RESUMO
The roots of Fibraurea recisa are recognized as a rich source of protoberberine and aporphine alkaloids, but the non-alkaloidal metabolites in this plant are underexplored. The present study investigated the chemical composition of the plant roots using untargeted metabolomics-based molecular networking and MS2LDA motif annotation, revealing the presence of a characteristic fragment motif related to several sinapoyl-functionalized metabolites. Guided by the targeted motif, two new sinapic acid-ecdysteroid hybrids, named 3-O-sinapoyl makisterone A (1) and 2-O-sinapoyl makisterone A (2), were isolated. The structures of these compounds, including their absolute configuration, were elucidated by HR-ESIQTOFMS, MS2 fragmentation, NMR spectroscopy, and chemical degradation coupled with optical rotation measurements. Although neither compound inhibited nitric oxide (NO) production or inducible nitric oxide synthase (iNOS) protein expression on lipopolysaccharide-induced RAW 264 cells, 2 significantly suppressed cyclooxygenase 2 (COX-2) protein expression at 1-30 µM. Additionally, decreased expression of COX-2 protein was barely observed after treatment with methyl sinapate or makisterone A, the steroid skeleton of 1 and 2. These results indicated that the presence of the sinapoyl moiety at C-2 on the C28-ecdysteroid skeleton played a key role in the selectivity for the suppression of the COX-2 protein expression.
Assuntos
Inibidores de Ciclo-Oxigenase 2 , Ecdisteroides , Ciclo-Oxigenase 2/metabolismo , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ecdisteroides/farmacologia , Ésteres , Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico , Lipopolissacarídeos/farmacologiaRESUMO
OBJECTIVE: An important factor in the aging of the face is a reduction in the volume of adipose tissue. This reduction in adipose tissue contributes to decreased skin elasticity, which is also part of the aging process. Overall, these lead to wrinkle formation. Fat injection is a common means of addressing this issue and is used to reduce the effects of aging on the face and to increase the fullness of the lips and breasts. However, fat injection is an invasive surgical procedure. This study aimed to discover novel cosmetic ingredients that increase the volume of subcutaneous (pre)adipocytes to create the appearance of more youthful skin. METHODS: We focused on the number of subcutaneous preadipocytes and the accumulation of lipid droplets. To discover natural ingredients that increase both of these, extracts of 380 natural products were prepared and screened for their effects on both growth and differentiation (i.e., lipid droplet accumulation) of human subcutaneous preadipocytes. One extract was found to have the desired effects, and this was further studied to determine the active compounds. We then evaluated its efficacy in a human clinical study. RESULTS: We found that Arnica montana L. flower extract (AFE) accelerates both the growth and the differentiation of human subcutaneous preadipocytes. AFE was found to significantly increase the volume of adipocyte spheroids. The active compounds 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin were found to be responsible for the effects of AFE on preadipocytes. In a human clinical study, gels containing 1% AFE successfully enhanced the volume of the lips and face with reduction of wrinkles with no adverse reactions. CONCLUSION: This is the first report to demonstrate that AFE and the included compounds, 6-O-methacryloylhelenalin and 6-O-isobutyrylhelenalin, act on preadipocytes. AFE would be ideal for use in products that plump the face to reduce wrinkles and create a more youthful appearance.
OBJECTIF: Un facteur important du vieillissement du visage réside dans la réduction du volume du tissu adipeux. Cette réduction du tissu adipeux contribue à une diminution de l'élasticité de la peau qui fait également partie du processus de vieillissement. Globalement, ces facteurs induisent la formation des rides. L'injection de graisse est un moyen courant pour remédier à ce problème et sert à réduire les effets du vieillissement sur le visage et à augmenter la plénitude des lèvres et des seins. Cependant, l'injection de graisse est une intervention chirurgicale invasive. Cette étude visait à découvrir des ingrédients cosmétiques innovants qui augmentent le volume des (pré)adipocytes sous-cutanés pour créer l'apparence d'une peau plus jeune. MÉTHODES: Nous avons mis l'accent sur le nombre de préadipocytes sous-cutanés et sur l'accumulation de gouttelettes lipidiques. Pour découvrir des ingrédients naturels qui augmentent ces deux facteurs, des extraits de 380 produits naturels ont été préparés et analysés en vue de la détermination de leurs effets sur la croissance et la différenciation (c'est-à-dire l'accumulation de gouttelettes lipidiques) des préadipocytes humains sous-cutanés. Un extrait s'est avéré avoir les effets escomptés et il a fait l'objet d'études approfondies visant à déterminer les composés actifs. Nous avons ensuite évalué son efficacité dans une étude clinique chez l'homme. RÉSULTATS: Nous avons découvert que l'extrait de fleur de l'Arnica montana L. (AFE) accélère à la fois la croissance et la différenciation des préadipocytes humains sous-cutanés. L'AFE s'est avéré augmenter considérablement le volume des sphéroïdes des adipocytes. Les composés actifs 6-Ométhacryloyl-hélénaline et 6-O-isobutyryl-hélénaline se sont avérés responsables des effets de l'AFE sur les préadipocytes. Dans une étude clinique chez l'homme, des gels contenant 1 % d'AFE ont permis d'améliorer le volume des lèvres et du visage avec une réduction des rides sans effets indésirables. CONCLUSION: Il s'agit du premier rapport démontrant que l'AFE et les composés inclus, 6-O-méthacryloyl-hélénaline et 6-O-isobutyryl-hélénaline, agissent sur les préadipocytes. L'AFE serait idéal pour les produits qui repulpent le visage afin de réduire les rides et de donner un aspect rajeuni.
Assuntos
Arnica , Humanos , Tecido Adiposo , Adipócitos , Pele , Extratos Vegetais/farmacologia , Diferenciação CelularRESUMO
This study investigated the mechanism underlying anti-cancer cell migration activity of quercetin derivatives by investigating the binding mode of the target protein. Five flavonoid probes were newly synthesized, and pull down assay using synthesized flavonoid probes indicated matrix metalloproteinase-1 (MMP-1) as the target protein of quercetin derivatives. Quercetin and 3-O-methylquercetin (3MQ) inhibited MMP-1. SPR analysis demonstrated dose dependent interaction between quercetin derivatives and recombinant MMP-1 catalytic domain. And 1H-15N heteronuclear single quantum coherence (HSQC) NMR analysis using 15N-labeled MMP-1 catalytic domain indicated that 3MQ interacted around metal ions in the MMP-1. The development of flavonoid probes can broaden the possibility to discover the new target proteins and elucidate the core mechanisms of the multi bioactivity of flavonoids.
Assuntos
Flavonoides , Quercetina , Flavonoides/farmacologia , Metaloproteinase 1 da Matriz , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Quercetina/química , Quercetina/farmacologiaRESUMO
In this study, three new garcinoic acid dimers, δ,δ-bigarcinoic acid (1), δ,δ-bi-O-garcinoic acid (2), and γ,δ-bi-O-garcinoic acid (3), and a new benzophenone derivative, (8E)-4-geranyl-3,5-dihydroxybenzophenone (4), as well as seven known compounds (5-11) were isolated from the seeds of Garcinia kola. The structures of the new compounds were elucidated using MALDI-TOF-MS and spectroscopic data, including 1D and 2D NMR and electronic circular dichroism spectra. All of the isolated compounds were evaluated for their antimicrobial activity against two oral pathogens, Porphyromonas gingivalis and Streptococcus sobrinus. Among them, 4 and δ-garcinoic acid (6) exhibited antimicrobial activity against both of these microorganisms (MICs of 31.3-62.5 µM for P. gingivalis and 15.6-31.3 µM for S. sobrinus). These results indicate that some chemical constituents in G. kola seeds have potential application in the prevention of oral diseases.
Assuntos
Antibacterianos/farmacologia , Benzofenonas/farmacologia , Benzopiranos/farmacologia , Garcinia kola/metabolismo , Boca/microbiologia , Extratos Vegetais/farmacologia , Porphyromonas gingivalis/efeitos dos fármacos , Sementes/química , Streptomyces/efeitos dos fármacos , Antibacterianos/química , Benzofenonas/isolamento & purificação , Benzopiranos/química , Cromatografia Líquida de Alta Pressão , Humanos , Testes de Sensibilidade Microbiana , Análise Espectral/métodosRESUMO
In our previous study, the isolation of ugonin J, K, and L, which are luteolin derivatives, from the roots of Helminthostachys zeylanica and their identification as potent melanogenesis inhibitors, was described. The structure activity relationship (SAR) investigation in that study revealed that the catechol moiety in the B-ring of the flavone skeleton of ugonin K was important for its melanogenesis inhibitory activity, and the presence of the low polarity substituents at the C-7 position enhanced this activity. In order to further investigate the SAR of the C-7-substituent in the luteolin derivatives, different groups were selectively introduced at the C-7 position of luteolin after borax protection of the catechol hydroxyl group and the C-5 hydroxyl group. NMR and MS analysis of the borax protected derivatives revealed that the borax protects not only hydroxyl groups of catechol on the B ring but also the 5-hydroxyl group on the A ring. Eight luteolin derivatives were synthesized and evaluated for melanogenesis inhibitory effect in B16 melanoma cells. Two bulky groups and six alkoxyl groups were introduced at the C-7 position. The resulting luteolin derivatives showed improved melanogenesis and cell proliferation inhibitory activities. From among these derivatives, 7-O-hexylluteolin (7) showed the highest activity and inhibited the melanogenesis to 14% at 6.25⯵M. The present study also revealed that the length of the carbon chain rather than the bulky substituent was more important for the melanogenesis inhibitory activity.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Luteolina/farmacologia , Melanoma/tratamento farmacológico , Antineoplásicos Fitogênicos/síntese química , Antineoplásicos Fitogênicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Gleiquênias/química , Humanos , Luteolina/síntese química , Luteolina/química , Melanoma/patologia , Estrutura Molecular , Relação Estrutura-AtividadeRESUMO
We investigated the tumor necrosis factor-alpha (TNF-α) inhibitory activity of sesquiterpenes from Saussurea lappa root extracts. According to the hexane and EtOAc extracts showing significant activity with IC50 values of 0.5 and 1.0 µg/mL, respectively, chromatographic fractionation of the extracts was performed and led to the isolation of 10 sesquiterpenes (1: -10: ). Costunolide (1: ), a major compound, and dehydrocostus lactone (4: ) exhibited high efficiency in decreasing TNF-α levels, with IC50 values of 2.05 and 2.06 µM, respectively. In addition, sesquiterpene analogues were synthesized to establish their structure-activity relationship (SAR) profile. Among the semi-synthetic analogues, compounds 6A: and 16: showed the most potent activity with IC50 values of 1.84 and 1.97 µM, respectively. More importantly, compound 6A: showed less toxicity than costunolide and 16: . These results provided the first SAR profile of sesquiterpene lactones and indicated that the α-methylene-γ-lactone moiety plays a crucial role in TNF-α inhibition. Additionally, the epoxide derivative 6A: might represent a lead compound for further anti-TNF-α therapies, owing to its potent activity and reduced toxicity.
Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Lactonas/farmacologia , Extratos Vegetais/farmacologia , Saussurea/química , Sesquiterpenos/farmacologia , Anti-Inflamatórios/química , Concentração Inibidora 50 , Lactonas/química , Lactonas/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Raízes de Plantas/química , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Relação Estrutura-Atividade , Fator de Necrose Tumoral alfa/efeitos adversosRESUMO
BACKGROUND: Grains of paradise (GP) is the seed of Aframomum melegueta, which is widely distributed throughout West Africa and has been used as a spice and a folk remedy for a long time. Anti-obesity effect of GP intake was demonstrated in a previous report. Aim of the present study was to isolate some compounds in GP and clarify the anti-obesity mechanism. RESULTS: Ten vanilloid compounds were isolated. Among them, 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-ol and 1-(4'-hydroxy-3'-methoxyphenyl)-3-octen-5-one were determined as novel compounds and 6-gingerol, 6-paradol and 6-shogaol were identified as the major constituents in GP extract. Moreover, the extract and 6-gingerol, which is one of the principal components of GP extract, were orally administered to rats to investigate the effect on sympathetic nerve activity (SNA) in brown adipose tissue (BAT). The injection of GP extract and 6-gingerol decreased BAT-SNA, whereas capsaicin, which is a major component of chili pepper, activates the sympathetic nervous system. CONCLUSION: This study suggested that GP extract and 6-gingerol were largely unrelated to the anti-obesity effect by the activation of interscapular BAT-SNA and had a different anti-obesity mechanism to capsaicin. © 2018 Society of Chemical Industry.
Assuntos
Obesidade/fisiopatologia , Extratos Vegetais/química , Sistema Nervoso Simpático/diagnóstico por imagem , Zingiberaceae/química , Tecido Adiposo Marrom/efeitos dos fármacos , Tecido Adiposo Marrom/inervação , Animais , Catecóis/administração & dosagem , Catecóis/química , Álcoois Graxos/administração & dosagem , Álcoois Graxos/química , Guaiacol/administração & dosagem , Guaiacol/análogos & derivados , Guaiacol/química , Humanos , Cetonas/administração & dosagem , Cetonas/química , Estrutura Molecular , Obesidade/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Ratos , Sementes/química , Sistema Nervoso Simpático/fisiopatologiaRESUMO
BACKGROUND: Periodontal diseases are one of the major health problems and among the most important preventable global infectious diseases. Porphyromonas gingivalis is an anaerobic Gram-negative bacterium which has been strongly implicated in the etiology of periodontitis. Additionally, matrix metalloproteinases-9 (MMP-9) is an important factor contributing to periodontal tissue destruction by a variety of mechanisms. The purpose of this study was to evaluate the selected Sudanese medicinal plants against P. gingivalis bacteria and their inhibitory activities on MMP-9. METHODS: Sixty two methanolic and 50% ethanolic extracts from 24 plants species were tested for antibacterial activity against P. gingivalis using microplate dilution assay method to determine the minimum inhibitory concentration (MIC). The inhibitory activity of seven methanol extracts selected from the 62 extracts against MMP-9 was determined by Colorimetric Drug Discovery Kit. In search of bioactive lead compounds, Combretum hartmannianum bark which was found to be within the most active plant extracts was subjected to various chromatographic (medium pressure liquid chromatography, column chromatography on a Sephadex LH-20, preparative high performance liquid chromatography) and spectroscopic methods (liquid chromatography-mass spectrometry, Nuclear Magnetic Resonance (NMR)) to isolate and characterize flavogalonic acid dilactone and terchebulin as bioactive compounds. RESULTS: About 80% of the crude extracts provided a MIC value ≤4 mg/ml against bacteria. The extracts which revealed the highest potency were: methanolic extracts of Terminalia laxiflora (wood; MIC = 0.25 mg/ml) followed by Acacia totrtilis (bark), Ambrosia maritima (aerial part), Argemone mexicana (seed), C. hartmannianum (bark), Terminalia brownii (wood) and 50% ethanolic extract of T. brownii (bark) with MIC values of 0.5 mg/ml. T. laxiflora (wood) and C. hartmannianum (bark) which belong to combretaceae family showed an inhibitory activity over 50% at the concentration of 10 µg/ml against MMP-9. Additionally, MMP-9 was significantly inhibited by terchebulin with IC50 value of 6.7 µM. CONCLUSIONS: To the best of our knowledge, flavogalonic acid dilactone and terchebulin were isolated from C. hartmannianium bark for the first time in this study. Because of terchebulin and some crude extracts acting on P. gingivalis bacteria and MMP-9 enzyme that would make them promising natural preference for preventing and treating periodontal diseases.
Assuntos
Antibacterianos/farmacologia , Combretum/química , Metaloproteinase 9 da Matriz/metabolismo , Doenças Periodontais , Extratos Vegetais/farmacologia , Plantas Medicinais , Porphyromonas gingivalis/efeitos dos fármacos , Acacia , Ambrosia , Argemone , Taninos Hidrolisáveis/isolamento & purificação , Taninos Hidrolisáveis/farmacologia , Lactonas/isolamento & purificação , Lactonas/farmacologia , Medicinas Tradicionais Africanas , Doenças Periodontais/tratamento farmacológico , Doenças Periodontais/microbiologia , Casca de Planta/química , Extratos Vegetais/química , Sudão , TerminaliaRESUMO
Six new chamigrane sesquiterpenes, merulinols AâF (1â6), and four known metabolites (7â10) were isolated from the culture of the basidiomycetous fungus XG8D, a mangrove-derived endophyte. Their structures were elucidated mainly by 1D and 2D NMR, while the structures of 1 and 2 were further confirmed by single-crystal X-ray diffraction analysis. The in vitro cytotoxicity of all compounds was evaluated against three human cancer cell lines, MCF-7, Hep-G2, and KATO-3. Compounds 3 and 4 selectively displayed cytotoxicity against KATO-3 cells with IC50 values of 35.0 and 25.3 µM, respectively.
Assuntos
Basidiomycota/química , Endófitos/química , Fungos/química , Rhizophoraceae/microbiologia , Sesquiterpenos/química , Linhagem Celular Tumoral , Cristalografia por Raios X/métodos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Sesquiterpenos/farmacologia , Tailândia , Difração de Raios X/métodosRESUMO
4'-O-ß-d-Glucopyranosyl-quercetin-3-O-ß-d-glucopyranosyl-(1â4)-ß-d-glucopyra-noside (3) was isolated from Helminthostachys zeylanica root extract as a melanogenesis acceleration compound and was synthesized using rutin as the starting material. Related compounds were also synthesized to understand the structure-activity relationships in melanin biosynthesis. Melanogenesis activities of the glycosides were determined by measuring intracellular melanin content in B16 melanoma cells. Among the synthesized quercetin glycosides, quercetin-3-O-ß-d-glucopyranoside (1), quercetin-3-O-ß-d-glucopyranosyl-(1â4)-ß-d-glucopyranoside (2), and 3 showed more potent intracellular melanogenesis acceleration activities than theophyline used as positive control in a dose-dependent manner with no cytotoxic effect.
Assuntos
Celobiose/análogos & derivados , Glucosídeos/síntese química , Glucosídeos/farmacologia , Melanoma Experimental/tratamento farmacológico , Quercetina/análogos & derivados , Quercetina/química , Animais , Sequência de Carboidratos , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Celobiose/síntese química , Celobiose/química , Celobiose/farmacologia , Técnicas de Química Sintética , Relação Dose-Resposta a Droga , Gleiquênias/química , Glucosídeos/química , Melaninas/biossíntese , Melanoma Experimental/metabolismo , Camundongos , Dados de Sequência Molecular , Estrutura Molecular , Raízes de Plantas/química , Quercetina/síntese química , Quercetina/farmacologia , Relação Estrutura-AtividadeRESUMO
In order to understand the effect of structure-activity relationships on melanogenesis using B16 melanoma cells, 19 quercetin derivatives were synthesized. Among the synthesized compounds, 3-O-methylquercetin (11) and 3',4',7-O-trimethylquercetin (14) increased melanin content more potently than the positive control theophylline, while exhibiting low cytotoxicity. Compound 11 exhibited less melanogenesis-stimulating activity than compound 14. However, 11 increased the expression of tyrosinase and tyrosinase-related protein 1 (TRP-1) to a greater extent than 14, thereby suggesting that melanogenesis in melanoma cells does not depend solely on the expression of the enzymes catalyzing melanin biosynthesis. Furthermore, 14 also stimulated the expression of the microphthalmia-associated transcription factor (MITF) and p-p38 mitogen activated protein kinase (MAPK), while they were not increased by 11. These results suggest that 11 may enhance the expression of tyrosinase and TRP-1 by regulating the proteasomal degradation of melanogenic enzymes and/or by activating other transcriptional factors regulating enzyme expression.
Assuntos
Melaninas/biossíntese , Fator de Transcrição Associado à Microftalmia/metabolismo , Quercetina/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Melaninas/química , Camundongos , Estrutura Molecular , Quercetina/síntese química , Quercetina/química , Relação Estrutura-Atividade , Células Tumorais CultivadasRESUMO
Dragon's blood is a red resin obtained from different plants and is considered highly efficacious and used in medicine owing its wound healing function. Two new compounds (7 and 8) were isolated from the dragon's blood of Daemonorops draco fruits, along with eight known compounds (1-6, 9, and 10). Their structures, including their absolute configurations, were elucidated by nuclear magnetic resonance (NMR), matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and electronic circular dichroism (ECD) analysis. According to the spectroscopic data, 8 was determined to be a quinone methide derivative of flavan and 7 was deduced to be a flavan trimer. All compounds were evaluated for their anti-osteoclastogenesis activity, compound 1 and 7 exhibited anti-osteoclastogenesis activity with IC50 values of 31.3 and 36.8 µM, respectively.
Assuntos
Calamus , Osteogênese , Extratos Vegetais , Estrutura Molecular , Extratos Vegetais/química , Plantas/química , Espectroscopia de Ressonância MagnéticaRESUMO
Blackcurrant is available as a traditional medicine in Europe. However, the detailed effects of blackcurrant on the human gut microbiota remain unknown. In this study, we investigated the prebiotic effects of a blackcurrant extract using a human fecal culture model in six healthy subjects. Feces were individually inoculated into a medium with or without the blackcurrant extract and then fermented for 48 hr under anaerobic conditions. The results obtained from analysis of samples from the fermented medium demonstrated that after 48 hr of fermentation, the pH of the medium with the blackcurrant extract was significantly decreased (control, 6.62 ± 0.20; blackcurrant extract, 6.41 ± 0.33; p=0.0312). A 16S rRNA gene sequencing analysis of the microbiota of the fermented medium showed a significant increase in the relative abundance of Bifidobacteriaceae. In measuring the concentrations of putrefactive components in the fermented medium, we found that the blackcurrant extract significantly reduced ammonia levels and displayed a tendency toward reduced indole levels. Our results suggest that blackcurrant extract could be a potential ingredient for relief of putrefactive components in the gut.
RESUMO
In this work, we identified novel physiological functions of glutathione in acetaldehyde tolerance in Saccharomyces cerevisiae. Strains deleted in the genes encoding the enzymes involved in glutathione synthesis and reduction, GSH1, GSH2 and GLR1, exhibited severe growth defects compared to wild-type under acetaldehyde stress, although strains deleted in the genes encoding glutathione peroxidases or glutathione transferases did not show any growth defects. On the other hand, intracellular levels of reduced glutathione decreased in the presence of acetaldehyde in response to acetaldehyde concentration. Moreover, we show that glutathione can trap a maximum of four acetaldehyde molecules within its molecule in a non-enzymatic manner. Taken together, these findings suggest that glutathione has an important role in acetaldehyde tolerance, as a direct scavenger of acetaldehyde in the cell.
Assuntos
Acetaldeído/antagonistas & inibidores , Antifúngicos/antagonistas & inibidores , Farmacorresistência Fúngica , Glutationa/metabolismo , Saccharomyces cerevisiae/fisiologia , Acetaldeído/metabolismo , Acetaldeído/toxicidade , Antifúngicos/toxicidade , Deleção de Genes , Glutamato-Cisteína Ligase/deficiência , Glutamato-Cisteína Ligase/metabolismo , Glutationa Sintase/deficiência , Glutationa Sintase/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismoRESUMO
Tannins are involved in the taste of foods and multi bioactivity of traditional herbal medicines. The characteristics of tannins are believed to derive from their connectivity with proteins. However, the mode of interaction between proteins and tannins is not yet understood because of the complexity of the tannin structure. Then this study aimed to elucidate the detail binding mode of tannin and protein by the 1H-15N HSQC NMR method using the 15N-labeled MMP-1that have not been used so far. The HSQC results suggested cross-link sites between MMP-1s, which cause protein aggregation and inhibit MMP-1 activity. This study presents the first 3D protein aggregation model of condensed tannins, which is important for understanding the bioactivity of polyphenols. Furthermore, it can broaden the understanding of the range of interactions between other proteins and polyphenols.
Assuntos
Plantas Medicinais , Proantocianidinas , Agregados Proteicos , Taninos/química , Polifenóis/farmacologia , Plantas Medicinais/metabolismoRESUMO
The lichen Usnea baileyi is a fruticose lichen belonging to the Usnea genus. It is well known as a rich source of natural xanthone dimers and possesses various bioactivities. Nevertheless, the chemical investigation on this type of lichen is still rare as most of researches reported its components without structural elucidation. Herein, in the continuous study on this type of lichen, we further isolate xanthone dimers from the dichloromethane extract and explore three new xanthone dimers, eumitrins F - H (1 - 3). Their structures were elucidated unambiguously by spectroscopic analyses, including high resolution electrospray ionisation mass spectrometry (HRESIMS), 1 D and 2 D nuclear magnetic resonance spectroscopy (1 D and 2 D NMR), and DP4 probability. All compounds were evaluated for their enzyme inhibition against α-glucosidase, tyrosinase, and antibacterial activity. They revealed moderate antimicrobial and weak tyrosinase inhibition. For α-glucosidase inhibition, compound 3 displayed the most significant inhibitory against α-glucosidase possessing an IC50 value of 64.2 µM.
Assuntos
Líquens , Usnea , Xantonas , alfa-Glucosidases , Monofenol Mono-Oxigenase , Usnea/química , Xantonas/química , Hidrogênio/química , Flúor/químicaRESUMO
In the continuing discovery and structure elucidation of natural xanthone dimers, which are still rarely reported in absolute configuration, three new xanthone dimers, eumitrins I-K (1-3) were isolated from the lichen Usnea baileyi, a rich source of natural xanthone dimers. Their structures were elucidated unambiguously by spectroscopic analyses, including high-resolution electrospray ionization mass spectrometry (HRESIMS), 1D and 2D nuclear magnetic resonance spectroscopy (1D and 2D NMR). The absolute configuration of all three compounds was established through DP4 probability and ECD calculation. All compounds revealed weak activity for their enzymatic inhibition against α-glucosidase and tyrosinase, as well as antibacterial activity.
Assuntos
Líquens , Xantonas , Estrutura Molecular , Xantonas/químicaRESUMO
With the aid of a feature-based molecular networking strategy, five undescribed C2 and C1 symmetric chromene dimers, namely, melptelchromenes A-E, were isolated from the leaves of Melicope pteleifolia. Four asymmetric dimers were found to be racemates and were resolved by chiral phase HPLC analyses. Their structures, including absolute configurations, were elucidated by HRMS, NMR spectroscopy, and quantum mechanical calculations of ECD spectra and NMR chemical shifts. Melptelchromenes A-D possess a unique ethylidene linkage via two 2H-chromene cores, while melptelchromene E represents the first example of a dimeric chromene featuring a 1,3-diarylbutan-1-ol moiety. Of these compounds, 6,6'-linked dimeric chromenes showed nitric oxide inhibitory activities on lipopolysaccharide-induced RAW 264 cells, and (-)- and (+)-melptelchromene E were the two most potent compounds (IC50, 3.0 and 5.1 µM, respectively).
Assuntos
Rutaceae , Anti-Inflamatórios/farmacologia , Benzopiranos/química , Estrutura Molecular , Óxido Nítrico , Folhas de Planta/química , Rutaceae/químicaRESUMO
A new benzoic acid, 3-[2-(2-hydroxyphenyl)acetoxy]benzoic acid (1), and two new caffeoyl derivatives, methyl (3E,5Z)-di-O-caffeoylquinate (2) and dhurrin 6'-O-caffeate (3), along with 20 known compounds were isolated from the leaves of Ilex kaushue collected in Vietnam. Their structures were elucidated on the basis of 1 D and 2 D NMR spectroscopy, and high-resolution MS spectrometry. The absolute configuration of 2 and 3 was unambiguously established by comparison of experimental and calculated ECD spectra and/or chemical reactivity. In addition, new compounds were evaluated for inhibitory effects of their tumor necrosis factor-α (TNF-α) production and cell cytotoxicity on lipopolysaccharide-induced RAW264 macrophage cells. All of those moderately suppressed TNF-α production in ratios of approximately 50% or higher at 25-100 µM, without cell cytotoxicity.
Assuntos
Ilex , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Ácido Benzoico/farmacologia , Ilex/química , Estrutura Molecular , Folhas de Planta/química , Fator de Necrose Tumoral alfaRESUMO
Obesity is now recognized as an epidemic, requiring rapid intervention. We previously demonstrated that vanilloids from the African spice known as Grains of Paradise (GOP) exhibit strong anti-obesity effects. Here, the molecular mechanism behind the obesity prevention property of the GOP extract was investigated by employing molecular networking-based lipid profiling and 16S rRNA sequencing. Administration of either GOP extract or two of its components, 6-paradol and 6-gingerol, reversed the unbalanced gut microbiota composition induced by a high-fat diet (HFD) with a decrease in Firmicutes / Bacteroidetes ratio and increase in genera Bifidobacterium and Akkermansia. Moreover, GOP extract ameliorated abnormal fatty acid metabolism in gut bacteria. Furthermore, lipid molecular networking revealed differences in lipid composition, such as triglycerides and bile acids, in the feces. These results suggest that 6-paradol and 6-gingerol can restore an unhealthy gut environment and prevent lipid absorption, a possible consequence of the reconstruction of the gut microbiota.