RESUMO
UNLABELLED: In this study, we found out a previously undefined function of icariin which restored the dynamic balance between osteogenic and adipogenic differentiation of mesenchymal stem cells (MSCs) in patients with osteonecrosis of femoral head (ONFH) via ABCB1-promoter demethylation. These findings provided important information regarding potential implication of icariin targeting epigenetic changes for the treatment of steroid -associated ONFH. INTRODUCTION: Here, we investigated whether icariin can also exert a beneficial role in the reactivation of MSCs in the patients with steroid-associated ONFH via ABCB1-promoter demethylation. METHODS: Bone marrow was collected from the proximal femur in patients with steroid-associated ONFH (n = 20) and patients with new femoral neck fractures (n = 22), and then MSCs were isolated. We investigated cell viability, intracellular reactive oxygen species (ROS) level, mitochondrial membrane potential (MMP), P-glycoprotein (P-gp) activity, the transcript levels of ABCB1 and oxidative stress-related genes, methylation extent at CpG islands of ABCB1 promoter, and osteogenic and adipogenic differentiation ability of MSCs from the femoral neck fractures group and from the steroid-associated ONFH group treated with or without icariin. RESULTS: We observed that MSCs from the steroid-associated ONFH group showed reduced proliferation ability, elevated ROS level, depressed MMP, weakened osteogenesis, and enhanced adipogenesis while low P-gp activity, transcription level of ABCB1, and oxidative stress-related genes as well as aberrant CpG islands hypermethylation of ABCB1 were also noted in steroid-associated ONFH group. Treatment with icariin obviously induced de novo P-gp expression, decreased oxidative stress, and promoted osteogenesis. CONCLUSION: Icariin may be a potential drug targeting epigenetic changes for the treatment of steroid-associated ONFH.
Assuntos
Metilação de DNA/efeitos dos fármacos , Necrose da Cabeça do Fêmur/induzido quimicamente , Flavonoides/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Adipogenia/efeitos dos fármacos , Adulto , Idoso , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/farmacologia , Epigênese Genética/efeitos dos fármacos , Feminino , Necrose da Cabeça do Fêmur/metabolismo , Necrose da Cabeça do Fêmur/patologia , Glucocorticoides/efeitos adversos , Humanos , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Osteogênese/efeitos dos fármacos , Regiões Promotoras Genéticas , Espécies Reativas de Oxigênio/metabolismoRESUMO
Physalin F and physalin D were isolated and characterized from the ethanolic extract of the whole plant of Physalis angulata L. (Solanaceae). Systematic fractionation of the ethanolic extract of the plant led to characterization of physalin F from the fraction PAIV-2 as an active ingredient which showed cytotoxicity in vitro by DEA and MTT assays on 8 cancer cell lines, five human cancer cell lines: HA22T(hepatoma), HeLa(cervix uteri), KB(nasopharynx), Colo-205(colon) and Calu-1(lung); and three animal cancer cell lines: H1477(melanoma), Hep-2(laryngeal) and 8401(glioma). It was found that the anti-hepatoma action is the strongest, and the anti-HeLa is the next. Physalin F also had an antitumor effect in vivo against P388 lymphocytic leukemia in mice whereas physalin D was inactive both in vitro and in vivo.
Assuntos
Antineoplásicos Fitogênicos/química , Divisão Celular/efeitos dos fármacos , Lactonas/química , Plantas Medicinais , Esteroides , Antineoplásicos Fitogênicos/isolamento & purificação , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular , Cromatografia , Ensaios de Seleção de Medicamentos Antitumorais , Células HeLa , Humanos , Células KB , Lactonas/isolamento & purificação , Lactonas/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Conformação Molecular , Estrutura Molecular , Neoplasias , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Secoesteroides , Solubilidade , Células Tumorais CultivadasRESUMO
The immunomodulatory effects of Physalis angulata L. extract fraction VII (PA-VII), PA-VII-A, PA-VII-B and PA-VII-C were investigated in this study. The results showed that PA-VII and PA-VII-C strongly enhanced blastogenesis response, PA-VII-B had moderate activity, and PA-VII-A exerted only slight effect on cell proliferation. A synergistic effect was observed when the suboptimal dosage of phytohemagglutinin (PHA) or lipopolysaccharide (LPS) was added to the culture. Furthermore, PA-VII and PA-VII-C possessed stimulatory activity on B cells and less effect on T cells. The antibody responses were also augmented by PA-VII, PA-VII-B and PA-VII-C, but not by PA-VII-A. The enhancement of antibody response could be observed both in BALB/c and C3H/HeJ mice.
Assuntos
Antineoplásicos Fitogênicos/imunologia , Medicamentos de Ervas Chinesas/farmacologia , Lactonas/imunologia , Ativação Linfocitária/efeitos dos fármacos , Esteroides , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/classificação , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/classificação , Lactonas/química , Lactonas/classificação , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C3H , Fito-Hemaglutininas/imunologia , SecoesteroidesRESUMO
beta-Sitosterol (SI-0), beta-sitosterol glucoside (SI-1), dioscin (SI-2), methyl protoprosapogenin A of dioscin (SI-3), methyl protodioscin (SI-4) and protodioscin (SI-5) were isolated and characterized from the whole plant of Solanum indicum L. (Solanaceae). Except for beta-sitosterol, these compounds have not been previously isolated from Solanum indicum L. Both CHCl3 soluble (SI-IV) and insoluble (SI-V) fractions of the ethanolic extract (SI-I) showed cytotoxicity on seven cancer cell lines: Colo-205 (colon), KB (nasopharynx), HeLa (uterine cervix), HA22T (hepatoma), Hep-2 (laryngeal epidermoid), GBM8401/TSGH (glioma) and H1477 (melanoma). The purified constituents, SI-2 and SI-4 showed more potent effects by DEA and MTT assay. SI-2,3,4 and 5 also demonstrated cytotoxicity on cultured C6 glioma cells by PRE assay, ans SI-3,4 and 5 showed a tumor inhibitory effect in vivo in C6 glioma cells. In addition, SI-2 had an inhibitory effect on the DNA synthesis of C6 glioma cells at 10 micrograms/ml.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Diosgenina/análogos & derivados , Diosgenina/química , Diosgenina/isolamento & purificação , Diosgenina/uso terapêutico , Ensaios de Seleção de Medicamentos Antitumorais , Glioma/tratamento farmacológico , Medicina Tradicional Chinesa , Saponinas/química , Saponinas/isolamento & purificação , Saponinas/uso terapêutico , Sitosteroides/química , Sitosteroides/isolamento & purificação , Sitosteroides/uso terapêutico , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
In an extensive ethnobotanical survey of the folk medicines of Taiwan, 69 kinds of crude drugs and 107 species of medicinal plants were found to be used for hepatitis treatments. The present paper is to update a list of medicinal plants used in the treatment of hepatitis and evaluate their liver protection by ethnopharmacological and pathological studies. Results show that some of these drugs have prominent therapeutic effects. Further investigation regarding the anti-hepatotoxic principles will be made.
Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Hepatite/tratamento farmacológico , Fígado/efeitos dos fármacos , Botânica/classificação , Medicamentos de Ervas Chinesas/classificação , Medicamentos de Ervas Chinesas/farmacologia , Fígado/patologia , Terminologia como AssuntoRESUMO
The genus Murraya has been widely used in traditional medicine in east Asia. In view of the recent isolation of the anti-implantation alkaloid yuehchukene from M. paniculata a search has now been made for other natural sources of this alkaloid within the genus. In this paper we report findings for nine taxa of Murraya.