The study of sporadic Alzheimer’s disease etiology, now more than ever, needs an infusion of new concepts. Despite ongoing interest in Alzheimer’s disease, the basis of this entity is not yet clear. At present, the best-established and accepted “culprit” in Alzheimer’s disease pathology by most scientists is the amyloid, as the main molecular factor responsible for neurodegeneration in this disease. Abnormal upregulation of amyloid production or a disturbed clearance mechanism may lead to pathological accumulation of amyloid in brain according to the “amyloid hypothesis.” We will critically review these observations and highlight inconsistencies between the predictions of the “amyloid hypothesis” and the published data. There is still controversy over the role of amyloid in the pathological process. A question arises whether amyloid is responsible for the neurodegeneration or if it accumulates because of the neurodegeneration. Recent evidence suggests that the pathophysiology and neuropathology of Alzheimer’s disease comprises more than amyloid accumulation, tau protein pathology and finally brain atrophy with dementia. Nowadays, a handful of researchers share a newly emerged view that the ischemic episodes of brain best describe the pathogenic cascade, which eventually leads to neuronal loss, especially in hippocampus, with amyloid accumulation, tau protein pathology and irreversible dementia of Alzheimer type. The most persuasive evidences come from investigations of ischemically damaged brains of patients and from experimental ischemic brain studies that mimic Alzheimer-type dementia. This review attempts to depict what we know and do not know about the triggering factor of the Alzheimer’s disease, focusing on the possibility that the initial pathological trigger involves ischemic episodes and ischemia-induced gene dysregulation. The resulting brain ischemia dysregulates additionally expression of amyloid precursor protein and amyloid-processing enzyme genes that, in addition, ultimately compromise brain functions, leading over time to the complex alterations that characterize advanced sporadic Alzheimer’s disease. The identification of the genes involved in Alzheimer’s disease induced by ischemia will enable to further define the events leading to sporadic Alzheimer’s disease-related abnormalities. Additionally, knowledge gained from the above investigations should facilitate the elaboration of the effective treatment and/or prevention of Alzheimer’s disease.

Phenolic acid composition, antioxidant, and cytotoxic activities in leaves of four Kalanchoe (Crassulaceae) species were evaluated. Determination of phenolic acid contents were conducted by an optimized LC-ESI-MS/MS method. The results show that Kalanchoe daigremontiana Raym.-Hamet & H. Perrier (using ASE extraction) and Kalanchoe pinnata (Lam.) Pers. contain the highest amounts of phenolic acids, while Kalanchoe nyikae Engl. the lowest ones. Among phenolic acids ferulic, caffeic and protocatechuic acids were occurring in the highest quantities in the analysed species. The greatest amounts of ferulic and protocatechuic acids were found in K. daigremontiana and K. pinnata. Moreover, the antiradical and cytotoxic activities of Kalanchoe extracts were investigated. All tested extracts possessed antioxidant activity. The obtained IC50 values (μg/mL) ranged from 49.9 μg/mL to 1410 μg/mL, indicating a large variation of the activity of the analysed extracts. Cytotoxicity assays revealed dose-dependent effects in the cells lines tested. Only K. pinnata extract showed a high cytotoxicity against the H-9 human T cell line. Other extracts (K. daigremontiana, Kalanchoe milloti, K. nyikae) showed more pronounced cytotoxicity towards J45.01 cells (human acute lymphoblastic leukaemia T cells). The present study demonstrated that Kalanchoe extracts have significant antioxidant and cytotoxic effects. This suggests that these species can be used as new sources of natural antioxidants and potential anticancer compounds.

The interaction between brain ischemia and Alzheimer’s disease (AD) has been intensively investigated recently. Nevertheless, we have not yet understood the nature and mechanisms of the ischemic episodes triggering the onset of AD and how they influence its slow progression. The assumed connection between brain ischemia and the accumulation of amyloid-β (Aβ) peptide awaits to be clearly explained. In our research, we employed a rat cardiac arrest model to study the changes in gene expression of amyloid-β protein precursor (AβPP) and its cleaving enzymes, β- and γ -secretases (including presenilins) in hippocampal CA1 sector, following transient 10-min global brain ischemia. The quantitative reverse-transcriptase PCR assay demonstrated that the expression of all above genes that contribute to Aβ peptide generation was dysregulated during 30 days in postischemic hippocampal CA1 area. It suggests that studied Aβ peptide generation-related genes can be involved in AβPP metabolism, following global brain ischemia and will be useful to identify the molecular mechanisms underpinning that cerebral ischemia might be an etiological cause of AD via dysregulation of AβPP and its cleaving enzymes, β- and γ -secretases genes, and subsequently, it may increase Aβ peptide production and promote the gradual and slow development of AD neuropathology. Our data demonstrate that brain ischemia activates delayed neuronal death in hippocampus in an AβPP-dependent manner, thus defining a new and important mode of ischemic cell death.

In this study, the antioxidative and anti-inflammatory potential of crude extracts (CE), anthocyanin-rich fractions (ARF), and phenolic fractions (PF) from raspberry (R) and raspberry juice (J) were evaluated. The antioxidant properties were evaluated with three complementary assays: DPPH radical scavenging activity, chelating Fe(II) power, and ferric reducing power. The highest antioxidant activity was determined for the crude extract from raspberry pulp (RCE) in the case of all methods used. The anti-inflammatory activity was demonstrated by inhibitory effect on lipoxygenase (LOX) and cyclooxygenase-2 (COX-2) activity in vitro. The highest efficiency in inhibiting the activity of both enzymes was exhibited by RCE, 0.79 and 0.59 mg FW/mL, respectively. In turn, JARF had the lowest ability to inhibit LOX (EC50 = 4.5 mg FW/mL) and JPF caused the lowest COX-2 inhibition (1.75 mg FW/mL). Additionally, we have performed a pilot study of in vitro cytotoxic activity using two human leukemia cell lines: J45 and HL60. All examined extracts inhibited the viability of J45 cells more effectively than HL60. The highest cytotoxic effect was observed in the J45.01 cell line after exposure to RCE (EC50 = 0.0375 mg FW/mL).