RESUMO
Breast cancer (BC) is the second most common cause of brain metastasis onset in patients, with the cerebellum accounting for the 33% of cases. In the current study, using a 4T1 triple-negative mouse BC model, we revealed that an orally administered medicinal mushrooms (MM) blend, rich in ß-glucans, played a direct and specific anti-cancer action on cerebellar metastases, also bettering locomotor performances. The neuroprotective effect of the MM blend plays through (i) a direct and specific inhibition of cerebellar metastatization pattern typical of TNBC (with an induced reduction of about 50% of metastases density) and (ii) the regulation of apoptosis and proliferation-related genes, as suggested by expression changes of specific molecular markers, i.e. PCNA, p53, Bcl2, BAX, CASP9, CASP3, Hsp70 and AIF. Therefore, inhibiting the metastatization process, triggering a significant apoptosis increase, and lessening cell proliferation, this MM supplement, employed as adjuvant treatment in association with conventional therapy, could represent a promising approach, in the field of Integrative Oncology, for patients' management in both prevention and treatment of brain metastases from BC.
Assuntos
Agaricales , Neoplasias Encefálicas , Neoplasias de Mama Triplo Negativas , Humanos , Animais , Camundongos , Neoplasias de Mama Triplo Negativas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Encefálicas/secundário , ApoptoseRESUMO
Phenotypic frailty is characterized by a progressive decline in physical functioning. During ageing, morphological and functional alterations involve the brain, and chief theories involve oxidative stress, free radical accumulation, and reduced antioxidant defenses as the most implicated mechanisms. From boosting the immune system to fighting senescence, medicinal mushrooms have been found to have a number of health and longevity benefits. Among them, Hericium erinaceus (He) has been demonstrated to display a variety of physiological effects, including anti-aging properties. Thus, He represents an attractive natural source for developing novel medicines and functional foods, based on the identification of its active ingredients and metabolites. Particularly, H. erinaceus primordium (He2) extract contains a high amount of Ergothioneine (ERGO), the longevity vitamin. Herein, we revealed the preventive effect of ERGO-rich He2 extract in a preclinical model, focusing on locomotor decline during ageing monitored through spontaneous behavioral test. This effect was accompanied by a significant decrease in some oxidative stress markers (NOS2, COX2) paralleled by an increase in P53, showed in cerebellar cortex cells and fibres by immunohistochemistry. In summary, we demonstrated the neuro-protective and preventive effects of He2 extract during aging, probably due to its peculiarly high ERGO content.
Assuntos
Ergotioneína , Longevidade , Ergotioneína/farmacologia , Hericium , Vitaminas/farmacologiaRESUMO
Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.