RESUMO
Guaiane-type sesquiterpenoids are most prevalent in the genus Cinnamomum. Hence this study investigates the structures, anti-nociceptive and IL-6 targeted anti-inflammatory potential of three novels C-14 guaiane-type sesquiterpenoids and two new monoterpenoids, isolated from Cinnamomum migao. The structures were precisely confirmed and characterized through the modern chromatographic and spectroscopic techniques of HRESIMS, 1D NMR, 2D NMR, experimental circular dichroism (ECD), and calculated (ECD). Novel sesquiterpenoids 1 and 2 exhibited significant anti-inflammatory activities against the NO production and pro-inflammatory cytokines. Their IC50 values were determined as 9.52 and 13.42 µΜ against IL-6 mRNA, respectively. Similarly, subcutaneous injection of n-BuT and EA extracts showed a dose-dependent suppression of formalin-induced tonic biting/licking responses during the tonic antinociceptive phase. Furthermore, absorption, distribution, metabolism, excretion, and toxicity (ADMET) analysis of guaiane-type sesquiterpenoids 1 and 2 displayed that both compounds have a high level of GIT absorption, with a high zone of safety for cardiac and hepatotoxicity and no inhibition of cytochromes. In addition, molecular docking and simulation studies strengthen the anti-inflammatory potential of sesquiterpene 2 which showed a good binding affinity with IL-6 protein. Overall the inclusive results showed that the extracts and newly isolated guaiane-type sesquiterpenoids from C. migao will provide new evidence for the traditional use of this species to treat inflammation and nociception.
Assuntos
Interleucina-6 , Sesquiterpenos , Simulação de Acoplamento Molecular , Estrutura Molecular , Anti-Inflamatórios/farmacologia , Sesquiterpenos de Guaiano/farmacologia , Extratos Vegetais , Sesquiterpenos/químicaRESUMO
Twelve flavonoids were isolated and purified from the ethyl acetate fraction of 95% ethanol extract of Dalbergia odorifera by heat reflux extraction, solvent extraction, recrystallization, normal phase silica gel, Sephadex LH-20, MCI gel and HPLC methods. The structures were identified with multiple spectroscopic methods, including 1 D-NMR, 2 D-NMR and MS. The compounds were identified as 6,7,8-trimethoxy-5,4'-dihydroxy isoflavone(1), medicarpin(2), 7,2'-dihydroxy-4'-methoxy-isoflavanol(3), biochanin A(4), prunetin(5), genistein(6), pratensein(7), 3-(4-hydroxyphenyl)-6-isopentenyl-7-methoxy-4H-chromen-4-one(8), tectorigenin(9), irisolidone(10), vestitol(11), and formononetin(12). Compound 1 was a new isoflavone, and compound 8 was isolated from D. odorifera for the first time. The results showed that compounds 1-3 had inhibitory effects on tyrosinase, with inhibition rates of 35.58%, 38.63% and 51.34% at the concentration of 1.0 mmol·L~(-1), respectively.
Assuntos
Dalbergia , Isoflavonas , Dalbergia/química , Etanol , Flavonoides/química , Genisteína , Isoflavonas/química , Isoflavonas/farmacologia , Monofenol Mono-Oxigenase , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sílica Gel , SolventesRESUMO
Kaixinsan powder (KXS), a classic prescription of traditional Chinese Medicine (TCM), is widely used in the treatment of depression, but its mechanism remains unclear. The network pharmacology method was used to constructe the "herb-component-target" network, and elucidated KXS potential mechanisms of action in the treatment of depression. Moreover, molecular docking was applied to valid the important interactions between the ingredients and the target protein. The "herb-component-target" network indicated that the ingredients of Girinimbin, Gomisin B and Asarone, and the protein targets of ESR, AR and NR3C1 mostly contribute to the antidepressant effect of KXS. KEGG pathway analysis highlighted the most significant pathways associated with depression treatment, including neuroactive ligand-receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway. Go enrichment analysis indicated that the mechanism of KXS in treating depression was involved in the biological process of GPCR signal transduction, hormone metabolism and nerve cell apoptosis. Moreover, molecular docking results showed that Polygalaxanthone III, Girinimbine and Pachymic acid performed greater binding ability with key antidepressant target 5-HTR. In conclusion, this study preliminarily revealed key active components in KXS, including Gomisin B, Asarone, Ginsenoside Rg1, Polygalaxanthone III and Pachymic acid, could interact with multiple targets (5-HTR, DR, ADRA, AR, ESR, NR3C1) and modulate the activation of multiple pathways (Neuroactive ligand -receptor interaction pathway, serotonergic synapse pathway, PI3K-Akt signaling pathway and MAPK signaling pathway).
Assuntos
Depressão , Fosfatidilinositol 3-Quinases , Pós , Simulação de Acoplamento Molecular , Depressão/tratamento farmacológico , Ligantes , Proteínas Proto-Oncogênicas c-akt , Antidepressivos/farmacologia , Antidepressivos/uso terapêuticoRESUMO
This report illustrated isolation and identification of 42 compounds comprising five (spicatainoids A-E) undescribed eremophilanolide type sesquiterpenoids and one undescribed nor-eremophilane (spicatainoid F) from Ligularia subspicata.. Among all the isolated new compounds, 4 is reported as the first enantiomeric form of novel eremophilanolide type sesquiterpenoid. Comprehensive analysis of HRESIMS, 1D/2D NMR, experimental circular dichroism (CD), calculated ECD analysis, and X-ray crystallographic (XRD) analysis validated the complete configuration and confirmation of these isolated compounds. All the isolated compounds were tested for the anti-inflammatory potential by measuring the amount of nitric oxide production. Among the tested compounds, 4 was the most effective with 90% NO-inhibition activity. Compounds 1, 2, 3, 9, 10 18, 29, 34, 35 exhibited moderate inhibitory effects against the production of NO, while other compounds displayed no activity even at the concentration of 50 µM. Additionally, compounds 1, 3 and 4 presented moderate anti-inflammatory activity by inhibiting the release of pro-inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in LPS-stimulated N9 cells. The IC50 values of compounds 1, 3 and 4 were calculated 39.6 ± 2.7, 42.5 ± 3.8 and 27.60 ± 1.9 µΜ.
Assuntos
Anti-Inflamatórios/farmacologia , Ligularia/química , Sesquiterpenos Policíclicos/farmacologia , Sesquiterpenos/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Linhagem Celular , China , Citocinas/metabolismo , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Sesquiterpenos Policíclicos/isolamento & purificação , Sesquiterpenos/isolamento & purificaçãoRESUMO
Chinese medicine (CM) is usually prescribed as CM formula to treat disease. The lack of effective research approach makes it difficult to elucidate the molecular mechanisms of CM formula owing to its complicated chemical compounds. Network pharmacology is increasingly applied in CM formula research in recent years, which is identified suitable for the study of CM formula. In this review, we summarized the methodology of network pharmacology, including network construction, network analysis and network verification. The aim of constructing a network is to achieve the interaction between the bioactive compounds and targets and the interaction between various targets, and then find out and validate the key nodes via network analysis and network verification. Besides, we reviewed the application in CM formula research, mainly including targets discovery, bioactive compounds screening, toxicity evaluation, mechanism research and quality control research. Finally, we proposed prospective in the future and limitations of network pharmacology, expecting to provide new strategy and thinking on study for CM formula.
Assuntos
Descoberta de Drogas , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional ChinesaRESUMO
Five new guaiane-type sesquiterpenoid dimers vielopsides A-E, connecting patterns through two direct CC bonds (C-2 to C-2', C-4 to C-1'), were isolated from the roots of Xylopia vielana. Their absolute configurations were established by NOE analysis, the Cu Kα X-ray crystallographic and circular dichroism (CD) experiment. Among them, compound 5 showed moderate activity IC50 values of 33.8⯵M on NO production in RAW 264.7 macrophages.
Assuntos
Compostos Fitoquímicos/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Xylopia/química , Animais , China , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Compostos Fitoquímicos/farmacologia , Raízes de Plantas/química , Células RAW 264.7 , Sesquiterpenos/farmacologiaRESUMO
Three new aporphine alkaloids, xylopialoids A-C (1-3), along with three known aporphine alkioids (4-6) and three other known compounds (7-9) were isolated from the roots of Xylopia vielana. Among these three new aporphine alkaloids, xylopialoid C (3) showed a special carbamido group directly connected to the nitrogen. The chemical structures of these nine compounds were determined by a combination of 1D and 2D NMR, MS, CD spectrum and Cu Kα X-ray crystallographic analyses. All these six alkaloids were firstly tested for the inhibitory activities against the production of NO in RAW264.7 cells stimulated by lipopolysaccharide (LPS). Among these compounds, 4 showed a potential inhibitory activity against the production of nitric oxide with IC50 value of 1.39⯵M.
Assuntos
Alcaloides/isolamento & purificação , Anti-Inflamatórios/isolamento & purificação , Raízes de Plantas/química , Xylopia/química , Alcaloides/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7RESUMO
Seven new lignan glycosides (1-3, 8-10, and 14) and 17 known compounds were isolated from the branches of Alangium kurzii Craib var. laxifolium. Their structures were established by spectroscopic analysis and circular dichroism (CD) and X-ray analysis. The isolated compounds were evaluated for their antibacterial activities against Staphylococcus aureus CI1011, Streptococcus suis CI1608, Salmonella gallinarum CI0912, Enterococcus faecalis CI1304, Aeromonas hydrophila CI1008, Escherichia coli CI151012, Vibrio parahaemolyticus CI150506, Klebsiella pneumoniae CI131216, Pseudomonas aeruginosa CI1011, Staphylococcus epidermidis CI1110, and Streptococcus agalactiae CI1302. Their minimum inhibitory concentrations (MICs) were determined by serial dilution in 96-well culture plates.
Assuntos
Alangiaceae/química , Antibacterianos/química , Glicosídeos/química , Lignanas/química , Antibacterianos/isolamento & purificação , Glicosídeos/isolamento & purificação , Lignanas/isolamento & purificação , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
Eight new γ-lactam alkaloids, hemerominors A-H (1-8), including two pair of epimers (1-4), together with six known compounds (9-14) were isolated from the roots of Hemerocallis minor Mill. The structures of 1-8 were established on the basis of extensive NMR studies and HR-MS measurements as well as comparison with literature data. The absolute configurations of 1-8 were determined by CD spectral analysis and modified Mosher's method. All of compounds were evaluated for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 13 exhibited moderate inhibitory activity against NO production and with IC50 value of 18.0 µM.
Assuntos
Alcaloides/química , Hemerocallis/química , Lactamas/química , Alcaloides/isolamento & purificação , Animais , Lactamas/isolamento & purificação , Macrófagos/efeitos dos fármacos , Camundongos , Estrutura Molecular , Óxido Nítrico , Raízes de Plantas/química , Células RAW 264.7RESUMO
A phytochemical investigation on the roots of Campylotropis hirtella afforded nine new isoflavones (3-9, 12, 15), two new isoflavans (10 and 11), one new coumestan (1), and three new prenylated benzoic acid derivatives (2, 13, 14), together with twenty-four known compounds. Their structures were established by spectroscopic analysis and circular dichroism data. The isolated compounds were also evaluated for their antibacterial activities against Enterococcus faecalis, Salmonella gallinarum, Streptococcus suis, Streptococcus agalactiae, Aeromonas hydrophila, Pseudomonas aeruginosa, Bacillus subtilis, Riemerella anatipestifer, and Vibrio alginolyticus.
Assuntos
Antibacterianos/isolamento & purificação , Fabaceae/química , Extratos Vegetais/isolamento & purificação , Antibacterianos/química , Antibacterianos/farmacologia , Testes de Sensibilidade Microbiana , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Raízes de Plantas/químicaRESUMO
In the post-genomic era, biological studies are characterized by the rapid development and wide application of a series of "omics" technologies, including genomics, proteomics, metabolomics, transcriptomics, lipidomics, cytomics, metallomics, ionomics, interactomics, and phenomics. These "omics" are often based on global analyses of biological samples using high through-put analytical approaches and bioinformatics and may provide new insights into biological phenomena. In this paper, the development and advances in these omics made in the past decades are reviewed, especially genomics, transcriptomics, proteomics and metabolomics; the applications of omics technologies in pharmaceutical research are then summarized in the fields of drug target discovery, toxicity evaluation, personalized medicine, and traditional Chinese medicine; and finally, the limitations of omics are discussed, along with the future challenges associated with the multi-omics data processing, dynamics omics analysis, and analytical approaches, as well as amenable solutions and future prospects.
Assuntos
Pesquisa Biomédica/métodos , Genômica , Metabolômica , Farmacologia , Proteômica , Perfilação da Expressão GênicaRESUMO
One new phenolic compound (1) and one new flavan (2), together with eight known compounds (3-10) were isolated from the stems and twigs of Euonymus glabra Roxb. Their structures were elucidated mainly on the basis of 1D and 2D spectroscopic methods and circular dichroism analysis. In addition, compounds 1-10 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages. Compounds 1-5 and 7 exhibited moderate inhibitory activities with IC50 values ranged from 5.1 to 11.9 µM.
Assuntos
Euonymus/química , Flavonoides/química , Fenóis/química , Estrutura Molecular , Componentes Aéreos da Planta/químicaRESUMO
One new 1,10-secoeudesmanolide (1), two eudesmanolides (2 and 3), together with nine known compounds (4-12) were isolated from the aerial parts of Inula britannica. The structures of the new compounds were elucidated by detailed spectroscopic analysis, including HRESIMS and 2D-NMR spectroscopic method. In addition, compounds 1-4 were tested for their inhibitory effects against LPS-induced NO production in RAW264.7 macrophages.
Assuntos
Inula , Lactonas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Animais , Linhagem Celular , Cristalografia , Lactonas/química , Lactonas/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Componentes Aéreos da Planta , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
γ-Hydroxynitrile glucosides (prinsepicyanosides A-E) were isolated alongside 11 known compounds from seeds of Prinsepia utilis Royle. Their structures were determined by detailed analysis of NMR and MS spectroscopic data. The relative configuration of prinsepicyanoside C was established by Cu-Kα X-ray crystallography. Prinsepicyanoside A, osmaronin, and 4-(hydroxylmethyl)-5H-furan-2-one exhibited borderline antibacterial activity against Salmonella gallinarum, Vibrio parahaemolyticus, and Vibrio cholera with MIC values of 30.1, 20.7, and 22.8µg/mL, respectively.
Assuntos
Antibacterianos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Furanos/isolamento & purificação , Glucosídeos/isolamento & purificação , Nitrilas/isolamento & purificação , Rosaceae/química , Sementes/química , Antibacterianos/química , Antibacterianos/farmacologia , Cristalografia por Raios X , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Furanos/química , Furanos/farmacologia , Glucosídeos/química , Glucosídeos/farmacologia , Testes de Sensibilidade Microbiana , Conformação Molecular , Estrutura Molecular , Nitrilas/química , Ressonância Magnética Nuclear Biomolecular , Salmonella/efeitos dos fármacos , Estereoisomerismo , Vibrio/efeitos dos fármacosRESUMO
Eight new (1-8) and two known (9 and 10) sesquiterpenic acids featuring α-methylene-γ-carboxyl units were isolated from the whole plants of Inula wissmanniana, along with two new germacranolides (11 and 12). Their structures were elucidated based on detailed spectroscopic analysis, including HRESIMS, 1D and 2D NMR, and X-ray crystallography. Notably, the skeleton of 1 was firstly discovered from nature, while that of 2 was discovered for the second time. All the compounds were evaluated for their inhibition against LPS-induced nitric oxide (NO) production in RAW264.7 macrophages. Compound 11 exhibited the strongest activity with the IC50 value of 1.04 µM.
Assuntos
Inula/química , Óxido Nítrico/metabolismo , Sesquiterpenos/farmacologia , Animais , Cristalografia por Raios X , Concentração Inibidora 50 , Lipopolissacarídeos/metabolismo , Macrófagos/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Medicina Tradicional Chinesa , Camundongos , Estrutura Molecular , Componentes Aéreos da Planta/química , Plantas Medicinais , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Sesquiterpenos de Germacrano/química , Sesquiterpenos de Germacrano/isolamento & purificação , Sesquiterpenos de Germacrano/farmacologiaRESUMO
Phytochemical investigation of the aerial parts of Prinsepia utilis Royle resulted in the isolation and identification of ten pentacyclic triterpenoids, including two new triterpenoids, 2α-O-trans-p-coumaroyl-3ß,19α-dihydroxy-urs-12-en-28-oic acid (1) and 2α-O-cis-p-coumaroyl-3ß,19α-dihydroxy-urs-12-en-28-oic acid (2), along with eight known pentacyclic triterpenoids (3-10). The structures were elucidated by extensive spectroscopic methods and by comparison to previously reported spectroscopic data. Most of these compounds showed significant cytotoxic activities against four human cancer cell lines (A549, HCT116, MDA-MB-231, and CCRF-CEM), and the structure-activity relationships are also discussed.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Triterpenos Pentacíclicos/isolamento & purificação , Rosaceae/química , Antineoplásicos Fitogênicos/química , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Estrutura Molecular , Triterpenos Pentacíclicos/química , Plantas Medicinais/química , Relação Estrutura-AtividadeRESUMO
Aphanamgrandiol A (1), a novel triterpenoid with a bicyclo[3,2,1]octane ring skeleton produced by 2,3-ring opening and 2,6-ring closure, was isolated from the stems of Aphanamixis grandifolia. The structures were established on the basis of extensive spectroscopic methods, including 1D and 2D NMR techniques, and determined unambiguously by X-ray crystal diffraction. Aphanamgrandiol A showed moderate cytotoxicities against MCG-803, SKOV-3, HCT116 and HepG2 cell lines.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Meliaceae/química , Extratos Vegetais/química , Triterpenos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Carbono/química , Células HCT116 , Células Hep G2 , Humanos , Estrutura Molecular , Neoplasias/tratamento farmacológico , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Triterpenos/química , Triterpenos/farmacologia , Triterpenos/uso terapêuticoRESUMO
Four new sesquiterpene lactones, (1 S,5 R,6 S,7 S,8 R,9 R,10 S,11 S)-6-acetoxy-9-hydroxy-4-oxo-pseudoguai-2(3)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-ethoxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, (1 S,2 R,5 R,6 S,7 R,8 S,10 R)-6-acetoxy-2-hydroxy-4-oxo-pseudoguai-11(13)-en-12,8-olide, and 14-acetoxy-1 ß,5 α,7 αH-4 ß-hydroxy-guai-9(10),11(13)-dien-12,8 α-olide, along with 26 known sesquiterpene lactones, were isolated from the whole plants of Inula hookeri C. B. Clarke. Their structures were established based on spectroscopic methods including HRESIMS, 1D and 2D NMR, and CD techniques. All compounds were evaluated for their cytotoxic activities against HepG2, HeLa, PC-3, and MGC-803 cell lines by CCK-8 assay. Some of the isolates, especiallly pseudoguaianolides and guaianolides, exhibited significant cytotoxicities against these four examined cell lines.
Assuntos
Inula/química , Lactonas/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Sesquiterpenos/isolamento & purificação , Bioensaio , Linhagem Celular Tumoral , Sobrevivência Celular , China , Feminino , Humanos , Lactonas/química , Lactonas/farmacologia , Masculino , Medicina Tradicional Chinesa , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Sesquiterpenos/química , Sesquiterpenos/farmacologiaRESUMO
Quantitative composition-activity relationship (QCAR) study makes it possible to discover active components in traditional Chinese medicine (TCM) and to predict the integral bioactivity by its chemical composition. In the study, 28 samples of Radix Tinosporae were quantitatively analyzed by high performance liquid chromatography, and their analgesic activities were investigated via abdominal writhing tests on mice. Three genetic algorithms (GA) based approaches including partial least square regression, radial basis function neural network, and support vector regression (SVR) were established to construct QCAR models of R. Tinosporae. The result shows that GA-SVR has the best model performance in the bioactivity prediction of R. Tinosporae; seven major components thereof were discovered to have analgesic activities, and the analgesic activities of these components were partly confirmed by subsequent abdominal writhing test. The proposed approach allows discovering active components in TCM and predicting bioactivity by its chemical composition, and is expected to be utilized as a supplementary tool for the quality control and drug discovery of TCM.
Assuntos
Algoritmos , Analgésicos/análise , Medicamentos de Ervas Chinesas/química , Relação Estrutura-Atividade , Tinospora/química , Dor Abdominal , Analgésicos/química , Analgésicos/farmacologia , Animais , Comportamento Animal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Descoberta de Drogas , Medicamentos de Ervas Chinesas/farmacologia , Análise dos Mínimos Quadrados , Masculino , Medicina Tradicional Chinesa , Camundongos , Camundongos Endogâmicos ICR , Modelos Biológicos , Raízes de Plantas , Controle de Qualidade , Análise de Regressão , Máquina de Vetores de SuporteRESUMO
Ten steroidal alkaloids - cyclopamine, veratramine, jervine, 3, 15-diangyloylgermine, 3-angyloylzygadenine, 3-veratroyl zygadenine, 15-veratroylgermine, germine, veratrosine and pseudojervine - from Veratrum dahuricum, together with the ethanol extract and total alkaloids, were evaluated for their antitumor and antiplatelet activities. Cyclopamine, veratramine and germine significantly inhibited the hedgehog pathway in NIH/3T3 cells. Cyclopamine exerted a potent inhibitory effect against the growth of PANC-1 tumors in mice, with inhibition rates of 40.64%, 44.37%, 46.77% at doses of 5.0, 15.0 and 50.0 mg kg-1, respectively. Veratroylgermine was found to produce the strongest inhibition against the platelet aggregation induced by arachidonic acid, with inhibition rate of 92.0% at 100 microM.