RESUMO
We investigated the pharmacologic activities of four garlic preparations, raw garlic juice (RGJ), heated garlic juice (HGJ), dehydrated garlic powder (DGP) and aged garlic extract (AGE). The study used three animal models, i.e., testicular hypogonadism (hypospermatogensis and impotence) induced by warm water treatment, intoxication of acetaldehyde and growth of inoculated tumor cells. RGJ was found to be effective only in recovery of testicular function. The efficacy of HGJ was observed in three models; however, it did not improve impotence. DGP was effective in recovery of spermatogenesis and stimulated acetaldehyde detoxification. Significant beneficial effects of AGE were found in all three models. Although all four garlic preparations significantly enhanced natural killer (NK) and killer cell activities of the spleen cells of tumor-bearing mice, only AGE and HGJ inhibited the growth of inoculated tumor cells. These results suggest that different types of garlic preparations have different pharmacologic properties, and among the four garlic preparations studied, AGE could be the most useful garlic preparation.
Assuntos
Antineoplásicos/farmacologia , Manipulação de Alimentos/métodos , Alho/uso terapêutico , Hipogonadismo/tratamento farmacológico , Células Matadoras Naturais/efeitos dos fármacos , Fitoterapia , Plantas Medicinais , Testículo/efeitos dos fármacos , Acetaldeído/toxicidade , Animais , Divisão Celular/efeitos dos fármacos , Desidratação , Modelos Animais de Doenças , Temperatura Alta/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Extratos Vegetais/farmacologia , Intoxicação/prevenção & controle , Baço/efeitos dos fármacos , Baço/imunologia , Testículo/fisiologia , Células Tumorais CultivadasRESUMO
This study examined the effect of S:-allylcysteine (SAC), a major thioallyl compound found in aged garlic extract, on the memory deficit and age-related changes of senescence-accelerated mice. Senescence-accelerated prone P8 mice fed a diet supplemented with 40 mg SAC/kg diet for 8 mo had a significantly attenuated decrease in the conditioned avoidance response compared with those not given SAC. In the elevated plus-maze test using senescence-accelerated prone P10 mice, the percentage of time spent on the open arm was greater compared with the senescence-resistant control mice. Chronic dietary treatment with 40 mg SAC/kg diet decreased the time in the open arm in senescence-accelerated prone P10 mice. These studies suggest that diet supplementation with SAC may reduce age-related learning disabilities and cognitive disorders in senescence-accelerated mice.
Assuntos
Envelhecimento/efeitos dos fármacos , Cisteína/análogos & derivados , Cisteína/farmacologia , Alho/química , Transtornos da Memória/tratamento farmacológico , Plantas Medicinais , Envelhecimento/psicologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Cisteína/uso terapêutico , Alho/uso terapêutico , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Fitoterapia , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The effect of aged garlic extract (AGE) on stress induced hyperglycemia was investigated using the immobilization stress model in mice. After the exposure to immobilization stress for 16 hr per day for 2 consecutive days, the adrenal glands of the mice hypertrophied, and their serum glucose level and corticosterone secretion became elevated, but insulin secretion did not change. These results suggest that the elevation of serum glucose was probably due to the stimulation of the pituitary-adrenocortical axis by the stress. Pretreatment of AGE (5 and 10 ml/kg, p.o.) significantly prevented adrenal hypertrophy, hyperglycemia and elevation of corticosterone, but did not alter serum insulin level. The efficacy of AGE was the same as that of diazepam (5 mg/kg, p.o.). From these results, it is suggested that AGE may prevent stress-induced hyperglycemia, which is the risk of suffering from diabetes mellitus and its progression.
Assuntos
Alho , Hiperglicemia/prevenção & controle , Imobilização/efeitos adversos , Extratos Vegetais/uso terapêutico , Plantas Medicinais , Estresse Fisiológico/complicações , Glândulas Suprarrenais/patologia , Animais , Glicemia/metabolismo , Corticosterona/sangue , Modelos Animais de Doenças , Hiperglicemia/sangue , Hiperglicemia/etiologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Masculino , Camundongos , Tamanho do Órgão , Sistema Hipófise-Suprarrenal/fisiopatologia , Extratos Vegetais/farmacologiaRESUMO
Molecular genetic studies of extracellular-superoxide dismutase (EC-SOD) have shown that individuals with high serum EC-SOD content have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of this enzyme [Sandström, J. et al. (1994) J. Biol. Chem. 269, 19163-19166], which causes the impairment of its binding ability to endothelial cell surface [Adachi, T. et al. (1996) Biochem. J. 313, 235-239]. Serum EC-SOD in healthy individuals without the above mutation is heterogeneous with regard to heparin affinity and consists of five fractions, forms (I) to (V), of which (IV) and (V) are the main fractions with high affinity for heparin [Adachi, T. et al. (1995) J. Biochem. 117, 586-590], whereas the major fraction in hemodialysis patients was serum EC-SOD form (I), which is thought to be the proteolytic truncated form. On the other hand, serum EC-SOD in both healthy individuals and hemodialysis patients with the R213G mutation consisted mainly of the high heparin-affinity type. This observation suggests that the susceptibility of EC-SOD to proteinases is reduced by the R213G mutation. The affinity of normal EC-SOD (n-EC-SOD) for heparin decreased by the treatment with trypsin, accompanied by a reduction in the molecular mass. The IC50 of trypsin for the heparin affinity of R213G mutant EC-SOD (m-EC-SOD) was 0.15 microgram/ml, fivefold that for n-EC-SOD. Heparin affinity of n-EC-SOD was again more susceptible to neutrophils than that of m-EC-SOD. These results suggested that m-EC-SOD is more resistant to trypsin and neutrophil-release trypsin-like proteinases than n-EC-SOD, which causes the heparin affinity of serum EC-SOD to differ in individuals with and without the R213G mutation.
Assuntos
Mutação , Serina Endopeptidases/farmacologia , Superóxido Dismutase/efeitos dos fármacos , Tripsina/farmacologia , Animais , Arginina , Cromatografia de Afinidade , Glicina , Heparina/metabolismo , Humanos , Masculino , Peso Molecular , Neutrófilos/enzimologia , Ratos , Ratos Wistar , Diálise Renal , Inibidores de Serina Proteinase/farmacologia , Superóxido Dismutase/sangue , Superóxido Dismutase/química , Superóxido Dismutase/genética , Tosilina Clorometil Cetona/farmacologiaRESUMO
Extracellular-superoxide dismutase (EC-SOD) levels in sera divide into two discontinuous groups: a low-level group below 400 ng/ml and a high-level group above 400 ng/ml [Adachi, Nakamura, Yamada, Futenma, Kato and Hirano (1994) Clin. Chim. Acta 229, 123-131]. Molecular genetic studies have shown that the donors in the high-level group have a single base substitution generating the exchange of glycine for arginine-213 (R213G) in the heparin-binding domain of EC-SOD [Sandström, Nilsson, Karlsson and Marklund (1994) J. Biol. Chem. 269, 19163-19166; Yamada, Yamada, Adachi, Goto, Ogasawara, Futenma, Kitano, Hirano and Kato (1995) Jpn. J. Hum. Genet. 40, 177-184]. The serum EC-SOD level in homozygote subjects was significantly higher than that in heterozygotes and in normal subjects. Serum EC-SOD from heterozygotes and homozygotes had equally decreased affinity for heparin, as judged by heparin-HPLC, as compared with that from normal donors. This result suggests that the serum EC-SOD in heterozygotes was mainly composed of the mutant form which has reduced heparin affinity. On the other hand, fibroblast cells derived from heterozygote subjects generated mRNA of both normal and mutant EC-SOD (m-EC-SOD), and expressed the corresponding proteins. EC-SOD is a tetrameric enzyme, and in heterozygote donors would be heterogeneous with regard to the constitution of normal and mutant subunits. The enzyme form consisting of only mutant subunits, the form with the weakest heparin affinity, can be preferentially driven out to the plasma phase, because EC-SOD in the vasculature exists in equilibrium between plasma and the endothelial cell surface. The binding of m-EC-SOD to bovine aortic endothelial cells was about 50-fold less than that of normal EC-SOD. This result suggests that the binding of m-EC-SOD to vascular endothelial cells is much decreased in vivo, which causes a high level of serum EC-SOD.