Alzheimer’s disease (AD) is the most common form of dementia characterized by progressive loss of cognitive functions due to neuronal death mainly in the hippocampal and cortical brain. Sulforaphene (SF) is one of the main isothiocyanates isolated from a Chinese herb Raphani Semen. In this study, we aimed to investigate the neuroprotective effects of SF usingin vitroandin vivomodels of AD. Streptozotocin (STZ) was intracranially injected into the rats; then, SF (25 and 50 mg/kg) was given orally once a day for 6 consecutive weeks. After drug treatment, the cognitive functions were assessed using the Morris Water Maze Test (MWMT). After the MWMT, the rats were euthanized and brain tissues were collected. In thein vitrotest, BV-2 microglia were pretreated with SF (1 and 2 μM) for 1 h and then stimulated with lipopolysaccharide (LPS) for another 23 h. Both molecular and histological methods were used to unravel the action mechanisms and elucidate the signaling pathway. The MWMT results showed that SF treatment significantly improved the STZ-induced cognitive deficits in rats. SF treatment markedly suppressed the production of tumor necrosis factor-α(TNF-α) and interleukin-6 (IL-6) but increased the release of IL-10 in the STZ-treated rats. In addition, SF significantly inhibited the phosphorylation of tau protein at Thr205, Ser396, and Ser404 sites, while enhancing the ratios of p-Akt (Ser473)/Akt and p-GSK-3β(Ser9)/GSK-3βin the hippocampus of the STZ-treated rats. On the other hand, SF (1 and 2 μM) treatment also markedly attenuated the cytotoxicity induced by LPS in BV-2 cells. In addition, SF treatment obviously suppressed the releases of nitric oxide (NO), TNF-α, and IL-6 in the LPS-stimulated BV-2 cells. Moreover, SF treatment significantly mitigated the nuclear translocation of p-NF-κB p65 and the ratio of p-GSK-3β(Ser9)/GSK-3βin LPS-stimulated BV-2 cells. Taken together, SF possessed neuroprotective effects against the STZ-induced cognitive deficits in rats and LPS-induced neuroinflammation in BV-2 cells via modulation of the PI3K/Akt/GSK-3βpathway and inhibition of the NF-κB activation, suggesting that SF is a promising neuroprotective agent worthy of further development into AD treatment.

Pogostemonis Herba has long been used in traditional Chinese medicine for the treatment of inflammation-related disorders. Patchouli alcohol (PA) isolated from Pogostemonis Herba is a tricyclic sesquiterpene that is known to exert a variety of pharmacological activities. The present study aimed to investigate the anti-inflammatory effect of PA on lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Pre-treatment with PA at concentrations of 10, 20 or 40 µM dose-dependently decreased the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, nitric oxide (NO) and prostaglandin E2 in LPS-stimulated RAW264.7 cells. In addition, PA treatment also reversed the increased mRNA expression of TNF-α, IL-1β, IL-6, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 caused by LPS in RAW264.7 cells. These results indicate that PA is an important anti-inflammatory constituent of Pogostemonis Herba and that its anti-inflammatory effect may be mediated, at least in part, by down-regulation of the mRNA expression of a panel of inflammatory mediators, such as TNF-α, IL-1β, IL-6, iNOS and COX-2.