A novel nutraceutical formulation increases telomere length and activates telomerase activity in middle­aged rats.

Telomeres are major contributors to cell fate and aging through their involvement in cell cycle arrest and senescence. The accelerated attrition of telomeres is associated with aging­related diseases, and agents able to maintain telomere length (TL) through telomerase activation may serve as potential treatment strategies. The aim of the present study was to assess the potency of a novel telomerase activator on TL and telomerase activity in vivo. The administration of a nutraceutical formulation containing Centella asiatica extract, vitamin C, zinc and vitamin D3 in 18­month­old rats for a period of 3 months reduced the telomere shortening rate at the lower supplement dose and increased mean the TL at the higher dose, compared to pre­treatment levels. TL was determined using the Q­FISH method in peripheral blood mononuclear cells collected from the tail vein of the rats and cultured with RPMI­1640 medium. In both cases, TLs were significantly longer compared to the untreated controls (P≤0.001). In addition, telomerase activity was increased in the peripheral blood mononuclear cells of both treatment groups. On the whole, the present study demonstrates that the nutraceutical formulation can maintain or even increase TL and telomerase activity in middle­aged rats, indicating a potential role of this formula in the prevention and treatment of aging­related diseases.

Vitamin Status as Predictors in Rheumatoid Arthritis.

Musculoskeletal disorders are the leading cause of long term disability in EU with a significant impact on health care system and with increased social and economic costs. Despite of recent advances in Rheumatoid arthritis (RA) research field, here is still lacking of specific biomarkers that can be used in order to distinguish between different RA patterns and the clinical criteria are still the main tool used only for classification of diseases. Our hypothesis is that the vitamin deficiency associated with chronic inflammation can lead to a mild increase in Hcy level in blood that can act as predictor of increased risk of complication in RA patients. The aim of our study was to identify a correlation between level of Hcy in peripheral blood samples collected from RA patients and to establish if the Hcy level can be validate as potential predictive biomarker in RA patients treated with different DMARDs. Our findings suggest that Hcy level in plasma and CRP are independent predictors of chronic inflammatory status and are useful biomarkers in order to estimate the risk of complication in RA patients. To our knowledge to date, studies before had a controversial findings regarding the efficiency of folate and B12 vitamins supplements on decreasing the cardiovascular events risk. We showed that the folic acid and B12 supplements are important.

Reversal of brain aging by targeting telomerase: A nutraceutical approach.

Telomeres, the protective caps of chromosomes, shorten with age, as telomerase, the enzyme responsible for the compensation of telomere erosion, is inactive in the majority of cells. Telomere shortening and subsequent cell senescence lead to tissue aging and age­related diseases. Neurodegenerative disorders, characterized by the progressive loss of neurons among other hallmarks of aged tissue, and poor cognitive function, have been associated with a short telomere length. Thus, telomerase activity has emerged as a therapeutic target, with novel agents being under investigation. The present study aimed to examine the effects of a novel natural telomerase activator, 'Reverse™', containing Centella asiatica extract, vitamin C, zinc and vitamin D3 on the brains of 18­month­old rats. The administration of the 'Reverse™' supplement for 3 months restored telomerase reverse transcriptase (TERT) expression in the brains of rats, as revealed by ELISA and immunohistochemistry. In addition, the findings from PCR­ELISA demonstrated an enhanced telomerase activity in the cerebellum and cortex cells in the brains of rats treated with the 'Reverse™' supplement. The histopathological findings confirmed a structural reversibility effect close to the differentiation observed in the young control group of rats treated with two capsules/kg body weight of the 'Reverse™' supplement. On the whole, the findings of the present study provide a strong indication that an increased telomerase activity and TERT expression may be achieved not only in the postnatal or embryonic period, but also in the brains of middle­aged rats through nutraceutical supplementation. The use of the 'Reverse™' supplement may thus contribute to the potential alleviation of a number of central nervous system diseases.

Crosstalk between vitamin D axis, inflammation and host immunity mechanisms: A prospective study.

Tuberculosis (TB) remains a public health burden, after many years at attempts for its eradication. Vitamin D (VD) status has been suggested to be related to TB susceptibility because it has the ability to regulate multiple axes of the innate and adaptive host immune response. VD mediates cathelicidin (LL-37) synthesis, a cationic bactericidal peptide, through the expression of vitamin D receptor (VDR). Host innate defense mechanisms include autophagy and apoptosis of alveolar macrophages. The present study aimed to assess the relationship between VD status, inflammation and host defense mechanisms before and after two months of first-line anti-TB pharmacotherapy. The study included newly diagnosed individuals with pulmonary TB without co-morbidities (HIV infection, diabetes, cancer) and without VD supplementation or other therapies interfering with VD serum levels. We measured serum levels of 25-hydroxyvitamin D (25-(OH)-D), the major circulating form of vitamin D, VDR, LL-37, beclin-1 (an autophagy marker) and M30 (an apoptosis biomarker) before and after two months of anti-TB treatment. Individuals presented lower levels of 25-(OH)-D before receiving first-line anti-TB treatment (T0) in comparison with its plasmatic levels after two-months of therapy (T2). At T2, patients were divided in two subgroups according the results of sputum-culture conversion. After two-months of therapy, decreased values of LL-37, beclin-1 and M30 were observed in the culture-negative patients compared to the culture-positive patients. Control of anti-TB treatment outcome could be improved by appraisal of VD status and host defense mechanisms such as autophagy and apoptosis.

A Novel Nutraceutical Formulation Can Improve Motor Activity and Decrease the Stress Level in a Murine Model of Middle-Age Animals.

Ageing is a genetically programmed physiological process that is modulated by numerous environmental factors, associated with decreasing physiological function, decreasing reproductive rate and increasing age-related mortality rate. Maintaining mobility performance and physical function in the elderly is the main objective of the successful ageing concept. In this study, we aimed to evaluate the beneficial effect of a novel nutraceutical formulation containing Centella asiatica L. extract, vitamin C, zinc and vitamin D3 (as cholecalciferol) on motor activity and anxiety with the use of a murine model of old animals, as a means of providing proof for clinical use in the elderly, for enhancing physical strength and improving life quality. Eighteen Sprague Dawley 18 months old male rats were divided into three groups and received corn oil (the control group) or 1 capsule/kg bw Reverse supplement (treatment group 1) or 2 capsules/kg bw Reverse supplement (treatment group 2), for a period of 3 months. The Reverse supplement (Natural Doctor S.A, Athens, Greece) contains 9 mg Centella asiatica L. extract, vitamin C (200 mg as magnesium ascorbate), zinc (5 mg as zinc citrate), vitamin D3 (50 µg as cholecalciferol) per capsule. Before and after the treatment, the motor function and behavioral changes for anxiety and depression were evaluated using the open-field test, elevated plus-maze test and rotarod test. The supplementation with Reverse (Natural Doctor S.A) supplement can improve the locomotor activity in old rats in a dose-dependent manner, as demonstrated by an increase in the latency to leave from the middle square, in the number of rearings in the open field test, in the time spent in the open arms and time spent in the center in the elevated plus-maze test and the latency to all in all three consecutive trials in the rotarod test. Stress also decreased significantly in a dose-dependent manner, following the treatment with Reverse supplement, as was demonstrated by the decrease in the number of groomings at the open field test and time spent in the dark and the number of groomings at the elevated plus-maze test.

Oxidative Stress and Vitamin D as Predictors in Multiple Sclerosis.

Multiple Sclerosis (MS) is a multifactorial demyelinating diseases that affect mostly the young and active people. Here, is crucial to identify new strategies in order to slow down the diseases progression and maintain a good functional outcome. Our hypothesis was that the interconnection between anti-oxidant molecules and anti-inflammatory or neuroprotective molecules can act as predictors of diseases progression. In the study were included 36 patients with MS. Inclusion criteria were the following: patients over 18 years old were divided in three groups, 16 relapsing-remitting MS (RRMS) group, 10 secondary progressive MS (SPMS) group and 10 healthy control group. We showed that the vitamin D sufficiency did not improve de EDSS score in the later stage of diseases. Also, we showed that in the early stage (RRMS) the vitamin D status can significantly improve the EDSS and IADL score and may slow down the diseases progression. started with the early stage of diseases (RRMS) we found that catalase activity, an enzyme that act as anti-oxidant, is significantly decreased compare with healthy people, and can be associated with a low level of vitamin D. we concluded that a pro-oxidative and anti-oxidative balance is an important player in the multifactorial mechanism of MS diseases progression and additional prospective studies are needed to determine optimal vitamin D levels that lead to clinical and immunological benefits for patients with MS. Long-term follow-up studies using high-dose vitamin D supplementation are needed to confirm the preliminary results of the studies.