RESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Maidong (Liliaceae) is used as a yin-nourishing medication for the treatment of cardiovascular disease, inflammation, and assistant cancer chemotherapy in the clinic. Ophiopogonin B (OP-B), a major saponin extracted from Maidong, is reported to have potential antitumor activities against various human cancers. However, the effects of OP-B on human ovarian cancer (OC) and the potential mechanisms of action are yet elusive. AIM OF THE STUDY: In this study, we aimed to explore the potential molecular mechanisms of OP-B in the treatment of OC using network pharmacology. In vivo and in vitro experiments were conducted to further verify the therapeutic effects of OP-B on OC. MATERIALS AND METHODS: To investigate the functions of OP-B against OC holistically, the related targets of OP-B and OC were each predicted based on four public databases. Subsequently, the identified PPI network was constructed to detect the hub potential targets. In addition, GO and KEGG enrichment analysis were applied by Metascape database. Furthermore, we simultaneously investigated the anticancer effects of OP-B on SKOV3 and A2780 human ovarian cancer cells using a cell viability assay, transwell assay, and an image-based cytometric assay. The quantitative real-time PCR and western-blot assay were used to validate the RNA and protein levels of target genes in OP-B treated OC cells. At last, SKOV3-bearing BALB/c nude mice were applied to observe the effectiveness and toxicity of OP-B. RESULTS: Through network pharmacological analysis, OP-B was found to play a critical role in OC via multiple targets and pathways, especially the STAT3 signaling pathways. In addition, in vitro experiments found OP-B suppressed SKOV3 and A2780 cells proliferation in a time and concentration dependent manner, and markedly impaired cancer cell migration. Flow cytometry analysis revealed that OP-B significantly increased early and late apoptosis, induced G2/M phase cell cycle arrest in SKOV3 cells and G0/G1 phase cell cycle arrest in A2780 cells. Moreover, OP-B administration down-regulated the expression of p-STAT3 protein, whereas the RNA expression and total protein levels of STAT3 were not altered. Finally, in vivo experiments confirmed the therapeutic effects of OP-B on OC in nude mice with low toxicity in heart, liver, lung, and kidney. CONCLUSION: OP-B could efficiently suppress OC cellular proliferation, migration and induce apoptosis, cell cycle arrest mainly via the regulation of STAT3 signaling pathway. This study provides a promising potential application for an alternative to chemotherapy in ovarian cancer.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Liliaceae/química , Neoplasias Ovarianas/tratamento farmacológico , Saponinas/farmacologia , Espirostanos/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Farmacologia em Rede , Neoplasias Ovarianas/patologia , Fator de Transcrição STAT3/metabolismo , Saponinas/administração & dosagem , Saponinas/isolamento & purificação , Transdução de Sinais/efeitos dos fármacos , Espirostanos/administração & dosagem , Espirostanos/isolamento & purificação , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: Atopic dermatitis (AD) is a pruritic, chronic, relapsing inflammatory skin disease. The research aims to study the effects of Sarsasapogenin and its combination with Fluticasone in 2, 4-Dinitrofluorobenzene (DNFB) induced atopic dermatitis in BALB/c mice. MATERIAL AND METHODS: Thirty male Balb/c mice were divided into 5 groups: (i) Normal control (NC), (ii) Disease control (DNFB), (iii) Sarsasapogenin (SG) (50 µg/mice), (iv) Fluticasone (FC) (50 µg/mice), (v) Sarsasapogenin + Fluticasone (SG + FC) combination (25 µg/mice). Dermatitis was induced by repeated application of DNFB in Balb/c mice. On topical application of SG, FC, and SG + FC combination on the ear and skin lesions, body weight, ear weight, ear thickness, erythema score, spleen weight, cytokines, immunoglobulin E (IgE) levels, nitric oxide (NO) level, hematological parameters, and oxidative stress markers were evaluated. Histological analysis of the ear tissue was also done. RESULTS: The results stated that SG and SG + FC treatment to mice considerably decrease the ear weight, ear thickness, spleen weight, serum IgE, cytokines, NO levels, and restoration of antioxidant stress markers with elevation in the hematological parameters. The observations were further confirmed by histopathological analysis of ear tissue. CONCLUSION: These data specify that SG has been demonstrated as a probable therapy for the treatment of allergic skin diseases in combination with FC by decreasing its dose from 50 to 25 µg/mice to avoid the chronic side effects of FC. Hence, it can be concluded that SG and SG + FC combination significantly improved the AD-like symptoms in the DNFB sensitized mice through mitigating the production of proinflammatory mediators and restoration of oxidative stress markers.
Assuntos
Dermatite Atópica/tratamento farmacológico , Fármacos Dermatológicos/administração & dosagem , Dinitrofluorbenzeno/toxicidade , Medicamentos de Ervas Chinesas/administração & dosagem , Fluticasona/administração & dosagem , Espirostanos/administração & dosagem , Animais , Dermatite Atópica/induzido quimicamente , Dermatite Atópica/metabolismo , Quimioterapia Combinada , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Testes de Toxicidade Aguda/métodosRESUMO
Podocyte injury following abnormal podocyte autophagy plays an indispensable role in diabetic nephropathy (DN), therefore, restoration of podocyte autophagy is considered as a feasible strategy for the treatment of DN. Here, we investigated the preventive effects of sarsasapogenin (Sar), the main active ingredient in Anemarrhena asphodeloides Bunge, on the podocyte injury in diabetic rats, and tried to illustrate the mechanisms underlying the effects in high glucose (HG, 40 mM)-treated podocytes (MPs). Diabetes model was established in rats with single streptozocin (60 mg· kg-1) intraperitoneal administration. The rats were then treated with Sar (20, 60 mg· kg-1· d-1, i.g.) or a positive control drug insulin (INS) (40 U· kg-1· d-1, i.h.) for 10 weeks. Our results showed that both Sar and insulin precluded the decreases of autophagy-related proteins (ATG5, Beclin1 and LC3B) and podocyte marker proteins (podocin, nephrin and synaptopodin) in the diabetic kidney. Furthermore, network pharmacology was utilized to assess GSK3ß as the potential target involved in the action of Sar on DN and were substantiated by significant changes of GSK3ß signaling in the diabetic kidney. The underlying protection mechanisms of Sar were explored in HG-treated MPs. Sar (20, 40 µM) or insulin (50 mU/L) significantly increased the expression of autophagy- related proteins and podocyte marker proteins in HG-treated MPs. Furthermore, Sar or insulin treatment efficiently regulatedphosphorylation at activation and inhibition sites of GSK3ß. To sum up, this study certifies that Sar meliorates experimental DN through targeting GSK3ß signaling pathway and restoring podocyte autophagy.
Assuntos
Autofagia/efeitos dos fármacos , Nefropatias Diabéticas/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Glicogênio Sintase Quinase 3 beta/metabolismo , Podócitos/efeitos dos fármacos , Espirostanos/administração & dosagem , Animais , Autofagia/fisiologia , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Masculino , Podócitos/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Recently, a new drug combination GRS comprising ginsenoside Rb1 (G-Rb1), ruscogenin (R-Rus) and schisandrin (S-SA) was screened based on ShengMai preparations, which exhibited a prominent cardioprotective effects against myocardial ischemia/reperfusion (MI/R) injury. AIM OF THE STUDY: To investigate their systemic and individual mechanism of each compound in combination GRS. MATERIALS AND METHODS: The mice model of MI/R and hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury were performed to explore the respective characteristics of each compound in GRS against myocardial injury. RESULTS: Each component in the combination GRS attenuated MI/R injury as evidenced by decreased myocardial infarct size, ameliorated histological features, and improved biochemical indicators. Meanwhile, ingredient G, R and S in combination also individually performed a significant decrease of apoptotic index in MI/R mice and H/R-induced cardiomyocytes injury. Mechanistically, component G in GRS could markedly increase the ATP content in cardiomyocytes through activation of AMPKα phosphorylation. Interestingly, the anti-apoptotic actions of G were profoundly attenuated by knockdown of AMPKα, while no alteration was observed on composition R and S. Moreover, component R in GRS significantly reduced the IL-6 and TNF-α mRNA expression, as well as the content of IL-6 via the modulation of NF-κB signaling pathway. Further, component S exhibited the most powerful anti-oxidative capacity in GRS and remarkably decreased the production of MDA and ROS, and potential mechanisms might at least in part through activating the Akt-14-3-3 signaling pathway and inhibiting the phosphorylation of Bad and ERK1/2. CONCLUSIONS: Our results indicated that the respective mechanism of each compound in combination GRS against MI/R injury might closely associated with energy metabolism modulation, suppression of inflammation and oxidative stress.
Assuntos
Ciclo-Octanos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Ginsenosídeos/administração & dosagem , Lignanas/administração & dosagem , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Compostos Policíclicos/administração & dosagem , Espirostanos/administração & dosagem , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Ciclo-Octanos/isolamento & purificação , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Ginsenosídeos/isolamento & purificação , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Lignanas/isolamento & purificação , Masculino , Camundongos , Camundongos Endogâmicos ICR , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Compostos Policíclicos/isolamento & purificação , Ratos , Espirostanos/isolamento & purificação , Resultado do TratamentoRESUMO
Objective: Asthma is a very common airway inflammatory disease for which the existing drug therapy options are insufficient. In this study, we explored the mechanisms underlying the anti-inflammatory potential of Sarsapogenin (SG) and its combination with Fluticasone (FC) in ovalbumin (OVA)-induced allergic asthma in mice.Methods: In a standard experimental model, asthma in mice was sensitized and challenged by OVA. The mice were treated with SG and SG + FC during OVA challenge. At the completion, lung weight, inflammatory cell count in bronchoalveolar lavage fluid (BALF), serum cytokines levels, immunoglobulin E (IgE) levels, lung nitrate/nitrite (NO) levels, and lung tissue oxidative stress biomarkers were determined. Histopathological evaluation of the lung tissue was also performed.Key findings: Treatment of mice with SG and SG + FC combination intensely diminished the trafficking of total and differential inflammatory cells count into BALF. SG and SG + FC administration significantly reduced the production of inflammatory cytokines, serum IgE levels and restoration of antioxidant stress markers. Histopathological analysis of lung samples effectually weakened bronchial inflammation and mucus production in the lung with a significant reduction in inflammation and mucus score.Conclusion: Our study results suggested that SG and SG + FC effectively reduced allergic airway inflammation via inhibiting pro-inflammatory cytokines, NO expressions and oxidative stress parameters. So, it could be used as a therapeutic potential agent for the treatment of asthma by decreasing its dose in combination with FC to avoid the chronic adverse effects of FC.
Assuntos
Antiasmáticos/uso terapêutico , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fluticasona/uso terapêutico , Pulmão/efeitos dos fármacos , Espirostanos/uso terapêutico , Animais , Antiasmáticos/administração & dosagem , Asma/sangue , Asma/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Fluticasona/administração & dosagem , Imunoglobulina E/sangue , Pulmão/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina/imunologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/imunologia , Espirostanos/administração & dosagemRESUMO
BACKGROUND/OBJECTIVE: The present study investigated the potent therapeutic effects of Ruscogenin, main steroid sapogenin of traditional Chinese plant called 'Ophiopogon japonicas', on chronic ulcer model established with acetic acid in rats. METHODS: 24 rats were attenuated to the sham (2 ml/kg/day isotonic solution), control (untreated ulcer) and treatment (3 ml/kg/day ruscogenin) groups. After treatment for 2 weeks, gastric tissues were collected and prepared for light microscopic (H&E), immunohistochemical (Collagen I, III and IV) and biochemical analysis [Epidermal growth factor (EGF), Prostaglandin E2 (PGE2), Tumor Necrosis Factor alpha (TNF-α), Interleukin 6 and 8 (IL-6 and IL-8), Lipid Peroxidase (LPO), Myeloperoxidase (MPO), Glutathione (GSH) and Glutathione Peroxidase (GSH-Px)] and transmission electron microscopy (TEM). RESULTS: Macroscopic scoring showed that the ulceration area of ruscogenin-treated group decreased compared with control group. Immunohistochemical analysis revealed ruscogenin ameliorated and restored the levels of Collagen I and IV to the levels of sham group. Tissue levels of EGF and PGE2 enhanced significantly in untreated ulcer group while were higher in treated ulcer group than the control group. TNF-α, IL-6, IL-8, LPO, MPO levels increased significantly in control group whereas decreased in treated rats after ruscogenin treatment. However, levels of GSH and GSH-Px increased significantly in treatment group. TEM showed chief cells and parietal cells of ulcer group having degenerated organelles while ruscogenin group had normal ultrastructure of cells. CONCLUSION: There are potent anti-inflammatory and anti-oxidant effects of ruscogenin on gastric ulcer and may be successfully used as a safe and therapeutic agent in treatment of peptic ulcer.
Assuntos
Fitoterapia , Espirostanos/administração & dosagem , Úlcera Gástrica/tratamento farmacológico , Animais , Doença Crônica , Colágeno/metabolismo , Citocinas/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/metabolismo , Feminino , Microscopia Eletrônica de Transmissão , Ophiopogon/química , Células Parietais Gástricas/patologia , Células Parietais Gástricas/ultraestrutura , Peroxidases/metabolismo , Ratos Sprague-Dawley , Espirostanos/isolamento & purificação , Úlcera Gástrica/metabolismo , Úlcera Gástrica/patologia , Fator de Necrose Tumoral alfa/metabolismoRESUMO
GRS is a drug combination of three active components including ginsenoside Rb1, ruscogenin and schisandrin. It derived from the well-known TCM formula ShengMai preparations, a widely used traditional Chinese medicine for the treatment of cardiovascular diseases in clinic. The present study explores the cardioprotective effects of GRS on myocardial ischemia/reperfusion (MI/R) injury compared with ShengMai preparations and investigates the underlying mechanisms. GRS treatment significantly attenuated MI/R injury and exhibited similar efficacy as Shengmai preparations, as evidenced by decreased myocardium infarct size, ameliorated histological features, the decrease of LDH production and improved cardiac function, and also produced a significant decrease of apoptotic index. Mechanistically, GRS alleviated myocardial apoptosis by inhibiting the mitochondrial mediated apoptosis pathway as reflected by inhibition of caspase-3 activity, normalization of Bcl-2/Bax levels and improved mitochondrial function. Moreover, GRS prevented cardiomyocytes mitochondrial fission and upregulated AMPKα phosphorylation. Interestingly, AMPK activation prevented hypoxia and reoxygenation induced mitochondrial fission in cardiomyocytes and GRS actions were significantly attenuated by knockdown of AMPKα. Collectively, these data show that GRS is effective in mitigating MI/R injury by suppressing mitochondrial mediated apoptosis and modulating AMPK activation-mediated mitochondrial fission, thereby providing a rationale for future clinical applications and potential therapeutic strategy for MI/R injury.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Cardiotônicos/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Animais , Apoptose/efeitos dos fármacos , Ciclo-Octanos/administração & dosagem , Combinação de Medicamentos , Quimioterapia Combinada , Dinaminas/metabolismo , Ginsenosídeos/administração & dosagem , Lignanas/administração & dosagem , Masculino , Camundongos Endogâmicos ICR , Dinâmica Mitocondrial/efeitos dos fármacos , Traumatismo por Reperfusão Miocárdica/patologia , Compostos Policíclicos/administração & dosagem , Espirostanos/administração & dosagemRESUMO
Ophiopogonin B (OP-B), a saponin compound isolated from Radix Ophiopogon japonicus, was verified to inhibit cell proliferation in numerous non-small cell lung cancer (NSCLC) cells in our previous study. However, the precise mechanisms of action have remained unclear. In the present study, we mainly investigated the effects of OP-B on adenocarcinoma A549 cells to further elaborate the underlying mechanisms of OP-B in different NSCLC cell lines. Detection by high content screening (HCS) and TUNEL assay verified that OP-B induced apoptosis in this cell line, while detection of Caspase-3, Bcl-2 and Bax showed that OP-B induced cell death was caspase and mitochondrial independent. Further experiments showed that OP-B induced cell cycle arrest in the S and G2/M phases by inhibiting the expression of Myt1 and phosphorylation of Histone H3 (Ser10), which resulted in mitotic catastrophe in the cells. Transmission electron microscopy (TEM) observation of cell micro-morphology combined with detection of Atgs by western blot analysis showed that OP-B induced autophagy in this cell line. Autophagy inhibition by the lysosome inhibitor CQ or Beclin1-siRNA knockdown both attenuated cell viability, demonstrated that autophagy also being the vital reason resulted in cell death. More importantly, the xenograft model using A549 cells provided further evidence of the inhibition of OP-B on tumor proliferation. Immunohistochemistry detection of LC3 and Tunel assay both verified that high dose of OP-B (75 mg/kg) induced autophagy and apoptosis in vivo, and western blot detection of p-Histone H3 (Ser10), Survivin and XIAP further indicated the molecular mechanism of OP-B in vivo. As our findings revealed, multiple types of cell death overlapped in OP-B treated A549 cells, it displayed multitarget characteristics of the compounds extracted from the Chinese herbal, which may be used as candidate anticancer medicine in clinic.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Mitose/efeitos dos fármacos , Saponinas/administração & dosagem , Espirostanos/administração & dosagem , Células A549 , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem do Ciclo Celular , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/administração & dosagem , Regulação Neoplásica da Expressão Gênica , Humanos , RNA Interferente Pequeno , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The protective effects of ruscogenin on nonalcoholic steatohepatitis in hamsters fed a high-fat diet were investigated. Ruscogenin (0.3, 1.0, or 3.0 mg/kg/day) was orally administered by gavage once daily for eight weeks. A high-fat diet induced increases in plasma levels of total cholesterol, triglycerides, and free fatty acids, while the degree of insulin resistance was lowered by ruscogenin. High-fat diet-induced hepatic steatosis and necroinflammation were improved by ruscogenin. Gene expression of inflammatory cytokines and activity of nuclear transcription factor-κB were also increased in the high-fat diet group, which were attenuted by ruscogenin. Ruscogenin decreased hepatic mRNA levels of sterol regulatory element-binding protein-1c and its lipogenic target genes. The hepatic mRNA expression of peroxisome proliferator-activated receptor α, together with its target genes responsible for fatty acid ß-oxidation were upregulated by ruscogenin. In conclusion, these findings suggest that ruscogenin may attenuate high-fat diet-induced steatohepatitis through anti-inflammatory mechanisms, reducing hepatic lipogenic gene expression, and upregulating proteins in the fatty acid oxidation process.
Assuntos
Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Substâncias Protetoras/farmacologia , Espirostanos/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Cricetinae , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Regulação da Expressão Gênica/efeitos dos fármacos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Oxirredução/efeitos dos fármacos , Substâncias Protetoras/administração & dosagem , Substâncias Protetoras/química , Espirostanos/administração & dosagem , Espirostanos/química , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Triglicerídeos/metabolismoRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: 'SHENMAI' injection (SMI) has been widely used in cardioprotection and modulation of the immune system because of its great efficacy. SMI primarily comprises the saponins from Panax ginseng and Ophiopogon japonicas. The profiles of saponins in SMI during long-term toxicokinetics remain unclear. MiR-146a possesses excellent sensitivity as a bio-marker in the innate immunity modification effect of SMI. AIM OF THE STUDY: Is to monitor the exposure level of SMI during a one-month toxicokinetic experiment, an analytical method involving ESI-LC-MS/MS technology was developed to determine 20 (S)-protopanaxadiol-type ginsenoside (Rb1, Rb2, Rc, Rd), 20 (S)-protopanaxatriol-type ginsenoside (Rg1, Re, Rf), oleanolic acid-type ginsenoside (Ro), and ophiopogonin D in rats. The levels of AST, CK, ALT, SOD, GSH-pX, MDA, miR-146a, and ECG were measured to explore the effects of SMI in cardiologic function and immune activity. RESULTS: Results show that the levels of AST, CK, and MDA decreased upon the administration of SMI. The level of miR-146a increased upon the administration of SMI dosage. During the administration of SMI, increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides were also observed. CONCLUSION: The 20 (S)-protopanaxadiol-type ginsenosides were considered potential PK/TK markers because of their high exposure levels that continuously increased. Oxidative stress was slightly alleviated during the toxicokinetic study. Based on the level of miR-146a, negatively regulated innate immunity was observed. The regulation became more serious with increasing exposure levels of 20 (S)-protopanaxadiol-type ginsenosides. Negatively regulated innate immunity could be induced by long-term administration of SMI (>0.4g/kg).
Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Ginsenosídeos/toxicidade , Imunidade Inata/efeitos dos fármacos , Saponinas/toxicidade , Espirostanos/toxicidade , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Creatina Quinase/sangue , Relação Dose-Resposta a Droga , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacocinética , Etnofarmacologia , Feminino , Ginsenosídeos/administração & dosagem , Ginsenosídeos/sangue , Imunidade Inata/imunologia , Masculino , Medicina Tradicional Chinesa , MicroRNAs/sangue , Ratos Sprague-Dawley , Saponinas/administração & dosagem , Saponinas/sangue , Espirostanos/administração & dosagem , Espirostanos/sangue , Fatores de Tempo , ToxicocinéticaRESUMO
OBJECTIVE To identify whether sarsasapogenin, a sapogenin from the Chinese medicinal herb Anemarrhena Asphodeloides Bunge, would augment the efficacy of risperidone and significantly improve cognitive functions in patients with negative symptoms dominated schizophrenia. METHODS The trial was a double-blind, placebo-controlled, parallel-group design. The eligible patients were randomized into 2 treatment groups: sarsasapogenin group (sarsasapogenin plus risperidone for 8 weeks, n = 41) and placebo group (risperidone only for 8 weeks, n = 39). At the baseline, as well as at weeks 2, 4 and 8 of treatment, the therapeutic response was measured by using scales including Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS), Clinical Global Impression (CGI) and Brief Psychiatry Rating Scale (BPRS). The study period for each subject was 8 weeks and duration of overall trial was 2 years. RESULTS Patients treated with sarsasapogenin plus risperidone demonstrated no statistically significant differences in changes in PANSS, WMS or mWAIS score at the end-point of the trial compared with patients treated with placebo plus risperidone. The incidence of treatment-emergent adverse events in patients treated with sarsasapogenin was not different from that observed in placebo group. CONCLUSION Sarsasapogenin did not augment the efficacy of risperidone in treating negative symptoms dominated schizophrenia. Sarsasapogenin at a dosage of 200 mg per day added to a flexible dosage of risperidone at 2-4 mg per day is safe and well tolerated by patients with negative symptoms dominated schizophrenia.
Assuntos
Antipsicóticos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Risperidona/uso terapêutico , Esquizofrenia/tratamento farmacológico , Espirostanos/uso terapêutico , Adolescente , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Escalas de Graduação Psiquiátrica/estatística & dados numéricos , Risperidona/administração & dosagem , Risperidona/efeitos adversos , Esquizofrenia/diagnóstico , Espirostanos/administração & dosagem , Espirostanos/efeitos adversos , Escalas de Wechsler/estatística & dados numéricosRESUMO
A new steroidal sapogenin molecule 1 having unique characteristics, 21-nor and unusual C19 carboxylic acid has been isolated from the roots of Asparagus racemosus. On the basis of chemical evidence, extensive spectroscopic analysis including two dimensional (2D) NMR and X-ray studies of single crystal, the structure of 1 was determined as (1S,2R,3S,8S,9S,10S,13S,14S,16S,17R,22R,25R)-21-nor-18ß,27α-dimethyl-1ß,2ß,3ß-trihydroxy-25-spirost-4-en-19ß-oic acid. 1 crystallizes in monoclinic space group P21 with a=9.295(2), b=11.238(2), c=11.376(2) Å; ß=91.993(4)°, Z=2, D(cal)=1.344 Mg/m³. The structure was solved by direct methods and refined by full-matrix least-squares procedure to a final R-value of 0.0561 for 4064 observed reflections. 1 was tested against the type of immune responses generated during treatment in normal and immune-suppressed animals and detailed biological activity evaluation suggests it to be a potent immunostimulator.
Assuntos
Adjuvantes Imunológicos/administração & dosagem , Asparagus/química , Extratos Vegetais/administração & dosagem , Raízes de Plantas/química , Espirostanos/administração & dosagem , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/isolamento & purificação , Animais , Antígenos CD/metabolismo , Cristalografia por Raios X , Ciclosporina/farmacologia , Citocinas/metabolismo , Hospedeiro Imunocomprometido , Imunossupressores/farmacologia , Levamisol/farmacologia , Camundongos , Estrutura Molecular , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Espirostanos/química , Espirostanos/isolamento & purificação , EstereoisomerismoAssuntos
Dermatite Alérgica de Contato/diagnóstico , Espirostanos/efeitos adversos , Administração Cutânea , Adulto , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/patologia , Diagnóstico Diferencial , Feminino , Hemorroidas/tratamento farmacológico , Humanos , Testes do Emplastro , Fitoterapia , Extratos Vegetais/administração & dosagem , Extratos Vegetais/efeitos adversos , Ruscus/efeitos adversos , Espirostanos/administração & dosagemRESUMO
In our continuous studies of anticancer activity of steroidal saponins from the rhizomes of Dioscorea collettii var. hypoglauca (Dioscoreaceae), methyl protoneogracillin (NSC-698793) and gracillin (NSC-698787) were tested for cytotoxicity against human cancer cell lines from leukemia and eight solid tumor diseases. As a result, methyl protoneogracillin was cytotoxic against all the test cell lines with GI(50) < 100 micro M, especially selectively against two leukemia lines (CCRF-CEM and RPMT-8226), one colon cancer line (KM12), two central nervous system (CNS) cancer lines (SF-539 and U251), one melanoma line (M14), one renal cancer line (786-0), one prostate cancer line (DU-145), and one breast cancer line (MDA-MB-435), with GI(50) < or = 2.0 micro M. Leukemia, CNS cancer, and prostate cancer were the most sensitive subpanels, while ovarian cancer was the least sensitive subpanels. The preliminary toxicity studies showed that the maximum tolerant dose was 600 mg/kg for methyl protoneogracillin to mice. Gracillin was cytotoxic against most cell lines with GI(50), TGI and LC(50) at micromolar levels, but no activity against EKVX (non-small cell lung cancer), HT29 (colon cancer), OVCAR-5 (ovarian cancer), and SN12C (renal cancer). Based on structure-activity relationship, C-25 R/S con fi guration was critical for leukemia selectivity between methyl protoneogracillin and methyl protogracillin. F-ring was critical to selectivity between furostanol (methyl protoneogracillin and methyl protogracillin) and spirostanol (gracillin) saponins in this study. By an analysis of COMPARE software, no compounds in the NCI's database had similar mean graphs to those of methyl protoneogracillin and gracillin, respectively, indicating potential novel mechanism(s) of action involved. Put all in together, methyl protoneogracillin has been selected as a potential anticancer candidate for hollow fi ber assay to nude mice, but gracillin will not be pursued due to lack of selectivity against human cancer diseases.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Dioscorea , Fitoterapia , Saponinas/farmacologia , Espirostanos/farmacologia , Esteroides/farmacologia , Animais , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Dose Letal Mediana , Leucemia/tratamento farmacológico , Masculino , Melanoma/tratamento farmacológico , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Raízes de Plantas , Neoplasias da Próstata/tratamento farmacológico , Saponinas/administração & dosagem , Saponinas/uso terapêutico , Espirostanos/administração & dosagem , Espirostanos/uso terapêutico , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Escherichia coli K-12 was exposed to Quillaja saponaria saponins from various commercial firms (Sigma, Roth and Nor-feed) and to an extract of Yucca schidigera plant powder (DK Sarsaponin 30) at different concentrations (0.05-1.0% w/v). A concentration-dependent response was observed. Quillaja saponaria saponins from Sigma increased growth up to 0.1% (w/v) level, whereas Nor-feed and Roth saponins produced maximum growth at a much higher level (0.5 and 0.75%, w/v, respectively). These results suggest that quillaja saponins from various sources differ in their biological activity, although all three saponins had the same content of vanillin-sulphuric acid reactive moieties. The lyophilized water extract from the DK Sarsaponin powder showed maximum growth at 0.1% (w/v) level. The levels at which maximum growth was observed did not change on subjecting the quillaja or yucca saponins to heat treatment in an autoclave (121 degrees C for 30 min). All the saponins and the plant extract increased growth of Escherichia coli up to a certain concentration and thereafter decreased growth. In spite of the decreased growth at higher levels of saponins, it was higher compared to the control (without saponin) up to levels of 1% (w/v) for all saponins except Quillaja saponins from Sigma, for which the growth was lower at levels of 0.25% (w/v) and higher. Saponins have the potential to modulate microbial growth in natural and artificial fermenters.
Assuntos
Escherichia coli/efeitos dos fármacos , Extratos Vegetais/farmacologia , Saponinas/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/isolamento & purificação , Antibacterianos/farmacologia , Escherichia coli/crescimento & desenvolvimento , Liliaceae/química , Extratos Vegetais/administração & dosagem , Extratos Vegetais/isolamento & purificação , Plantas Medicinais/química , Saponinas/administração & dosagem , Saponinas/isolamento & purificação , Espirostanos/administração & dosagem , Espirostanos/isolamento & purificação , Espirostanos/farmacologia , Árvores/químicaRESUMO
We examined the antinociceptive effect of smilaxin B administered intracerebroventricularly (i.c.v.) in ICR mice. The tail-flick test was used as an analgesic assay. Smilaxin B showed a strong antinociceptive effect in a dose-dependent manner. Sulfated cholecystokinin (CCK-8s, 0.5 ng), muscimol (50ng), or MK-801 [(+/-)-5-methyl-10, 11-dihydro-5H-dibenzo [a,d]cyclohepten-5, 10-imine maleate, 1 microgram] injected i.c.v. significantly reduced inhibition of the tail-flick response induced by smilaxin B administered i.c.v. However, naloxone (2 microgram), baclofen (10 ng), or CNQX (6-cyano-7- nitroquinoxaline-2,3-dione, 0.5 microgram) injected i.c.v. did not affect inhibition of the tail-flick response induced by similaxin B administered i.c.v. The intrathecal (i.t.) injection of yohimbine (20 micrograms), but not methysergide (20 micrograms) and naloxone (2 microgram), significantly attenuated inhibition of the tail-flick response. induced by smilaxin B administered i.c.v. Our results suggest that GABAA or NMDA receptors but not opioid, GABAB, and non-NMDA receptors located at the supraspinal level may play important roles in the production of antinociception induced by smilaxin B administered supraspinally. Furthermore, smilaxin B administered supraspinally. may produce its antinociception by activating descending noradrenergic- but not opioidergic- and serotonergic-neurons.
Assuntos
Ventrículos Cerebrais/fisiologia , Glicosídeos/farmacologia , Espirostanos/farmacologia , 6-Ciano-7-nitroquinoxalina-2,3-diona/farmacologia , Animais , Baclofeno/farmacologia , Ventrículos Cerebrais/efeitos dos fármacos , Maleato de Dizocilpina/farmacologia , Glicosídeos/administração & dosagem , Injeções Intraventriculares , Injeções Espinhais , Masculino , Metisergida/farmacologia , Camundongos , Camundongos Endogâmicos ICR , Muscimol/farmacologia , Naloxona/farmacologia , Dor , Sincalida/farmacologia , Medula Espinal/efeitos dos fármacos , Medula Espinal/fisiologia , Espirostanos/administração & dosagem , Ioimbina/farmacologiaRESUMO
Plant glycosides were incorporated into the liposomal surface to study their sugar-specific uptake by various tissues. Two steroid glycosides, namely floribundasaponin D, with rhamnose as terminal sugar, and gracillin, with glucose and rhamnose as end sugars, were selected for the purpose. 125I-human IgG encapsulated liposomes composed of egg lecithin (phosphatidylcholine), cholesterol, dicetyl phosphate (optional) and either floribundasaponin D or gracillin, when injected into the tail vein of rat, showed significantly higher uptake in the rat liver than in appropriate controls. Whereas the uptake of floribundasaponin D liposomes was observed to be non-specific, the increased uptake of the gracillin liposomes, as judged from the inhibition studies with asppropriate sugars, was specific for glucose, although the receptor was unable to distinguish between the alpha and beta anomers ('anomerically blind'). The liver-perfusion studies showed that the uptake of gracillin liposomes was mostly by non-parenchymal cells.