RESUMO
A naturally occurring stilbene, resveratrol, shows promising effects in the treatment of malignant pleural mesothelioma (MPM) both as a single agent and in combination with chemotherapeutic drugs. To discover new anticancer agents targeting MPM, stilbene-targeted isolation was performed on the roots of Polygonum multiflorum Thunb., an herbal medicine rich in stilbene compounds. In this study, seven stilbene glycosides (1-7) were isolated, along with four non-stilbenes (8-11), of which compounds 4 and 9-11 have not previously been isolated from this species. Stiquinoside A (1) is a previously undescribed stilbene glycoside, and its structure was elucidated as (E)-2,3,5,4'-tetrahydroxystilbene 2-O-ß-d-quinovopyranoside based on 1D and 2D-NMR, HR-ESI-MS, and acid hydrolysis experiments. Compounds 1, 4, 6, and 8 significantly inhibit the growth of MPM cancer cells H2452. These results demonstrate the potential utility of stilbenes in new strategies for the treatment of MPM.
Assuntos
Antineoplásicos Fitogênicos , Fallopia multiflora , Mesotelioma Maligno , Raízes de Plantas , Estilbenos , Humanos , Estilbenos/farmacologia , Estilbenos/isolamento & purificação , Raízes de Plantas/química , Estrutura Molecular , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/isolamento & purificação , Mesotelioma Maligno/tratamento farmacológico , Fallopia multiflora/química , Compostos Fitoquímicos/farmacologia , Compostos Fitoquímicos/isolamento & purificação , Glicosídeos/farmacologia , Glicosídeos/isolamento & purificação , Mesotelioma/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , ChinaRESUMO
Metals are important cofactors in the metabolic processes of cyanobacteria, including photosynthesis, cellular respiration, DNA replication, and the biosynthesis of primary and secondary metabolites. In adaptation to the marine environment, cyanobacteria use metallophores to acquire trace metals when necessary as well as to reduce potential toxicity from excessive metal concentrations. Leptochelins A-C were identified as structurally novel metallophores from three geographically dispersed cyanobacteria of the genus Leptothoe. Determination of the complex structures of these metabolites presented numerous challenges, but they were ultimately solved using integrated data from NMR, mass spectrometry and deductions from the biosynthetic gene cluster. The leptochelins are comprised of halogenated linear NRPS-PKS hybrid products with multiple heterocycles that have potential for hexadentate and tetradentate coordination with metal ions. The genomes of the three leptochelin producers were sequenced, and retrobiosynthetic analysis revealed one candidate biosynthetic gene cluster (BGC) consistent with the structure of leptochelin. The putative BGC is highly homologous in all three Leptothoe strains, and all possess genetic signatures associated with metallophores. Postcolumn infusion of metals using an LC-MS metabolomics workflow performed with leptochelins A and B revealed promiscuous binding of iron, copper, cobalt, and zinc, with greatest preference for copper. Iron depletion and copper toxicity experiments support the hypothesis that leptochelin metallophores may play key ecological roles in iron acquisition and in copper detoxification. In addition, the leptochelins possess significant cytotoxicity against several cancer cell lines.
Assuntos
Cianobactérias , Cianobactérias/metabolismo , Cianobactérias/química , Cianobactérias/genética , Humanos , Família Multigênica , Linhagem Celular Tumoral , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismoRESUMO
Three new cyclic heptapeptides, talaromides A-C (1-3), were isolated from cultures produced by the fungus Talaromyces siglerae (Ascomycota), isolated from an unidentified sponge. The structures, featuring an unusual proline-anthranilic moiety, were elucidated by analysis of spectroscopic data and chemical transformations, including the advanced Marfey's method and GITC derivatization. Talaromides A and B inhibited migration activity against PANC-1 human pancreatic cancer cells without significant cytotoxicity.
Assuntos
Peptídeos Cíclicos , Poríferos , Talaromyces , Talaromyces/química , Animais , Poríferos/microbiologia , Humanos , Estrutura Molecular , Peptídeos Cíclicos/farmacologia , Peptídeos Cíclicos/química , Peptídeos Cíclicos/isolamento & purificação , Ensaios de Seleção de Medicamentos Antitumorais , Biologia Marinha , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/isolamento & purificaçãoRESUMO
Lung cancer, which has a high incidence and mortality rates, often metastasizes and exhibits resistance to radiation therapy. Seongsanamide B has conformational features that suggest it has therapeutic potential; however, its antitumor activity has not yet been reported. We evaluated the possibility of seongsanamide B as a radiation therapy efficiency enhancer to suppress γ-irradiation-induced metastasis in non-small cell lung cancer. Seongsanamide B suppressed non-small cell lung cancer cell migration and invasion caused by γ-irradiation. Furthermore, it suppressed γ-irradiation-induced upregulation of Bcl-XL and its downstream signaling molecules, such as superoxide dismutase 2 (SOD2) and phosphorylated Src, by blocking the nuclear translocation of phosphorylated STAT3. Additionally, seongsanamide B markedly modulated the γ-irradiation-induced upregulation of E-cadherin and vimentin. Consistent with the results obtained in vitro, while seongsanamide B did not affect xenograft tumor growth, it significantly suppressed γ-irradiation-induced metastasis by inhibiting Bcl-XL/SOD2/phosphorylated-Src expression and modulating E-cadherin and vimentin expression in a mouse model. Thus, seongsanamide B may demonstrate potential applicability as a radiation therapy efficiency enhancer for lung cancer treatment.
RESUMO
Wear particleinduced osteolysis is a serious complication that occurs in individuals with titanium (Ti)based implants following longterm usage due to loosening of the implants. The control of excessive osteoclast differentiation and inflammation is essential for protecting against wear particleinduced osteolysis. The present study evaluated the effect of britanin, a pseudoguaianolide sesquiterpene isolated from Inula japonica, on osteoclastogenesis in vitro and Ti particleinduced osteolysis in vivo. The effect of britanin was examined in the osteoclastogenesis of mouse bone marrowderived macrophages (BMMs) using TRAP staining, RTPCR, western blotting and immunocytochemistry. The protective effect of britanin was examined in a mouse calvarial osteolysis model and evaluated using microCT and histomorphometry. Britanin inhibited osteoclast differentiation and Factin ring formation in the presence of macrophage colonystimulating factor and receptor activator of nuclear factor kB ligand in BMMs. The expression of osteoclastspecific marker genes, including tartrateresistant acid phosphatase, cathepsin K, dendritic cellspecific transmembrane protein, matrix metallopeptidase 9 and nuclear factor of activated Tcells cytoplasmic 1, in the BMMs was significantly reduced by britanin. In addition, britanin reduced the expression of B lymphocyteinduced maturation protein1, which is a transcriptional repressor of negative osteoclastogenesis regulators, including interferon regulatory factor8 and Bcell lymphoma 6. Conversely, britanin increased the expression levels of antioxidative stress genes, namely nuclear factor erythroid2related factor 2, NAD(P)H quinone oxidoreductase 1 and heme oxygenase 1 in the BMMs. Furthermore, the administration of britanin significantly reduced osteolysis in a Ti particleinduced calvarial osteolysis mouse model. Based on these findings, it is suggested that britanin may be a potential therapeutic agent for wear particleinduced osteolysis and osteoclastassociated disease.
Assuntos
Osteogênese , Osteólise , Humanos , Animais , Camundongos , Osteólise/tratamento farmacológico , Osteólise/etiologia , Titânio/efeitos adversos , Osteoclastos , Citoesqueleto de Actina , Modelos Animais de DoençasRESUMO
During the screening of the cytotoxicity of rare Korean endemic plants, the extract of Thuja koraiensis Nakai displayed potent cytotoxicity against the adenocarcinomic human alveolar basal epithelial A549 cell line. Through a series of separations via column chromatography, three undescribed abietanes, an undescribed labdane along with a labdane, and a biflavonoid were purified from methylene chloride (CH2Cl2) fraction possessing a potent cytotoxic effect. Extensive 1D and 2D NMR spectroscopic data analyses, in combination with quantum chemical calculations were conducted to establish the planar and absolute configurations of thujakoraienes A-C. The chemical structure of thujakoraiene D was elucidated by spectroscopic data analysis and competing enantioselective acylation. Thujakoraienes A and C along with 7,7â³-di-O-methylamentoflavone, showed cytotoxic effects on A549 cells, with IC50 values of 64.86, 47.97, and 16.14 µM, respectively. Finally, thujakoraiene C and 7,7â³-di-O-methylamentoflavone were identified as potent cytotoxic compounds in A549 cells, followed by an additional cytotoxicity test in the normal human lung fibroblast MRC-5 cell line. This is the first study on the non-volatile chemicals in the extract of T. koraiensis and comparison of chemical profiles of T. orientalis and T. koraiensis.
Assuntos
Antineoplásicos , Diterpenos , Thuja , Humanos , Células A549 , Thuja/química , Estrutura Molecular , Antineoplásicos/farmacologia , Diterpenos/química , Extratos Vegetais/farmacologia , Linhagem Celular TumoralRESUMO
Potentiation of stem cell potency is critical for successful tissue engineering, especially for bone regeneration. Three-dimensional cell culture and bioactive molecule co-delivery with cells have been proposed to achieve this effect. Here, we provide a uniform and scalable fabrication of osteogenic microtissue constructs of mesenchymal stem cell (MSC) spheroids surface-engineered with dexamethasone-releasing polydopamine-coated microparticles (PD-DEXA/MPs) to target bone regeneration. The microparticle conjugation process was rapid and cell-friendly and did not affect the cell viability or key functionalities. The incorporation of DEXA in the conjugated system significantly enhanced the osteogenic differentiation of MSC spheroids, as evidenced by upregulating osteogenic gene expression and intense alkaline phosphatase and alizarin red S staining. In addition, the migration of MSCs from spheroids was tested on a biocompatible macroporous fibrin scaffold (MFS). The result showed that PD-DEXA/MPs were stably anchored on MSCs during cell migration over time. Finally, the implantation of PD-DEXA/MP-conjugated spheroid-loaded MFS into a calvarial defect in a mouse model showed substantial bone regeneration. In conclusion, the uniform fabrication of microtissue constructs containing MSC spheroids with drug depots shows a potential to improve the performance of MSCs in tissue engineering.
Assuntos
Células-Tronco Mesenquimais , Esferoides Celulares , Camundongos , Animais , Osteogênese , Regeneração Óssea , Diferenciação Celular , Engenharia Tecidual/métodos , Dexametasona/farmacologia , Dexametasona/metabolismoRESUMO
A new secondary metabolite, ulleungdolin (1), was isolated from the co-culture of an actinomycete, Streptomyces sp. 13F051, and a fungus, Leohumicola minima 15S071. Based on the NMR, UV, and MS data, it was deduced that the planar structure of 1 comprised an isoindolinone (IsoID) with an octanoic acid, a tripeptide, and a sugar. The tripeptide has the unprecedented amino acids norcoronamic acid, 3-hydroxy-glutamine, and 4-hydroxy-phenylglycine and is linked by a C-N bond with IsoID. The absolute configurations were determined by chemical derivatization, extensive spectroscopic methods, and electronic circular dichroism calculations and supported by bioinformatic analyses. Bioactivity evaluation studies indicated that 1 had an antimigration effect on MDA-MB-231 breast cancer cells.
Assuntos
Ascomicetos , Policetídeos , Streptomyces , Streptomyces/química , Policetídeos/farmacologia , Policetídeos/química , Técnicas de Cocultura , Estrutura Molecular , PeptídeosRESUMO
Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) are indispensable analytical tools to provide chemical fingerprints in metabolomics studies. The present study evaluated radiation breeding wheat lines for chemical changes by non-targeted NMR-based metabolomics analysis of bran extracts. Multivariate analysis following spectral binning suggested pyrrole-2-carbaldehydes as chemical markers of four mutant lines with distinct NMR fingerprints in a δH range of 9.28-9.40 ppm. Further NMR and MS data analysis, along with chromatographic fractionation and synthetic preparation, aimed at structure identification of marker metabolites and identified five pyrrole-2-carbaldehydes. Quantum-mechanical driven 1H iterative full spin analysis (QM-HiFSA) on synthetic pyrrole-2-carbaldehydes provided a precise description of complex peak patterns. Biological evaluation of pyrrole-2-carbaldehydes was performed with nine synthetic products, and six compounds showed hepatoprotective effects via modulation of reactive oxygen species production. Given that three out of five identified in wheat bran of radiation were described for hepatoprotective activity, the value of radiation mutation to greatly enhance pyrrole-2-carbaldehyde production was supported.
Assuntos
Fibras na Dieta , Metabolômica , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas , Metabolômica/métodos , Pirróis , Espécies Reativas de OxigênioRESUMO
Nardostachys jatamansi is close to Valerian in consideration of their same psychoactive effects, such as sedation and neuroprotection. Valeriana-type iridoids are major active components of Valerian, but few valeriana-type iridoids have been isolated from N. jatamansi. Iridoid-targeting chemical investigation of the rhizomes of N. jatamansi resulted in the isolation of seven valeriana-type iridoid glycosides, four of which are previously undescribed. Their structures were determined through NMR spectroscopy, high-resolution mass spectrometry, and optical rotation experiments. In addition, the inaccurate configurations of patrinalloside and 6â³-acetylpatrinalloside from previous reports were corrected. These compounds, unstable due to alcoholic solvents, were more stable in the mixtures than in purified forms, as monitored by the qNMR method, supporting the use of natural products as mixtures. Furthermore, the isolates, as well as crude and solvent partition extracts, were found to have a protective effect against hydrogen-peroxide-induced toxicity in human neuroblastoma cells, as confirmed by assays for cell viability and antioxidation. These findings suggest the potential therapeutic application of the valeriana-type iridoid glycosides isolated herein with improved biochemical stability.
Assuntos
Produtos Biológicos , Nardostachys , Neuroblastoma , Valeriana , Humanos , Hidrogênio/análise , Peróxido de Hidrogênio/análise , Glicosídeos Iridoides/farmacologia , Iridoides/química , Estresse Oxidativo , Extratos Vegetais/química , Raízes de Plantas/química , Rizoma , Solventes , Valeriana/químicaRESUMO
[This corrects the article DOI: 10.3389/fnut.2021.806744.].
RESUMO
We report a method for the simultaneous determination of the sequence and absolute configuration of peptide amino acids using a combination of Edman degradation and HPLC-MS/CD. Phenylthiohydantoin (PTH) derivatives of 20 pairs of standard D- and L-amino acids were synthesized by the Edman reaction. The CD spectra of the derivatives revealed that each pair of the PTH derivatives exhibited the absorption with opposite signs at around 270 nm. These standard PTH derivatives showed well-resolved resolution without interference from byproducts in the ion chromatogram and clear positive/negative CD absorptions when subjected on a reversed phase HPLC-MS system coupled with a CD-2095 HPLC detector. This method was applied for the detection of a synthetic pentapeptide and a natural depsipeptide (halicylindramide C). The sequence and configuration of the pentapeptide and up to eight residues of halicylindramide C were successfully analyzed by this method. The amino acid configuration of the pentapeptide was also determined successfully by subjecting its acid hydrolysates to the Edman reaction followed by HPLC-MS/CD.
Assuntos
Aminoácidos , Feniltioidantoína , Aminas , Aminoácidos/química , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas , Peptídeos/química , Feniltioidantoína/químicaRESUMO
A cyclic depsipeptide, nobilamide I (1), along with the known peptide A-3302-B/TL-119 (2), was isolated from the saline cultivation of the marine-derived bacterium Saccharomonospora sp., strain CNQ-490. The planar structure of 1 was elucidated by interpretation of 1D and 2D NMR and MS spectroscopic data. The absolute configurations of the amino acids in 1 were assigned by using the C3 Marfey's analysis and comparing them with those of 2 based on their biosynthetic pathways. Nobilamide I (1) decreased cell motility by inhibiting epithelial-mesenchymal transition markers in A549 (lung cancer), AGS (gastric cancer), and Caco2 (colorectal cancer) cell lines. In addition, 1 modulated the expression of the matrix metalloproteinase (MMP) family (MMP2 and MMP9) in the three cell lines.
RESUMO
Luquilloamides A-G (1-7) were isolated from a small environmental collection of a marine cyanobacterium found growing on eelgrass (Zostera sp.) near Luquillo, Puerto Rico. Structure elucidation of the luquilloamides was accomplished via detailed NMR and MS analyses, and absolute configurations were determined using a combination of advanced Mosher's method, J-based configuration analysis, semisynthetic fragment analysis derived from ozonolysis, methylation, Baeyer-Villiger oxidation, Mosher's esterification, specific rotations, and ECD data. Except for 2, the luquilloamides share a characteristic tert-butyl-containing polyketide fragment, ß-alanine, and a proposed highly modified polyketide extension. While compound 1 is a linear lipopeptide with two α-methyl branches and a vinyl chloride functionality in the polyketide portion, compounds 4, 6, and 7 possess a cyclohexanone structure with methylation on the α- or ß-positions of the polyketide as well as an acetyl group. Interestingly, the absolute configuration at C-5 and C-6 on the cyclohexanone unit in 7 is opposite to that of 4-6. Compound 3 was revealed to have a tert-butyl-containing polyketide, ß-alanine, and a PKS/NRPS-derived γ-isopropyl pyrrolinone. Compound 2 may be a hydrolysis product of 3. Of the seven new compounds, 1 showed the most potent cytotoxicity to human H-460 lung cancer cells.
Assuntos
Lipopeptídeos/farmacologia , Oscillatoria , Linhagem Celular Tumoral , Humanos , Biologia Marinha , Estrutura Molecular , Oscillatoria/química , Porto RicoRESUMO
Lentil (Lens culinaris; Fabaceae), one of the major pulse crops in the world, is an important source of proteins, prebiotics, lipids, and essential minerals as well as functional components such as flavonoids, polyphenols, and phenolic acids. To improve crop nutritional and medicinal traits, hybridization and mutation are widely used in plant breeding research. In this study, mutant lentil populations were generated by γ-irradiation for the development of new cultivars by inducing genetic diversity. Molecular networking via Global Natural Product Social Molecular Networking web platform and dipeptidyl peptide-IV inhibitor screening assay were utilized as tools for structure-based discovery of active components in active mutant lines selected among the lentil population. The bioactivity-based molecular networking analysis resulted in the annotation of the molecular class of phosphatidylcholine (PC) from the most active mutant line. Among PCs, 1-stearoyl-2-hydroxy-sn-glycero-3-phosphocholine (18:0 Lyso PC) was selected for further in vivo study of anti-obesity effect in a high-fat diet (HFD)-induced obese mouse model. The administration of 18:0 Lyso PC not only prevented body weight gain and decreased relative gonadal adipose tissue weight, but also attenuated the levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol, and leptin in the sera of HFD-induced obese mice. Additionally, 18:0 Lyso PC treatment inhibited the increase of adipocyte area and crown-like structures in adipose tissue. Therefore, these results suggest that 18:0 Lyso PC is a potential compound to have protective effects against obesity, improving obese phenotype induced by HFD.
Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Fármacos Antiobesidade , LDL-Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Lens (Planta) , Obesidade , Fosfatidilcolinas , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Lens (Planta)/química , Lens (Planta)/genética , Masculino , Camundongos , Obesidade/sangue , Obesidade/induzido quimicamente , Obesidade/tratamento farmacológico , Fosfatidilcolinas/química , Fosfatidilcolinas/genética , Fosfatidilcolinas/farmacologiaRESUMO
Liver fibrosis, which means a sort of the excessive accumulation of extracellular matrices (ECMs) components through the liver tissue, is considered as tissue repair or wound-healing status. This pathological stage potentially leads to cirrhosis, if not controlled, it progressively results in hepatocellular carcinoma. Herein, we investigated the pharmacological properties and underlying mechanisms of Gardeniae Fructus (GF) against thioacetamide (TAA)-induced liver fibrosis of mice model. GF not only attenuated hepatic tissue oxidation but also improved hepatic inflammation. We further confirmed that GF led to ameliorating liver fibrosis by ECMs degradations. Regarding the possible underlying mechanism of GF, we observed GF regulated epigenetic regulator, Sirtuin 1 (SIRT1), in TAA-injected liver tissue. These alterations were well supported by SIRT1 related signaling pathways through regulations of its downstream proteins including, AMP-activated protein kinase (AMPK), p47phox, NADPH oxidase 2, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1, respectively. To validate the possible mechanism of GF, we used HepG2 cells with hydrogen peroxide treated oxidative stress and chronic exposure conditions via deteriorations of cellular SIRT1. Moreover, GF remarkably attenuated ECMs accumulations in transforming growth factor-ß1-induced LX-2 cells relying on the SIRT1 existence. Taken together, GF attenuated liver fibrosis through AMPK/SIRT1 pathway as well as Nrf2 signaling cascades. Therefore, GF could be a clinical remedy for liver fibrosis patients in the future.
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The epithelial-mesenchymal transition (EMT) of cancer cells is a crucial process in cancer cell metastasis. An Aquimarina sp. MC085 extract was found to inhibit A549 human lung cancer cell invasion, and caprolactin C (1), a new natural product, α-amino-ε-caprolactam linked to 3-methyl butanoic acid, was purified through bioactivity-guided isolation of the extract. Furthermore, its enantiomeric compound, ent-caprolactin C (2), was synthesized. Both 1 and 2 inhibited the invasion and γ-irradiation-induced migration of A549 cells. In transforming growth factor-ß (TGF-ß)-treated A549 cells, 2 inhibited the phosphorylation of Smad2/3 and suppressed the EMT cell marker proteins (N-cadherin, ß-catenin, and vimentin), as well as the related messenger ribonucleic acid expression (N-cadherin, matrix metalloproteinase-9, Snail, and vimentin), while compound 1 did not suppress Smad2/3 phosphorylation and the expression of EMT cell markers. Therefore, compound 2 could be a potential candidate for antimetastatic agent development, because it suppresses TGF-ß-induced EMT.
Assuntos
Antineoplásicos/farmacologia , Caproatos/farmacologia , Flavobacteriaceae/química , Lactonas/farmacologia , Células A549 , Animais , Organismos Aquáticos , Linhagem Celular Tumoral/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Fator de Crescimento Transformador beta/metabolismoRESUMO
Fourteen azaphilone-type polyketides (1-14), including nine new ones (1-6 and 8-10), were isolated from cultures of Vitex rotundifolia-associated Penicillium sp. JVF17, and their structures were determined by spectroscopic analysis together with computational methods and chemical reactions. Neuroprotective effects of the isolated compounds were evaluated against glutamate-induced neurotoxicity. Treatment with compounds 3, 6, 7, and 11-14 increased cell viabilities of hippocampal neuronal cells damaged by glutamate, with compound 12 being the most potent. Compound 12 markedly decreased intracellular Ca2+ and nuclear condensation levels. Mechanistically, molecular markers of apoptosis induced by treatment with glutamate, i.e., phosphorylation of MAPKs and elevated Bax/Bcl-2 expression ratio, were significantly lowered by compound 12. The azaphilones with an isoquinoline core structure were more active than those with pyranoquinones, but N-substitution decreased the activity. This study, including the structure-activity relationship, indicates that the azaphilone scaffold is a promising lead toward the development of novel neuroprotective agents.
Assuntos
Benzopiranos/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Penicillium/química , Pigmentos Biológicos/farmacologia , Policetídeos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Hipocampo/citologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Estrutura Molecular , Proteínas Proto-Oncogênicas c-bcl-2 , República da Coreia , Relação Estrutura-Atividade , Vitex/microbiologia , Proteína X Associada a bcl-2RESUMO
Acremonamide (1) was isolated from a marine-derived fungus belonging to the genus Acremonium. The chemical structure of 1 was established using MS, UV, and NMR spectroscopic data analyses. Acremonamide (1) was found to contain N-Me-Phe, N-Me-Ala, Val, Phe, and 2-hydroxyisovaleric acid. The absolute configurations of the four aforementioned amino acids were determined through acid hydrolysis followed by the advanced Marfey's method, whereas the absolute configuration of 2-hydroxyisovaleric acid was determined through GC-MS analysis after formation of the O-pentafluoropropionylated derivative of the (-)-menthyl ester of 2-hydroxyisovaleric acid. As an intrinsic biological activity, acremonamide (1) did not exert cytotoxicity to cancer and noncancer cells and increased the migration and invasion. Based on these activities, the wound healing properties of acremonamide (1) were confirmed in vitro and in vivo.
Assuntos
Acremonium/química , Peptídeos Cíclicos/farmacologia , Cicatrização/efeitos dos fármacos , Animais , Organismos Aquáticos/química , Células CACO-2 , Células HaCaT , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Células NIH 3T3 , Peptídeos Cíclicos/isolamento & purificaçãoRESUMO
Estrogen replacement therapy is a treatment to relieve the symptoms of menopause. Many studies suggest that natural bioactive ingredients from plants resemble estrogen in structure and biological functions and can relieve symptoms of menopause. The fruit of V. rotundifolia, called "Man HyungJa" in Korean, is a traditional medicine used to treat headache, migraine, eye pain, neuralgia, and premenstrual syndrome in Korea and China. The aim of the present study was to confirm that V. rotundifolia fruit extract (VFE) exerts biological functions similar to those of estrogen in menopausal syndrome. We investigated its in vitro effects on MCF-7 cells and in vivo estrogen-like effects on weight gain and uterine contraction in ovariectomized rats. Using the polar extract, the active constituents of VFE (artemetin, vitexicarpin, hesperidin, luteolin, vitexin, and vanillic acid) with estrogen-like activity were identified in MCF-7 cells. In animal experiments, the efficacy of VFE in ameliorating body weight gain was similar to that of estrogen, as evidenced from improvements in uterine atrophy. Vitexin and vitexicarpin are suggested as the active constituents of V. rotundifolia fruits.