Health Benefits of Berries: Strawberries

Epidemiological studies have noted a consistent association between the consumption of diets rich in fruits and vegetables and a lower risk for chronic diseases including cancer and cardiovascular disease. There is accumulating evidence that much of the health-promoting potential of these plant foods may come from phytochemicals, bioactive compounds not designated as traditional nutrients. In strawberries, the most abundant of these are ellagic acid, and certain flavonoids: anthocyanin, catechin, quercetin and kaempferol. These compounds in strawberries have potent antioxidant power. Antioxidants help lower risk of cardiovascular events by inhibition of LDL-cholesterol oxidation, promotion of plaque stability, improved vascular endothelial function, and decreased tendency for thrombosis. Furthermore, strawberry extracts have been shown to inhibit COX enzymes in vitro, which would modulate the inflammatory process. Individual compounds in strawberries have demonstrated anticancer activity in several different experimental systems, blocking initiation of carcinogenesis, and suppressing progression and proliferation of tumors. Preliminary animal studies have indicated that diets rich in strawberries may also have the potential to provide benefits to the aging brain.

In vitro and in vivo experiments were performed on inhibition of nitrosation by strawberry, garlic, and kale extracts. Strawberry, garlic, and kale extracts inhibited nitrosation in vitro. However, garlic extract has a greater ability to inhibit the chemical nitrosation in vitro than strawberry and kale extracts. The garlic methanol-soluble fraction of the garlic extract was fractionated into G1-G4 fractions by Prep-LC. Fraction G1 inhibited N-nitrosodimethylamine (NDMA) formation by 84+/-1%. We studied the formation of the carcinogen NDMA in humans after administration of nitrate (400 mg/day) in combination with an amine-rich diet and its possible inhibition by administration of whole strawberries (300 g), garlic juice (200 g: 75 g garlic juice in drinking water), or kale juice (200 g) in 27 males and 13 females (ten healthy volunteers in each group) of age 24+/-3 years. Nitrate intake resulted in a significant rise in mean salivary nitrate and nitrite concentrations. Also, nitrate excretion in urine during the experimental day was significantly increased compared with the control days. When whole strawberries, garlic juice, or kale juice was provided immediately after an amine-rich diet with a nitrate, NDMA excretion was decreased by 70, 71, and 44%, respectively, compared with NDMA excretion after ingestion of an amine-rich diet with a nitrate. These results suggest that consumption of whole strawberries, garlic juice, or kale juice can reduce endogenous NDMA formation.

Freeze-dried fruits of two strawberry cultivars, Sweet Charlie and Carlsbad, and two blueberry cultivars, Tifblue and Premier, were sequentially extracted with hexane, 50% hexane/ethyl acetate, ethyl acetate, ethanol, and 80% acetone/water at ambient temperature. Solvents were then evaporated at 40° C. The extracts were tested against in vitro cultures of two aggressive cervical cancer cell lines (CaSki and SiHa) and two breast cancer cell lines with different requirements for estrogen (MCF-7 and T47-D). The metabolic activity of the cultures was assessed with MTS viability assay. The Ames assay for mutagenesis was used to evaluate the anticarcinogenic effects of phytochemicals with a 90% accuracy. Ethanol extracts from all four fruits strongly inhibited CaSki and SiHa cervical cancer cell lines and MCFF-7 and T47-D breast cancer cell lines. An unfractionated aqueous extract of raspberry and the ethanol extract of Premier blueberry significantly inhibited mutagenesis by both direct-acting and metabolically activated carcinogenesis.

In the present study, we examined the ability of dietary freeze-dried strawberries to inhibit N-nitrosomethylbenzylamine (NMBA)-induced tumorigenesis in the rat esophagus. Initially, we conducted a bioassay to determine the effects of dietary freeze-dried strawberries on esophageal tumor development. Two weeks prior to NMBA treatment, animals were placed on a control diet or diets containing 5 and 10% freeze-dried strawberries. NMBA treatment was once per week for 15 weeks. At 30 weeks, 5 and 10% freeze-dried strawberries in the diet caused significant reductions in esophageal tumor multiplicity of 24 and 56%, respectively. Based on these results, we conducted studies to determine potential mechanisms by which freeze-dried strawberries inhibit tumorigenesis. In a short-term bioassay, we evaluated the effects of dietary freeze-dried strawberries on the formation of O6-methylguanine in the rat esophagus. Animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries for two weeks. At the end of this period, animals received a single subcutaneous dose of NMBA and were killed 24 h later. A significant decrease in O6-methylguanine levels was observed in the esophageal DNA of animals fed strawberries, suggesting that one or more components in strawberries influence the metabolism of NMBA to DNA-damaging species. Finally, in order to evaluate post-initiation effects, we conducted a study where freeze-dried strawberries were administered in the diet only following NMBA treatment. Animals were placed on control diet and dosed with NMBA three times per week for 5 weeks. Immediately following NMBA treatment, animals were placed on control diet or diets containing 5 and 10% freeze-dried strawberries. At 25 weeks, 5 and 10% freeze-dried strawberries in the diet significantly reduced tumor multiplicity by 38 and 31%, respectively. Our data suggest that dietary freeze-dried strawberries effectively inhibit NMBA-induced tumorigenesis in the rat esophagus.

Age-related neurodegenerative conditions are the principal cause of declining cognitive and motor function during aging. Evidence support that fruits and vegetables containing generous amounts of antioxidant nutrients are important for neurological function. We investigated the effect of diets enriched with fruits or vegetables but low in vitamin E and a diet high in vitamin E on the distribution of vitamins C and E in the brain and dopamine release of Fischer 344 rat model, over an 8-month period. The low-vitamin E diet resulted in lowered alpha-tocopherol levels in brain and peripheral tissues, whereas the animals that received a diet enriched in vitamin E showed a significant increase, between 500-900%. Vitamin C concentration in plasma, heart, and liver was reduced in the vitamin E-supplemented group. It is concluded that supplementation or depletion of alpha-tocopherol for 8 months results in marked changes in vitamin E levels in brain tissue and peripheral tissues, and varied distribution of alpha-tocopherol throughout the different brain regions examined. In addition, compared to control group, rats supplemented with strawberry, spinach, or vitamin E showed a significant enhancement in striatal dopamine release. These findings suggest that other nutrients present in fruits and vegetables, in addition to the well-known antioxidants, may be important for brain function.

The free radical theory of aging predicts that reactive oxygen species are involved in the decline in function associated with aging. The present paper reports that diets supplemented with either spinach, strawberries or blueberries, nutritional sources of antioxidants, reverse age-induced declines in beta-adrenergic receptor function in cerebellar Purkinje neurons measured using electrophysiological techniques. In addition the spinach diet improved learning on a runway motor task, previously shown to be modulated by cerebellar norepinephrine. Motor learning is important for adaptation to changes in the environment and is thus critical for rehabilitation following stroke, spinal cord injury, and the onset of some neurodegenerative diseases. These data are the first to indicate that age-related deficits in motor learning and memory can be reversed with nutritional interventions.

A group of arylalkyl isothiocyanates were tested for their abilities to inhibit tumorigenicity and DNA methylation induced by the esophageal-specific carcinogen, <it>N-nitrosomethylbenzylamine (NMBA) in the F344 rat esophagus. Phenylpropyl isothiocyanate (PPITC) was more potent than either phenylethyl isothiocyanate (PEITC) or benzyl isothiocyanate (BITC). Phenylbutyl isothiocyanate (PBITC), however, had a lesser inhibitory effect on esophageal tumorigenesis, and phenylhexyl isothiocyanate (PHITC) actually enhanced esophageal tumorigenesis. Thus, the two- and three-carbon isothiocyanates were more effective inhibitors of NMBA-esophageal carcinogenesis than the longer chain isothiocyanates. The effects of the isothiocyanates on tumorigenesis were well correlated as to their effects on DNA adduct formation. The most likely mechanism of inhibition of tumorigenesis by these isothiocyanates is via inhibition of the cytochrome P450 enzymes responsible for the metabolic activation of NMBA in rat esophagus. A freeze-dried strawberry preparation was also evaluated for its ability to inhibit NMBA-esophageal tumorigenesis. It proved to be an effective inhibitor, although not as potent as either PEITC or PPITC. The inhibitory effect of the berries could not be attributed solely to the content of the chemopreventive agent, ellagic acid, in the berries.

Recent research has indicated that increased vulnerability to oxidative stress may be the major factor involved in CNS functional declines in aging and age-related neurodegenerative diseases, and that antioxidants, e.g., vitamin E, may ameliorate or prevent these declines. Present studies examined whether long-term feeding of Fischer 344 rats, beginning when the rats were 6 months of age and continuing for 8 months, with diets supplemented with a fruit or vegetable extract identified as being high in antioxidant activity, could prevent the age-related induction of receptor-mediated signal transduction deficits that might have a behavioral component. Thus, the following parameters were examined: (1) oxotremorine-enhanced striatal dopamine release (OX-K+-ERDA), (2) cerebellar beta receptor augmentation of GABA responding, (3) striatal synaptosomal 45Ca2+ clearance, (4) carbachol-stimulated GTPase activity, and (5) Morris water maze performance. The rats were given control diets or those supplemented with strawberry extracts (SE), 9.5 gm/kg dried aqueous extract (DAE), spinach (SPN 6.4 gm/kg DAE), or vitamin E (500 IU/kg). Results indicated that SPN-fed rats demonstrated the greatest retardation of age-effects on all parameters except GTPase activity, on which SE had the greatest effect, whereas SE and vitamin E showed significant but equal protection against these age-induced deficits on the other parameters. For example, OX-K+-ERDA enhancement was four times greater in the SPN group than in controls. Thus, phytochemicals present in antioxidant-rich foods such as spinach may be beneficial in retarding functional age-related CNS and cognitive behavioral deficits and, perhaps, may have some benefit in neurodegenerative disease.