17β-estradiol modulates cardioprotective effects of nutraceutical compounds

Cardiovascular disease rarely manifests in pre-menopausal women meanwhile, the incidence of these pathologies dramatically increases after the menopause suggesting the possibility that sex hormones could have a key role. 17β-estradiol is the main female circulating hormone in the premenopausal period and showed protective effects on the cardiovascular system. Moreover, recent evidences underlie the importance to take into account the gender in clinical studies as it can influence the response to cardiovascular medications. Therefore, we hypothesize that sex hormones can also influence the cardioprotective effects of nutraceutical compounds, such as sulforaphane, isothiocyanate present in Brassica vegetables. This study was designed to investigate the protective effects of sulforaphane in presence of 17β-estradiol against H2O2-induced oxidative damage in cardiomyocytes. 17β-estradiol enhanced sulforaphane cardioprotection against H2O2-induced cell death with respect to 17β-estradiol or sulforaphane alone, as measured by 3-(4,5-dimethylthiazol-2-yl)-2,5diphenyl-tetrazolium bromide and lactate dehydrogenase assays. Moreover, 17β-estradiol boosted sulforaphane antioxidant activity, reducing intracellular reactive oxygen species and 8-hydroxy-2′-deoxyguanosine levels and increasing the expression of phase II enzymes. The observed effects seem to be not mediated by estrogen receptor α and β, as we used specific antagonists. Otherwise, ERK1/2 and Akt signaling pathways seem to be involved, as the treatment with specific inhibitors reduced the protective effect of sulforaphane/17β-estradiol co-treatment. Furthermore, estrogen receptor β and G protein-coupled receptor 30 seem to contribute to Akt activation, as using receptor specific agonists sulforaphane-induced Akt phosphorylation was enhanced. The activation of Akt kinase is also involved in the activation of Nrf2 transcription factor elicited by sulforaphane/17β-estradiol co-treatment, as treated cells with Akt-inhibitor, the co-treatment-induced Nrf2 activation was prevented. Our results demonstrated, for the first time, that estrogen could enhance sulforaphane protective effects, suggesting that nutraceutical efficacy might be modulated by sex hormones

Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from 'Gorilla Glue' was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-kappa B pathway. Moreover, the sesquiterpenes (E)-caryophyllene, alpha-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils' anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of alpha-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation

Agri-Food Wastes as Natural Source of Bioactive Antioxidants

Nowadays, the health of the ecosystem and quality of life are jeopardized by the growing quantities of waste that are released into the environment [...

Agri-Food Wastes as Natural Source of Bioactive Antioxidants

Nowadays, the health of the ecosystem and quality of life are jeopardized by the growing quantities of waste that are released into the environment [...

Icariin and Its Metabolites as Potential Protective Phytochemicals Against Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder affecting more than 35 million people worldwide. As the prevalence of AD is dramatically rising, there is an earnest need for the identification of effective therapies. Available drug treatments only target the symptoms and do not halt the progression of this disorder; thus, the use of natural compounds has been proposed as an alternative intervention strategy. Icariin, a prenylated flavonoid, has several therapeutic effects, including osteoporosis prevention, sexual dysfunction amelioration, immune system modulation, and improvement of cardiovascular function. Substantial studies indicate that icariin may be beneficial to AD by reducing the production of extracellular amyloid plaques and intracellular neurofibrillary tangles and inhibiting phosphodiesterase-5 activity. Moreover, increasing evidence has indicated that icariin exerts a protective role in AD also by limiting inflammation, oxidative stress and reducing potential risk factors for AD such as atherosclerosis. This mini-review discusses the multiple potential mechanisms of action of icariin on the pathobiology of AD including explanation regarding its bioavailability, metabolism and pharmacokinetic

STUDY OF THE EFFECTS OF PTEROSTILBENE ON LONGEVITY AND NEUROINFLAMMATION

Increasing experimental data suggests that the regular intake of polyphenols represents a potential way to improve the quality of life in aging. Pterostilbene is a derivative of the polyphenols resveratrol that has higher bioavailability and neuroprotective activity than resveratrol itself. The present study was carried out to investigate the anti-aging and anti-inflammatory effects of a lifelong dietary supplementation of pterostilbene in Drosophila melanogaster focusing on the expression of genes related to lifespan and senescence regulation (SIRT1; FOXO; p16; NOTCH) or to inflammatory response (DOME and Eiger1), after 2 weeks (T1) or 2 months (T2) of pterostilbene supplementation. To test the anti-neuroinflammatory effect of pterostilbene, the expression of IL1 and iNOS has been investigated by RT-PCR in BV2 microglial cells stimulated with LPS. Pterostilbene supplementation significantly increased the mean life span of both male and female fruit flies. Consistently, pterostilbene supplementation significantly increased NOTCH and SIRT1 expression in female flies at T1 and T2, whereas only at T2 in males. FOXO and p16 were up-regulated at T1 in females and at T2 in males. Eiger and DOME were reduced only in females at T1 and T2, respectively. The anti-inflammatory effect was also observed in BV-2 cells were PTS significantly reduced the up-regulation of IL1 and iNOS induced by LPS. These data confirmed the the anti-inflammatory activity of pterostilbene and suggest that it is influenced by gender.

17\u3b2-estradiol modulates sulforaphane protection against oxidative stress in cardiomyocytes

It has been shown that hormones can influence the response to cardiovascular medications in males and females, but no studies have been carried out on hormone-related response to nutraceuticals. This study investigated the protective effect of sulforaphane (SF) in the presence/absence of 17\u3b2-estradiol (E2) against oxidative stress in primary rat cardiomyocytes. Cells were treated with SF and/or E2 and oxidative stress induced by H2O2. SF and E2 co-treatment led to a higher level of protection against H2O2 and reduced intracellular ROS levels in respect to SF or E2 alone. Co-treatment increased GSH level and the expression of several antioxidant enzymes in respect to SF or E2. The co-treatment induced a higher activation of Akt and ERK1/2 signaling pathways in respect to SF and E2. Transmission electron microscopy analysis revealed that co-treatment was more effective in counteracting H2O2-induced alteration of cell organelles than E2 or SF. Our results demonstrate for the first time that estrogens could enhance SF protective effects, suggesting that nutraceutical efficacy might be different in males and females. This work was supported by Fondazione del Monte di Bologna e Ravenn