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1.
Eur J Med Chem ; 187: 111904, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31806537

RESUMO

Aiming to develop potent autotaxin (ATX) inhibitors for fibrosis diseases, a novel series of tetrahydropyrido[4,3-d]pyrimidine derivatives was designed and synthesized based on our previous study. The enzymatic assay combined with anti-proliferative activities against cardiac fibroblasts (CFs) and hepatic stellate cell (HSC) in vitro were applied for preliminary evaluation of anti-fibrosis potency of target compounds, resulting in two outstanding ATX inhibitors 8b and 10g with the IC50 values in a nanomolar range (24.6 and 15.3 nM). Differently, 8b was the most prominent compound against CFs with inhibition ratio of 81.5%, while 10g exhibited the maximum inhibition ratio of 83.7% against t-HSC/Cl-6 cells. In the further pharmacological evaluations in vivo, collagen deposition assay demonstrated the conspicuous capacity of 8b to suppress TGF-ß-mediated cardiac fibrosis. Simultaneously, H&E and Masson stains assays of mice liver validated 10g as an excellent anti-hepatofibrosis candidate, which reduced CCl4-induced hepatic fibrosis level prominently. Besides, the molecular binding models identified the essential interactions between 8b and ATX which was coincided with the SARs.

2.
J Agric Food Chem ; 67(36): 10245-10255, 2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31389238

RESUMO

Ginseng has been widely used as a functional food in the world because of its well-defined health benefits. Previous studies have confirmed that AD-1, a new ginsenoside derived from ginseng, can ameliorate thioacetamide-induced liver injury and fibrosis in mice. Simultaneously, amino acid supplementation is getting more attention as an important adjuvant therapy in the improvement of hepatopathy. The aim of this study was to conjugate AD-1 with several selected amino acids and investigate the cytotoxicity of the obtained conjugates in activated t-HSC/Cl-6 cells and normal human liver cells (LO2). Structure-activity relationships of conjugates and underlying mechanisms of the effect are also explored. The results indicated that conjugate 7c remarkably inhibited cell proliferation in activated t-HSC/Cl-6 cells (IC50 = 3.8 ± 0.4 µM) and appeared to be nontoxic to LO2. Besides, conjugate 7c had a relatively good plasma stability. Further study demonstrated that inducing S-phase arrest and activation of mitochondrial-mediated apoptosis were included in the mechanisms underlying the efficiency of conjugate 7c. These findings provided further insight into designing functional foods (ginsenoside and amino acid) for the application in prevention or improvement of liver fibrosis.


Assuntos
Aminoácidos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/farmacologia , Células Estreladas do Fígado/citologia , Aminoácidos/química , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ginsenosídeos/química , Células Estreladas do Fígado/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase S do Ciclo Celular/efeitos dos fármacos
3.
Fitoterapia ; 137: 104279, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31356850

RESUMO

20(R)-25-hydroxyprotopanaxadiol (25-OH-PPD) is a natural compound showing a variety of anti-tumor effects. In an attempt to search for a new anti-cancer compound with higher antitumor activities, we designed and synthesized a series of 25-OH-PPD derivatives. Cytotoxicity assay of these derivatives towards MCF-7, A549, U87, HO-8901, Hela cancer cell lines and normal IOSE144 cell lines were tested by MTT assay. Results showed that compared with compound 25-OH-PPD, Compounds 4, 5, 6, 10, 11 showed strong anticancer activity, and all compounds showed low toxicity or no toxicity for normal cells. In particular, compound 6 exhibited the best anti-tumor activity in all cancer cell lines (MCF-7, A549, U87, HO-8901, and Hela) with IC50 values of 5.04 µM, 1.36 µM, 3.24 µM, 3.47 µM, 4.57 µM, respectively. Among the five cell lines, all the compounds showed strong inhibition on A549 cells. Further studies showed that Compound 6 significantly inhibited the proliferation of A549 cells by inducing apoptosis. Our results indicate that Compound 6 is a potential anticancer inhibitor and provides a theoretical basis for further research.


Assuntos
Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Ginsenosídeos/farmacologia , Acilação , Antineoplásicos/síntese química , Linhagem Celular Tumoral , Ginsenosídeos/síntese química , Humanos , Estrutura Molecular , Relação Estrutura-Atividade
4.
Food Funct ; 10(7): 3992-4000, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31206110

RESUMO

Ginseng is a type of medicinal and edible homologous plant that is very common in medicine, food and even cosmetics. Ginsenosides are the main active constituents of ginseng, which has many pharmacological activities. AD-2 is a type of ginsenoside extracted from ginseng and prepared in large quantities in our laboratory. However, the anti-fibrosis effects and mechanism of ginsenosides are rarely reported. In this study, the anti-fibrosis pharmacodynamics of AD-2 were evaluated. The results revealed that AD-2 could reduce the expression of collagen I, TIMP-1 and MMP-13, inhibit the deposition of extracellular matrix, and play an role in anti-hepatic fibrosis. The mechanism and related pathways of AD-2 against liver fibrosis have also been studied. Inflammatory factors (including TNF-α, IL-1ß, caspase-1 and IL-6) associated with hepatic fibrosis, and the p-JNK and the p38-ERK pathways, have been shown to be associated with the anti-fibrotic effect of AD-2. In conclusion, our study reveals that AD-2, as a small-molecule, targeted drug for improving liver function, needs further study.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/tratamento farmacológico , Ginsenosídeos/farmacologia , Cirrose Hepática/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Tioacetamida/efeitos adversos , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Colágeno Tipo I/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Ginsenosídeos/química , Fígado/efeitos dos fármacos , Fígado/patologia , Cirrose Hepática/patologia , Masculino , Camundongos , Panax/química , Extratos Vegetais/farmacologia , Plantas Medicinais , Inibidor Tecidual de Metaloproteinase-1/metabolismo
5.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1114-1115: 134-145, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878379

RESUMO

Industrial processing of glycyrrhizic leads to a lot of residues which are usually threw away randomly or used as feed. Therefore, the purpose of this study was to study licorice residues as a source of bioactive compounds with potentially applications. In this study, the enrichment and purification of total flavones from the licorice residues was achieved by using macroporous resins. The performances and separation characteristics of four selected macroporous resins with different chemical and physical properties were investigated. HPD-100 resin was the most effective, the content of total flavones increased from 50.94% in the original extract to 82.98% in the 80% ethanol fraction (a 1.63-fold increase). Further purification treatment by polyamide resin, licochalcone A with a purity of 80.28% was obtained in a 45% ethanol fraction, and a higher purity (>85%) of licochalcone A can be obtained by single crystallization operation. And hypoglycemic effect of the total flavones from licorice residues on high fat diet and STZ induced diabetic c57 mice was preliminary investigated. The results showed: the fasting blood glucose of mice in the low and medium dose total flavones group decreased significantly. The proposed technique is uncomplicated, easily managed, cost-effective, and environmentally friendly and is proper for both large-scale licorice residues application and waste management.


Assuntos
Glicemia/efeitos dos fármacos , Chalconas/análise , Flavonas/análise , Glycyrrhiza/química , Extratos Vegetais/farmacologia , Adsorção , Animais , Chalconas/isolamento & purificação , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental/metabolismo , Flavonas/isolamento & purificação , Hipoglicemiantes/análise , Hipoglicemiantes/farmacologia , Cinética , Modelos Lineares , Masculino , Camundongos , Extratos Vegetais/química , Ratos Sprague-Dawley , Reprodutibilidade dos Testes
6.
J Ethnopharmacol ; 238: 111835, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-30917929

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Cacumen Platycladi (CP) is the leaves of Platycladus orientalis which has been traditionally used to resist alopecia and promote hair growth. However, no study has been reported on the effects of CP on proliferation of dermal papilla cells (DPCs). And there is also no complete and systematic research on hair re-growth efficacies of CP. AIM OF THE STUDY: To evaluate the hair-growth activity of their extracts on the proliferation of DPCs and the promotion of hair reproduction in C57BL/6 mice. MATERIALS AND METHODS: For the DPCs, different extract fractions of CP were investigated. The hair growth effect of CP volatile oil on C57BL/6 mice was evaluated for 28 days. Meanwhile, the chemical constituents of the volatile oil from Cacumen Platycladi were isolated and identified by GC-MS. RESULTS: The study showed that the extracts of CP could promote the proliferation of DPCs, and the activity of volatile oil was the best. CP volatile oil (100 µg/mL) resulted in stronger proliferation of DPCs by 239.8% compared with control (100%) and minoxidil (130.3%) during the 48 h incubation. And no obvious cytotoxic activity was observed when volatile oil was dosed up to 500 µg/mL. At different growth stages, mice treated with 0.2 g/kg CP volatile oil required shorter time than 2% minoxidil. Hair length for 0.2 g/kg CP volatile oil treated group was longer than those of minoxidil and control. Further histological observation indicated that CP volatile oil could prolonged the anagen phase of hair follicles. Moreover, thirty four components, with contents of 81.9% of the total volatile oils, were separaed and identified. CONCLUSION: The CP volatile oil may have the potential therapeutic agent for the treatment of alopecia.


Assuntos
Cupressaceae , Cabelo/efeitos dos fármacos , Óleos Voláteis/farmacologia , Alopecia/tratamento farmacológico , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Derme/citologia , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Cabelo/crescimento & desenvolvimento , Camundongos Endogâmicos C57BL , Óleos Voláteis/química , Folhas de Planta
7.
Environ Toxicol Pharmacol ; 68: 13-18, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30852303

RESUMO

Alternate forms of drug crystals display different physicochemical properties. These include stability, dissolution rate, bioavailability and solubility, which can affect pharmacokinetics and pharmacodynamics. It is therefore important to compare the crystal forms of cedrol to obtain optimal anti-inflammatory and analgesic effects. This study, for the first time, obtained and reports three novel forms (I-III) of cedrol polymorphs. The three forms of cedrol were recrystallized from seven organic solvents by slow cooling or volatilization and identified by thermal analysis, fourier transform infrared spectroscopy, scanning electron microscopy and powder X-ray diffraction analysis. Form I originated from acetone and cyclohexane. Form II was obtained from ethanol, ethyl acetate, acetonitrile and n-hexane. Form III was recrystallized from methanol. The anti-inflammatory and analgesic activities of the three crystalline forms were evaluated by acetic acid induced writhing in mice, the hot plate method, carrageenan induced mouse paw edema models, Xylene-induced mouse ear edema models and cotton pellet-induced mouse granuloma models. Experimental results revealed that the highest performance was achieved from Form I. These findings are of great significance during the early research study of cedrol polymorphs.


Assuntos
Analgésicos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Edema/tratamento farmacológico , Granuloma/tratamento farmacológico , Dor/tratamento farmacológico , Terpenos/uso terapêutico , Ácido Acético , Animais , Carragenina , Fibra de Algodão , Edema/induzido quimicamente , Feminino , Temperatura Alta , Camundongos , Dor/induzido quimicamente , Xilenos
8.
Regul Toxicol Pharmacol ; 103: 229-236, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30703409

RESUMO

Perilla seeds are used as food and traditional medicine in China. This study aimed to investigate the toxicity profile of Perilla seed oil (PSO), which is the main constituent of Perilla seeds in rodents and Beagle dogs. No significant treatment-associated toxicity or mortality was observed at PSO dosages of up to 50 g/kg and 20 g/kg in KM mice and Wistar rats, respectively, suggesting that PSO was well tolerated by the experimental rodents. Sub-chronic oral toxicity of PSO was studied in dogs at doses of 3, 6 and 12 g/kg/d for 90 days followed by a 30 day recovery period. The results indicated that the body weight increased in all-dose groups more than control group, typical of animals on diets rich in fatty acids. Treatment-related side effects, including changes in hematology and serum biochemistry parameters, histopathology of liver and lymph glands, were observed in the high and moderate-dose dogs. However, these changes disappeared after the doses were withdrawn during the recovery period, except for alteration of liver in the high-dose group. In conclusion, the "no observed adverse effect level" (NOAEL) of oral administration of PSO for 90 days in Beagle dogs was considered to be 3 g/kg/d.


Assuntos
Fígado/efeitos dos fármacos , Linfonodos/efeitos dos fármacos , Ácido alfa-Linoleico/administração & dosagem , Ácido alfa-Linoleico/toxicidade , Administração Oral , Animais , Cães , Relação Dose-Resposta a Droga , Feminino , Masculino , Camundongos , Camundongos Endogâmicos , Óleos Vegetais/administração & dosagem , Óleos Vegetais/toxicidade , Ratos , Ratos Wistar , Testes de Toxicidade Subcrônica
9.
Curr Drug Metab ; 20(4): 292-300, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30599107

RESUMO

BACKGROUND: The progression of liver disease causes metabolic transformation in vivo and thus affects corresponding endogenous small molecular compounds. Metabonomics is a powerful technology which is able to assess global low-molecular-weight endogenous metabolites in a biological system. This review is intended to provide an overview of a metabonomics approach to the drug toxicology of diseases of the liver. METHODS: The regulation of, and relationship between, endogenous metabolites and diseases of the liver is discussed in detail. Furthermore, the metabolic pathways involved in drug interventions of liver diseases are reviewed. Evaluation of the protective mechanisms of traditional Chinese medicine in liver diseases using metabonomics is also reviewed. Examples of applications of metabolite profiling concerning biomarker discovery are highlighted. In addition, new developments and future prospects are described. RESULTS: Metabonomics can measure changes in metabolism relating to different stages of liver disease, so metabolic differences can provide a basis for the diagnosis, treatment and prognosis of various diseases. CONCLUSION: Metabonomics has great advantages in all aspects of the therapy of liver diseases, with good prospects for clinical application.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hepatopatias/metabolismo , Fígado/metabolismo , Medicina Tradicional Chinesa , Metabolômica/métodos , Fitoterapia , Biomarcadores , Humanos , Fígado/patologia
10.
J Ethnopharmacol ; 231: 486-493, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30472401

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenque is an acupoint located in the umbilicus and connected with the meridians. Thus, acupoint herbs applied at Shenque plays a pivotal role in the Chinese traditional medicine due to its sensitivity, permeability, and absorption. Many studies reported the use of Shenque point as a successful therapeutic approach. However, the effect of garlic oil (GO) applied at Shenque point to combat obesity is unmet. Consequently, we investigated the potential benefit of GO applied at Shenque point against obesity. AIM OF THE STUDY: To investigate GO effects on obese rats applied at Shenque acupoint and orally administered, and to identify the chemical constituents of GO. MATERIALS AND METHODS: Rats were randomly divided into 2 groups: naive and model group. The model group rats were fed with a high fat diet for 7 weeks to induce obesity, and then they were randomly divided into 5 groups: model, GO Shenque point treated groups (25, 50 and 100 mg/kg/day) and oral group (50 mg/kg/day). Biochemical indexes in the serum, weight of adipose tissue and liver histopathology were evaluated after 6 weeks of GO treatment using a Hitachi 7080 analyzer (Hitachi, Japan). Moreover, GO chemical components were detected by gas chromatography-mass spectrometer (GC-MS). RESULTS: Compared with the naive rats, model rats exhibited higher body and liver weight, increased fat deposition, higher triglyceride concentration and alveolar development. In contrast, GO Shenque point treated groups showed a substantial decrease in body weight (P = 0.358, 0.028, 0.031, respectively), fat mass, cholesterol (P = 0.004, 0.041, 0.001, respectively), triglyceride (P = 0.001, 0.001, 0.001, respectively), and low density lipoprotein concentrations (P = 0.001, 0.000, 0.001, respectively). The effect was more remarkable than the GO orally administered. In addition, twelve GO organosulfur compounds were identified by GC-MS and diallyl trisulfide (DATS) was detected as the main compound, with a 32.08% concentration. CONCLUSIONS: These findings demonstrated that GO had a significant anti-obesity effect on obese rats by reducing the body weight and protecting the liver from damage, and the effect of Shenque point treatment was better than oral administration, suggesting that GO was an effective weight-loss drug and Shenque point administration might be considered as a new anti-obesity approach.


Assuntos
Pontos de Acupuntura , Compostos Alílicos/administração & dosagem , Fármacos Antiobesidade/administração & dosagem , Obesidade/tratamento farmacológico , Sulfetos/administração & dosagem , Compostos Alílicos/química , Animais , Fármacos Antiobesidade/química , Dieta Hiperlipídica , Vias de Administração de Medicamentos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Compostos Fitoquímicos/administração & dosagem , Compostos Fitoquímicos/análise , Ratos Wistar , Sulfetos/química
11.
Bioorg Med Chem Lett ; 29(2): 189-193, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30527868

RESUMO

Previously we have reported that 25-OCH3-PPD could suppress the reproduction of cancer cells and cause apoptosis without obvious toxicity. Herein, we aimed to enhance its bioactivity by introducing aromatic groups to its dammarane-type skeleton. These synthesized derivatives were tested for their inhibitory activities against five cancer cell lines. Of them, compounds 3a, 14a and 18a had the strongest antiproliferative activities against tumor cells (IC50 < 15 µM, 5-fold to 10-fold increases than 25-OCH3-PPD). Especially compound 14a displayed the most potent activity against DU145, MCF-7 and HepG2 cells (IC50 = 6.7 ±â€¯0.8, 4.3 ±â€¯0.8 and 5.8 ±â€¯0.6 µM, respectively). Structure-activity relationships demonstrated that having aromatic ester at the C3 position could improve the bioactivity. The data provided new insights into exploring novel antiproliferative lead compounds.


Assuntos
Antineoplásicos/farmacologia , Ginsenosídeos/farmacologia , 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 , Ginsenosídeos/síntese química , Ginsenosídeos/química , Células Hep G2 , Humanos , Células MCF-7 , Estrutura Molecular , Relação Estrutura-Atividade
12.
J Nat Med ; 73(1): 318-330, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30426288

RESUMO

Our previous research revealed resin of Dracaena cochinchinensis as a candidate for therapy of neurodegenerative diseases. In the present study, the material basis of Chinese Dragon's blood and the primary mechanism of the effective components are discussed. Multiple chromatography and spectra analysis were utilized to identify effective constituents. The production of NO was determined using nitrite assay in BV-2 microglial cells stimulated with lipopolysaccharide (LPS). Cell viability was tested using MTT assay. The mRNA level of inducible nitric oxide synthase (iNOS) was investigated by quantitative real-time PCR (qRT-PCR), and the production of IL-6 and TNF-α in the cell supernatants was tested by ELISA. The bioassay-directed separation of the effective extract of D. cochinchinensis afforded two new compounds, a stilbene-flavane dimer (2) and a quinoid flavonoid (11), in addition to 25 known compounds. The evaluation of their anti-neuroinflammatory activities showed that 5, 9, 12, 13, and 14 could exhibit significant anti-neuroinflammatory effects without cytotoxities at the tested concentration, compared to a positive control, minocycline (21.87 ± 2.36 µM). A primary mechanistic study revealed that the effective components could inhibit over-activation of microglial through decreasing the expressions of iNOS, proinflammatory cytokines IL-6 and TNF-α in LPS- induced BV2 microglial cells. Chalcone 9, homoisoflavane 5 and flavone 12-14 are considered to be responsible for the anti-neuroinflammatory effects of Chinese Dragon's blood. These could inhibit neuroinflammation by reducing the expressions of iNOS, IL-6 and TNF-α in over-activated microglial. Furthermore, the SAR is briefly discussed.


Assuntos
Dracaena/química , Lipopolissacarídeos/uso terapêutico , Microglia/metabolismo , Doenças Neurodegenerativas/tratamento farmacológico , Resinas Vegetais/química , Lipopolissacarídeos/farmacologia , Doenças Neurodegenerativas/patologia
13.
Molecules ; 23(11)2018 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-30463224

RESUMO

To increase the antitumor activity of ginsenosides and acetylsalicylic acid, acid hydrolysis products of Panaxnotoginseng saponin were used as raw materials to be combined with salicylic acid to obtain ginsenoside salicylic acid derivatives. All derivatives were assessed for anti-cancer activity. A total of 20 target compounds were designed and synthesized. The cytotoxic activity on five cancer cell lines, including human colon cancer (HT-29), gastric cancer (BGC-823), cervical cancer (Hela), human breast cancer (MCF-7), human lung cancer cells (A549), and two normal cancer cell lines (human gastric epithelial cells (GES-1), and human ovarian epithelial cells (IOSE144)) was evaluated following treatment with the compounds. The results showed that all compounds inhibited the growth of cancer cells. Compounds 1a, 3a, 7a, 1b, 2b, 3b and 8b showed strong anticancer activity. For MCF-7 cells, compound 3b showed the strongest inhibitory activity, IC50 = 2.56 ± 0.09 µM. In the cytotoxicity test, all compounds showed low toxicity or no toxicity (IC50 > 100 µM). In addition, a cell cycle distribution assay and wound healing assay demonstrated that compound 3b specifically inhibited MCF-7 proliferation and migration ability. Our results indicate that compound 3b represents a promising compound for further cancer studies.


Assuntos
Antineoplásicos , Neoplasias/tratamento farmacológico , Panax notoginseng , Saponinas , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Panax notoginseng/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Saponinas/química , Saponinas/farmacologia
14.
Chin J Nat Med ; 16(8): 610-614, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30197126

RESUMO

The present study was designed to further investigate the C21 steroidal glycosides in Cynanchum plants. Two new steroidal glycosides based on a 13, 14:14, 15-disecopregnane-type aglycone, komaroside P (1) and komaroside Q (2), together with three known compounds (3-5) were isolated from the whole herbs of Cynanchum komarovii. The aglycones of compounds 1 and 2 were two new disecopregnane. Their structures were elucidated on the basis of 1D, 2D NMR spectroscopic data and acid hydrolysis. All the compounds (1-5) showed potent inhibitory activities against human leukemia cell lines (HL-60) with IC50 values ranging from 16.6 to 26.3 µmol·L-1, compared to the positive control 5-fluorouracil (6.4 µmol·L-1).


Assuntos
Cynanchum/química , Glicosídeos/química , Esteroides/química , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/isolamento & purificação , Glicosídeos/farmacologia , Células HL-60 , Humanos , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Esteroides/isolamento & purificação , Esteroides/farmacologia
15.
Biomed Pharmacother ; 99: 33-42, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29324310

RESUMO

Oxidative stress injury and apoptosis are the main mechanisms of myocardial ischemia-reperfusion injury (MI/RI). Compounds with anti-oxidant properties can treat MI/RI. Therefore, identification of natural antioxidants such as herbs or botanical drugs is an ideal strategy to develop safe and effective anti-MI/RI drugs. Cardioprotective effects of Ginseng are well documented and are attributable to its anti-oxidant, anti-inflammatory, anti-tumorigenic, anti-arrhythmic, anti-ischemic properties. Ginseng monomer 20®-dammarane -3 beta,6 alpha,12 beta,20,25-pentol(25-hydroxyl-Protopanaxatriol,25-OH-PPT), a novel compound, which belongs to panaxatriol category, is extracted from the leaves and stem of ginseng. It was first investigated for its anti-tumorigenic properties. In this study, we explored whether 25-OH-PTT plays a role in antioxidant stress injury and anti-apoptosis in cardiomyocytes. We also explored the mechanisms in order to provide a theoretical basis to develop 25-OH-PPT as a new drug for treatment of MI/RI. First, we used H2O2 to induce H9c2 cardiomyocytes in vitro resulting in an oxidative stress injury model and pretreated with 25-OH-PPT. Secondly, we examined the viability of H9c2 cells by MTT assay, the reactive oxygen species (ROS) content and mitochondrial membrane potential by flow cytometry as well as cell apoptosis by flow cytometry Annexin-FITC/PI and Hoechst 33258 staining. Furthermore, we pretreated H9c2 cells with PI3K inhibitor, LY294002, and observed the above phenomenon. Lastly, we examined the expressions of proteins related to the PI3K/Akt signaling pathway and the apoptotic proteins. We found that 25-OH-PPT can protect H9c2 cells against H2O2-induced injury, decrease apoptosis of H9c2 cells and ROS generation, and increase the mitochondrial membrane potential. It can also upregulate the protein expressions of p-Akt, p-eNOS, and Bcl-2 and down-regulate apoptotic proteins Bax and Caspase-3. Our results indicate that 25-OH-PPT inhibits H2O2-induced H9c2 cardiomyocytes injury through PI3K/Akt pathway. It may become a potential safe and effective traditional Chinese medicine monomer for treatment of MI/RI.


Assuntos
Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Ginsenosídeos/farmacologia , Peróxido de Hidrogênio/toxicidade , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Caspase 3/metabolismo , Linhagem Celular , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromonas/farmacologia , Ginsenosídeos/química , Morfolinas/farmacologia , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Trapidil/farmacologia , Proteína X Associada a bcl-2/metabolismo
16.
J Asian Nat Prod Res ; 20(9): 875-882, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29171292

RESUMO

As a part of our continuing research for bioactive constituents from Cynanchum limprichtii Schltr., two new C21 steroidal glycosides limproside A (1) and limproside B (2) were isolated from the roots of Cynanchum limprichtii. Their structures were elucidated on the basis of 1D- and 2D-NMR spectroscopic data as well as HR-ESI-MS analysis. The cytotoxicity of two compounds against two selected human cancer cell lines was assayed.


Assuntos
Cynanchum/química , Fitosteróis/isolamento & purificação , Saponinas/isolamento & purificação , Linhagem Celular Tumoral , Humanos , Espectroscopia de Ressonância Magnética , Fitosteróis/química , Fitosteróis/farmacologia , Raízes de Plantas/química , Saponinas/química , Saponinas/farmacologia
17.
Steroids ; 129: 1-8, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29129719

RESUMO

As active components of ginseng, 25-methoxylprotopanaxadiol and 25-hydroxyprotopanaxadiol exhibited an ability to inhibit the growth and proliferation or to induce the differentiation and apoptosis of tumour cells. We modified 25-OCH3-PPD and 25-OH-PPD with non-protein amino acids and a series of derivatives was obtained by chromatographic separation, purification and spectroscopy analysis. Thirteen derivatives of 25-OCH3-PPD (compounds 1-13) and 12 derivatives of 25-OH-PPD (compounds 14-25) were synthesised. The anti-cancer activities of the derivatives were evaluated on HCT-116 and BGC-823 cell lines by MTT assay. Compound 9 and compound 14 exhibited considerable anti-tumour activity for HCT-116 and BGC-823 cell lines, exhibited higher cytotoxic activity than 25-OCH3-PPD and 25-OH-PPD. Therefore, these ginsenoside derivatives could be used as potential lead for the development of a new type of anticancer agent.


Assuntos
Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ginsenosídeos/química , Ginsenosídeos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células HCT116 , Humanos
18.
Molecules ; 22(11)2017 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-29099071

RESUMO

Coptis chinensis Franch has been used in Traditional Chinese Medicine (TCM) for treating infectious and inflammatory diseases for over two thousand years. Berberine (BN), an isoquinoline alkaloid, is the main component of Coptis chinensis. The pharmacological basis for its therapeutic effects, which include hepatoprotective effects on liver injuries, has been studied intensively, yet the therapy of liver injuries and underlying mechanism remain unclear. We investigated the detoxification mechanism of Coptis chinensis and berberine using metabolomics of urine and serum in the present study. After the treatment with Coptis chinensis and berberine, compared with the cinnabar group, Coptis chinensis and berberine can regulate the concentration of the endogenous metabolites. PLS-DA score plots demonstrated that the urine and serum metabolic profiles in rats of the Coptis chinensis and berberine groups were similar those of the control group, yet remarkably apart from the cinnabar group. The mechanism may be related to the endogenous metabolites including energy metabolism, amino acid metabolism and metabolism of intestinal flora in rats. Meanwhile, liver and kidney histopathology examinations and serum clinical chemistry analysis verified the experimental results of metabonomics.


Assuntos
Berberina/farmacologia , Coptis/química , Compostos de Mercúrio/toxicidade , Metabolômica/métodos , Substâncias Protetoras/farmacologia , Animais , Sangue/efeitos dos fármacos , Sangue/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Nefropatias/induzido quimicamente , Nefropatias/metabolismo , Nefropatias/patologia , Nefropatias/prevenção & controle , Espectroscopia de Ressonância Magnética , Masculino , Metaboloma/efeitos dos fármacos , Ratos Wistar , Urina/química
19.
J Ethnopharmacol ; 208: 94-104, 2017 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-28687505

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), as a classical herbal formula for the treatment of "Shaoyang syndrome" has been demonstrated to exert an antidepressant effect in multiple animal models of depression as shown in our previous studies. However, the effects of XCHT on social isolation (SI)-reared mice have not been investigated. This study aims to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice, and its implicated mechanisms, including alterations in the monoaminergic system, neurogenesis and neurotrophin expression. MATERIALS AND METHODS: Male C57 BL/6J mice (aged 4 weeks after weaning) were reared isolatedly for 8 weeks and XCHT (0.8, 2.3, 7.0g/kg) were given by gavage once a day. Forced swimming test (FST), tail suspension test (TST), open field test (OFT), elevated-plus maze test (EPM) and intruder-induced aggression test were used to explore the effects of XCHT on depressive/anxiety-like behaviors of SI-reared mice after administration of XCHT for 6 weeks. HPLC-MS/MS was performed to quantify the levels of neurotransmitters in the hippocampus by in vivo microdialysis, while western immunoblotting was used to evaluate the action of XCHT on the synthesis, transport and degradation of monoamine neurotransmitters. Immunofluorescence was used to study the effects of XCHT on neurogenesis and neurotrophin expression, including Ki-67, DCX, BrdU and BDNF. RESULTS: Our results showed that administration of XCHT (0.8, 2.3 and 7.0g/kg) for 6 weeks significantly attenuated the increase in immobility time in TST and FST, improved the anxiety-like behaviors in OFT and EPM, and improved the aggressive behaviors of SI-reared mice. XCHT significantly elevated monoamine neurotransmitters levels and inhibited 5-HT turnover (5-HIAA/5-HT) in hippocampal microdialysates of SI-reared mice. In addition, we found XCHT enhanced monoamine neurotransmitter synthesis enzymes (TPH2 and TH) expressions, inhibited serotonin transporter (SERT) expression and decreased monoamine neurotransmitter degradation enzyme (MAOA) expression in the hippocampus of SI-reared mice for the first time. Moreover, XCHT significantly augmented hippocampal neurogenesis and BDNF expression in hippocampus of SI-reared mice. CONCLUSIONS: Our results showed for the first time that XCHT improved depressive/anxiety-like behaviors of SI-reared mice by regulating the monoaminergic system, neurogenesis and neurotrophin expression. The findings indicate that XCHT may have a therapeutic application for early-life stress model of depression and in turn provide further evidence supporting XCHT a novel potential antidepressant from a distinct perspective.


Assuntos
Ansiolíticos/uso terapêutico , Antidepressivos/uso terapêutico , Ansiedade/tratamento farmacológico , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Animais , Ansiolíticos/farmacologia , Antidepressivos/farmacologia , Ansiedade/metabolismo , Comportamento Animal/efeitos dos fármacos , Monoaminas Biogênicas/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Depressão/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Elevação dos Membros Posteriores , Masculino , Aprendizagem em Labirinto , Camundongos Endogâmicos C57BL , Monoaminoxidase/metabolismo , Neurogênese/efeitos dos fármacos , Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo , Isolamento Social , Natação , Triptofano Hidroxilase/metabolismo , Tirosina 3-Mono-Oxigenase/metabolismo
20.
Front Pharmacol ; 8: 271, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28567014

RESUMO

Objectives: Baicalin is the main bioactive flavonoid constituent isolated from Scutellaria baicalensis Georgi. The mechanisms of protection of liver remain unclear. In this study, 1H NMR-based metabonomics approach has been used to investigate the alleviation effect of Baicalin. Method:1H NMR metabolomics analyses of urine and serum from rats, was performed to illuminate the alleviation effect of Baicalin on mineral medicine (cinnabar)-induced liver and kidney toxicity. Results: The metabolic profiles of groups receiving Baicalin at a dose of 80 mg/kg were remarkably different from cinnabar, and meanwhile, the level of endogenous metabolites returned to normal compared to group cinnabar. PLS-DA scores plots demonstrated that the variation tendency of control and Baicalein are apart from Cinnabar. The metabolic profiles of group Baicalein were similar to those of group control. Statistics results were confirmed by the histopathological examination and biochemical assay. Conclusion: Baicalin have the alleviation effect to the liver and kidney damage induced by cinnabar. The Baicalin could regulate endogenous metabolites associated with the energy metabolism, choline metabolism, amino acid metabolism, and gut flora.

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