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1.
Chem Pharm Bull (Tokyo) ; 68(1): 91-95, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902904

RESUMO

Magnolia Flower is a crude drug used for the treatment of headaches, toothaches, and nasal congestion. Here, we focused on Magnolia kobus, one of the botanical origins of Magnolia Flower, and collected the flower parts at different growth stages to compare chemical compositions and investigate potential inhibitory activities against interleukin-2 (IL-2) production in murine splenic T cells. After determining the structures, we examined the inhibitory effects of the constituents of the bud, the medicinal part of the crude drug, against IL-2 production. We first extracted the flower parts of M. kobus from the bud to fallen bloom stages and analysed the chemical compositions to identify the constituents characteristic to the buds. We found that the inhibitory activity of the buds against IL-2 production was more potent than that of the blooms. We isolated two known compounds, tiliroside (1) and syringin (2), characteristic to the buds from the methanol (MeOH) extract of Magnolia Flower. Moreover, we examined the inhibitory activities of both compounds against IL-2 production and found that tiliroside (1) but not syringin (2), showed strong inhibitory activity against IL-2 production and inhibited its mRNA expression. Thus, our strategy to examine the relationship between chemical compositions and biological activities during plant maturation could not only contribute to the scientific evaluation of medicinal parts of crude drugs but also assist in identifying biologically active constituents that have not yet been reported.


Assuntos
Interleucina-2/metabolismo , Magnolia/química , Extratos Vegetais/química , Animais , Linhagem Celular , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Flores/química , Flores/metabolismo , Glucosídeos/química , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Interleucina-2/genética , Magnolia/metabolismo , Camundongos , Fenilpropionatos/química , Fenilpropionatos/isolamento & purificação , Fenilpropionatos/farmacologia , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
2.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 35(4): 376-380, 2019 Jul 28.
Artigo em Chinês | MEDLINE | ID: mdl-31701727

RESUMO

OBJECTIVE: To investigate whether salidroside (Sal) plays a part in protecting myocardial cell through reducing the myocardial ischemia and the apoptosis pathway of both death receptors and mitochondria in acute exhausted rats. METHODS: Male SD rats were randomly divided into 4 groups (n=6): control group(Con), acute exhaustive swimming group (EE), low-dose and high-dose Sal pre-treatment exhaustive swimming group (SLE, SHE). Rats were treated with Sal solution (15 or 30 mg/(kg·d)) or 0.9%NaCl (3 ml/(kg·d)) by intraperitoneal injection for 15 d, respectively. The Con group did not carry out swimming training. The next day after the end of intraperitoneal administration, the rats in EE, SLE and SHE group were forced to swim until they were exhausted followed the standard of Thomas. After the end of exhaustive exercise, the rats were anesthetized and the blood samples and hearts were collected immediately. The myocardial ischemia and hypoxia area and myocardial apoptosis index (AI) were also observed. Serum ischemia modified albumin (IMA), cardiac troponin I (cTnI), brain natriuretic peptide(BNP) and myocardial cell Bcl-2-associated X protein (Bax), B-cell lymphoma-2 (Bcl-2) were determined. The expressions of myocardial TNF receptor superfamily member 6 (Fas), cytochrome C (Cyto-c), aspartate proteolytic enzyme-3(Caspase-3), aspartate proteolytic enzyme-8(Caspase-8), and aspartate proteolytic enzyme-9(Caspase-9) were detected. RESULTS: Compared with the Con group, the myocardial ischemia and hypoxia area in EE group was increased significantly. The serum levels of IMA, cTnI and BNP, AI and Bax levels and cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 protein expressions of EE group were also increased significantly (P<0.01), while the protein expression of Bcl-2 in cardiac tissues was decreased significantly (P<0.01). Compared with the EE group, the myocardial ischemia and hypoxia area, serum levels of IMA, cTnI and BNP, AI and Bax levels, and the protein expressions of cardiac Fas, Cyto-C, Caspase-3, Caspase-8 and Caspase-9 in Sal group were all decreased significantly(P<0.01). while the protein expression of cardiac Bcl-2 in Sal group were increased significantly (P<0.01). CONCLUSION: Sal plays a role in protecting myocardial cell through reducing the myocardial ischemia and inhibiting myocardial cell apoptosis in exhaustive exercise rats. The mechanism of reducing myocardial cell apoptosis may be related to inhibiting the expressions of Fas, Cyto-C, Caspase-3, Caspase-8, Caspase-9 and increasing the expression of Bcl-2.


Assuntos
Apoptose , Fadiga/fisiopatologia , Glucosídeos/farmacologia , Coração/efeitos dos fármacos , Isquemia Miocárdica/tratamento farmacológico , Fenóis/farmacologia , Animais , Biomarcadores/sangue , Feminino , Masculino , Miocárdio/citologia , Condicionamento Físico Animal , Ratos , Ratos Sprague-Dawley
3.
Cell Physiol Biochem ; 53(5): 865-886, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724838

RESUMO

BACKGROUND/AIMS: Heart failure is characterized by chronic low-grade vascular inflammation, which in itself can lead to endothelial dysfunction. Clinical trials showed reductions in heart failure-related hospitalizations of type 2 diabetic patients using sodium glucose co-transporter 2 inhibitors (SGLT2i's). Whether and how SGLT2i's directly affect the endothelium under inflammatory conditions is not completely understood. The aim of the study was to investigate whether the SGLT2i Empagliflozin (EMPA) and Dapagliflozin (DAPA) reduce tumor necrosis factor α (TNFα) induced endothelial inflammation in vitro. METHODS: Human coronary arterial endothelial cells (HCAECs) and human umbilical vein endothelial cells (HUVECs) were (pre-)incubated with 1 µM EMPA or DAPA and subsequently exposed to 10 ng/ml TNFα. ROS and NO were measured using live cell imaging. Target proteins were either determined by infrared western blotting or fluorescence activated cell sorting (FACS). The connection between Cav-1 and eNOS was determined by co-immunoprecipitation. RESULTS: Nitric oxide (NO) bioavailability was reduced by TNFα and both EMPA and DAPA restored NO levels in TNFα-stimulated HCAECs. Intracellular ROS was increased by TNFα, and this increase was completely abolished by EMPA and DAPA in HCAECs by means of live cell imaging. eNOS signaling was significantly disturbed after 24 h when cells were exposed to TNFα for 24h, yet the presence of both SGLT2is did not prevent this disruption. TNFα-induced enhanced permeability at t=24h was unaffected in HUVECs by EMPA. Similarly, adhesion molecule expression (VCAM-1 and ICAM-1) was elevated after 4h TNFα (1.5-5.5 fold increase of VCAM-1 and 4-12 fold increase of ICAM-1) but were unaffected by EMPA and DAPA in both cell types. Although we detected expression of SGLT2 protein levels, the fact that we could not silence this expression by means of siRNA and the mRNA levels of SGLT2 were not detectable in HCAECs, suggests aspecificity or our SGLT2 antibody and absence of SGLT2 in our cells. CONCLUSION: These data suggest that EMPA and DAPA rather restore NO bioavailability by inhibiting ROS generation than by affecting eNOS expression or signaling, barrier function and adhesion molecules expression in TNFα-induced endothelial cells. Furthermore, the observed effects cannot be ascribed to the inhibition of SGLT2 in endothelial cells.


Assuntos
Compostos Benzidrílicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Glucosídeos/farmacologia , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Vasos Coronários/citologia , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Molécula 1 de Adesão Intercelular/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Permeabilidade/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transportador 2 de Glucose-Sódio/genética , Transportador 2 de Glucose-Sódio/metabolismo , Molécula 1 de Adesão de Célula Vascular
4.
Zhongguo Zhong Yao Za Zhi ; 44(14): 2960-2965, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602840

RESUMO

The study aimed to investigate the mechanism of hepatoprotective effect of C-21 steroidal glucosides from Cynanchum auriculatum( Baishouwu) on oxidative stress in mice with liver injury. Mice were randomly divided into normal group,model group,positive control group,Baishouwu high group and Baishouwu low group. The liver injury model was induced by intraperitoneal injection of CCl4 peanut oil solution. All mice were sacrificed to collect blood and liver specimens. The activities of serum levels of ALT and AST were detected. The content of MDA and the activity of SOD in liver homogenate were examined by colorimetry method. Tissues were stained with hematoxylin-eosin for histological examination. The hepatic protein expressions of NF-κB p65,p-IκBα,i NOS and COX-2 were detected by Western blot. The mRNA expressions of TNF-α and IL-6 were determined by RT-PCR. It was found that treatment with C-21 steroidal glucosides from Baishouwu successfully attenuated liver injury induced by CCl4,as shown by decreased levels of serum biochemical indicators( AST,ALT)( P<0. 01). Administration of total C-21 steroidal glucosides enhanced the activity of SOD( P<0. 01) and decreased the content of MDA( P<0. 01) in liver homogenate. Microscopic features suggested that treatment with C-21 steroidal glucosides from Baishouwu was effective in inhibiting CCl4-induced hepatocyte edema and degeneration. Further studies showed that NF-κB p65 overexpression induced by CCl4 was decreased by C-21 steroidal glucosides,leading to the markedly down-regulated protein expression levels of p-IκBα,i NOS and COX-2,as well as the depression of TNF-α and IL-6 mRNA expressions. In conclusion,total C-21 steroidal glucosides from Baishouwu exhibited potent effect on oxidative stress pathway in mice with liver injury induced by CCl4,with enhanced activity of SOD,decreased content of MDA,and down-regulated levels of NF-κB p65,p-IκBα,i NOS and COX-2.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Cynanchum/química , Glucosídeos/farmacologia , Estresse Oxidativo , Animais , Tetracloreto de Carbono , Hepatócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Camundongos , Distribuição Aleatória
5.
Life Sci ; 237: 116925, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610201

RESUMO

Inflammatory disorders result from abnormal immune response and their incidence has increased recently. Thus, there is an urgent need to discover new treatments for inflammatory disorders. In recent years, the natural products contained in Chinese herbs have attracted much attention worldwide owing to their anti-inflammatory effects. Paeoniflorin (PF) is a bioactive compound purified from the Chinese herb Paeonia lactiflora and reports have recently emerged suggesting the great potential of P. lactiflora as an agent to counter inflammatory disorders. The anti-inflammatory effects of PF have been revealed by in vitro studies and in vivo animal experiments of different inflammatory disorders, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, and asthma. This review systematically describes the recent progress of studies on the mechanism of PF and its therapeutic potential in inflammatory disorders.


Assuntos
Anti-Inflamatórios não Esteroides/farmacologia , Glucosídeos/farmacologia , Inflamação/prevenção & controle , Monoterpenos/farmacologia , Animais , Humanos
6.
Chem Pharm Bull (Tokyo) ; 67(10): 1072-1075, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31582627

RESUMO

Shikonin, a natural naphthoquinone, has attracted much attention due to its various biological activities. Two shikonin glucosides, shikonin-1',8-di-O-ß-D-glucopyranoside (1) and shikonin-1'-O-ß-D-glucopyranoside (2), were biosynthesized through in vitro enzymatic glycosylation and their structures were elucidated using spectroscopic techniques. The water-solubility and stability of compounds 1 and 2 were significantly higher than those of the parent compound. Furthermore, compound 2 showed moderate cytotoxicity against six cancer cell lines, with IC50 values ranging from 36.10 to 67.47 µM. This research indicated that in vitro enzymatic glycosylation of shikonin is an effective strategy to improve it water solubility and chemical stability.


Assuntos
Antineoplásicos/metabolismo , Glucosídeos/biossíntese , Glicosiltransferases/metabolismo , Naftoquinonas/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Glucosídeos/química , Glucosídeos/farmacologia , Glicosilação , Humanos , Concentração de Íons de Hidrogênio , Estrutura Molecular , Naftoquinonas/química , Naftoquinonas/farmacologia , Solubilidade , Relação Estrutura-Atividade , Temperatura Ambiente
7.
J Biol Regul Homeost Agents ; 33(5): 1425-1436, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576730

RESUMO

Aconitine (ACO), the main active component in Aconitum carmichaelii Debeaux (family: Ranunculaceae), has high cardiotoxicity, however the mechanisms of this effect remain unclear. Paeoniflorin (PF), the main chemical ingredient in herbaceous peony, can protect the heart from damage through antioxidant, vasodilatory and other effects. In this study, we focused on the mechanism by which PF reduces ACO cardiotoxicity. We selected H9c2 cells as the experimental model. MTT assay, Western blot analysis and real-time PCR were used to measure cell proliferation, apoptosis, ion channels and oxidative stress. Cell proliferation was significantly increased, the Bcl-2/Bax ratio and p53 level were upregulated, and Caspase-3 was slightly reduced in the ACO+PF group compared with the ACO group. SCN5A mRNA expression was significantly increased in the ACO+PF group compared with the ACO group, while RyR2 and Cx43 mRNA expression was decreased. Compared with the ACO group, the ACO+PF group showed marked decreases in extracellular lactate dehydrogenase (LDH) and intracellular malondialdehyde (MDA), while there was no difference in intracellular superoxide dismutase (SOD). The above data demonstrate that the cardiotoxicity of ACO in H9c2 cells was significantly decreased by PF.


Assuntos
Aconitina/efeitos adversos , Cardiotoxinas/efeitos adversos , Glucosídeos/farmacologia , Monoterpenos/farmacologia , Mioblastos/efeitos dos fármacos , Animais , Apoptose , Linhagem Celular , Estresse Oxidativo , Ratos
8.
Life Sci ; 237: 116893, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31606381

RESUMO

AIM: Gastric cancer (GC) is a common human malignancy tumor of digestive tract in worldwide. Physcion 8-O-ß-glucopyranoside (PG) exhibits anti-tumor effects in various cancer cells. This study aimed to explore the biological behavior effects of PG on GC cells, and determine its underlying mechanism. MATERIAL AND METHODS: The effect of PG treatment on the ferroptotic GC cell death was detected by ROS level, intracellular Fe2+ level and malondialdehyde (MDA) generation in vitro. The mRNA expression was detected by RT-qPCR. The interaction between miR-103a-3p and glutaminase 2 (GLS2) were verified by dual-luciferase reporter gene assay. Cell proliferation, invasion and migration were examined by CCK-8 and Transwell assay. Western blot was used to examine the expression of GLS2, SLC1A5 and epithelial-mesenchymal transition (EMT) related proteins. We also evaluated the influence of PG on the tumor growth and metastasis in vivo. RESULTS: PG-induced ferroptosis in GC cells through upregulating ROS level, intracellular Fe2+ level and MDA generation. Besides, PG also significantly enhanced the protein level of GLS2, which was an important transporter of glutamine to glutamate. Importantly, miR-103a-3p directly interacted with GLS2 and suppressed its expression. Mechanistically, PG treatment significantly promoted ferroptosis and anti-tumorigenesis by downregulating inhibitory effect of miR-103a-3p on GLS2 expression. CONCLUSION: Our studies confirmed that PG exerts pro-ferroptosis and anti-tumor effects in vitro and in vivo through regulating miR-103a-3p/GLS2 axis, thereby highlighting its therapeutic potential in GC.


Assuntos
Apoptose/efeitos dos fármacos , Emodina/análogos & derivados , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glutaminase/metabolismo , Ferro/metabolismo , MicroRNAs/genética , Neoplasias Gástricas/patologia , Animais , Proliferação de Células/efeitos dos fármacos , Emodina/farmacologia , Feminino , Glutaminase/genética , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Espécies Reativas de Oxigênio/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 54(9): 632-638, 2019 Sep 09.
Artigo em Chinês | MEDLINE | ID: mdl-31550788

RESUMO

Objective: To investigate the regulation of curculigoside on osteogenic differentiation of MG63 and the protective effect on osteoporosis model mice. Methods: The effects of curculigoside on the survival rate of dexamethasone or H(2)O(2) treated MG63 were detected by methyl thiazolyl tetrazolium (MTT). The specimens were divided into six groups: blank control group, blank administration group, model group (dexamethasone or H(2)O(2) treatment group), low dose group (dexamethasone or H(2)O(2)+1.0 µmol/L curculigoside), medium dose group (dexamethasone or H(2)O(2)+2.5 µmol/L curculigoside) and high dose group (dexamethasone or H(2)O(2)+5.0 µmol/L curculigoside), the sample size of each group was 10. Western blotting was used to detect the expression of osteogenic differentiation-related proteins [type Ⅰ collagen, integrin ß1, osteoblast-specific transcription factor (Osterix), osteocalcin and osteopontin] in MG63 cells after 1, 7 and 14 days incubated with 0, 1.0, 2.5 and 5.0 µmol/L of curculigoside. The sample size for each group at each time point was six. The experimental mice were divided into 4 groups: blank group, model group (dexamethasone treatment group), curculigoside low-dose group (dexamethasone+5 mg/kg curculigoside) and high-dose group (dexamethasone+45 mg/kg curculigoside), twenty each. After treatment, the tibia of the mice in each group were subjected to sacral HE staining. The number of osteoclasts was counted, and the levels of oxidative related factors in serum were determined by enzyme-linked immunosorbent assay (ELISA). Results: The MTT results showed that compared with the blank control group [(100±3.7)%], the cell survival rate decreased to (44.1±5.7)% after treatment with dexamethasone, and the survival rate increased to (79.7±3.8)% after treatment with 5.0 µmol/L of curculigoside. The cell survival rate decreased to (59.1±4.7)% after H(2)O(2) treatment, and the survival rate increased to (80.8±3.5)% after treatment with 2.5 µmol/L of curculigoside. The results of Western blotting showed that the expression of type Ⅰ collagen and integrin ß1 in MG63 cells was significantly increased after 1.0, 2.5 and 5.0 µmol/L of curculigoside for 1, 7 and 14 days compared with 0 µmol/L of curculigo side for the same period. After increasing (P<0.05), the expression of Osterix and osteocalcin was significantly increased after 1 day of incubation (P<0.05). However, compared with 0 µmol/L curculigoside treatment, the expression of osteopontin in MG63 cells was not significantly different after incubation with 1.0, 2.5, 5.0 µmol/L of curculigoside for 7 and 14 days (P>0.05). Compared with the blank group, the number of tibia osteoclasts in the osteoporosis model group increased. In the low-dose and high-dose groups of curculigoside, the tibia cortex was more continuous and the number of osteoclasts decreased. Compared with the blank group, the activity of oxygen in the osteoporosis model group was significantly increased (P<0.05), and superoxide dimutase and catalase were significantly decreased (P<0.05). Conclusions: Curculigoside promotes the differentiation of MG63 cells by increasing the expression of osteoblast differentiation-related proteins, and has a certain therapeutic effect on dexamethasone-induced osteoporosis mice.


Assuntos
Benzoatos , Glucosídeos , Osteogênese , Osteoporose , Animais , Benzoatos/farmacologia , Modelos Animais de Doenças , Glucosídeos/farmacologia , Peróxido de Hidrogênio , Camundongos , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico
10.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(3): 289-295, 2019 May 25.
Artigo em Chinês | MEDLINE | ID: mdl-31496161

RESUMO

OBJECTIVE: To investigate the effect and mechanism of glucosides of chaenomeles speciosa (GCS) on ischemia/reperfusion-induced brain injury in mouse model. METHODS: Fifty 8-week C57BL/C mice were randomly divided into five groups with 10 in each group:sham group, model group, GCS 30 mg/kg group, GCS 60 mg/kg group and GCS 90 mg/kg group, and the GCS was administrated by gavage (once a day) for 14 d. HE staining was performed to investigate the cell morphology; the Zea-Longa scores were measured for neurological activity; TUNEL staining was performed to investigate the cell apoptosis; ELISA was used to detected the oxidative stress and inflammation; Western Blot was performed to investigate the key pathway and neurological functional molecules. RESULTS: Compared with the sham group, the brain tissues in model group were seriously damaged, presenting severe cell apoptosis, oxidative stress and inflammation, associated with increased NF-κB P65 and TNF-α levels as well as decreased myelin associate glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (OMgp)levels (all P<0.01). Compared with the model group, the brain tissues in GCS groups were ameliorated, and cell apoptosis, oxidative stress and inflammation were inhibited, associated with decreased NF-κB P65 and TNF-α levels as well as increased MAG and OMgp levels (all P<0.01), which were more markedly in GCS 60 mg/kg group. CONCLUSIONS: GCS can inhibit the NF-κB P65 and TNF-α, reduce the oxidative stress and inflammation, decrease the cell apoptosis in mouse ischemia/reperfusion-induced brain injury model, and 60 mg/kg GCS may be the optimal dose.


Assuntos
Lesões Encefálicas , Glucosídeos , Rosaceae , Fator de Necrose Tumoral alfa , Animais , Encéfalo/efeitos dos fármacos , Lesões Encefálicas/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Estresse Oxidativo/efeitos dos fármacos , Extratos Vegetais/farmacologia , Distribuição Aleatória , Rosaceae/química , Fator de Necrose Tumoral alfa/genética
11.
Fitoterapia ; 138: 104292, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31398451

RESUMO

Three new sesquiterpenoids (1-3) and two new sesquiterpenoid glucosides (4 &5), along with 24 known analogues (6-29), were obtained from the flowers of Inula japonica. Structures of the new compounds were determined by interpretation of spectroscopic data, and their absolute configurations were established via comparison of experimental with computed ECD curves. All the isolates were tested in an in vitro cytotoxic assay against human A549, MCF-7 and MDA-MB-231 cancer cell lines, and selective ones displayed significant activity close to the positive control adriamycin. The new molecules 1-5 were also evaluated for their nitric oxide (NO) release inhibitory effect in murine macrophage RAW264.7 cells, with compound 1 showing comparable activity (IC50 16.2 ±â€¯0.8 µM) to the positive control dexamethasome. A preliminary mechanistic study of the effect of 8 toward A549 cells revealed that it could arrest cell cycle at G2/M phase and induce cell apoptosis in a dose-dependent manner.


Assuntos
Flores/química , Glucosídeos/farmacologia , Inula/química , Sesquiterpenos/farmacologia , Células A549 , Animais , Apoptose , Pontos de Checagem do Ciclo Celular , China , Glucosídeos/isolamento & purificação , Humanos , Células MCF-7 , Camundongos , Estrutura Molecular , Óxido Nítrico/metabolismo , Células RAW 264.7 , Sesquiterpenos/isolamento & purificação
12.
Sheng Li Xue Bao ; 71(4): 575-580, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31440754

RESUMO

The aim of the present study was to investigate the effect of salidroside (Sal) on inflammatory activation induced by lipopolysaccharide (LPS) in the co-culture of rat alveolar macrophages (AM) NR 8383 and type II alveolar epithelial cells (AEC II) RLE-6TN. CCK-8 colorimetric method was used to detect cell proliferation percentage. The enzyme-linked immunosorbent assay (ELISA) was used to determine the content of tumor necrosis factor alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2) and interleukin-10 (IL-10) in the supernatant. Western blot was used to examine the expression levels of phosphorylated AKT (p-AKT) and total AKT protein. The results showed that pretreatment of RLE-6TN cells or co-culture of RLE-6TN and NR 8383 cells with 32 and 128 µg/mL Sal for 1 h, followed by continuous culture for 24 h, significantly increased the cell proliferation (P < 0.05). Compared with control group, 32 and 128 µg/mL Sal pretreatment significantly increased the ratio of p-AKT/AKT in RLE-6TN cells (P < 0.05). Pretreatment of 32 µg/mL Sal not only inhibited the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05), but also enhanced the inhibitory effect of RLE-6TN and NR 8383 cells co-culture on the secretion of TNF-α and MIP-2 by NR 8383 cells induced by LPS (P < 0.05). In addition, 32 µg/mL Sal pretreatment promoted LPS-induced IL-10 secretion by NR 8383 cells (P < 0.05), and enhanced the promoting effect of co-culture of RLE-6TN and NR 8383 cells on the IL-10 secretion by LPS-induced NR 8383 cells (P < 0.05). In conclusion, Sal may directly inhibit LPS-induced inflammatory activation of AM (NR 8383), promote the proliferation of AEC II (RLE-6TN) through PI3K/AKT signaling pathway, and enhance the regulatory effect of AEC II on LPS-induced inflammatory activation of AM.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Glucosídeos/farmacologia , Macrófagos Alveolares/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais , Células Epiteliais Alveolares/metabolismo , Animais , Linhagem Celular , Quimiocina CXCL2/metabolismo , Técnicas de Cocultura , Interleucina-10/metabolismo , Lipopolissacarídeos , Macrófagos Alveolares/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Fator de Necrose Tumoral alfa/metabolismo
13.
Life Sci ; 232: 116622, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31271767

RESUMO

AIMS: This study was designed to compare the effects of empagliflozin monotherapy and its combination with metformin on glucose and lipid modulations in T2DM mice. MAIN METHODS: Nine-week-old male C57BLKS/J db/db mice (n = 32) were used as T2DM model, and their age-matched C57BLKS/J db/m mice (n = 8) were used as normal control. A total of 32 db/db mice were randomly divided into four groups (n = 8/group): the DMT1 group, treated with metformin (250 mg/kg/day); the DMT2 group, treated with metformin (250 mg/kg/day) plus empagliflozin (10 mg/kg/day); the DMT3 group, treated with empagliflozin (10 mg/kg/day); the T2DM control group (DM), received 0.5% Natrosol. The db/m mice received same administration as DM group. KEY FINDINGS: After four-week treatments, compared with T2DM control (DM), the empagliflozin or its combination with metformin dramatically increased the levels of plasma HDL-C (139.6% and 154.9%, respectively), with significant decrease in plasma TC (22.9% and 13.7%, respectively) and plasma TG (26% and 19.7%, respectively) and in hepatic TG (30.3% and 28.6%, respectively). The protein expressions of SREBP1c (75.3% and 54.0%, respectively) and APOC-III (51.2% and 50.2%, respectively) were reduced, while CPT1A (304.0% and 221.4%, respectively) and ApoA1 levels (90.0% and 85.3%, respectively) were enhanced. Although both interventions improve above-mentioned lipid homeostasis, there were no statistic differences between two groups (p > 0.05). SIGNIFICANCE: Our study demonstrated that current dose of combination therapy may have no higher amelioration than empagliflozin monotherapy for glucose and lipid metabolism in male T2DM mice when it followed a treatment shorter than that expected during clinical treatment.


Assuntos
Compostos Benzidrílicos/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/farmacologia , Animais , Compostos Benzidrílicos/metabolismo , Glicemia/efeitos dos fármacos , Modelos Animais de Doenças , Quimioterapia Combinada/métodos , Glucose/metabolismo , Glucosídeos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metformina/metabolismo , Metformina/farmacologia , Camundongos , Camundongos Endogâmicos C57BL , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Resultado do Tratamento
14.
Artif Cells Nanomed Biotechnol ; 47(1): 2618-2623, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31220953

RESUMO

Cellular senescence is strongly tied to vascular disease. The current study aims to examine ways that endothelial cellular senescence can be prevented and the mechanisms by which prevention of senescence occurs. Human umbilical vein endothelial cells were exposed to TNF-α to induce senescence; then salicin was administered in two doses - 50 and 100 µM - to establish a dose-dependent effect of salicin on SA-ß-Gal, G1 cell cycle arrest, expression of p21 and PAI-1, p53 acetylation at K382, NRF2 and oxidative stress. NRF2 was examined as a mediating mechanism of salicin's impact on cellular senescence and was found to account for salicin's impact on SA-ß-Gal, p21, PAI-1 and p53. Together, these results provide a compelling case that salicin has a substantial impact on numerous factors tied to cellular senescence in human endothelial cells. Thus, treatment with salicin may hold promise as a means of preventing aging-related vascular disease. Furthermore, salicin appears to operate via a functional pathway that is different from that affected by anti-inflammatory drugs (e.g. aspirin).


Assuntos
Álcoois Benzílicos/farmacologia , Senescência Celular/efeitos dos fármacos , Glucosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Fator de Necrose Tumoral alfa/farmacologia , Acetilação/efeitos dos fármacos , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Peróxido de Hidrogênio/farmacologia , Lisina/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Proteína Supressora de Tumor p53/química , Proteína Supressora de Tumor p53/metabolismo
15.
Molecules ; 24(11)2019 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-31212689

RESUMO

Verbascoside is found in many medicinal plant families such as Verbenaceae. Important biological activities have been ascribed to verbascoside. Investigated in this study is the potential of verbascoside as an adjuvant during tuberculosis treatment. The present study reports on the in vitro metabolism in human hepatic microsomes and cytosol incubations as well as the presence and quantity of verbascoside within Lippia scaberrima. Additionally, studied are the inhibitory properties on human hepatic CYP enzymes together with antioxidant and cytotoxic properties. The results yielded no metabolites in the hydrolysis or cytochrome P450 (CYP) oxidation incubations. However, five different methylated conjugates of verbascoside could be found in S-adenosylmethionine incubation, three different sulphate conjugates with 3'-phosphoadenosine 5'-phosphosulfate (PAPS) incubation with human liver samples, and very low levels of glucuronide metabolites after incubation with recombinant human uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A7, UGT1A8, and UGT1A10. Additionally, verbascoside showed weak inhibitory potency against CYP1A2 and CYP1B1 with IC50 values of 83 µM and 86 µM, respectively. Potent antioxidant and low cytotoxic potential were observed. Based on these data, verbascoside does not possess any clinically relevant CYP-mediated interaction potential, but it has effective biological activity. Therefore, verbascoside could be considered as a lead compound for further drug development and as an adjuvant during tuberculosis treatment.


Assuntos
Sistema Enzimático do Citocromo P-450/metabolismo , Glucosídeos/farmacologia , Fenóis/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Compostos de Bifenilo/antagonistas & inibidores , Proliferação de Células/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Ativação Enzimática/efeitos dos fármacos , Glucosídeos/química , Células Hep G2 , Humanos , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Oxirredução/efeitos dos fármacos , Fenóis/química , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Picratos/antagonistas & inibidores , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
16.
Int J Mol Sci ; 20(12)2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31216684

RESUMO

Acteoside, an active phenylethanoid glycoside compound isolated from herbs of Cistanche, was chosen for the investigation of anti-osteoporotic effect on postmenopausal osteoporosis by using an ovariectomized (OVX) mice model. The results from in vivo experiments showed that after daily oral administration of acteoside (20, 40, and 80 mg/kg body weight/day) for 12 weeks, bone mineral density and bone biomechanical properties of OVX mice were greatly enhanced, with significant improvement in bone microarchitecture. Furthermore, biochemical parameters of bone resorption markers as well as bone formation index, including tartrate-resistant acid phosphatase, cathepsin K, deoxypyridinoline, alkaline phosphatase, and bone gla-protein, were ameliorated by acteoside treatment, whereas the body, uterus, and vagina wet weights were seemingly not impacted by acteoside administration. Acteoside significantly affected osteoclastogenesis by attenuating nuclear factor kappa B (NF-κB) and stimulating phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signal pathways through down-regulated levels of tumor-necrosis factor receptor-associated factor 6 (TRAF6), receptor activator of nuclear factor kappa B ligand (RANKL), RANK, NFKBIA, IκB kinase ß, nuclear factor of activated T-cells c2 (NFAT2), and up-regulated expressions of PI3K, AKT, and c-Fos. Accordingly, the current research validated our hypothesis that acteoside possesses potent anti-osteoporotic properties and may be a promising agent for the prevention of osteoporosis in the future.


Assuntos
Glucosídeos/farmacologia , Osteoporose/etiologia , Osteoporose/metabolismo , Ovariectomia/efeitos adversos , Fenóis/farmacologia , Substâncias Protetoras/farmacologia , Animais , Biomarcadores , Peso Corporal , Densidade Óssea/efeitos dos fármacos , Reabsorção Óssea/tratamento farmacológico , Reabsorção Óssea/genética , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Modelos Biológicos , Tamanho do Órgão , Osteoporose/tratamento farmacológico , Osteoporose/patologia , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Fator 6 Associado a Receptor de TNF/metabolismo
17.
J Agric Food Chem ; 67(26): 7289-7296, 2019 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-31244195

RESUMO

The flower buds of Rosa rugosa Thunb. have been commonly used as a source of rose oil and as an ingredient in tea in eastern Asia, including China, Japan, and Korea. Repeated chromatography of a hot water extract from the flower buds of R. rugosa led to the isolation and characterization of three new depside glucosides, rosarugosides A-C (1-3), along with three phenolic compounds, one ionone glucoside, four flavonoids, and two tannins having known chemical structures. Linarionoside A and 2-phenylethyl-(6- O-galloyl)-ß-d-glucopyranoside were isolated from R. rugosa for the first time in this study. The structures of the new compounds 1-3 were elucidated by interpreting one- and two-dimensional nuclear magnetic resonance spectroscopic and mass spectrometric data. Among the isolates, a new depside glucoside (1) and two major phenolic glucosides (4 and 5) improved MK-801-induced sensorimotor gating deficits, which were measured via an acoustic startle response test in mice.


Assuntos
Fármacos do Sistema Nervoso Central/química , Depsídeos/química , Flores/química , Glucosídeos/química , Extratos Vegetais/química , Rosa/química , Animais , Fármacos do Sistema Nervoso Central/isolamento & purificação , Fármacos do Sistema Nervoso Central/farmacologia , Depsídeos/isolamento & purificação , Depsídeos/farmacologia , Glucosídeos/isolamento & purificação , Glucosídeos/farmacologia , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Filtro Sensorial/efeitos dos fármacos
18.
Environ Toxicol ; 34(10): 1085-1093, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31184425

RESUMO

Geraniin has been reported to have numerous biological activities, including antiviral, antihypertensive, antihyperglycaemic, liver protective, antidiabetic, and apoptotic activities. However, the anti-migration effects of geraniin on oral cancer remain elusive. In this study, we revealed the potential antitumor mechanisms of geraniin through the inhibition of the migration and invasion of human oral cancer cell lines SCC-9 and SCC-14. The results of gelatin zymography and Western blot assays revealed that geraniin significantly reduced the activity and expression of matrix metalloproteinase-2 (MMP-2) of oral cancer cells in a concentration-dependent manner. Furthermore, geraniin potently suppressed the phosphorylation of focal adhesion kinase (FAK), Src, and extracellular signal-regulated kinase (ERK)1/2 but did not affect the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase 1/2. Moreover, blocking the MAPK/ERK1/2 pathway significantly enhanced the anti-migration ability of geraniin in oral cancer cells. In conclusion, we demonstrated that geraniin inhibits the motility of SCC-9 and SCC-14 cells in vitro through a molecular mechanism that involves the attenuation of MMP-2 expression and activity mediated by decreased FAK/Src and ERK1/2 pathways.


Assuntos
Antineoplásicos/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Glucosídeos/farmacologia , Taninos Hidrolisáveis/farmacologia , Metaloproteinase 2 da Matriz/metabolismo , Neoplasias Bucais/metabolismo , Quinases da Família src/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proteína-Tirosina Quinases de Adesão Focal/genética , Geranium/química , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Metaloproteinase 2 da Matriz/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/fisiopatologia , Quinases da Família src/genética
19.
Int J Mol Sci ; 20(11)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31159225

RESUMO

Flavonoids have been demonstrated to affect the activity of many mammalian enzyme systems. Their functional phenolic groups are able to mediate antioxidant effects by scavenging free radicals. Molecules of this class have been found able to modulate the activity of kinases, phospholipase A2, cyclooxygenases, lipoxygenase, glutathione S-transferase, and many others. Recently, it has been demonstrated that luteolin, in the form of Luteolin-7-O-ß-d-glucoside (LUT-7G) is able to induce the keratinocyte differentiation process in vitro. This flavonoid is able to counteract the proliferative effects of IL-22/IL6 pathway by the inhibition of STAT3 activity also in vivo in a psoriatic mouse model. Observations on energy metabolism changes of differentiating cells led us to perform a complete metabolomics analysis using human primary keratinocytes treated with LUT-7G. Our results show that LUT-7G, is not only able to impair the nuclear translocation of STAT3, but it also blocks the energy metabolism pathway, depressing the glycolytic and Krebs pathway by the inhibition of hexokinase 2 activity. These data confirm that LUT-7G can be proposed as a potential candidate for the treatment of inflammatory and proliferative diseases, but its role as a hexokinase 2 (HEK2) inhibitor opens new perspectives in nutritional science, and especially in cancer therapy, in which the inhibition of the Warburg effect could be relevant.


Assuntos
Metabolismo Energético/efeitos dos fármacos , Glucosídeos/metabolismo , Glucosídeos/farmacologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Luteolina/metabolismo , Luteolina/farmacologia , Receptor EphB3/metabolismo , Trifosfato de Adenosina/metabolismo , Cálcio/metabolismo , Glucosídeos/química , Hexoquinase/química , Hexoquinase/metabolismo , Humanos , Luteolina/química , Redes e Vias Metabólicas , Metaboloma , Metabolômica/métodos , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Receptor EphB3/química , Relação Estrutura-Atividade
20.
J Food Sci ; 84(7): 1721-1729, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31206192

RESUMO

The fruit of Terminalia chebula Retz., or Tibet Olive, is widely used as a food supplement in China. It possesses some natural antimicrobial properties; however, its chemical composition and antivirulence effects have not been identified. In this work, 29 compounds were identified from the peel of T. chebula fruit by ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. Both the extract of T. chebula and its phenolic acid, corilagin, showed antivirulent activity against Staphylococcus aureus. Specifically, they inhibited biofilm formation. The half maximal inhibitory concentration was 0.13 and 3.18 µg/mL for the extract and corilagin, respectively, whereas for α-hemolysin secretion, the respective concentrations were 30 and 10 µg/mL. Its mechanism of action may be due to reducing the transcription of genes related to quorum sensing. These genes included staphylococcal accessory regulator A, intercellular adhesion accessory gene regulator A, and RNAIII. These findings provide evidence that this food supplement could be an effective antivirulent with corilagin as its active ingredient. PRACTICAL APPLICATION: Corilagin from the fruit of Terminalia chebula Retz. may be used as an antibacterial for its antivirulent activity against Staphylococcus aureus.


Assuntos
Antibacterianos/farmacologia , Extratos Vegetais/farmacologia , Terminalia/química , Antibacterianos/análise , China , Frutas/química , Glucosídeos/análise , Glucosídeos/farmacologia , Taninos Hidrolisáveis/análise , Taninos Hidrolisáveis/farmacologia , Extratos Vegetais/análise , Percepção de Quorum/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/patogenicidade , Staphylococcus aureus/fisiologia , Virulência/efeitos dos fármacos
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