A Comprehensive Assessment of Apigenin as an Antiproliferative, Proapoptotic, Antiangiogenic and Immunomodulatory Phytocompound.

Apigenin (4',5,7-trihydroxyflavone) (Api) is an important component of the human diet, being distributed in a wide number of fruits, vegetables and herbs with the most important sources being represented by chamomile, celery, celeriac and parsley. This study was designed for a comprehensive evaluation of Api as an antiproliferative, proapoptotic, antiangiogenic and immunomodulatory phytocompound. In the set experimental conditions, Api presents antiproliferative activity against the A375 human melanoma cell line, a G2/M arrest of the cell cycle and cytotoxic events as revealed by the lactate dehydrogenase release. Caspase 3 activity was inversely proportional to the Api tested doses, namely 30 µM and 60 µM. Phenomena of early apoptosis, late apoptosis and necrosis following incubation with Api were detected by Annexin V-PI double staining. The flavone interfered with the mitochondrial respiration by modulating both glycolytic and mitochondrial pathways for ATP production. The metabolic activity of human dendritic cells (DCs) under LPS-activation was clearly attenuated by stimulation with high concentrations of Api. Il-6 and IL-10 secretion was almost completely blocked while TNF alpha secretion was reduced by about 60%. Api elicited antiangiogenic properties in a dose-dependent manner. Both concentrations of Api influenced tumour cell growth and migration, inducing a limited tumour area inside the application ring, associated with a low number of capillaries.

Botanical Therapeutics: Phytochemical Screening and Biological Assessment of Chamomile, Parsley and Celery Extracts against A375 Human Melanoma and Dendritic Cells.

Chamomile, parsley, and celery represent major botanical sources of apigenin, a well-known flavone with chemopreventive properties. The aim of this study was to assess the phytochemical composition, antioxidant, and anti-inflammatory potential of methanol extracts obtained from chamomile, parsley, and celery collected from Romania, as well as the biological activity against A375 human melanoma and human dendritic cells. Results have shown that all three extracts are rich in polyphenolic compounds and flavonoids, and they generate a radical scavenger capacity, iron chelation potential, as well as lipoxygenase inhibition capacity. Chamomile and celery extracts present weak antiproliferative and pro-apoptotic properties in the set experimental conditions, while parsley extract draws out significant pro-apoptotic potential against A375 human melanoma cells. Parsley and chamomile extracts affected the fibroblast-like morphology of the screened tumor cell line. On the other hand, chamomile and celery extracts abrogated the expansion of LPS-activated dendritic cells, while the metabolic activity was attenuated by stimulation with celery extract; chamomile and parsley extracts had no effect upon this parameter. Chamomile and parsley extracts incubation with naive dendritic cells did not trigger cytokine secretion (TNF-alpha, IL-6, IL-10), but celery extract stimulation significantly reduced the anti-inflammatory, cytokine IL-10.

Gender inequalities in the treatment of osteoporosis.

INTRODUCTION: Our aim was to perform both gender- and age-specific analysis regarding the utilisation of anti-osteoporotic drugs in Hungary, between 2007 and 2011, and to compare our results with other European countries. METHODS: The database of the Hungarian National Health Insurance Fund was screened for anti-osteoporotic medications, covering 100% of the Hungarian population (10 million people). ICD coding system (International Classification of Diseases) and WHO ATC/DDD methodology were used for medication screening and analysis. RESULTS: In Hungary, the total bisphosphonate use was 6.66 DDD/TID (Defined Daily Dose/1000 inhabitants/day) in 2007, and 6.22 DDD/TID in 2011; the rate of bisphosphonate combinations slightly increased from 1.60 to 2.81 DDD/TID. The total vitamin D use almost doubled (13.73 DDD/TID in 2011), while the calcium supplementation tripled (4.47 DDD/TID in 2011), and so did the strontium ranelate utilisation (0.70 DDD/TID in 2011) within the investigated time period. Denosumab consumption was marginal. Male patients were disproportionately, 10-20 times undertreated in all age groups, and treatment choice was restricted among men. Several differences were seen in our results compared to those in Baltic countries, Finland and in Norway. CONCLUSIONS: Men were significantly undertreated in all age groups, compared to women. The 10 to 20-fold difference calls attention to this unrecognised problem.

[Drug-related problems in the elderly]. / Az idoskori gyógyszeralkalmazás problémái.

The aging population in developed countries is a growing problem nowadays. The burden on healthcare is particularly high, since the prevalence of the diseases, especially chronic diseases increases with age. Prevalence of polypharmacy is common among elderly patients. While comorbidities require usage of several active agents with evidence based indication, polypharmacy increases the likelihood of interactions and adverse drug reactions, reduces patient compliance, affects quality of life and puts a significant financial burden on the patient and society. In order to reduce drug-related problems among the elderly, different lists of potentially inappropriate drugs and doses were created. One of the earliest known lists is the "Beers criteria". The use of listed drugs is risky and not recommended for elderly patients. Following foreign examples, a list was compiled and adapted to the Hungarian drug spectrum based on the main concerns and alternative therapeutic suggestions.