Rg3-enriched ginseng extract ameliorates scopolamine-induced learning deficits in mice.

BACKGROUND: Ginseng (Panax ginseng C.A. Meyer) has been used as a traditional herb in the treatment of many medical disorders. Ginsenosides, which are triterpene derivatives that contain sugar moieties, are the main pharmacological ingredients in ginseng. This study was designed to investigate the effect of ginsenoside Rg3-enriched ginseng extract (Rg3GE) on scopolamine-induced memory impairment in mice. METHODS: Rg3GE (50 and 100 mg/kg) were administered to C57BL/6 mice by oral gavage for 14 days (days 1-14). Memory impairment was induced by scopolamine (1 mg/kg, intraperitoneal injection) for 6 days (days 914). The Morris water maze test was used to assess hippocampus-dependent spatial memory. The effects of scopolamine with or without Rg3GE on acetylcholinesterase and nuclear factor-κB (NF-κB) in the hippocampus were also examined. RESULTS: Mice with scopolamine treatment alone showed impairments in the acquisition and retention of spatial memory. Mice that received Rg3GE and scopolamine showed no scopolamine-induced impairment in the acquisition of spatial memory. Oral administration of Rg3GE suppressed the scopolamine-mediated increase in acetylcholinesterase activity and stimulation of the NF-κB pathway (i.e., phosphorylation of p65) in the hippocampus. CONCLUSION: These findings suggest that Rg3GE may stabilize scopolamine-induced memory deficits through the inhibition of acetylcholinesterase activity and NF-κB signaling in the hippocampus.

Cocoa phytochemicals: recent advances in molecular mechanisms on health.

Recent reports on cocoa are appealing in that a food commonly consumed for pure pleasure might also bring tangible benefits for human health. Cocoa consumption is correlated with reduced health risks of cardiovascular diseases, hypertension, atherosclerosis, and cancer, and the health-promoting effects of cocoa are mediated by cocoa-driven phytochemicals. Cocoa is rich in procyanidins, theobromine, (-)-epicatechin, catechins, and caffeine. Among the phytochemicals present in consumed cocoa, theobromine is most available in human plasma, followed by caffeine, (-)-epicatechin, catechin, and procyanidins. It has been reported that cocoa phytochemicals specifically modulate or interact with specific molecular targets linked to the pathogenesis of chronic human diseases, including cardiovascular diseases, cancer, neurodegenerative diseases, obesity, diabetes, and skin aging. This review summarizes comprehensive recent findings on the beneficial actions of cocoa-driven phytochemicals in molecular mechanisms of human health.

Kaempferol attenuates 4-hydroxynonenal-induced apoptosis in PC12 cells by directly inhibiting NADPH oxidase.

Kaempferol, a natural flavonoid isolated from various plant sources, has been identified as a potential neuroprotectant. In this study, we investigated the protective effect of kaempferol against 4-hydroxynonenal (HNE)-induced apoptosis in PC12 rat pheochromocytoma cells. Kaempferol inhibited 4-HNE-mediated apoptosis, characterized by nuclear condensation, down-regulation of antiapoptotic protein Bcl-2, and activation of proapoptotic caspase-3. Kaempferol inhibited 4-HNE-induced phosphorylation of c-Jun N-terminal protein kinase (JNK). More importantly, kaempferol directly bound p47(phox), a cytosolic subunit of NADPH oxidase (NOX), and significantly inhibited 4-HNE-induced activation of NOX. The antiapoptotic effects of kaempferol were replicated by the NOX inhibitor apocynin, suggesting that NOX is an important enzyme in its effects. Our results suggest that kaempferol attenuates 4-HNE-induced activation of JNK and apoptosis by binding p47(phox) of NOX and potently inhibiting activation of the NOX-JNK signaling pathway in neuron-like cells. Altogether, these results suggest that kaempferol may be a potent prophylactic against NOX-mediated neurodegeneration.

Decaffeinated coffee prevents scopolamine-induced memory impairment in rats.

INTRODUCTION: Several human studies have reported that coffee consumption improves cognitive performance. In the present study, we investigated whether instant decaffeinated coffee also ameliorates cognitive performance and attenuates the detrimental effects of scopolamine on memory. METHODS: Memory performance was evaluated in Morris water maze test and passive avoidance test. Instant decaffeinated coffee (p.o.) at 120 or 240 mg/kg in Sprague-Dawley rats, which is equivalent to approximately three or six cups of coffee, respectively, in a 60 kg human, was administered for two weeks. RESULTS: Oral gavage administration of instant decaffeinated coffee inhibited scopolamine-induced memory impairment, which was measured by Morris water maze test and passive avoidance test. Instant decaffeinated coffee suppressed scopolamine-mediated elevation of tumor necrosis factor-α (TNF-α) and stimulation of nuclear factor-κB (NF-κB) pathway (i.e., phosphorylation of IκBα and p65) in the rat hippocampus. DISCUSSION: These findings suggest that caffeine-free decaffeinated coffee may prevent memory impairment in human through the inhibition of NF-κB activation and subsequent TNF-α production.

Licorice-derived dehydroglyasperin C increases MKP-1 expression and suppresses inflammation-mediated neurodegeneration.

Recent studies have demonstrated that microglial hyperactivation-mediated neuroinflammation is involved in the pathogenesis of several neurodegenerative diseases. Thus, inhibiting microglial production of the neurotoxic mediator tumor necrosis factor-α (TNF-α) is considered a promising strategy to protect against neurodegeneration. Here, we investigated the inhibitory effect of licorice-derived dehydroglyasperin C (DGC) on lipopolysaccharide (LPS)-induced TNF-α production and inflammation-mediated neurodegeneration. We found that DGC pre-treatment attenuated TNF-α production in response to LPS stimulation of BV-2 microglia. DGC pre-treatment attenuated LPS-induced inhibitor of κB-α (IκB-α) and p65 phosphorylation and decreased the DNA binding activity of nuclear factor-κB (NF-κB). DGC pre-treatment also inhibited LPS-mediated phosphorylation of p38 mitogen-activated protein kinases (MAPKs) and extracellular signal-regulated kinase (ERK). Interestingly, DGC treatment of BV-2 microglia significantly increased MAPK phosphatase 1 (MKP-1) mRNA and protein expression, which is a phosphatase of p38 MAPK and ERK, suggesting that the DGC-mediated increase in MKP-1 expression might inhibit LPS-induced MAPKs and NF-κB activation and further TNF-α production. We also found that LPS-mediated microglial neurotoxicity can be attenuated by DGC. The addition of conditioned media (CM) from DGC- and LPS-treated microglia to neurons helped maintain healthy cell body and neurite morphology and increased the number of microtubule-associated protein 2-positive cells and the level of synaptophysin compared to treatment with CM from LPS-treated microglia. Taken together, these data suggest that DGC isolated from licorice may inhibit microglia hyperactivation by increasing MKP-1 expression and acting as a potent anti-neurodegenerative agent.

Caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid up-regulate NQO1 expression and prevent H2O2-induced apoptosis in primary cortical neurons.

Neurodegenerative disorders are strongly associated with oxidative stress, which is induced by reactive oxygen species including hydrogen peroxide (H2O2). Epidemiological studies have suggested that coffee may be neuroprotective, but the molecular mechanisms underlying this effect have not been clarified. In this study, we investigated the protective effects of caffeinated coffee, decaffeinated coffee, and the phenolic phytochemical chlorogenic acid (5-O-caffeoylquinic acid), which is present in both caffeinated and decaffeinated coffee, against oxidative neuronal death. H2O2-induced apoptotic nuclear condensation in neuronal cells was strongly inhibited by pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid. Pretreatment with caffeinated coffee, decaffeinated coffee, or chlorogenic acid inhibited the H2O2-induced down-regulation of anti-apoptotic proteins Bcl-2 and Bcl-X(L) while blocking H2O2-induced pro-apoptotic cleavage of caspase-3 and pro-poly(ADP-ribose) polymerase. We also found that caffeinated coffee, decaffeinated coffee, and chlorogenic acid induced the expression of NADPH:quinine oxidoreductase 1 (NQO1) in neuronal cells, suggesting that these substances protect neurons from H2O2-induced apoptosis by up-regulation of this antioxidant enzyme. The neuroprotective efficacy of caffeinated coffee was similar to that of decaffeinated coffee, indicating that active compounds present in both caffeinated and decaffeinated coffee, such as chlorogenic acid, may drive the effects.