Neuron apoptosis induced by β-amyloid (Aβ) is an important precipitating factor in the pathogenesis of Alzheimer's disease (AD). In the present study, the effects of piceatannol (PT) and pterostilbene (PS) against Aβ-induced apoptosis in PC12 cells were evaluated. PT and PS both showed observable anti-apoptosis activity. Increased cell viability, decreased apoptosis rate and declining intracellular ROS were observed after PT and PS treatment. For the signaling pathway, PT significantly promoted phosphorylation of Akt and Bad, further suppressed Bcl-2/Bax expression and inhibited cleavage of caspase-9, caspase-3 and PARP. PS promoted phosphorylation of Akt without affecting the other factors. The experimental results, for the first time, unambiguously suggested that PT showed a comprehensive protective effect against Aβ-induced apoptosis in PC12 cells via a novel PI3K/Akt/Bad signaling pathway and downstream mitochondria-mediated and caspase-dependent signaling pathway. Unlike PT, PS inhibited apoptosis against Aβ through a different PI3K/Akt signaling pathway in which the downstream targets need to be further investigated. The results also provide the basis for dietary intervention involved in the prevention and adjunctive therapy of AD.

Antioxidant activity and neuroprotective activity of three stilbenoids, namely, trans-4-hydroxystilbene (THS), trans-3,5,4′-trihydroxy-stilbene (resveratrol, RES), and trans-3′,4′,3,5-tetrahydroxy-stilbene (piceatannol, PIC), against β-amyloid (Aβ)-induced neurotoxicity in rat primary cortex neurons were evaluated. THS, RES, and PIC significantly scavenged DPPH• and •OH radicals. All three stilbenoids were able to inhibit Aβ neurotoxicity by decreasing intracellular reactive oxygen species (ROS) via the PI3K/Akt signalling pathway. Specifically, stilbenoids significantly promoted Akt phosphorylation; suppressed Bcl-2/Bax expression; and inhibited caspase-9, caspase-3, and PARP cleavage. Molecular docking between stilbenoids with Akt indicated that stilbenoids could form hydrogen bond interactions with the COOH-terminal region of Akt. Additionally, the neuroprotective activity of stilbenoids correlated with the number and position of hydroxyl groups. The lack of meta-dihydroxyl groups on THS did not affect its neuroprotective activity in comparison with RES, whereas the ortho-dihydroxyl moiety on PIC significantly enhanced neuroprotective activity. These results provide new insights into the correlation between the biological activity and chemical structure of stilbenoids.

Background and Aims: Stilbenes are an important group of phenolic substances that exist in roots, stems, leaves, skins and seeds. But little work has been performed to characterise the composition of grape root or to measure the antioxidant capacity of several stilbenes with hydroxyl radicals,1,1-diphenyl-2-picrylhydrazyl and nitric oxide free radicals. Methods and Results: Stilbenes were analysed by HPLC-MS/MS, and the radicals scavenging ability was determined by electron paramagnetic resonance. The root contained the highest concentration of stilbenes, followed by the stem and grape skin. The concentration of the following stilbenes increased in the order: piceatannol, δ-viniferin, trans-piceid, trans-resveratrol and ε-viniferin. All stilbenes had a high hydroxyl radical scavenging ability, with the scavenging rate above 50% for stilbenes at a concentration of 5 μmol/L; the same concentration of stilbenes had the lowest scavenging capacity for the nitric oxide free radicals model, with the rate below 50%. Conclusions: Five stilbenes were determined in three grape tissues. The root contained the highest concentration of stilbenes. All stilbenes had radical scavenging ability. The highest antioxidant activity was found in piceatannol. Significance of the Study: The results provide a more detailed tissue-specific profile for where these health-promoting substances can be extracted from in the grape.

A method for preparative separation and purification of trans-resveratrol, δ-viniferin, ε-viniferin and trans-vitisin B from the roots of Vitis vinifera L. cv. Cabernet Sauvignon was successfully established and is reported on in this paper. The four important stilbenes were purified by high-speed counter-current chromatography (HSCCC) with a suitable quaternary solvent system composed of chloroform-methanoln-butanol-water (4:3:0.05:2, v/v). A total of 7.1 mg ± 0.2 mg of trans-resveratrol, 1.1 mg ± 0.1 mg of δ-viniferin, 18.7 mg ± 0.5 mg of ε-viniferin, and 12.2 mg ± 0.2 mg of trans-vitisin B, with purities of 97.89%, 90.61%, 94.37% and 78.38% respectively, were obtained from 241 mg of crude sample in a one-step HSCCC separation. The chemical structures of trans-resveratrol and δ-viniferin were further confirmed with the retention time using the method of standard addition, while the structural identification of ε-viniferin and trans-vitisin B was performed with LC-ESI/MS, 1 H-NMR, and 13 C-NMR.