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1.
Drug Chem Toxicol ; 46(5): 931-943, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35950554

RESUMO

Cervical cancer ranks fourth in incidence among women worldwide. Cisplatin is currently the first-line drug of treatment for cervical cancer; however, it causes serious adverse effects. Therefore, it is crucial to explore natural products for cervical cancer treatment. Prosopis laevigata is a medicinal plant frequently used for ophthalmological and gastrointestinal infections. In this study, we used the MTT cell viability assay to evaluate the cytotoxic effect of a wood extract from Prosopis laevigata (Extract T7) in SiHa, HeLa, Ca Ski, and C-33 A cancer cell lines. Phosphatidylserine translocation and cell cycle evaluations were performed to determine the mechanism of cellular death. The extract's safety was evaluated using the Ames test with Salmonella typhimurium strains, in vivo acute toxicity assay, and repeated dose toxicity assay in mice. We also identified phenolic compounds of Extract T7 through liquid chromatography/mass spectrometry. Naringin, catechin, and eriodictyol demonstrated a higher concentration in Extract T7. Additionally, Extract T7 exhibited a cytotoxic effect against cervical cancer cells, where C-33 A was the most sensitive (IC50= 22.58 ± 1.10 µg/mL and 14.26 ± 1.11 µg/mL at 24 h and 48 h respectively). Extract T7 induced death by apoptosis and cell cycle arrest in the G2 phase in C-33 A. Extract T7 was not mutagenic. No toxicological effects were observed during acute toxicity and repeated dose toxicity for 28 days. Therefore, further evaluations of Extract T7 should be conducted to identify the complete mechanism of action for potential anti-tumoral activity and safety before conducting studies in animal models.


Assuntos
Antineoplásicos , Prosopis , Neoplasias do Colo do Útero , Humanos , Feminino , Animais , Camundongos , Neoplasias do Colo do Útero/tratamento farmacológico , Extratos Vegetais/toxicidade , Extratos Vegetais/uso terapêutico , Madeira , Antineoplásicos/farmacologia , Células HeLa , Apoptose , Linhagem Celular Tumoral
2.
Nat Prod Res ; 36(16): 4293-4309, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34459687

RESUMO

The study of medicinal plants for cancer treatment has gained attention due to an increasing incidence of cancer worldwide and antineoplastics-related undesirable secondary effects. Most of the natural products of medicinal plants that have been evaluated for cytotoxic activity, are derived from leaves, bark, roots and flowers. However, natural products derived from wood have demonstrated a cytotoxic effect with promising results. Moreover, some fractions and compounds have been isolated of wood in order to increase the effect. This review presents in vitro experimental evidence of cytotoxic effect of natural products from wood against cancer cell lines. It also provides considerations and recommendations to obtain herbal medicines over time.


Assuntos
Neoplasias , Plantas Medicinais , Madeira , Antineoplásicos/farmacologia , Linhagem Celular Tumoral/efeitos dos fármacos , Humanos , Neoplasias/tratamento farmacológico , Madeira/metabolismo
3.
Nutrients ; 13(8)2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34444736

RESUMO

Pomegranate juice (Punica granatum) has been used since ancient times in traditional medicine (Unani Medicine, Ayurveda); its main compounds are anthocyanins and ellagic acid, which have anti-inflammatory, antioxidant, hepatoprotective, and cardiovascular health effects. The objective was to evaluate the effect of pomegranate juice on inflammation, blood pressure, and vascular and physiological markers associated with obesity induced by a high-fat diet in a murine model. The results show that pomegranate juice reduces the concentration of low-density lipoprotein cholesterol (cLDL) 39% and increases the concentration of high-density lipoprotein cholesterol (cHDL) by 27%, leading to a 12%-18% decrease in the risk of cardiovascular diseases (CVD). In addition to reducing blood pressure by 24%, it also had an antiatherogenic effect by decreasing sE-selectin levels by 42%. On the other hand, the juice significantly increased adiponectin levels in adipose tissue, decreased levels of inflammation markers (tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-17A (IL-17A), interleukin-6 (IL-6), interleukin-1ß (IL-1ß)), and inhibited the monocyte chemoattractant protein-1 (MCP-1). Pomegranate juice requires clinical studies to prove its immunoregulatory and therapeutic effects on cardiovascular and atherogenic risks.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/prevenção & controle , Sucos de Frutas e Vegetais , Fatores de Risco de Doenças Cardíacas , Inflamação , Obesidade/fisiopatologia , Punica granatum , Adiponectina/metabolismo , Tecido Adiposo/imunologia , Animais , Biomarcadores/análise , Pressão Sanguínea , Doenças Cardiovasculares/etiologia , Quimiocina CCL2/antagonistas & inibidores , Citocinas/metabolismo , Dieta Hiperlipídica , Ingestão de Energia , Sucos de Frutas e Vegetais/análise , Lipídeos/sangue , Masculino , Obesidade/complicações , Ratos , Ratos Wistar
4.
Nutr Cancer ; 73(11-12): 2287-2305, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32959676

RESUMO

BACKGROUND: Echinacea spp. displays different biological activities, such as antiviral, immunomodulatory, and anticancer activities. Currently, high sales of hydroalcoholic extracts of Echinacea have been reported; hence, the importance of studies on Echinacea. AIM: To establish the effects of Echinacea angustifolia DC extract obtained with ethyl acetate (Ea-AcOEt) in breast cancer cell lines. METHODS: Cytotoxicity, cell cycle arrest, and cell death were evaluated. Besides, the safety of the extract, as well as its effect in combination with paclitaxel were investigated. RESULTS: The echinacoside and caffeic acid content in the Ea-AcOEt extract were quantified by HPLC, and its antioxidant activity was assessed. The Ea-AcOEt extract showed cytotoxic activity on breast cancer MDA-MB-231 cells (IC50 28.18 ± 1.14 µg/ml) and MCF-7 cells (19.97 ± 2.31 µg/ml). No effect was observed in normal breast MCF-10 cells. The Ea-AcOEt extract induced cell cycle arrest in the G1 phase and caspase-mediated apoptosis. No genotoxicity was found in vitro or in vivo, and the extract showed no signs of toxicity or death at 2,000 mg/kg in rodents. In vitro, the combination of Ea-AcOEt extract and paclitaxel showed a synergistic effect on both cancer cell lines. CONCLUSION: The Ea-AcOEt extract is a potential candidate for breast cancer treatment.


Assuntos
Neoplasias da Mama , Echinacea , Apoptose , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Células MCF-7 , Paclitaxel/farmacologia , Extratos Vegetais/farmacologia
5.
Int J Mol Sci ; 19(12)2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30486412

RESUMO

In this study, an ethanol extract of Agave lechuguilla was evaluated against six carcinogenic cell lines (HCT-15, MCF-7, PC-3, U-251, SK-LU-1 and K-562) with an inhibition of 75.7 ± 2.3% against the SK-LU-1 line. Based on the previous result, the extract was hydrolyzed and fractionated, to which the IC50 was determined; the cell line was more sensitive to the fractionated extract with an IC50 6.96 ± 0.15 µg/mL. Characterization by mass spectrometry showed the presence of kaempferol, quercetin and a flavonoid dimer formed by afzelechin-4ß-8-quercetin, according to the generated fragmentation pattern. The fractionated extract presented cell death by apoptosis with 39.8% at 24 h. Molecular docking was performed with the molecules found to try to describe cell death by apoptosis through death receptors such as FasCD95, TNF-R1, DR4/5 and blocking signaling on the EGFR and K-Ras MAPK/ERK pathway, as well as through the intrinsic pathway activating tBID, which promotes the amplification of the apoptotic signal due to the activation of caspase-3, and consequently caspase-7. In addition to the activation of the IIb complex associated with cell death due to necroptosis.


Assuntos
Agave/química , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Adenocarcinoma de Pulmão , Antioxidantes/química , Antioxidantes/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Ligação de Hidrogênio , Modelos Moleculares , Conformação Molecular , Estrutura Molecular , Compostos Fitoquímicos/química , Compostos Fitoquímicos/farmacologia , Relação Estrutura-Atividade
6.
Artigo em Inglês | MEDLINE | ID: mdl-30224932

RESUMO

Diabetes is one the world's most widespread diseases, affecting over 327 million people and causing about 300,000 deaths annually. Despite great advances in prevention and therapy, existing treatments for this disorder have serious side effects. Plants used in traditional medicine represent a valuable source in the search for new medicinal compounds. Hamelia patens Jacq. has been used for treating diabetes and, so far, no reports have been made on the in vivo antihyperglycemic activity of this plant. The present study on H. patens aimed to test the antihyperglycemic effect of repeated administrations of the crude and fractional methanolic extracts (CME and FME, respectively) on rats with hyperglycemia induced by streptozotocin. After 10 administrations (20 days), each extract had lowered blood glucose to a normal level. The extracts produced effects similar to metformin. Of the five compounds identified by chromatographic analysis of the extracts, epicatechin and chlorogenic acid demonstrated antihyperglycemic effect. The antioxidant activity of the extracts was evidenced by their IC50 values (51.7 and 50.7 µg/mL, respectively). The LD50≥2000 mg/Kg suggests low toxicity for both CME and FME. Thus, considering that the antihyperglycemic and antioxidant effects of metformin and extracts from H. patens were comparable, the latter may be efficacious for treating diabetes.

7.
J Ethnopharmacol ; 222: 133-147, 2018 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-29730133

RESUMO

ETHNOPHARMACOLOGICAL IMPORTANCE: Kalanchoe flammea Stapf (Crassulaceae) is a medicinal plant grown in the South of Mexico (State of Tabasco), which is commonly used in traditional medicine for the treatment of fever, wounds, inflammation, and cancer. AIM OF THE STUDY: To establish the potential of K. flammea for the treatment of prostate cancer, evaluating its cytotoxic activity, its probable mechanism of action, and carrying out some toxicological safety studies. MATERIALS AND METHODS: The cytotoxic activity of the ethyl acetate extract of K. flammea (Kf-EtOAc) was evaluated in several cell lines of prostate cancer by MTT viability assay. The cellular death mechanism was studied by evaluating the translocation of phosphatidylserine (Annexin V); overproduction of reactive oxygen species [2'-7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) assay]; release of Cytochrome C; activation of caspase-3 and -9, and regulation of Bcl-2, XIAP, and PKCε proteins by Western Blot analysis. For the evaluation of the safety of Kf-EtOAc, the Ames test, Micronucleus assay, and acute toxicity study were determined. RESULTS: Kf-EtOAc exhibited selective cytotoxic activity against prostate cell lines as follows: PC-3, LNCaP, and PrEC (IC50 = 1.36 ±â€¯0.05; 2.06 ±â€¯0.02, and 127.05 ±â€¯0.07 µg/mL, respectively). The F82-P2 fraction (rich in coumaric acid and palmitic acid) obtained by bioassay-guided fractionation of Kf-EtOAc also demonstrated selective cytotoxic activity against PC-3 cells (IC50 = 1.05 ±â€¯0.06 µg/mL). Kf-EtOAc induces apoptosis by the intrinsic pathway; this mechanism of cell death was confirmed after observing that the extract produces phosphatidylserine translocation, overproduction of reactive oxygen species, release of Cytochrome C at mitochondrial level, and activation of caspase-3 and -9. It was also observed that Kf-EtOAc produces significant downregulation of apoptosis-related proteins Bcl-2, XIAP, and PKCε and induces DNA fragmentation and cell cycle arrest. In addition, Kf-EtOAc is non-genotoxic in vitro by Ames test and non-genotoxic in vivo by Micronucleus assay, and no signs of toxicity or death were reported after the administration of a single acute exposure of 2000 mg/kg. CONCLUSION: K. flammea is a potential candidate for the development of new drugs for the treatment of prostate cancer. However, to propose their use in clinical trials, additional studies are required to understand their pharmacokinetic behavior, as well as the development of a suitable pharmaceutical form.


Assuntos
Antineoplásicos/farmacologia , Kalanchoe , Extratos Vegetais/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Masculino , Camundongos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Testes de Mutagenicidade , Neoplasias da Próstata/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Testes de Toxicidade Aguda
8.
Bioorg Med Chem Lett ; 26(16): 4086-91, 2016 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-27397496

RESUMO

Pyranocoumarins are compounds with an important pharmacological profile, such as anti-inflammatory, antioxidant, cytotoxic, antiviral, antibacterial, and hypoglycemic effects. These molecules have a widespread presence as secondary metabolites in medicinal plants used to treat Diabetes Mellitus (DM). The aim of this work was to evaluate antidiabetic activity in Streptozotocin (STZ)-induced diabetic rats and the antioxidant effects of 3',4'-Di-O-acetyl-cis-khellactone (DOAcK), as well as its toxic potential. We obtained DOAcK with an enantiomeric excess of 70% by chemical synthesis. Our results showed that this compound exerts an important antidiabetic effect: blood glucose decreased in groups treated with DOAcK by 60.9% at dose of 15mg/kg (p<0.05) compared with the diabetic control group, and demonstrated a statistically significant increase in weight gain (45.7±9.7 in the group treated with DOAcK vs. -23.0±33.1 in the group with diabetes). In a biochemical profile, DOAcK did not modify lipid metabolism and did not cause damage at the renal level. DOAcK administration increased the activities of Catalase (CAT), Glutathione Peroxidase (GPx), and Super Oxide Dismutase (SOD) to levels near those of the healthy group. Histopathological analysis exhibited morphology similar to that of the healthy group and the group treated with DOAcK. DOAcK is not mutagenic by Ames test for Salmonella typhimurium strains TA98, TA100, or TA102, and is not genotoxic by Micronucleus assay; median lethal dose (LD50) >2000mg/kg and, at this dose, no signs of toxicity or death were reported after 14days of observation. These results indicate that DOAcK can improve glucose metabolism, which may be due to the increased antioxidant activity of CAT, GPx and SOD. In addition, DOAcK is not toxic in the studies tested.


Assuntos
Antioxidantes/química , Cumarínicos/química , Hipoglicemiantes/química , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Glicemia/análise , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Cumarínicos/farmacologia , Cumarínicos/uso terapêutico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Glutationa/metabolismo , Glutationa Peroxidase/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Mutagenicidade , Estresse Oxidativo/efeitos dos fármacos , Ratos , Salmonella typhimurium/efeitos dos fármacos , Salmonella typhimurium/genética , Estreptozocina/toxicidade , Superóxido Dismutase/metabolismo
9.
Acupunct Med ; 32(6): 486-94, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25267728

RESUMO

OBJECTIVE: To investigate the antihyperglycaemic activity of laser acupuncture stimulation at 650 and 980 nm at BL20 in streptozotocin (STZ)-induced diabetic rats. METHODS: Seventy healthy adult male albino Wistar rats weighing 250±50 g were divided into seven groups of 10 animals each. Groups I-III comprised healthy control rats which were untreated (I) or stimulated with laser acupuncture at 650 nm (II) and 980 nm (III), respectively. Groups IV-VII underwent induction of diabetes with a single intraperitoneal administration of STZ at 50 mg/kg. Animals with blood glucose levels of ≥200 mg/dL on the fifth day were used for the experiments and were left untreated (group IV), treated with glibenclamide (group V) or stimulated with laser acupuncture at 650 nm (group VI) and 980 nm (group VII), respectively. Laser acupuncture was applied at BL20 on alternate days for a total of 12 sessions over a 28-day period. RESULTS: After 28 days of treatment, STZ-induced diabetic rats stimulated with laser acupuncture at 650 and 980 nm had significantly lower glucose levels compared with untreated diabetic rats (242.0±65.0 and 129.8±33.2 vs 376.5±10.0 mg/dL, both p≤0.05). Treatment at 980 nm also attenuated the increase in glucose between day 1 and day 28 compared with the glibenclamide-treated diabetic group (41.5±19.6 mg/dL vs 164.1±13.7 g/dL, p<0.05). Laser acupuncture treatment did not affect the blood count or biochemical profile and was not associated with any morphological changes in the pancreas, liver, kidney or spleen. CONCLUSIONS: Stimulation with laser acupuncture at 650 and 980 nm at BL20 in STZ-induced diabetic rats has antihyperglycaemic activity. The results support further evaluation of laser acupuncture as an alternative or complementary treatment for the control of hyperglycaemia.


Assuntos
Terapia por Acupuntura , Glicemia/metabolismo , Diabetes Mellitus Experimental/terapia , Hiperglicemia/terapia , Terapia por Acupuntura/métodos , Animais , Lasers , Masculino , Ratos Wistar
10.
J Ethnopharmacol ; 152(1): 91-8, 2014 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-24373809

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arracacia tolucensis is a medicinal plant used in northeast of Mexico as a remedy to treat people with Diabetes mellitus (DM); however, there are no scientific studies that support this information. Thus, we evaluated the anti-hyperglycemic effect of the hexane, ethyl acetate and ethanol extracts from aerial parts in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: DM was induced in Wistar male rats by single intraperitoneal injection of streptozotocin (STZ 50mg/kg). After STZ-induction, hyperglycemic rats were treated with all three extracts orally at a single dose (250 mg/kg) each 48 h for 21 days. Glibenclamide (1mg/kg) was used as a reference drug. The fasting blood glucose levels, the hematic biometry and biochemical profiles, and the inhibition of inflammatory cytokines expression were estimated. Histopathology analysis of pancreas, liver, spleen, and kidney tissue was carried out. RESULTS: Ours results showed that ethyl acetate extract decreased blood glucose levels significantly (75%, p< 0.05) when compared to diabetic rats and controlled the body weight loss; the lipids level did not change, but the enzyme levels of aspartate aminotransferase and alanine aminotransferase decreased significantly (60.83% and 66.16%, respectively, p< 0.05) and inhibited the expression of inflammatory cytokines,with respect to diabetic rats. Histopathology injury was not observed; by contrast repair of islet of Langerhans was exhibited. CONCLUSION: These results validate the use of Arracacia tolucensis as a treatment against DM and suggests it is suitable to continue studies for its safe therapeutic use.


Assuntos
Apiaceae/química , Diabetes Mellitus Experimental/tratamento farmacológico , Hipoglicemiantes/farmacologia , Extratos Vegetais/farmacologia , Animais , Glicemia/efeitos dos fármacos , Citocinas/metabolismo , Etnofarmacologia , Hipoglicemiantes/isolamento & purificação , Mediadores da Inflamação/metabolismo , Masculino , México , Componentes Aéreos da Planta , Ratos , Ratos Wistar , Solventes/química , Estreptozocina
11.
Biochem Cell Biol ; 90(3): 425-34, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22332957

RESUMO

Entamoeba histolytica is the causative agent of amoebiasis, a disease that produces dysentery as a result of the perforation of the large intestine. This parasite often invades other organs, primarily the liver, leading to an amoebic liver abscess (ALA), which can cause death. Metronidazole is the drug of choice for the treatment of ALA; however, it produces toxic side effects in patients. Lactoferrin (Lf) is a glycoprotein of the innate immune response that sequesters iron in the mucosae. Lf possesses immune-regulatory properties, such as antiinflammatory and antioxidant activities. Moreover, the microbicidal activity of apoLf, which lacks bound iron, has been shown. In this study, we evaluated the therapeutic effect of bovine Lf (bLf) against ALA in a model of hepatic amoebiasis in hamsters. Interestingly, hamsters treated intragastrically with Lf (2.5 mg/100 g mass) over a period of 8 days showed no clinical signs of disease and ALA was effectively decreased, with only 0.63% detectable lesion, compared with 63% in untreated animals. Furthermore, liver function and blood cells approached normal levels among those receiving bLf treatment. These results suggest that bLf may aid in the therapy of amoebiasis, likely without producing undesirable effects in patients.


Assuntos
Amebicidas/uso terapêutico , Entamoeba histolytica/efeitos dos fármacos , Lactoferrina/uso terapêutico , Abscesso Hepático Amebiano/tratamento farmacológico , Metronidazol/uso terapêutico , Fosfatase Alcalina/metabolismo , Amebicidas/farmacologia , Animais , Bilirrubina/metabolismo , Bovinos , Cricetinae , Avaliação Pré-Clínica de Medicamentos , Quimioterapia Combinada , Lactoferrina/farmacologia , Fígado/metabolismo , Fígado/parasitologia , Fígado/patologia , Abscesso Hepático Amebiano/parasitologia , Masculino , Mesocricetus , Metronidazol/farmacologia , Valores de Referência
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