RESUMO
The prevalence and socioeconomic impact of metabolic diseases is rapidly growing. The limited availability of effective and affordable treatments has fuelled interest in the therapeutic potential of natural compounds as they occur in selected food sources. These compounds might help to better manage the current problems of treatment availability, affordability, and adverse effects that, in combination, limit treatment duration and efficacy at present. Specifically, berries garnered interest given a strong epidemiological link between their consumption and improved metabolic functions, making the analysis of their phytochemical composition and the identification and characterization of biologically active ingredients an emerging area of research. In this regard, the present review focuses on the South American maqui berry Aristotelia chilensis, which has been extensively used by the indigenous Mapuche population for generations to treat a variety of disease conditions. An overview of the maqui plant composition precedes a review of pre-clinical and clinical studies that investigated the effects of maqui berries and their major components on metabolic homeostasis. The final part of the review highlights possible technologies to conserve maqui berry structural and functional integrity during passage through the small intestine, ultimately aiming to augment their systemic and luminal bioavailability and biological effects. The integration of the various aspects discussed herein can assist in the development of effective maqui-based therapies to benefit the growing population of metabolically compromised patients.
Assuntos
Frutas , Homeostase , Frutas/química , Frutas/metabolismo , Humanos , Animais , Elaeocarpaceae/química , Extratos Vegetais/farmacologiaRESUMO
BACKGROUND: In male mice, a circadian rhythm in myogenic reactivity influences the extent of brain injury following subarachnoid haemorrhage (SAH). We hypothesized that female mice have a different cerebrovascular phenotype and consequently, a distinct SAH-induced injury phenotype. METHODS: SAH was modelled by pre-chiasmatic blood injection. Olfactory cerebral resistance arteries were functionally assessed by pressure myography; these functional assessments were related to brain histology and neurobehavioral assessments. Cystic fibrosis transmembrane conductance regulator (CFTR) expression was assessed by PCR and Western blot. We compared non-ovariectomized and ovariectomized mice. FINDINGS: Cerebrovascular myogenic reactivity is not rhythmic in females and no diurnal differences in SAH-induced injury are observed; ovariectomy does not unmask a rhythmic phenotype for any endpoint. CFTR expression is rhythmic, with similar expression levels compared to male mice. CFTR inhibition studies, however, indicate that CFTR activity is lower in female arteries. Pharmacologically increasing CFTR expression in vivo (3 mg/kg lumacaftor for 2 days) reduces myogenic tone at Zeitgeber time 11, but not Zeitgeber time 23. Myogenic tone is not markedly augmented following SAH in female mice and lumacaftor loses its ability to reduce myogenic tone; nevertheless, lumacaftor confers at least some injury benefit in females with SAH. INTERPRETATION: Female mice possess a distinct cerebrovascular phenotype compared to males, putatively due to functional differences in CFTR regulation. This sex difference eliminates the CFTR-dependent cerebrovascular effects of SAH and may alter the therapeutic efficacy of lumacaftor compared to males. FUNDING: Brain Aneurysm Foundation, Heart and Stroke Foundation and Ted Rogers Centre for Heart Research.