Bioavailability Study of an Innovative Orobuccal Formulation of Glutathione.

Alteration of the ubiquitous thiol tripeptide glutathione (GSH) is involved in oxidative stress, which plays a role in ageing; consequently, GSH is closely related to this process characterized by progressive decline in the efficiency of physiological function and increased susceptibility to disease. When circulating GSH decreases, oral administration might be considered a therapeutic benefit. Unfortunately, due to the hydrolysis of the tripeptide by intestinal γ-glutamyltransferase, dietary glutathione is not a major determinant for its increase. Aim of this work was to evaluate improvement of GSH systemic availability testing, in vitro and in vivo, an optimized orobuccal fast-slow release formulation tablet containing pure stabilized GSH. In vitro evaluation of the penetration capability of the innovative GSH-release formulation showed that GSH was well absorbed by the reconstructed oral epithelium and its absorption has features of time-dependence. In addition, in vivo results, obtained from 15 healthy volunteers, were in favor of GSH level improvement in blood showing fast (after 30 and 60 minutes) absorption through oral mucosa. In conclusion, the intake of GSH formulated through optimized orobuccal fast-slow release tablets gave positive results in raising GSH blood concentration.

Anti-inflammatory Dietary Interventions and Supplements to Improve Performance during Athletic Training.

Despite the numerous positive effects of physical exercise, some negative physiological changes occur in long-lasting heavy training with transient dysfunction of the immune system, increased inflammation, and oxidative stress. This is the case of elite athletes, who train intensively to compete at the highest levels. However, these athletes can counteract the negative effects of heavy training, reducing acute and chronic inflammations and supporting the immune system, with nutritional and supplementation countermeasures. For this purpose, macronutrient manipulation with an appropriate use of certain supplements can be considered as an intervention to reduce exercise-induced immune changes and inflammatory risk. For example, branched-chain amino acid (BCAA) supplementation may promote such immune responses in skeletal muscle. Furthermore, micronutrients play an important role in immune function; in particular, the antioxidant capacity of several dietary micronutrients (e.g., tocopherols, docosahexaenoate, and flavonoids) is very interesting to support the endogenous antioxidant defense systems of the athletes, counterbalancing the negative effects of oxidative damage due to free radicals. Some of these nutrients have potential anti-inflammatory properties as assessed by the attenuated levels of interleukin-6 (IL-6) and C-reactive protein (CRP). Key Teaching Points: Long-lasting heavy training plan and competition can lead to chronic immune suppression in athletes, increasing infection risk. Chronic exercise increases mobilization of neutrophils, decreases mobilization of lymphocytes, and decreases the absolute and relative numbers of neutrophils at rest. Nutritional deficiencies alter the immuno-system and increase infection risk. Nutrition can influence exercise-induced immune suppression. Elite athletes competing at the highest levels can benefit from nutritional and supplementation support to improve immunity and reduce acute and chronic inflammations.

Resveratrol-procyanidin blend: nutraceutical and antiaging efficacy evaluated in a placebocontrolled, double-blind study.

BACKGROUND: Skin is constantly exposed to pro-oxidant environmental stress from several sources, including air pollutants, ultraviolet solar light, and chemical oxidants. Reactive oxygen species have been implicated in age-related skin disorders. Dietary bioactive antioxidant compounds, such as polyphenols, have beneficial effects on skin health. The advantage of a nutritional administration route is that blood delivers nutraceutical bioactive compounds continuously to all skin compartments, ie, the epidermis, dermis, and subcutaneous fat. The purpose of this study was to evaluate the topical and systemic effects of a dietary supplement containing resveratrol and procyanidin on age-related alterations to the skin, the skin antioxidant pool, and systemic oxidative stress levels. METHODS: An instrumental study was performed in 50 subjects (25 treated with supplements and 25 with placebo) to identify clinical features induced by chronoaging or photoaging. Product efficacy was evaluated after 60 days of treatment in terms of in vivo and in situ skin hydration, elasticity, and skin roughness levels, systemic oxidative stress levels by plasmatic derivatives of reactive oxygen metabolites and oxyadsorbent tests, and extent of the skin antioxidant pool. RESULTS: After 60 days of treatment, values for systemic oxidative stress, plasmatic antioxidant capacity, and skin antioxidant power had increased significantly. Additionally, skin moisturization and elasticity had improved, while skin roughness and depth of wrinkles had diminished. Intensity of age spots had significantly decreased, as evidenced by improvement in the individual typological angle. CONCLUSION: Nutraceutical and pharmacological intervention with a supplement characterized by a specific blend of resveratrol and procyanidin may be a promising strategy to support treatments for the reduction of skin wrinkling, as well as reducing systemic and skin oxidative stress.

In vitro hepatoprotective and antioxidant activities of crude extract and isolated compounds from Ficus gnaphalocarpa.

The in vitro hepatoprotective effect of the methanolic extract from Ficus gnaphalocarpa (Miq.) Steud. ex A. Rich (Moraceae) on the CCl4-induced liver cell damage as well as the possible antioxidant mechanisms involved in this protective effect, were investigated. The phytochemical investigation of this methanolic extract led to the isolation of six compounds identified as: betulinic acid (1); 3-methoxyquercetin (2); catechin (3); epicatechin (4); quercetin (5); and quercitrin (6). The hepatoprotective activity of these compounds was tested in vitro against CCl4-induced damage in rat hepatoma cells. In addition, radical-scavenging activity, ß-carotene-linoleic acid model system, ferric-reducing antioxidant parameter and microsomal lipid peroxidation assays were used to measure antioxidant activity of crude extract and isolated compounds. Silymarin and trolox were used as standard references and, respectively, exhibited significant hepatoprotective and antioxidant activities. (5), (6) and (2) showed significant antioxidant and hepatoprotective activities as indicated by their ability to prevent liver cell death and lactate dehydrogenase leakage during CCl4 intoxication. These results suggest that the protective effects of crude extract of F. gnaphalocarpa against the CCl4-induced hepatotoxicity possibly involve the antioxidant effect of these compounds.

Antihepatotoxic and antioxidant activities of methanol extract and isolated compounds from Ficus chlamydocarpa.

Free radicals, in particular radical oxygen species (ROS), play an important role in the aetiology and pathogenesis of various diseases. Current research in many countries focuses on the use of local medicinal plants as a promising source of liver protective agents. This paper describes the hepatoprotective effects of the methanol extract and four isolated compounds from Ficus chlamydocarpa on CCl4-induced liver damage, as well as the possible antioxidant mechanisms involved in this protection. The DPPH test, along with the beta-Carotene-Linoleic Acid Model System and Ferric-Reducing Antioxidant Power assays, as well as the inhibition of microsomal lipid peroxidation were used to measure radical-scavenging and antioxidant activities. Pretreatment of rats with the methanol extract of F. chlamydocarpa before CCl4 administration, significantly prevented serum increase of hepatic enzyme markers, glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT), in a dose-dependent manner. The hepatoprotection was also associated with a significant enhancement in hepatic reduced glutathione (GSH) and a marked decrease of liver malondialdehyde (MDA). Among the four compounds 1-4, isolated from the methanol extract, alpha-amyrin acetate (1) and luteolin (4) showed a significant hepatoprotective activity, as indicated by their ability to prevent liver cell death and lactate dehydrogenase (LDH) leakage during CCl4 intoxication.

Human skeletal muscle aging and the oxidative system: cellular events.

As we age, the aerobic and functional capacities of our major physiological systems progressively decline. In the case of the neuromuscular system, reductions in strength and mobility cause a deterioration in motor performance and in turn a greater tendency to fall (with increased risk of fractures), impaired mobility, disability and loss of independence in the elderly. Given the increase in our life expectancy and the consequent growth in the elderly population, these conditions will have an increasing impact on modern healthcare systems, and their prevention and attenuation needs to be addressed. Several intervention strategies have been used to improve motor performance among the aging. At the cellular level, aging is caused by a progressive decline in mitochondrial function that results in the accumulation of reactive oxygen species (ROS) generated by the addition of a single electron to the oxygen molecule As the level of oxidative stress in skeletal muscle increases with age, the production of some antioxidant enzymes increases adaptively to compensate in part. The aging process is characterized by an imbalance between an increase in the production of reactive oxygen species in the organism and the antioxidant defences as a whole. The goal of this review is to examine the results of existing studies on oxidative stress in aging human skeletal muscles, taking into account different physiological factors (sex, fiber composition, muscle type and function).

Human muscle aging: ROS-mediated alterations in rectus abdominis and vastus lateralis muscles.

Aging is related to the accumulation of reactive oxygen species (ROS)-mediated oxidative damage. Considering the heterogeneity of age-related changes and the involvement of muscles in different functions, we compared the aging process in different functional muscles. We studied age-related changes in rectus abdominis (RA) and vastus lateralis (VL) in subjects of different age (18-48- and 66-90-year-old). We analysed fiber distribution, antioxidant enzymatic systems: Mn and CuZn superoxide dismutase (MnSOD, CuZnSOD), glutathione peroxidase (GSHPx), catalase (CAT), as well as oxidative damage markers: lipoperoxide levels (LPO), carbonylated proteins (CP), reduced and oxidized glutathione (GSH, GSSG) content and the GSH/GSSG ratio. In the muscles analysed, type I fiber increases during aging with a consequent decrease in type II distribution. In the elderly group RA MnSOD showed higher activity than VL. Furthermore, in RA MnSOD was higher in the elder group than in the younger group. CuZnSOD, as well as GSHPx and CAT activities remained unchanged. LPO levels in VL increase with age; moreover, in the elderly group VL showed higher value than RA. CP, GSH and GSSG remained unchanged, while GSH/GSSG decreases in RA during aging. In conclusion, a relationship between aging and ROS seems to exist, but oxidative processes could evolve in different ways in muscles with different functions.

Antioxidant pathways in human aged skeletal muscle: relationship with the distribution of type II fibers.

Type II fiber loss and reactive oxygen species (ROS)-induced damage are hallmarks of muscle aging. The aim of this study was to analyze whether there exists a relationship between age-dependent changes in cellular antioxidant capacity and type II fiber loss in aged human skeletal muscles. Forty-five male and female subjects ranging in age from 65 to 90 year-old were divided into +40 and -40% type II fiber groups. We measured both total and Mn superoxide dismutase (total and MnSOD), glutathione peroxidase (GSHPx) and catalase (CAT) activities. We also measured the reduced and oxidized forms of glutathione (GSH and GSSG) and lipid peroxide (LPO) levels. Total SOD activity was lower in the -40% type II fiber group than in the +40% group; MnSOD tended to be lower but data are not statistically consistent. Both GSHPx and CAT activities remained unchanged; as did GSH, GSSG and GSH/GSSG ratio. Finally, muscle samples with -40% type II fibers had a significantly higher LPO content compared to those with +40% type II fibers. In summary, a relationship between human skeletal muscle aging, type II fiber loss and ROS reactions seems to exist.