 200 µg/mL). The antiproliferative activity was evaluated against different tumor cell lines: breast adenocarcinoma (MCF-7), human cervical adenocarcinoma (HeLa), and human gliobastoma (M059J). A normal human cell line (GM07492A, lung fibroblasts) was included. The antiproliferative activity was evaluated using the XTT assay and the results were expressed as IC50. The essential oil showed significantly lower IC50 values against MCF-7 and M059J lines than that obtained for the normal line, showing selectivity. Our results suggest that the essential oil of Psidium guajava L. has promising biological activities and can be considered a new source of bioactive compounds.

Resumo Este estudo avaliou as atividades antibacteriana e antiproliferativa do óleo essencial das folhas frescas de Psidium guajava (PG-OE), tradicionalmente utilizadas na medicina popular. O óleo essencial foi obtido por hidrodestilação das folhas frescas, utilizando aparelho do tipo Clevenger. Os principais constituintes químicos de PG-OE identificados por CG-EM e CG-DIC foram: β-cariofileno (16,1%), α-humuleno (11,9%), óxido de aromadendreno (14,7%), δ-selineno (13,6%) e selin-11-en-4α-ol (12,5%). A atividade antibacteriana do óleo essencial das folhas de P. guajava foi determinada em termo de sua concentração inibitória mínima (CIM) utilizando o método de microdiluição de caldo em microplacas de 96 poços. PG-OE apresentou moderada atividade contra Streptococcus mutans (CIM = 200 μg/mL), S. mitis (CIM = 200 μg/mL), S. sanguinis (CIM = 400 μg/mL), S. sobrinus (CIM = 100 μg/mL) e S. salivarius (CIM = 200 μg/mL). A atividade antiproliferativa foi avaliada frente a diferentes linhagens de células tumorais como: adenocarcinoma de mama (MCF-7), adenocarcinoma cervical humano (HeLa) e gliobastoma humano (M059J). Foi incluída uma linhagem celular humana normal (GM07492A, fibroblastos pulmonares). A atividade antiproliferativa foi avaliada utilizando o ensaio XTT e os resultados foram expressos como CI50. As linhagens MCF-7 e M059J mostraram valores significativamente mais baixos de CI50 do que os obtidos para a linhagem normal, mostrando seletividade. Nossos resultados sugerem que o óleo essencial das folhas frescas de Psidium guajava L. possui atividades biológicas promissoras e pode ser considerado como uma nova fonte de compostos bioativos.

Effects of huperzine A on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia

Abstract Purpose To investigate the effects of huperzine A (HupA) on hippocampal inflammatory response and neurotrophic factors in aged rats after anesthesia. Methods Thirty-six Sprague Dawley rats (20-22 months old) were randomly divided into control, isofluran, and isoflurane+HupA groups; 12 rats in each group. The isoflurane+HupA group was intraperitoneally injected with 0.2 mg/kg of HupA. After 30 min, isoflurane inhalation anesthesia was performed in the isoflurane and isoflurane+HupA groups. After 24 h from anesthesia, Morris water maze experiment and open-field test were performed. Hippocampal inflammatory and neurotrophic factors were determined. Results Compared with isoflurane group, in isofluran+HupA group the escape latency of rats was significantly decreased (P < 0.05), the original platform quadrant residence time and traversing times were significantly increased (P < 0.05), the central area residence time was significantly increased (P < 0.05), the hippocampal tumor necrosis factor α, interleukin 6 and interleukin 1β levels were significantly decreased (P < 0.05), and the hippocampal nerve growth factor, brain derived neurotrophic factor and neurotrophin-3 levels were significantly increased (P < 0.05). Conclusion HupA may alleviate the cognitive impairment in rats after isoflurane anesthesia by decreasing inflammatory factors and increasing hippocampal neurotrophic factors in hippocampus tissue.

Identificación y determinación estructural de un sesquiterpeno de las hojas de Tessaria integrifolia Ruiz & Pav. y evaluación de su actividad leishmanicida / Identification and structural determination of a sesquiterpene of Tessaria integrifolia Ruiz & Pav. leaves and evaluation of its leishmanicidal activity

RESUMEN Objetivos. Identificar y determinar la estructura del fitoconstituyente de hojas de Tessaria integrifolia Ruiz & Pav con efecto leishmanicida. Materiales y métodos. Se preparó un extracto fluido de hojas de Tessaria integrifolia Ruiz & Pav. que fue concentrado a extracto blando y se utilizó para evaluar la actividad leishmanicida en Mesocricetus auratus con leishmaniasis experimental, administrando vía intramuscular la dosis de 250 mg/kg del extracto blando por 15 días. El extracto fue fraccionado en columna cromatográfica de 45 cm, con un diámetro de 2,5 cm que contiene silicagel G-60, de 70-230 mesh (Sigma-Aldrich®), las nueve fracciones obtenidas fueron evaluadas sobre macrófagos infectados con Leishmania sp para determinar la fracción activa y aislar el compuesto activo, mediante separación, purificación y cristalización, siendo analizado por resonancia magnética nuclear (RMN) de 1H, 13C, y cromatografía líquida acoplada a espectroscopía de masas (LC/MS). Resultados. El extracto fluido de las hojas de Tessaria integrifolia Ruiz & Pav. presenta actividad leishmanicida en Mesocricetus auratus y la fracción F8 es activa sobre macrófagos infectados a dosis de 14 µg/mL. Se elucidó en esa fracción un sesquiterpeno tipo eudesmano ((4aS, 5R,6R,8aR)-6-hidroxi-5,8a-dimetil-3-(1-metiletiliden) octahidronaftalen-2(1H)-ona), según análisis de RMN 1H, 13C, y LC/MS. Conclusiones. El extracto fluido de hojas de Tessaria integrifolia Ruiz & Pav. presenta actividad leishmanicida sobre Mesocricetus auratus. La fracción F8 presenta actividad leishmanicida sobre macrófagos infectados a dosis de 14 µg/mL. Se elucidó en la fracción activa un sesquiterpeno tipo eudesmano según los análisis de RMN 1H, 13C, y LC/MS.

ABSTRACT Objective. To identify and determine the phytoconstituent structure of Tessaria integrifolia Ruiz & Pav. leaves with leishmanicidal activity. Materials and Methods. Fluid extract of leaves was prepared, concentrated to soft extract, and used to evaluate leishmanicidal activity in Mesocricetus auratus with experimental leishmaniasis, at the dose of 250 mg/kg of soft extract by intramuscular route for 15 days. Extract was fractionated in 45 cm column chromatography with a 2.5 cm diameter, containing G-60 silica gel, and 70-230 mesh (Sigma-Aldrich®). Nine fractions were obtained and assessed on macrophages infected with Leishmania sp to determine the active fraction and isolate the active compound, by separation, purification, and crystallization, analyzed by nuclear magnetic resonance (NMR) of 1H, 13C, and liquid chromatography coupled to mass spectroscopy (LC/ MS). Results. Fluid extract from the leaves of T. integrifolia presents leishmanicidal activity in M. auratus. Fraction F8 is active on infected macrophages at a dose of 14 μg/mL. An eudesman type sesquiterpene ((4aS, 5R, 6R, 8aR) -6-hydroxy-5, 8a-dimethyl-3- (1-methylethylidene) octahydronaphthalen-2 (1H) -one) was identified, by RMN 1 H, 13C, and LC / MS analysis. Conclusions. Fluid extract of leaves of Tessaria integrifolia Ruiz & Pav. presents leishmanicidal activity on Mesocricetus auratus with experimental leishmaniasis. Fraction F8 presents leishmanicidal activity on infected macrophages at a dose of 14 μg/mL. An eudesman type sesquiterpene was identified, according to 1 H, 13C, and LC / MS NMR analysis.

Chemical Composition and Antibacterial Activity of the Essential Oil of Vitex agnus-castus L. (Lamiaceae)

ABSTRACT Abnormal multiplication of oral bacteria causes dental caries and dental plaque. These diseases continue to be major public health concerns worldwide, mainly in developing countries. In this study, the chemical composition and antimicrobial activity of the essential oil of Vitex agnus-castus leaves (VAC‒EO) collected in the North of Brazil against a representative panel of cariogenic bacteria were investigated. The antimicrobial activity of VAC-EO was evaluated in terms of its minimum inhibitory concentration (MIC) values by using the broth microdilution method in 96-well microplates. The chemical constituents of VAC-EO were identified by gas chromatography (GC‒FID) and gas chromatography‒mass spectrometry (GC‒MS). VAC‒EO displayed some activity against all the investigated oral pathogens; MIC values ranged from 15.6 to 200 μg/mL. VAC-EO had promising activity against Streptococcus mutans (MIC= 15.6 μg/mL), Lactobacillus casei (MIC= 15.6 μg/mL), and Streptococcus mitis (MIC= 31.2 μg/mL). The compounds 1,8-cineole (23.8%), (E)-β-farnesene (14.6%), (E)-caryophyllene (12.5%), sabinene (11.4%), and α-terpinyl acetate (7.7%) were the major chemical constituents of VAC‒EO. VAC-EO displays antimicrobial activity against cariogenic bacteria. The efficacy of VAC-EO against S. mutans is noteworthy and should be further investigated.

Effects of Lippia sidoides essential oil, thymol, p-cymene, myrcene and caryophyllene on rat sciatic nerve excitability

Lippia sidoides Cham is a typical herb species of Northeast Brazil with widespread use in folk medicine. The major constituents of the essential oil of L. sidoides (EOLs) are thymol, p-cymene, myrcene, and caryophyllene. Several studies have shown that the EOLs and its constituents have pharmacological effects, including antibacterial, anti-inflammatory, antioxidant and neuroprotective activity. Therefore, this work aimed to investigate the effects of the EOLs and their main constituents on rat sciatic nerve excitability. The sciatic nerves of adult Wistar rats were dissected and mounted in a moist chamber. Nerves were stimulated by square wave pulses, with an amplitude of 40 V, duration of 100 μs to 0.2 Hz. Both EOLs and thymol inhibited compound action potential (CAP) in a concentration-dependent manner. Half maximal inhibitory concentration for CAP peak-to-peak amplitude blockade were 67.85 and 40 µg/mL for EOLs and thymol, respectively. CAP peak-to-peak amplitude was significantly reduced by concentrations ≥60 µg/mL for EOLs and ≥30 µg/mL for thymol. EOLs and thymol in the concentration of 60 µg/mL significantly increased chronaxie and rheobase. The conduction velocities of 1st and 2nd CAP components were also concentration-dependently reduced by EOLs and thymol in the range of 30-100 µg/mL. Differently from EOLs and thymol, p-cymene, myrcene and caryophyllene did not reduce CAP in the higher concentrations of 10 mM. These data demonstrated that EOLs and thymol inhibited neuronal excitability and were promising agents for the development of new drugs for therapeutic use.

Antibacterial activity of cuticular components from heliotropium species, against staphylococcus aureus and salmonella tiphymurium / Actividad antibacteriana de componentes cuticulares de especies de heliotropium frente a staphylococcus aureus y salmonella tiphymurium

In this communication the antibacterial activity of filifolinol (1), naringenin (2) 3-O-methylgalangin (3) and pinocembrin (4) isolated from the resinous exudates of Heliotropium filifolium and H. sinuatum, were evaluated by flow cytometry against Staphylococcus aureus and Salmonella tiphymurium. The results showed that filifolinol (1) and naringenin (2) were inactive in the range of concentrations used (10 to 1000 ug/mL). On the other hand, pinocembrin (4) produced a decrease in cell surface at 500 ug/mL and the total disappearance of both bacterial populations at 1000 ug/mL. Also, 3-O-methylgalangin (3) showed the total disappearance at 1000 ug/mL of both bacterial populations and a decrease at 200 μg/mL for S. typhimurium and at 500 μg/mL for S. aureus.

En esta comunicación, la actividad antibacteriana de filifolinol (1), naringenina (2), 3-O-methylgalangina (3) y pinocembrina (4) aislados de los exudados resinosos de Heliotropium filifolium y H. sinuatum, fueron evaluados por citometría de flujo frente a Staphylococcus aureus y Salmonella tiphymurium. Los resultados mostraron que filifolinol (1) y naringenina (2) fueron inactivos en el intervalo de concentraciones usadas (10 a 1000 μg / mL). Por otro lado, pinocembrina (4) produce una disminución de la superficie de las células a 500 ug/mL y la desaparición total de ambas poblaciones bacterianas a 1.000 ug/mL. También, 3-O-metilgalangina (3) mostró la desaparición total a 1.000 ug / mL tanto de ambas poblaciones de bacterias y una disminución a 200 ug/mL para S. typhimurium y en 500 μg/mL para S. aureus.

Effects of budlein A on human neutrophils and lymphocytes

ABSTRACT Sesquiterpene lactones (SLs) are the active constituents of a variety of medicinal plants used in traditional medicine for the treatment of inflammatory diseases and other ailments. Objective In this study, we evaluated whether budlein A modulates the activation of innate and adaptive immune cells such as neutrophils and lymphocytes. Material and Methods Our research group has investigated several plant species and several compounds have been isolated, identified, and their medical potential evaluated. Budlein A is a SL isolated from the species Aldama buddlejiformis and A. robusta (Asteraceae) and shows anti-inflammatory and anti-nociceptive activities. Advances in understanding how plant-derived substances modulate the activation of innate and adaptive immune cells have led to the development of new therapies for human diseases. Results Budlein A inhibited MPO activity, IL-6, CXCL8, IL-10, and IL-12 production and induces neutrophil apoptosis. In contrast, budlein A inhibited lymphocyte proliferation and IL-2, IL-10, TGF-β, and IFN-γ production, but it did not lead to cell death. Conclusions Collectively, our results indicate that budlein A shows distinct immunomodulatory effects on immune cells.

Induction of apoptosis by zerumbone isolated from Zingiber zerumbet (L.) Smith in protozoan parasite Leishmania donovani due to oxidative stress

Abstract In the present context of emergence of resistance aligned with the conventional anti-leishmanial drugs and occasional treatment failure compelled us to continue the search for replaceable therapeutic leads against Leishmaniainfection. Various ginger spices of the Zingiberaceae family are widely used as spices, flavouring agents, and medicines in Southeast Asia because of their unique flavour as well as due to their medicinal properties. Zerumbone, a natural component of Zingiber zerumbet (L.) Smith, has been studied for its pharmacological potential as antiulcer, antioxidant, anticancer, and antimicrobial. In this study, we have shown that zerumbone could induce ROS mediated apoptosis in Leishmania donovani promastigotes and also found effective in reducing intracellular amastigotes in infected-macrophages. We emphasized the potential of zerumbone to be employed in the development of new therapeutic drugs against L. donovaniinfection and provided the basis for future research on the application of transitional medicinal plants.

Rendimento, composição química e atividades antimicrobiana e antioxidante do óleo essencial de folhas de Campomanesia adamantium submetidas a diferentes métodos de secagem / Content, chemical composition and antimicrobial and antioxidant activities of the essential oil from leaves of Campomanesia adamantium submitted to different drying methods

RESUMO Campomanesia adamantium é muito utilizada na medicina popular no tratamento de hipertensão, reumatismo e diabetes. Objetivou-se com o presente trabalho avaliar o rendimento, a composição química, e as atividades antimicrobiana e antioxidante do óleo essencial de folhas de C. adamantium submetidas a diferentes métodos e tempos de secagem. O delineamento utilizado foi inteiramente casualizado, com oito tratamentos e três repetições. O óleo essencial foi extraído por hidrodestilação das folhas e analisado por CG-EM. O tipo de secagem das folhas de C. adamantium influenciou no teor e na composição química do óleo essencial. Os constituintes espatulenol, óxido cariofileno e germacreno-B apresentaram maior concentração na maioria das procedências avaliadas. O óleo essencial das folhas de C. adamantium apresentou moderada atividade antibacteriana em relação a todos os micro-organismos testados. A atividade antioxidante se deu empregando-se o método de redução do radical estável DPPH, sendo observada fraca atividade antioxidante por meio do ensaio utilizado.

ABSTRACT C. adamantiumis widely used in popular medicine for thetreatment of hypertension, rheumatism and diabetes. This study looked to evaluate the essential oil yield, the chemical composition and the antimicrobial and antioxidant activities of the essential oil from leaves of C. adamantium. A completely randomized design was used with eight treatments and three replications. The essential oil obtained by hydrodestillation of the leaves was analyzed by GC-MS. The results show that the drying type and the processing of the leaf influence the content and chemical composition of the essential oil. The compounds spathulenol, caryophyllene oxide and germacrene-B have higher concentrationsin mostorigins. The essentialoil from theleaves of C.adamantiumshowed moderate bacterial activityagainst all tested microorganisms. The antioxidant activity was determined by the methods of reduction of the DPPH stable radical. The antioxidant activity was weak in the test used.

Effect of (+)-dehydrofukinone on GABAA receptors and stress response in fish model

(+)-Dehydrofukinone (DHF) is a major component of the essential oil of Nectandra grandiflora (Lauraceae), and exerts a depressant effect on the central nervous system of fish. However, the neuronal mechanism underlying DHF action remains unknown. This study aimed to investigate the action of DHF on GABAA receptors using a silver catfish (Rhamdia quelen) model. Additionally, we investigated the effect of DHF exposure on stress-induced cortisol modulation. Chemical identification was performed using gas chromatography-mass spectrometry and purity was evaluated using gas chromatography with a flame ionization detector. To an aquarium, we applied between 2.5 and 50 mg/L DHF diluted in ethanol, in combination with 42.7 mg/L diazepam. DHF within the range of 10-20 mg/L acted collaboratively in combination with diazepam, but the sedative action of DHF was reversed by 3 mg/L flumazenil. Additionally, fish exposed for 24 h to 2.5-20 mg/L DHF showed no side effects and there was sustained sedation during the first 12 h of drug exposure with 10-20 mg/L DHF. DHF pretreatment did not increase plasma cortisol levels in fish subjected to a stress protocol. Moreover, the stress-induced cortisol peak was absent following pretreatment with 20 mg/L DHF. DHF proved to be a relatively safe sedative or anesthetic, which interacts with GABAergic and cortisol pathways in fish.

The effect of elemene on lung adenocarcinoma A549 cell radiosensitivity and elucidation of its mechanism

OBJECTIVE: To investigate the effect of elemene on the radiosensitivity of A549 cells and its possible molecular mechanism. METHODS: Apoptosis of A549 cells was detected by flow cytometry and fluorescence microscopy. The effect of double-strand break (DSB) damage repair in A549 cells was evaluated using the neutral comet assay. Protein expression levels were detected using western blotting, and the correlation between protein levels was analyzed. RESULTS: Elemene exhibited a radiosensitizing effect on A549 cells. The level of apoptosis induced by elemene combined with radiation was significantly greater (p<0.01) than that elicited by either radiation or elemene alone. Following radiation and subsequent repair for 24 h, the tail intensity of A549 cells treated with a combination of elemene and radiation was greater than that of cells treated with either elemene or radiation alone (p<0.01). This result indicates that elemene inhibits cellular DSB repair. Both elemene combined with radiation and radiation alone decreased the protein expression of DNA-PKcs and Bcl-2 compared to elemene alone (p<0.01), while p53 protein expression was increased (p<0.01). A negative correlation was observed between DNA-PKcs and p53 expression (r=−0.569, p=0.040), while a positive correlation was found between DNA-PKcs and Bcl-2 expression (r=0.755, p=0.012). CONCLUSIONS: Elemene exhibits a radiosensitizing effect on A549 cells, and its underlying molecular mechanism of action may be related to the downregulation of DNA-PKcs gene expression. .

Potential interaction of components from essential oils with dengue virus proteins / Potencial interacción de componentes de aceites esenciales con proteínas del virus del dengue

An antiviral drug for treatment of dengue is an urgent necessity. In this study in silico activities of essential oils components on dengue virus (DENV) were evaluated, and beta-Caryophyllene was subjected to biological examination to assess inhibition of DENV-2 replication. Components previously optimized were coupled with viral proteins prepared, using AutoDock Vina. Theoretical affinity values varied between -4.0 and -7.3 kcal/mol. alpha-copaene, beta-bourbonene, germacrene D, spathulenol, beta-caryophyllene, caryophyllene oxide and (+)- epi-bicyclosesquiphellandrene showed the greatest interaction with viral proteins. beta-caryophyllene inhibits DENV-2 in vitro (50 percent inhibitory concentration [IC50] = 22.5 +/- 5.6 uM [4.6 +/- 1.1 ug/mL] and resulted non-cytostatic with a selectivity index value of 71.1. The in silico results permit infer that DENV proteins are potential targets for the concomitant docking of various essential oils components. Biological examination suggest that beta-caryophyllene acts on very early steps of the viral replication cycle and it might prove virucidal.

Una droga antiviral para tratamiento del dengue es una necesidad urgente. En este estudio se evaluó la actividad in silico de componentes de aceites esenciales sobre el virus del dengue (VDEN) y el beta-cariofileno se seleccionó para evaluar la inhibición sobre la replicación in vitro del VDEN-2. Los componentes previamente optimizados fueron acoplados con proteínas virales preparadas, utilizando AutoDock Vina. Los valores de afinidad variaron entre -4.0 and -7.3 kcal/mol. alfa-Copaeno, beta-bourboneno, germacreno D, spatulenol, beta- cariofileno, óxido de cariofileno y (+)-epi-biciclosesquifellandreno presentaron la mayor interacción con las proteínas virales. beta-Cariofileno inhibió VDEN-2 in vitro (Concentración inhibitoria 50 [IC50] = 22.5 +/- 5.6 uM [4.6 +/- 1.1 ug/mL] y resultó no-citostático con índice de selectividad de 71.1. Los resultados in silico indican que proteínas del VDEN son blancos potenciales para varios componentes. El análisis biológico sugiere que el beta-cariofileno actúa en etapas tempranas de la replicación viral y podría ser virucida.