Multidrug resistance (MDR) is a major obstacle in the clinical therapy of hematological malignancies. P-glycoprotein (P-gp) overexpression results in reduction of intracellular drug concentration with a consequence that the cytotoxicity of anti-tumor drugs is decreased, which leads to MDR in K562/ADR cells. In this study, we found that resveratrol enhanced the anti-proliferative activity of bestatin in K562/ADR cells. Co-treatment with resveratrol, IC50 values of bestatin in K562/ADR cells significantly decreased and activation of caspase-3 and caspase-8 increased, which indicated that resveratrol potentiated bestatin-induced apoptosis. Resveratrol increased the intracellular concentration of bestatin through inhibiting P-gp function and downregulating P-gp expression at mRNA and protein levels, which increased anti-proliferative activity of bestatin in K562/ADR cells. Resveratrol decreased the phosphorylation of Akt and mTOR but did not affect the phosphorylations of JNK or ERK1/2. These results demonstrated that resveratrol could increase the anti-proliferative activity of bestatin through downregulating P-gp expression via suppressing the PI3K/Akt/mTOR signaling pathway.

The neurovascular unit (NVU) plays an important role in maintaining the function of the central nervous system (CNS). Emerging evidence has indicated that the NVU changes function and molecules at the early stage of Alzheimer's disease (AD), which initiates multiple pathways of neurodegeneration. Cell types in the NVU have become attractive targets in the interventional treatment of AD. The NVU transportation system contains a variety of proteins involved in compound transport and neurotransmission. Brain transporters can be classified as members of the solute carrier (SLC) and ATP-binding cassette (ABC) families in the NVU. Moreover, the transporters can regulate both endogenous toxins, including amyloid-beta (Aβ) and xenobiotic homeostasis, in the brains of AD patients. Genome-wide association studies (GWAS) have identified some transporter gene variants as susceptibility loci for late-onset AD. Therefore, the present study summarizes changes in blood-brain barrier (BBB) permeability in AD, identifies the location of SLC and ABC transporters in the brain and focuses on major SLC and ABC transporters that contribute to AD pathology.

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The amyloid-beta (Aβ) hypothesis that dyshomeostasis between Aβ production and clearance is a very early, key molecular factor in the etiology of Alzheimer’s disease (AD) has been proposed and examined in the AD research field. Scientists have focused on seeking natural products or drugs to influence the dynamic equilibrium of Aβ, targeting production and clearance of Aβ. There is emerging evidence that resveratrol (Res), a naturally occurring polyphenol mainly found in grapes and red wine, acts on AD in numerous in vivo and in vitro models. Res decreases the amyloidogenic cleavage of the amyloid precursor protein (APP), enhances clearance of amyloid beta-peptides, and reduces Aβ aggregation. Moreover, Res also protects neuronal functions through its antioxidant properties. This review discusses the action of Res on Aβ production, clearance and aggregation and multiple potential mechanisms, providing evidence of the useful of Res for AD treatment.

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