RESUMO
Podophyllotoxin (POD), a natural lignan distributed in podophyllum species, possesses significant antitumor and antiviral activities. But POD often causes serious side effects, such as myelosuppression, gastrointestinal toxicity, neurotoxicity, hepatic and renal dysfunction, and even death, which not only hinder its clinical application but also threaten the patient's health. Therefore, an effective treatment against POD-induced toxicity is important. Our preliminary study found that the total saponins from the stems and leaves of Panax quinquefolius L. (PQS) could significantly reduce the death of mice caused by POD. To reveal how PQS can alleviate POD-induced toxicity, further study was needed. Peripheral blood cell analysis, diarrhea score, and histological examination demonstrated that PQS could relieve myelosuppression and gastrointestinal side effects induced by POD. Then, metabolomics was performed to investigate the possible protective mechanism of PQS on POD-induced myelosuppression and gastrointestinal toxicity. Metabolomics analysis showed that metabolic changes caused by POD could be reversed by PQS to some extent; 23 metabolites altered significantly after POD exposure, and 11 metabolites significantly reversed by PQS pretreatment. Metabolic pathway analysis suggested that PQS might exhibit its protective effects by rebalancing disordered arginine, glutamine, and unsaturated fatty acid metabolism.
Assuntos
Metabolismo dos Lipídeos/efeitos dos fármacos , Panax/química , Podofilotoxina/toxicidade , Substâncias Protetoras/farmacologia , Saponinas/farmacologia , Animais , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Cromatografia Líquida de Alta Pressão , Trato Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/patologia , Masculino , Espectrometria de Massas , Metaboloma/efeitos dos fármacos , Metabolômica , Camundongos , Camundongos Endogâmicos ICR , Folhas de Planta/químicaRESUMO
BACKGROUND: The field bean (Vicia faba) is a valuable fodder plant of the Fabaceae family, grown as a main crop for its seed yield. Its phytochemical profile is characterized by the presence of a range of compounds with various biological activities. PURPOSE: The present study investigates the phytochemical profile of the extract from mature seeds of Vicia faba var. minor and examines its impact on preventing oxidative damage to various lipids, protein and DNA molecules in vitro. METHODS: Human plasma was treated with H2O2/Fe (an OH. donor) to induce oxidative damage to lipids and proteins, and the plant extract was then added. As oxidative stress may influence the biological activity of plasma, e.g. coagulation, and influence cardiovascular disease, the study also examined the effect of the plant extract on coagulation and monoamine oxidase activity (MAO, EC 1.4.3.4). RESULTS: The tested extract exerted a protective effect on plasma lipids and proteins treated with H2O2/Fe. However, while it appears to effectively protect the DNA in peripheral blood mononuclear cells from oxidative damage, it did not induce changes in the coagulation process, and significantly reduced MAO activity when applied at 1, 5, and 10 µg/mL. It is possible that the observed antioxidant potential may be due to the complex chemical composition of the extract: the phytochemical profile demonstrated a range of phenolic compounds, including catechins. CONCLUSION: Our findings indicate that extract from mature seeds of V. faba var. minor may be a promising source of antioxidants in multiple applications, including diseases associated with oxidative stress; however, more studies based on in vitro and in vivo models are needed to determine its biological properties.
Assuntos
Antioxidantes/fisiologia , Células Sanguíneas/efeitos dos fármacos , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Sementes/química , Vicia faba/química , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologiaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Cisplatin (CP), one of the most commonly used antitumor drugs in clinic, could induce reproductive and genetic toxicity. Traditional Chinese medicine believed that this side effect might be caused by the deficiency of both qi and blood. Panax notoginseng (Burk.) F. H. Chen (PN) is a traditional precious Chinese medicine for nourishing blood and hemostasis, which had the synergistic antitumor and reducing toxicity effects. However, the protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity were still unknown. AIM OF THE STUDY: This study was designed to illuminate the possible protective effect and mechanism of PN on CP-induced reproductive and genetic toxicity. MATERIALS AND METHODS: Network pharmacology was first applied to analyze the potential components and targets of PN against CP-induced reproductive and genetic toxicity. Then, the results of network pharmacology were validated in a mouse model of reproductive and genotoxicity induced by CP. Body weight, testis weight, epididymis weight, sperm count, sperm viability and sperm morphology were used to assess protective effects of PN on CP-induced reproductive toxicity. Tail moment in peripheral blood cells and micronucleus in bone marrow cells were used to assess protective effects of PN on CP-induced genetic toxicity. Finally, possible protective targets obtained from network pharmacology, including 8-hydroxy-2-deoxyguanosine (8-OHdG), malondialdehyde (MDA), total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px), were experimentally validated by ELISA. RESULTS: One hundred and nineteen components of PN and sixty-eight targets of reproductive/genetic toxicity were acquired and constituted as the component-target network. Network pharmacology analysis showed alleviating oxidative stress might play important role in therapeutic mechanism of PN. In verified experiments, PN significantly improved the decline of body weight, testis weight and epididymis weight, increased sperm count and viability, decreased abnormal sperm morphology rate induced by CP in mice. Moreover, PN also significantly decreased the tail moment in peripheral blood cells and micronucleus formation rate in bone marrow cells in CP-induced mice. Finally, not only the decrease of T-SOD and GSH-Px level but also the increase of 8-OHdG and MDA level in serum were restored under PN treatment. CONCLUSION: Current study found that PN could improve CP-induced reproductive and genetic toxicity, which were probably attributed to alleviating oxidative stress. This finding provided the new perspective for understanding the therapeutic effect of PN on CP-induced reproductive and genetic toxicity and facilitating the clinical use of PN.
Assuntos
Dano ao DNA/efeitos dos fármacos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Panax notoginseng/química , Reprodução/efeitos dos fármacos , 8-Hidroxi-2'-Desoxiguanosina/sangue , Animais , Células Sanguíneas/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Células da Medula Óssea/efeitos dos fármacos , Cisplatino/toxicidade , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/uso terapêutico , Epididimo/efeitos dos fármacos , Glutationa Peroxidase/sangue , Masculino , Malondialdeído/sangue , Camundongos , Estresse Oxidativo/efeitos dos fármacos , Mapas de Interação de Proteínas , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Superóxido Dismutase/sangue , Testículo/efeitos dos fármacosRESUMO
Galectins (GAL) are animal lectins that play important roles in the immune response through regulation of homeostasis and immune function. Bioactive polyphenols are able to bind and regulate galectins in inflammatory diseases. Cowpea is a nutritious and polyphenol-rich legume used as feed. The objective of the study was to evaluate the effect of cowpea polyphenol extract (CPE) on galectin gene transcription and translation in bovine peripheral blood. Blood from lactating cows (n = 10) were treated with CPE (10 µg/mL) or LPS (0.1 µg/mL), and control, to measure mRNA levels of bovine LGALS1, LGALS3, LGALS9, and some innate immune response genes. Secretion of GAL-1, GAL-3 and GAL-9 in plasma were measured using ELISAs. The mRNA expression of LGALS1, LGALS3 and LGALS9 decreased post CPE exposure. CPE decreased plasma GAL-1, but had no effect on GAL-3 and GAL-9. In addition, CPE decreased expression of TNFA, COX2 and upregulated TLR2, IL10 and IL4. LPS stimulation upregulated galectin genes expression and secretion. Overall, cowpea polyphenols modulated galectin expression, particularly GAL 1 in blood. The results provide a springboard for further studies on the use of polyphenol extracts from cowpea enriched feed supplements to target specific galectin genes for improved health and production in dairy cows.
Assuntos
Galectinas , Extratos Vegetais , Polifenóis , Vigna/química , Animais , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Bovinos , Células Cultivadas , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Feminino , Galectinas/sangue , Galectinas/genética , Galectinas/metabolismo , Expressão Gênica/efeitos dos fármacos , Extratos Vegetais/análise , Extratos Vegetais/farmacologia , Polifenóis/análise , Polifenóis/farmacologiaRESUMO
Ophiopogonin D (OPD) and Ophiopogonin D' (OPD') are two bioactive ingredients in Ophiopogon japonicus. Previously published studies have often focused on the therapeutic effects related to OPD's antioxidant capacity but underestimated the cytotoxicity-related side effects of OPD', which may result in unpredictable risks. In this study, we reported another side effect of OPD', hemolysis, and what was unexpected was that this side effect also appeared with OPD. Although hemolysis effects for saponins are familiar to researchers, the hemolytic behavior of OPD or OPD' and the interactions between these two isomers are unique. Therefore, we investigated the effects of OPD and OPD' alone or in combination on the hemolytic behavior in vitro and in vivo and adopted chemical compatibility and proteomics methods to explain the potential mechanism. Meanwhile, to explain the drug-drug interactions (DDIs), molecular modeling was applied to explore the possible common targets. In this study, we reported that OPD' caused hemolysis both in vitro and in vivo, while OPD only caused hemolysis in vivo. We clarified the differences and DDIs in the hemolytic behavior of the two isomers. An analysis of the underlying mechanism governing this phenomenon showed that hemolysis caused by OPD or OPD' was related to the destruction of the redox balance of erythrocytes. In vivo, in addition to the redox imbalance, the proteomics data demonstrated that lipid metabolic disorders and mitochondrial energy metabolism are extensively involved by hemolysis. We provided a comprehensive description of the hemolysis of two isomers in Ophiopogon japonicus, and risk warnings related to hemolysis were presented. Our research also provided a positive reference for the development and further research of such bioactive components.
Assuntos
Hemólise/efeitos dos fármacos , Ophiopogon/química , Saponinas/farmacologia , Espirostanos/farmacologia , Animais , Antioxidantes/efeitos adversos , Antioxidantes/química , Antioxidantes/isolamento & purificação , Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Isomerismo , Masculino , Camundongos , Oxirredução/efeitos dos fármacos , Proteoma/efeitos dos fármacos , Proteoma/metabolismo , Coelhos , Ratos , Ratos Wistar , Medição de Risco , Saponinas/efeitos adversos , Saponinas/química , Saponinas/isolamento & purificação , Espirostanos/efeitos adversos , Espirostanos/química , Espirostanos/isolamento & purificação , Testes de Toxicidade AgudaRESUMO
The present study was performed to determine the acaricidal activity of the cottonseed oil (CSO) against cattle tick Rhipicephalus microplus. CSO was analyzed using Gas Chromatograph with high-resolution Mass Spectrometer (GC-HRMS) to identify the presence of active compounds. In vitro bioassays were performed using larval packet test (LPT) and adult immersion test (AIT) by taking different concentrations of CSO (i.e. 0.1, 0.5, 1.5, 2.5, 5, 7.5, 10 and 12.5%). In vivo acaricidal activity of CSO was evaluated by its topical application on red Sahiwal calves for 144 h. Clinical safety of CSO was evaluated by performing skin irritancy test and examination of hematological profile of calves'. GC-HRMS analysis of CSO revealed the presence of many fatty acids including oleic acid, lauric acid, palmitic acid, stearic acid and other components. Results exhibited that all the concentrations of CSO were effective in reducing the number of ticks and their growth. However, CSO at concentrations of 10% (CSO7) and 12.5% (CSO8) exhibited 100% mortality of R. microplus larvae and adults in LPT and AIT, respectively. In vivo acaricidal assay revealed that CSO7 and CSO8 shown 85% and 89% inhibition of ticks, respectively on calves after 144 h as compared to the control group. CSO was clinically safe on calves' skin with mild erythema up to 20 min. Hematological profile of calves revealed no sign of toxicity after treatment with CSO. Thus, CSO can be used as an alternative and safe drug therapy against R. microplus.
Assuntos
Acaricidas/administração & dosagem , Doenças dos Bovinos/prevenção & controle , Óleo de Sementes de Algodão/administração & dosagem , Rhipicephalus/efeitos dos fármacos , Infestações por Carrapato/veterinária , Acaricidas/química , Acaricidas/uso terapêutico , Administração Tópica , Análise de Variância , Animais , Bioensaio/veterinária , Contagem de Células Sanguíneas/veterinária , Células Sanguíneas/efeitos dos fármacos , Bovinos , Doenças dos Bovinos/parasitologia , Óleo de Sementes de Algodão/química , Óleo de Sementes de Algodão/uso terapêutico , Relação Dose-Resposta a Droga , Ácidos Graxos/análise , Feminino , Cromatografia Gasosa-Espectrometria de Massas/veterinária , Testes Hematológicos/veterinária , Inseticidas/administração & dosagem , Inseticidas/farmacologia , Larva/efeitos dos fármacos , Nitrilas/administração & dosagem , Nitrilas/farmacologia , Piretrinas/administração & dosagem , Piretrinas/farmacologia , Infestações por Carrapato/parasitologia , Infestações por Carrapato/prevenção & controleRESUMO
Nutritional improvements in intensive aquaculture production systems is necessary for the reduction of stress, maximum utilization of nutritional components, and expression of the genetic potential of fish. The objective of this study was to evaluate the hemato-immunological, and histological parameters and gut microbiota of Nile tilapia fed with the microalga Schizochytrium sp. Males of Nile tilapia were distributed among eight net cages (6 m3), and fed for 105 days with two diets: control (CON), without Schizochytrium sp., and supplemented (SUP), with 1.2% Schizochytrium sp. in the diet. The final weight, mortality, hematocrit, total erythrocyte count (RBC), hemoglobin, hematimetric indices, white blood cell count (WBC), total protein, and serum lysozyme were measured. Alterations in intestinal morphology were evaluated. The gut microbiota was evaluated with next-generation sequencing. No significant differences (p>0.05) were found in the final weight and mortality between diets. Regarding the hematological parameters, a difference (p<0.05) was detected only in RBC, with there being lower values in the SUP, although this group also showed a tendency toward having an increased mean corpuscular hemoglobin level. There were no differences (p>0.05) in total protein and serum lysozyme concentrations or in WBCs between diets, except for lymphocytes, which presented lower values (p<0.05) in the SUP, suggesting immunomodulation by the polyunsaturated fatty acids present in the microalga. There was no difference (p>0.05) in the intestinal morphology between diets. Metagenomic data indicated greater richness (represented by the Chao index) and a higher abundance of the bacterial phylum Firmicutes in the gut microbiota of the tilapia fed with the SUP diet, demonstrating that the digestion and use of the components of the microalga could influence the microbial community. The results indicated that the microalga had modulatory effects on blood cells and the intestinal microbiota, without affecting the structure and integrity of the intestinal villi.
Assuntos
Ciclídeos/microbiologia , Suplementos Nutricionais , Microalgas , Animais , Células Sanguíneas/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ciclídeos/sangue , Ciclídeos/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Intestinos/anatomia & histologia , Intestinos/efeitos dos fármacos , Intestinos/imunologia , Masculino , Microbiota/efeitos dos fármacosRESUMO
Stevia rebaudiana Bertoni a non-caloric, safe and natural sweetener has been shown pharmaceutically important in the management of blood disorders. This study was designed to investigate hematology and safety of stevia aqueous extract through animal modeling. For this purpose, fifty albino rats were categorized into 5 groups and all the groups were received aqueous stevia extract at different dosage levels (200, 300, 400 and 500 ppm/kg b. wt) for 8 weeks except control group. Hematological and toxicological analyses were conducted using standard recommended procedures. The results indicated that biochemical parameters (RBC, HB, HCT, MCV, MCH, MCHC, WBC, eosinophils, lymphocytes and neutrophils) of albino rats significantly (P<0.05) increased and PLT, MPV and monocytes levels non-significantly decreased by using aqueous extract of stevia at different levels after eight weeks of study. Furthermore, Stevia aqueous extracts had non-toxic effect on liver functioning tests. However, stevia aqueous extracts were insignificant in their impression regarding organ to body weight ratios. The stevia aqueous extract has positive effect on hematological parameters of albino rats and is toxicologically safe. Therefore it could be used as a natural remedy for the management of hematological disorders without any health hazards.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Stevia , Animais , Células Sanguíneas/metabolismo , Testes Hematológicos , Fígado/enzimologia , Testes de Função Hepática , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta , Ratos , Medição de Risco , Stevia/química , Stevia/toxicidade , Testes de ToxicidadeRESUMO
RATIONALE: Specialized pro-resolving mediators (SPM-lipoxins, resolvins, protectins, and maresins) are produced via the enzymatic conversion of essential fatty acids, including the omega-3 fatty acids docosahexaenoic acid and n-3 docosapentaenoic acid. These mediators exert potent leukocyte directed actions and control vascular inflammation. Supplementation of animals and humans with essential fatty acids, in particular omega-3 fatty acids, exerts protective actions reducing vascular and systemic inflammation. Of note, the mechanism(s) activated by these supplements in exerting their protective actions remain poorly understood. OBJECTIVE: Given that essential fatty acids are precursors in the biosynthesises of SPM, the aim of the present study was to establish the relationship between supplementation and peripheral SPM concentrations. We also investigated the relationship between changes in plasma SPM concentrations and peripheral blood platelet and leukocyte responses. METHODS AND RESULTS: Healthy volunteers were enrolled in a double-blinded, placebo-controlled, crossover study, and peripheral blood was collected at baseline, 2, 4, 6, and 24 hours post administration of placebo or one of 3 doses of an enriched marine oil supplement. Assessment of plasma SPM concentrations using lipid mediator profiling demonstrated a time- and dose-dependent increase in peripheral blood SPM concentration. Supplementation also led to a regulation of peripheral blood cell responses. Here we found a dose-dependent increase in neutrophil and monocyte phagocytosis of bacteria and a decrease in the diurnal activation of leukocytes and platelets, as measured by a reduction in adhesion molecule expression. In addition, transcriptomic analysis of peripheral blood cells demonstrated a marked change in transcript levels of immune and metabolic genes 24 hours post supplementation when compared with placebo. CONCLUSIONS: Together, these findings demonstrate that supplementation with an enriched marine oil leads to an increase in peripheral blood SPM concentrations and reprograms peripheral blood cells, indicating a role for SPM in mediating the immune-directed actions of this supplement. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT03347006.
Assuntos
Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/sangue , Ácidos Graxos Ômega-3/farmacologia , Óleos de Peixe/farmacologia , Sistema Imunitário/efeitos dos fármacos , Lipoxinas/sangue , Adulto , Biomarcadores , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Moléculas de Adesão Celular/sangue , Ritmo Circadiano/efeitos dos fármacos , Estudos Cross-Over , Relação Dose-Resposta a Droga , Método Duplo-Cego , Ácidos Graxos Essenciais/fisiologia , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Óleos de Peixe/administração & dosagem , Ontologia Genética , Humanos , Masculino , Pessoa de Meia-Idade , Fagocitose/efeitos dos fármacos , Fator de Ativação de Plaquetas/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Transcrição Gênica/efeitos dos fármacos , Adulto JovemRESUMO
Phenolic groups of steroidal or nonsteroidal estrogens can redox cycle, leading to oxidative stress, where creation of reactive oxygen species are recognized as the main mechanism of their DNA damage properties. Dry olive (Olea europaea L.) leaf extract is known to contain bioactive and antioxidative components and to have an ability to modulate the effects of various oxidants in cells. The main goal of this study was to investigate antigenotoxic potential of a standardized dry olive leaf extract on DNA damage induced by 17ß-estradiol and diethylstilbestrol in human whole blood cells in vitro, using comet assay. Our results indicated that both hormones showed a genotoxic effect at a concentration of 100 µM (P < 0.05, n = 6). Dry olive leaf extract was efficient in reducing number of cells with estrogen-induced DNA damage at tested concentrations (0.125, 0.5 and 1 mg/mL) (P < 0.05, n = 6) and under two experimental protocols, pre-treatment and post-treatment, exhibiting antigenotoxic properties. Analysis of antioxidant properties of the extract revealed moderate ABTS radical scavenging properties and reducing power. Overall, our results suggested that the protective potential of dry olive leaf extract could arise from the synergistic effect of its scavenging activity and enhancement of the cells' antioxidant capacity.
Assuntos
Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Dietilestilbestrol/antagonistas & inibidores , Estradiol/toxicidade , Antagonistas de Estrogênios/farmacologia , Sequestradores de Radicais Livres/farmacologia , Olea/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Adulto , Ensaio Cometa , Dietilestilbestrol/toxicidade , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Masculino , Oxirredução , Estresse Oxidativo , Extratos Vegetais/isolamento & purificação , Espécies Reativas de Oxigênio , Adulto JovemRESUMO
Immune Assist (IA) is produced from extract of six species of medical mushrooms: Agaricus blazei - Cordyceps sinensis - Grifola frondosa - Ganoderma lucidum - Coriolus versicolor - Lentinula edodes. The genoprotective potential of IA was evaluated for the first time. Significant antigenotoxic effects were detected in human peripheral blood cells against H2O2 induced DNA damage, in the pretreatment and in the posttreatment. The most efficient concentration of IA in pretreatment was 500⯵g/mL, while in posttreatment it was the concentration of 250⯵g/mL. Kinetics of attenuation of H2O2 induced DNA damage in posttreatment with the optimal concentration of IA showed significant decrease in the number of damaged cells at all time periods (15-60â¯min), reaching the greatest reduction after 15 and 45â¯min. Remarkable ·OH scavenging properties and moderate reducing power, together with the modest DPPH scavenging activity, could be responsible for the great attenuation of DNA damage after 15â¯min of exposure to IA, while reduction of DNA damage after 45â¯min could be the result in additional stimulation of the cell's repair machinery. Our results suggest that IA displayed antigenotoxic and antioxidant properties. A broader investigation of its profile in biological systems is needed.
Assuntos
Agaricales/química , Antioxidantes/farmacologia , Células Sanguíneas/efeitos dos fármacos , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Radicais Livres/toxicidade , Extratos Vegetais/farmacologia , Adulto , Células Sanguíneas/química , DNA/sangue , DNA/efeitos dos fármacos , Feminino , Ferricianetos/toxicidade , Humanos , Peróxido de Hidrogênio/toxicidade , Radical Hidroxila/toxicidade , Técnicas In Vitro , Oxidantes/toxicidade , Extratos Vegetais/toxicidade , Análise de Célula Única , Adulto JovemRESUMO
Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.
Assuntos
Agricultura/métodos , Cumarínicos/metabolismo , Mikania/metabolismo , Extratos Vegetais/toxicidade , Plantas Medicinais/metabolismo , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Brasil , Sobrevivência Celular/efeitos dos fármacos , Cumarínicos/toxicidade , Dano ao DNA/efeitos dos fármacos , Humanos , Mikania/química , Testes de Mutagenicidade , Agricultura Orgânica/métodos , Extratos Vegetais/análise , Extratos Vegetais/químicaRESUMO
OBJECTIVE: In vitro cell and blood compatibility of three dietary supplements, comprised of multiple plant extracts, Pneumo Go (PG), Green active (GA) and Equistasi (Eq), and their main component, the phytocomplex Matrix U.B.® (Union Bio S.r.l.) (M), were evaluated. Moreover, preliminary in vivo tests were performed on GA in order to assess its ability to reduce pain in an animal model. METHODS: Cell compatibility was determined using fibroblasts (NIH3T3) and primary adult human microvascular endothelial cells (HMVECad) and the neutral red uptake test. Blood compatibility was evaluated by analyzing blood parameters after incubation of the products with sodium citrate anticoagulated whole blood. Thrombin time was determined by adding thrombin to aliquots of human plasma containing the samples. Clotting time was revealed by an automatic coagulometer. The in vivo analgesic effect of GA was evaluated in Wistar rats using the formalin test. RESULTS: M and PG reduced the percentage of viable NIH3T3 cells, indicating their interference in the cell cycle. GA and Eq stimulated fibroblast proliferation and neutralized the toxic effect of M. M and PG reduced HMVECad cell viability. GA and Eq did not affect cell viability as well as negative control. The hemocompatibility tests indicated that all the samples did not interfere with fibrinogen. The in vivo test carried out in male rats showed a significant analgesic effect of GA in all formalin-induced pain behaviors. CONCLUSION: No hemotoxicity and good cell compatibility were found for all the tested samples. GA and Eq were the best candidates for further biocompatibility testing. Moreover, GA reduced pain in the animal model.
Assuntos
Analgésicos/farmacologia , Suplementos Nutricionais/análise , Extratos Vegetais/farmacologia , Animais , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Endoteliais/citologia , Células Endoteliais/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Camundongos , Células NIH 3T3 , Ratos , Ratos Wistar , Tempo de TrombinaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Danggui buxue Decoction (DBD) has been frequently used to treat with blood deficiency, which consisted of Danggui (DG) and Huangqi (HQ) at a ratio of 1:5. Accumulating evidence showed that blood deficiency in traditional Chinese medicine (TCM) was similar to anemia in modern medicine. AIM OF THE STUDY: The purpose of this study was to explore its therapeutic mechanism of with network pharmacology approach. MATERIALS AND METHODS: We explored the chemical compounds of DBD and used compound ADME screening to identify the potential compounds. Targets for the therapeutic actions of DBD were obtained from the PharmMapper, Swiss, SEA and STITCH. GO analysis and pathway enrichment analysis was performed using the DAVID webserver. Cytoscape was used to visualize the compound-target-pathway network for DBD. The pharmacodynamics and crucial targets were also validated. RESULTS: Thirty-six potential active components in DBD and 49 targets which the active components acted on were identified. 47 KEGG pathways which DBD acted on were also come to light. And then, according to KEGG pathway annotation analysis, only 16 pathways seemed to be related to the blood nourishing effect of DBD, such as PI3K-AKT pathway, and so on. Only 32 targets participated in these 16 pathways and they were acted on by 29 of the 36 active compounds. Whole pharmacodynamic experiments showed that DBD had significant effects to blood loss rats. Furthermore, DBD could promote the up-regulation of hematopoietic and immune related targets and the down-regulation of inflammatory related targets. Significantly, with the results of effective rate, molecular docking and experimental validation, we predicted astragaloside IV in HQ, senkyunolide A and senkyunolide K in DG might be the major contributing compounds to DBD's blood enriching effect. CONCLUSION: In this study, a systematical network pharmacology approach was built. Our results provided a basis for the future study of senkyunolide A and senkyunolide K as the blood enriching compounds in DBD. Furthermore, combined network pharmacology with validation experimental results, the nourishing blood effect of DBD might be manifested by the dual mechanism of enhancing immunity and promoting hematopoiesis.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Medicina Tradicional Chinesa/métodos , Simulação de Acoplamento Molecular , Animais , Células CACO-2 , Regulação para Baixo/efeitos dos fármacos , Humanos , Masculino , Ratos , Ratos Sprague-Dawley , Regulação para Cima/efeitos dos fármacosRESUMO
Ginsenoside compound K (CK) is not a ginsenoside that naturally exists in Panax ginseng Meyer. However, CK is a major metabolite of ginsenoside Rb1, Rb2, or Rc in the intestine under the effects of bacteria. In this study, we first investigated the effects of CK on myelosuppression in mice induced by cyclophosphamide (CTX). The respective quantities of white blood cells, blood platelets, and bone marrow nucleated cells (BMNCs) were determined to be 8.54 ± 0.91 (109/L), 850.90 ± 44.11 (109/L), and 1.45 ± 0.22 (109/L) in the CK-H group by detecting peripheral blood cells and BMNCs. CK-H and CK-L both increased the thymus index by up to 0.62 ± 0.06 (mg/g) and 0.52 ± 0.09 (mg/g), respectively, and significantly increased the yields of colony formation units-granulocyte monocyte and colony formation units-megakaryocytic. According to our study, CK could control apoptosis and promote cells to enter the normal cell cycle by the bcl-2/bax signaling pathway and MEK/ERK signaling pathway. Therefore, the BMNCs could proliferate and differentiate normally after entering the normal cell cycle. So the peripheral blood cells could show a trend of returning to normal. The recovery of peripheral blood cells resulting in the level of cytokines tended to normal. This process may be the mechanisms of CK on myelosuppression. This study provides a reference for ginseng in the treatment of myelosuppression.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Células Mieloides/efeitos dos fármacos , Mielopoese/efeitos dos fármacos , Panax/química , Animais , Apoptose/efeitos dos fármacos , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Ciclo Celular , Células Cultivadas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Células Mieloides/citologia , Baço/citologia , Baço/efeitos dos fármacos , Timo/citologia , Timo/efeitos dos fármacosRESUMO
Las plantas de uso en medicina tradicional constituyen una fuente importante de compuestos con actividad inmunomoduladora; entre ellas las especies del género Baccharis, conocidas popularmente como "Jaguareteka´a" en nuestro país, son ampliamente empleadas. En este estudio se evaluó la actividad inmunomoduladora de extractos metanólicos de tres especies del género Baccharis (B. trimera, B. notosergilay B. punctulata) sobre la proliferación de células mononucleares humanas de sangre periférica. Los extractos de las tres especies estudiadas estimularon la proliferación de las células mononucleares. Específicamente, el extracto de B. notosergila estimuló la proliferación celular a todas las concentraciones probadas (5, 10, 25 y 50 µg/mL), mientras que los extractos de B. trimera y B. punctulata mostraron este efecto a 5 y 10 µg/mL. Además, por presentar mayor inducción de la proliferación, se realizó un fraccionamiento con diferentes solventes del extracto metanólico de B. notosergila y B. punctulata. La fracción de acetato de etilo de ambos extractos vegetales aumentó la proliferación celular, sugiriendo que compuestos de polaridad media son los responsables de esta actividad. Estos resultados demuestran que los extractos de B. trimera, B. notosergila y B. punctulata poseen actividad inmunomoduladora sobre células mononucleares humanas y servirán de base a otros estudios para determinar el o los componentes activos de los extractos sobre el sistema inmune(AU)
Plants used in traditional medicine are an important source of compounds with immunomodulatory activity. Species of the genus Baccharis, popularly known as "Jaguareteka'a" in our country, are used in folk medicine for the treatment of liver, gastrointestinal, inflammatory and infectious diseases. In this study, we evaluated the immunomodulatory activity of methanolic extracts of three species of the genus Baccharis (B. trimera, B. notosergila and B. punctulata) on the proliferation of human peripheral blood mononuclear cells. Extracts of the three species studied stimulated the proliferation of mononuclear cells. The extract of B. notosergila stimulated cell proliferation at all concentrations tested, while extracts of B. trimera and B. punctulata stimulated at 5 and 10 µg/mL. In addition, we carried out a separation with different solvents of the methanolic extract of B. notosergila and B. punctulata. The ethyl acetate fraction of both plant extracts induced the proliferation of immune cells. These results show that the extracts of B. trimera, B. notosergila and B. punctulata had immunomodulatory activity on human mononuclear cells. Future work will be required to identify the components responsible for the activity on the immune system(AU)
Assuntos
Células Sanguíneas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Baccharis , Proliferação de Células/efeitos dos fármacos , Imunomodulação/efeitos dos fármacos , Plantas Medicinais , Linfócitos/efeitos dos fármacos , Sobrevivência CelularRESUMO
Eruca sativa (ES) seed oil is used in food preparation and as source of natural medication. Eruca sativa (ES) seed oil was analysed for phenolic composition using high performance liquid chromatography with diode array detection (HPLC-DAD), pigment contents, quality characteristics. The oil was fed to rabbits for two weeks. Serum biochemistry, haematological and liver histological parameters were studied. Results showed that quercetin, caffeic acid and chlorogenic acids were the major phenolic compounds. Lycopene and other pigments were present in considerable amounts. Animal studies showed that the body weight of rabbits decreases with the increase of ES oil. The level of serum glucose, total cholesterols, triglycerides and LDL-cholesterol decrease significantly, while an increase was observed in the HDL-cholesterol. The level of white blood cells including lymphocytes and mean corpuscular haemoglobin concentration increases, while a significant increase occurred in platelets count with the increase of ES seed oil dose. In the present study microscopic observations in control and the treated groups showed similar cytoarchitecture of the liver with no significant histological changes. It is concluded that Eruca sativa seed oil is a rich source of important phytochemicals with anti-obesity properties in selected animals.
Assuntos
Brassicaceae/química , Óleos de Plantas/farmacologia , Substâncias Protetoras/farmacologia , Sementes/química , Animais , Células Sanguíneas/citologia , Células Sanguíneas/efeitos dos fármacos , Glicemia/análise , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Fígado/efeitos dos fármacos , Fígado/patologia , Óleos de Plantas/isolamento & purificação , Substâncias Protetoras/isolamento & purificação , Coelhos , Triglicerídeos/sangueRESUMO
A green solvent extraction technology involving a microwave processing method was used to increase the content of minor ginsenosides from Panax notoginseng. This article aims to investigate the optimization of preparation of the minor ginsenosides by this microwave processing method using single-factor experiments and response surface methodology (RSM), and discuss the blood-enriching activity and hemostatic activity of the extract of microwave processed P. notoginseng (EMPN) The RSM for production of the minor ginsenosides was based on a three-factor and three-level Box-Behnken design. When the optimum conditions of microwave power, temperature and time were 495.03 W, 150.68 °C and 20.32 min, respectively, results predicted that the yield of total minor ginsenosides (Y9) would be 93.13%. The actual value of Y9 was very similar to the predicted value. In addition, the pharmacological results of EMPN in vivo showed that EMPN had the effect of enriching blood in N-acetylphenylhydrazine (APH) and cyclophosphamide (CTX)-induced blood deficient mice because of the increasing content of white blood cells (WBCs) and hemoglobin (HGB) in blood. Hemostatic activity in vitro of EMPN showed that it had significantly shortened the clotting time in PT testing (p < 0.05). The hemostatic effect of EMPN was mainly caused by its components of Rh4, 20(S)-Rg3 and 20(R)-Rg3. This microwave processing method is simple and suitable to mass-produce the minor ginsenosides from P. notoginseng.
Assuntos
Células Sanguíneas/efeitos dos fármacos , Ginsenosídeos/síntese química , Ginsenosídeos/farmacologia , Química Verde/métodos , Hemostáticos/farmacologia , Micro-Ondas , Panax notoginseng/química , Animais , Cromatografia Líquida de Alta Pressão/métodos , Ciclofosfamida/toxicidade , Feminino , Ginsenosídeos/química , Hemoglobinas/efeitos dos fármacos , Masculino , Camundongos , Estrutura Molecular , Fenil-Hidrazinas/toxicidade , Extratos Vegetais/química , Saponinas/química , TemperaturaRESUMO
ãGroup A streptococcus is a bacterium that resides in the throat and skin and causes respiratory infection and occasionally glomerulonephritis and rheumatic fever. Streptolysin O (SLO) produced by Streptococcus pyogenes (S. pyogenes) binds to the cell membrane, particularly to that of white and red blood cells, and is toxic to the cells and tissue. In this study, we evaluated the inhibitory activity of water-soluble polyphenols in olives (Olea europaea) against SLO-induced hemolysis. Hydroxytyrosol inhibited SLO-induced hemolytic activity, and the amount required for 50% inhibition of hemolysis was 1.30 µg. These findings suggest that the water-soluble polyphenols contained in olives have inhibitory activity against SLO-induced hemolysis.
Assuntos
Anti-Infecciosos/metabolismo , Células Sanguíneas/efeitos dos fármacos , Hemólise/efeitos dos fármacos , Álcool Feniletílico/análogos & derivados , Estreptolisinas/antagonistas & inibidores , Animais , Anti-Infecciosos/isolamento & purificação , Proteínas de Bactérias/antagonistas & inibidores , Concentração Inibidora 50 , Olea/química , Álcool Feniletílico/isolamento & purificação , Álcool Feniletílico/metabolismo , Extratos Vegetais/química , CoelhosRESUMO
BACKGROUND/AIMS: Guanidinoacetic acid (GAA) is an experimental dietary additive and has been reported to induce methyl depletion when provided by the diet. However, no study evaluated whether supplemental GAA affects DNA methylation, a critical epigenetic process for genome regulation. METHODS: In this open-label, repeated-measure interventional trial, we evaluated the impact of 12 weeks of GAA supplementation on global DNA methylation in 14 healthy participants (8 women and 6 men, age 22.2 ± 2.3 years, body mass index 24.8 ± 5.7). RESULTS: Dietary provision of GAA had no effect on global DNA methylation, with 5-methylcytosine (m5C) nonsignificantly increased by 13.4% at postadministration when averaged across participants (95% confidence interval -5.5 to 32.3; p = 0.26). Notable DNA hypomethylation (corresponding to a 5% drop in m5C) was found in 3 of 14 participants at follow-up. CONCLUSION: Global DNA methylation seems to be unaltered by dietary provision of 3 g of GAA per day for 12 weeks in healthy men and women.