RESUMO
Human breast cancer cell lines MCF-7 (ER-positive) and Hs578T (ER-negative) were cultured and one lot incubated for 48 h with 5-50 mug/ml of a fermented phytocompound (MK: Manda-Koso, Innoshima, Japan). In vitro, it appeared a dose-dependent decrease of cell viability (5-57%) in MK group in both cell lines (P < 0.001, plateau: 30 microg/ml), decreased beta-galactosidase activity, enhanced apoptosis, and inversely increased Bax/Bcl2 ratio (P < 0.01) with an upregulation of p53 (P < 0.05). In the in vivo model, Balb-c mice were inoculated with tumor cells and the treatment group was fed with 20 mg of MK. Tumor weight in MK-fed group was time-course reduced by 22% to 51% at 2 and 4 weeks, respectively (P < 0.05) with increased survival (P < 0.05). Tumour tissue of MK-fed mice showed a downregulated Bcl-2 with increased Bax/Bcl-2 ratio, reduced PCNA, and activated caspase 3. Although more studies are ongoing to foster the clinical applicability of MK integrated within a rational chemopreventive and therapeutic strategy, a p53-mediated mechanism is likely to play a relevant role, besides its reported antioxidant capacity, NK cell activity enhancement, cancer-cytostatic activity properties.
Assuntos
Neoplasias da Mama/patologia , Divisão Celular/efeitos dos fármacos , Suplementos Nutricionais , Fermentação , Animais , Apoptose/efeitos dos fármacos , Neoplasias da Mama/enzimologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citometria de Fluxo , Humanos , Técnicas In Vitro , Camundongos , Camundongos Endogâmicos BALB C , beta-Galactosidase/metabolismoRESUMO
The aging process is paralleled by two- to fourfold increases in plasma/serum levels of inflammatory mediators, such as cytokines and acute-phase proteins. In this study we assessed the inflammatory profile and polymorphism of healthy elderly subjects and the influence of a nutraceutical supplement. Forty elderly, generally healthy subjects were recruited, divided into two matched groups, and given either a fermented papaya preparation 9 g/day by mouth or the same amount of placebo. Treatments were carried out in a cross-over manner with a 3-month supplementation period followed by a 6-week washout period between treatments. Ten healthy young subjects served as controls. Interleukin-6 (IL-6) promoter -174 G/C polymorphism genotype was determined together with blood levels for redox status, proinflammatory cytokines, high sensitivity C-reactive protein, and serum 70 kDa heat shock protein (Hsp70) concentrations. Tumor necrosis factor-alpha and IL-6 were higher in elderly subjects (P < 0.05 versus young controls). The concentration of Hsp70 inversely correlated with markers of inflammation in -174 G/C-negative subjects (r = 0.62, P < 0.05). Nutraceutical intervention normalized the inflammatory parameters (P < 0.05) with a rise of Hsp70 (P < 0.05). This suggests that healthy elderly individuals may have a proinflammatory profile playing as a downregulating factor for inducible Hsp70, particularly if -174 G/C-negative. A nutraceutical intervention seems able to beneficially modulate such a phenomenon.
Assuntos
Envelhecimento/sangue , Envelhecimento/genética , Carica , Interleucina-6/sangue , Interleucina-6/genética , Preparações de Plantas/administração & dosagem , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas/genética , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/efeitos dos fármacos , Proteína C-Reativa/análise , Proteína C-Reativa/genética , Carica/química , Estudos Cross-Over , Proteínas de Choque Térmico HSP70/sangue , Proteínas de Choque Térmico HSP70/genética , Humanos , Mediadores da Inflamação/sangue , Masculino , Oxirredução/efeitos dos fármacos , Preparações de Plantas/química , Distribuição Aleatória , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/genéticaRESUMO
T-maze test-selected prematurely senescent mice (PSM) were allocated into two groups: (A) those given DTS (150 mg/kg) orally for 30 days and (B) untreated PSM with age-matched fast T-maze performers as control. After sacrifice, the liver and kidney were analyzed for catalase (CAT) activity, glutathione peroxidase (GPx), superoxide dismutase (SOD), malondyaldehyde (MDA), and plasma thiols. Untreated PSM showed decreased plasma thiols and tissue level of CAT, SOD, GPx, with higher MDA (P < 0.01 vs. fast performers), while DTS (Denshichi-Tochiu-Sen) significantly improved glutathione and cysteine (P < 0.05) and tissue concentration of the above parameters (P < 0.05). Such preliminary data suggest that DTS mitigated oxidative damage in PSM, with likely action on the cytoplasm and mitochondrial matrix.
Assuntos
Envelhecimento/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Sulfonamidas/farmacologia , Tiadiazóis/farmacologia , Animais , Catalase/sangue , Glutationa Peroxidase/sangue , Glutationa Redutase/sangue , Rim/irrigação sanguínea , Rim/enzimologia , Rim/metabolismo , Fígado/irrigação sanguínea , Fígado/enzimologia , Fígado/metabolismo , Malondialdeído/análise , Camundongos , Camundongos Endogâmicos BALB C , Oxirredução , Estresse Oxidativo , Fitoterapia , Distribuição Aleatória , Superóxido Dismutase/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/análiseRESUMO
Twenty-month-old Swiss mice were allocated into three groups: (A) control; (B) infected group; and (C) infected but treated with 5 mg of the phytocompound MMT. Mice were infected intranasally with 30 microL of 75 HA viral units. MMT markedly blunted the nasal signs of virus infection and the febrile response. Formazan-positive cells, lung and plasma lipoperoxides, and TNF-alpha in lung tissue increased during viral infection, but improvement was seen in the MMT-treated group (P < 0.05). MMT also normalized SOD, catalase activities, and ascorbic acid and determined a significant decrease of lung but not nasal viral titer, although nasal inflammatory infiltrate dropped significantly. MMT has potential clinical applications with and has an excellent safety profile even in old animals.
Assuntos
Envelhecimento/metabolismo , Antioxidantes/administração & dosagem , Suplementos Nutricionais , Infecções por Orthomyxoviridae/dietoterapia , Administração Oral , Animais , Ácido Ascórbico/análise , Líquido da Lavagem Broncoalveolar/química , Catalase/análise , Quimiocina CCL5/análise , Modelos Animais de Doenças , Esquema de Medicação , Pulmão/enzimologia , Pulmão/metabolismo , Pulmão/virologia , Camundongos , Infecções por Orthomyxoviridae/virologia , Distribuição Aleatória , Superóxido Dismutase/análise , Resultado do Tratamento , Fator de Necrose Tumoral alfa/análise , Carga ViralRESUMO
Twelve (12) healthy elderly subjects were divided into two groups: (a) those given an antioxidant/NO-modulating fermented papaya preparation (FPP) 9 g/day for 4 weeks, and (b) a placebo group. No protein/lipid distribution in erythrocytes (RBC) membranes was noted among different ages and treatments. Higher RBC concentration of malondialdehyde and nitric oxide synthase were found in the elderly (p < 0.05 versus "young" controls), whereas superoxide dismutase was unaltered. Such abnormalities were prevented by FPP supplementation (p < 0.01). RBC and RBC ghosts showed an enhanced susceptibility to lipid peroxidation by using cumene hydroperoxide (p < 0.01 versus young) but FPP supplementation significantly protected intact RBC (p < 0.05). These preliminary data suggest that nutraceuticals with antioxidant/NO-regulating properties significantly protect from RBC oxidative damage, and are potential weapons for the aging process and chronic and degenerative diseases.
Assuntos
Envelhecimento/efeitos dos fármacos , Antioxidantes/farmacologia , Suplementos Nutricionais , Eritrócitos/metabolismo , Idoso , Envelhecimento/fisiologia , Carica , Fracionamento Celular , Membrana Eritrocítica/química , Membrana Eritrocítica/fisiologia , Humanos , Peróxido de Hidrogênio/sangue , Peroxidação de Lipídeos/fisiologia , Pessoa de Meia-Idade , Preparações de Plantas/farmacologia , alfa-Tocoferol/sangueRESUMO
Hepatocytes isolated from 20- and 4-month Wistar rats and cultured with or without alpha-linolenic acid (LNA) were then added with nutraceutical YHK or sylibin before the test with iron or copper. Overall, YHK proved to be more effective than sylibin in Fe/Cu-induced peroxidative damage on normal and LNA-loaded hepatocytes (p < 0.05). YHK exerted a significant protection against DPPH radical-scavenging activity in the "old" group (p versus sylibin) and against lipophilic generators in both age groups (p < 0.05 versus sylibin). Both compounds were ineffective on age-related increase of surface-charge density. These preliminary data suggest that age per se enhances the vulnerability of hepatocytes to xenobiotics, whereas some safe nutraceuticals seem to exert significant protective effects.
Assuntos
Suplementos Nutricionais , Fígado/efeitos dos fármacos , Extratos Vegetais/farmacologia , Xenobióticos/farmacologia , Animais , Células Cultivadas , Hepatócitos , Peroxidação de Lipídeos , Lisossomos/metabolismo , Masculino , Estresse Oxidativo , Ratos , Ratos Wistar , Soroalbumina Bovina , Ácido alfa-LinolênicoRESUMO
Ovariectomized Wistar rats received orally 15 mg/kg of a phytoestrogen compound (genistein, daidzein, glycitein, black cohosh, angelica sin., licorice, vitex agnus) for 2 weeks to test its ability to modulate inflammatory microglia response. Microglial proliferation was tested by trypan blue and by absorbance. Serial supernatant sampling was performed for 24 h to check TNF-alpha, IL-beta, IL-6, and TGF-beta. LPS caused a time course increase of all cytokines, with IL-beta and TNF-alpha peaking at the 12th hour, whereas IL-6 and TGF-beta peaked at the 24 h observation. Rats fed with the phytoestrogen displayed a significantly lower level of proinflammatory cytokines and a higher level of TGF-beta, as shown also by Western blot analysis. This finding may offer promise in the field of nutraceutical intervention.