RESUMO
The preliminary study revealed that the ethyl acetate eluate of Youngia japonica (YJ-E) could inhibit the expression of key proteins of p-p65, p-IκBα, p-IKKα/ß, and p-AKT in LPS stimulated BV2 cell. Further phytochemical study led to the isolation of eight compounds from YJ-E, including one new sesquiterpene lactone. Their structures were elucidated by several spectroscopic data, and comparing the NMR data of known compound. In addition, all of the isolates were evaluated for the anti-inflammatory effect. As a result, compounds 3 and 4 distinctly attenuated the expressions of p-IκBα, p-p65, and p-AKT in LPS stimulated BV2 cell, respectively.
RESUMO
In the process of searching for anti-breast cancer agents, five sesquiterpene lactones (1-5), including two previously undescribed ones, yjaponica B-C (1-2), were isolated from the herb of Youngia japonica. Their structures were elucidated by spectroscopic data analyses and Marfey's method. Cytotoxic activities of all compounds against A549, U87, and 4T1â cell lines were tested using the CCK8 assay. The result showed that compound 3 possessed the highest cytotoxic activity against 4T1 cells with an IC50 value of 10.60â µM. Furthermore, compound 3 distinctly induced apoptosis, inhibited immigration, and blocked the cell cycle of 4T1 cells. In addition, compound 3 induced the production of reactive oxygen species. Further anticancer mechanism studies showed that compound 3 significantly upregulated expression of the cleaved caspase 3 and PARP, whereas it downregulated the expression of Bcl-2, cyclin D1, cyclin A2, CDK4, and CDK2. Taken together, our results demonstrate that compound 3 has a high potential of being used as a leading compound for the discovery of new anti-breast cancer agent.
RESUMO
This study aims to investigate the protective effect of salidroside(SAL) on renal damage in diabetic nephropathy(DN) mice based on the receptor for advanced glycation end products/janus activated kinase 1/signal transduction and activator of transcription 3(RAGE/JAK1/STAT3) signaling pathway. The mouse DN model was established by high-fat/high-sucrose diets combined with intraperitoneal injection of streptozocin(STZ). Mice were randomly divided into normal group, model group, low-dose SAL group(20 mg·kg~(-1)), high-dose SAL group(100 mg·kg~(-1)), and metformin group(140 mg·kg~(-1)), with 12 mice in each group. After establishing the DN model, mice were given drugs or solvent intragastrically, once a day for consecutive 10 weeks. Body weight, daily water intake, and fasting blood glucose(FBG) were measured every two weeks. After the last dose, the glucose tolerance test was performed, and the samples of 24-hour urine, serum, and kidney tissue were collected. The levels of 24 hours urinary total protein(24 h-UTP), serum creatinine(Scr), blood urea nitrogen(BUN), triglyceride(TG), total cholesterol(TC), low density lipoprotein cholesterol(LDL-C), and high density lipoprotein cholesterol(HDL-C) were detected by biochemical tests. Periodic acid-schiff(PAS) staining was used to observe the pathological changes in the kidney tissue. The protein expressions of α-smooth muscle actin(α-SMA), vimentin, and advanced glycation end products(AGEs) in kidneys were detected by immunohistochemical staining. The activities of superoxide dismutase(SOD), catalase(CAT), glutathione peroxidase(GSH-PX), and the level of malondialdehyde(MDA) in kidneys were detected by using a corresponding detection kit. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of AGEs, carboxymethyllysine(CML), and carboxyethyllysine(CEL) in serum. The protein expressions of RAGE and the phosphorylation level of JAK1 and STAT3 in kidneys were detected by Western blot. Compared with the normal group, the levels of FBG, the area under the curve of glucose(AUCG), water intake, kidney index, 24 h-UTP, tubular injury score, extracellular matrix deposition ratio of the renal glomerulus, the serum levels of Scr, BUN, TG, LDL-C, AGEs, CEL, and CML, the level of MDA, the protein expressions of α-SMA, vimentin, AGEs, and RAGE, and the phosphorylation level of JAK1 and STAT3 in kidney tissue were increased significantly(P<0.01), while the level of HDL-C in serum and the activity of SOD, CAT, and GSH-PX in kidney tissue were decreased significantly(P<0.01). Compared with the model group, the above indexes of the high-dose SAL group were reversed significantly(P<0.05 or P<0.01). In conclusion, this study suggests that SAL can alleviate oxidative stress and renal fibrosis by inhibiting the activation of AGEs-mediated RAGE/JAK1/STAT3 signaling axis, thus playing a potential role in the treatment of DN.
Assuntos
Nefropatias Diabéticas , Glucosídeos , Janus Quinase 1 , Rim , Fenóis , Receptor para Produtos Finais de Glicação Avançada , Fator de Transcrição STAT3 , Transdução de Sinais , Animais , Camundongos , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/metabolismo , Glucosídeos/farmacologia , Glucosídeos/administração & dosagem , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Receptor para Produtos Finais de Glicação Avançada/genética , Transdução de Sinais/efeitos dos fármacos , Masculino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fenóis/farmacologia , Janus Quinase 1/metabolismo , Janus Quinase 1/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genética , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Humanos , Camundongos Endogâmicos C57BL , Glicemia/metabolismo , Glicemia/efeitos dos fármacosRESUMO
Fourteen sesquiterpenes, including one undescribed sesquiterpene lactone, were isolated from Youngia japonica, and their structures were identified by NMR, HRESIMS, ECD and calculated ECD. Cytotoxic activities of all isolates against A549, HeLa, and 4 T1 cell lines were detected by CCK8 assay. Among them, 2 showed obvious cytotoxic activity against A549 cells. Subsequently, the production of ROS, and apoptosis of A549 cells treated with 2 were evaluated. The result showed that 2 distinctly increased the ROS level, and induced the apoptosis of A549 cells. Further anticancer mechanism studies showed that 2 increased the expression of cleaved caspase 3. Taken together, our results demonstrated that 2 might become potential leading compounds for the treatment of lung cancer.
Assuntos
Antineoplásicos , Asteraceae , Sesquiterpenos , Humanos , Linhagem Celular Tumoral , Estrutura Molecular , Espécies Reativas de Oxigênio , Antineoplásicos/farmacologia , Apoptose , Sesquiterpenos/farmacologia , Sesquiterpenos/químicaRESUMO
Four undescribed coumarin derivatives, ficusalt A (1) and ficusalt B (2), a pair of racemic coumarins, (±) ficudimer A (3a/3b), along with ten known amides, were isolated from the roots of Ficus hirta. Their structures were elucidated by several spectroscopic data analyses, including HRESIMS, NMR, and X-ray single-crystal diffraction. The cytotoxic activities of all compounds against HeLa, HepG2, MCF-7, and H460 cell lines were detected using the MTT assay. Among these, 5 showed the highest activity against HeLa cells. Subsequently, the apoptotic, anti-invasive, and anti-migration effects of 5 on HeLa cells were determined by flow cytometer, transwell invasion assay, and wound-healing assay, respectively. The result suggested that 5 distinctly induced the apoptosis in HeLa cells and inhibited their invasion and migration. Further studies on anticancer mechanisms were conducted using Western blotting. As a result, 5 increased the cleavage of PARP and the expression of pro-apoptotic protein Bax. Moreover, 5 notably upregulated the phosphorylation of p38 and JNK, whereas inhibited the expression of p-ERK and p-AKT. Our results demonstrated that 5 could be a potential leading compound for further application in the treatment of cervical cancer.
Assuntos
Antineoplásicos , Ficus , Feminino , Humanos , Células HeLa , Ficus/química , Amidas/farmacologia , Cumarínicos/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , ApoptoseRESUMO
One undescribed lignan, one new natural product, along with fourteen known compounds, were isolated from the roots of Ficus hirta. The structures of the isolates were elucidated by comprehensive spectroscopic technologies, including UV, IR, HRESIMS, and NMR. The absolute configuration of 1 was determined by comparison of experimental and calculated ECD data. The cytotoxicity of all the compounds against HeLa and HepG2 cell lines was evaluated and compound 7 showed considerable cytotoxic effect towards HepG2 cells. Also, the apoptotic effect of 7 on HepG2 cells and the effect of 7 on the key proteins (p-JNK and p-p38) in MAPK (Mitogen-activated protein kinases) pathways were studied by flow cytometry and western blotting experiment. As a result, compound 7 induced the apoptosis of HepG2 cells, and dose-dependently increased the phosphorylation of JNK and p38. Thus, 7 might trigger HepG2 cells apoptosis via JNK/p38 MAPK signaling pathway.
Assuntos
Antineoplásicos , Ficus , Lignanas , Antineoplásicos/farmacologia , Apoptose , Ficus/química , Células Hep G2 , Humanos , Lignanas/análise , Lignanas/farmacologia , Raízes de Plantas/química , Proteínas Quinases p38 Ativadas por Mitógeno/análise , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/farmacologiaRESUMO
Cornusdiridoid A-F (1-6), six unusual cornuside-morroniside secoiridoid dimers, and their possible new biogenetic precursor, 3â³,5â³-dehydroxycornuside (7), together with four known secoiridoids (8-11), were obtained from the fruits of Cornus officinalis. Their structures were elucidated on the basis of various spectroscopic and chemical methods. A plausible biosynthetic pathway of compounds 1-11 was proposed. The α-glucosidase inhibitory, antioxidant and anti-inflammatory activities of these isolates were evaluated. Some of them emerged out as potent antidiabetic, anti-inflammatory and free radical scavenging agents. Molecular docking was also carried out for antidiabetic target α-glucosidase to investigate the possible binding modes of the most potent α-glucosidase inhibitor, vincosamide (9). These results revealed that the secoiridoids from C. officinalis fruits may be served as new potential antidiabetic agents to prevent and treat type 2 diabetes.
Assuntos
Antioxidantes/farmacologia , Cornus/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores de Glicosídeo Hidrolases/farmacologia , Iridoides/farmacologia , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Antioxidantes/química , Diabetes Mellitus Tipo 2/metabolismo , Descoberta de Drogas , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Iridoides/química , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7 , alfa-Glucosidases/metabolismoRESUMO
A pair of undescribed enantiomers, (±) ficusflavonid A (1a/1b), along with five known analogues, were isolated from the roots of Ficus hirta. Their structures were determined by the analysis of extensive spectroscopic data (including UV, IR, HRESIMS and NMR). Two enantiomers (1a and 1b) were successfully separated by chiral chromatographic column and their absolute configurations were assigned by the comparison of experimental and calculated ECD data. The cytotoxicity of all the isolates against HeLa, MCF-7, HepG2 and H460 cell lines were evaluated by MTT assay. Among them, 4 suppressed the proliferation of HeLa cells with the IC50 value of 28.88 µM. Furthermore, the apoptotic effect of 4 on HeLa cells and the level of several crucial proteins in AKT/MAPKs signaling pathways were analyzed by flow cytometer and western blot assay. As a result, 4 induced HeLa cell apoptosis in a dose dependent manner and significantly increased the protein levels of p-JNK and p-p38, whereas distinctly reduced the expression of p-AKT, and p-ERK. Thus, compound 4 might induce HeLa cells apoptosis via MAPK and AKT signaling pathways, which could be considered as a potential leading compound for the development of anticancer drugs.
Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Ficus/química , Flavonoides/farmacologia , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Antineoplásicos/síntese química , Antineoplásicos/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Flavonoides/síntese química , Flavonoides/química , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Estrutura Molecular , Proteínas Proto-Oncogênicas c-akt/metabolismo , Relação Estrutura-AtividadeRESUMO
Two new compounds, triacremoniate (1) and dietziamide C (2) along with known compounds ß-Adenosine (3) and acrepyrone A (4) were obtained from the mangrove-derived fungus Acremonium citrinum. MMF4. Their structures were unambiguously determined by extensive spectroscopic methods, including UV, IR, HRESIMS and NMR. Triacremoniate (1) can promote apoptosis of HeLa cells by increasing the PARP cleavage and the phosphorylation of JNK and p38.
Assuntos
Acremonium/química , Antineoplásicos/farmacologia , Produtos Biológicos/farmacologia , Antineoplásicos/isolamento & purificação , Produtos Biológicos/isolamento & purificação , China , Células HeLa , Humanos , Estrutura Molecular , Raízes de Plantas/microbiologia , Rhizophoraceae/microbiologiaRESUMO
Corni Fructus, also known as the fruit of Cornus officinalis Sieb. et Zucc., has long been used as a traditional Chinese medicine and is widely consumed as a nutritional food in the form of function drink and wine. Recently, Corni Fructus has attracted considerable interest because of its anti-diabetic effects. A systematic phytochemical investigation of Corni Fructus was performed to find anti-diabetic components, which led to the isolation of 10 unreported iridoid glycosides, cornusdiglycosides A-J (1-8, 9a/9b and 10a/10b). Their chemical structures were determined through spectroscopic analysis (ultraviolet [UV], infrared [IR], high-resolution electrospray ionisation mass spectroscopy [HRESIMS], one-dimensional [1D] and two-dimensional [2D] nuclear magnetic resonance [NMR]). Such morroniside-type diglycosides were first reported from natural sources, and all isolates were evaluated for α-glucosidase inhibitory activity. The results showed that all compounds (1-10) exhibited α-glucosidase (from Saccharomyces cerevisiae) inhibitory activities with IC50 values ranging from 78.9 ± 4.09 to 162.2 ± 9.17 µM, whereas acarbose, the positive control, displayed α-glucosidase inhibitory activity with IC50 value of 118.9 ± 7.89 µM.
Assuntos
Cornus/química , Inibidores de Glicosídeo Hidrolases/farmacologia , Glicosídeos/farmacologia , Glucosídeos Iridoides/farmacologia , Compostos Fitoquímicos/farmacologia , alfa-Glucosidases/metabolismo , Inibidores de Glicosídeo Hidrolases/química , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificação , Humanos , Glucosídeos Iridoides/química , Glucosídeos Iridoides/isolamento & purificação , Conformação Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Phytochemical study on the fruit of Cornus officinalis Sieb. et Zucc. yielded two new iridoid glucosides, named cornusglucoside A (1) and cornusglucoside B (2). The structures of 1 and 2 were elucidated via comprehensive NMR and HR-ESI-MS data analysis. Additionally, their inhibitory effects on IL-6-induced STAT3 activation were assessed.
Assuntos
Cornus/química , Frutas/química , Glucosídeos Iridoides/isolamento & purificação , Células Hep G2 , Humanos , Interleucina-6/antagonistas & inibidores , Interleucina-6/metabolismo , Glucosídeos Iridoides/química , Glucosídeos Iridoides/farmacologia , Conformação Molecular , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/metabolismoRESUMO
Five novel and rare cadinane-type sesquiterpene glycosides, cornucadinoside A-E (1-5) were isolated from water extract of the fruit of Cornus officinalis Sieb. et Zuuc.. The new chemical structures, together with their absolute configurations, were elucidated on the basis of extensive spectroscopic analysis, including a comparison of their experimental and calculated electronic circular dichroism (ECD) spectra. Their structures, which possess a naphthalene skeleton, are the first report on the occurrence of cadinane sesquiterpene glycosides in Cornus. Additionally, all the compounds exhibited marked α-glucosidase inhibitory activity except for 3in vitro.
Assuntos
Cornus/química , Frutas/química , Inibidores de Glicosídeo Hidrolases/química , Glicosídeos/química , Sesquiterpenos/química , Dicroísmo Circular , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Glicosídeos/isolamento & purificação , Naftalenos/química , Naftalenos/isolamento & purificação , Sesquiterpenos/isolamento & purificaçãoRESUMO
To investigate the chemical compounds from the ripe fruit of Cornus officinalis, a new phenylpropanoid glycoside 1-O-(6'-O-p-hydroxybenzoyl-ß-D-glucopyranosyl)-p-phenylpropanol, named cornuphenylpropanoid A (1), were separated and purified by D101 macroporous resin, silica gel and ODS column chromatography. Its structure was extensively determined on basis of ¹H-NMR, ¹³C-NMR, DEPT, HSQC, HMBC and HR-ESI-MS spectroscopic data.
Assuntos
Cornus/química , Frutas/química , Glicosídeos/química , Glicosídeos/isolamento & purificação , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificaçãoRESUMO
Fifteen new and rare iridoid glucoside dimers, cornusides A-O (1-15), and 10 known iridoid glucosides (16-25) were isolated from the fruit of Cornus officinalis. These new chemical structures were established through spectroscopic analysis (UV, IR, HRESIMS, 1D and 2D NMR). Compounds 1-25 were tested for their inhibitory activities by measuring IL-6-induced STAT3 promoter activity in HepG2 cells, and 3, 12, 17, 22, and 23 showed inhibitory effects, with IC50 values of 11.9, 12.2, 14.0, 7.0, and 6.9 µM, respectively.
Assuntos
Cornus/química , Frutas/química , Glucosídeos/química , Glucosídeos Iridoides/química , Iridoides/química , Piranos/química , Extratos Vegetais/químicaRESUMO
Four new and rare iridoid glucosides, cornusfuroside A-D (1-4), containing the furan ring were identified from water extract of the fruit of Cornus officinalis. These new chemical structures were determined through extensive spectroscopic analysis, including 1D and 2D NMR, IR, HRESIMS, experimental and calculated electronic circular dichroism (ECD). Notably, this study is the first report on the isolation of four iridoid glucoside structures with acetal functions in the sugar moiety. The neuroprotective effects of these compounds were also evaluated in vitro.
Assuntos
Cornus/química , Frutas/química , Glucosídeos Iridoides/química , Fármacos Neuroprotetores/química , Animais , Glucosídeos Iridoides/isolamento & purificação , Estrutura Molecular , Fármacos Neuroprotetores/isolamento & purificação , Células PC12 , RatosRESUMO
To investigate the chemical compounds from the fruit of Cornus officinalis, six compounds were isolated and determined by extensive spectroscopic analysis as 6'-O-acetyl-7α-O-ethyl morroniside (1), (-)-isolariciresinol 3α-O-ß-D-glucopyranoside(2), apigenin (3), cirsiumaldehyde(4), p-coumaric acid (5), caffeic acid (6). Compound 1 was a new iridoid glucoside,and compounds 2-4 were obtained from the Cornus genus for the first time. Compounds 2-6 were evaluated for the viability of PC12 cells when exposed in conditions of oxygen and glucose deprivation. The MTT results showed that compound 4 increased cell viability moderately in OGD/R treated PC12 cells at the concentration of 1.0 µmolâ¢L⻹.
Assuntos
Cornus/química , Frutas/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Animais , Glicosídeos Iridoides/química , Glicosídeos Iridoides/isolamento & purificação , Células PC12 , Compostos Fitoquímicos/química , RatosRESUMO
To investigate the chemical compounds from the twigs of Euonymus alatus, nine compounds were isolated and identified as(+)-delta(2,11)-enaminousnic acid(1), 11-keto-beta-boswellic acid(2), acetyl 11-keto-beta-boswellic acid(3), camaldulenic acid(4), betulinic acid(5), 6beta-hydroxy-stigmast-4-en-3-one(6), 5-hydroxy-6,7-dimethoxyflavone(7), ethyl 2,4-dihydroxy-6-methylbenzoate(8), 4,4'-dimethoxy-1,1'-biphenyl(9). Their structures were elucidated by extensive spectroscopic analysis. Among them, compound 1 was a new natural product. Compounds 2-4 and 7-9 were obtained from the Euonymus genus for the first time. In vitro study showed that compounds 2 and 3 showed significant anti-tumor activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1). The inhibition rate of compound 2 was 61.78% and 68.29%, whereas the inhibition rate of compound 3 had reached to 70.91% and 84.07%.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Euonymus/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , HumanosRESUMO
A new benzaldehyde, 3-hydroxy-4-(4-(2-hydroxyethyl) phenoxy) henzaldehyde(1), together with six known compounds, including isovanillic acid(2), pyrocatechol(3), glutinosalactone A(4), chrysoeriol(5), apigenin(6) and luteolin(7) were isolated from aerial part of Rehmannia glutinosa. The compounds were isolated by macroporous resin, silica gel, Sephadex LH-20 and HPLC chromatographies. The chemical structures of 1-7 were elucidated on the basis of spectral analysis (MS, 1D NMR and 2D NMR).
Assuntos
Benzaldeídos/química , Medicamentos de Ervas Chinesas/química , Componentes Aéreos da Planta/química , Rehmannia/química , Benzaldeídos/isolamento & purificação , Medicamentos de Ervas Chinesas/isolamento & purificação , Estrutura Molecular , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
To investigate the chemical compounds from aerial part of Rehmannia glutinosa, six compounds were isolated and deter- mined by extensive spectroscopic analysis as(+)-(7S, 8S, 8'S)-9-O-[ß-D-glucopyranoyl] asarininone(1), 2α,3ß,19α,23-tetrahydroxy-olean-12-en-28-oic acid(2),7,3'-dihydroxyl-5'-methoxyisoflavone (3), aeginetic acid (4), corchorifattty acid B (5), pinellic acid (6). Among them, compound 1 was a new natural product. Compounds 2, 3 and 5 were obtained from the Rehmannia genus for the first time. In vitro study showed that none of the six compounds exhibited obvious activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1).