Accumulating data have indicated that citrus polymethoxyflavones (PMFs) have the ability to affect brain function. In the present study, we showed that 3,5,6,7,8,3′,4′-heptamethoxy- flavone (HMF) given intraperitoneally to mice was immediately detected in the brain and that the permeability of the brain tissues to it was significantly higher than that of other citrus PMFs (nobiletin, tangeretin, and natsudaidain). The permeation of these PMFs into the brain well correlated with their abilities to suppress MK-801-induced locomotive hyperactivity, suggesting that HMF had the ability to act directly in the brain. We also obtained data suggesting that the suppressive effect of HMF on MK-801-induced locomotive hyperactivity was mediated by phosphorylation of extracellular signal-regulated kinases 1/2 (ERK1/2) in the hippocampus.

In vitro screening methods using cultured Neuro2a cells to examine the activation (phosphorylation) of extracellular signal-regulated kinase (ERK) 1/2 and promotion of neurite outgrowth revealed that the extracts of 5 Kampo (Japanese traditional) formulations have potential as medicines for the treatment of behavioral abnormalities. Since sansoninto (SAT) extract exerted stronger effects than the other candidates tested, we investigated whether its oral administration ameliorates the pathologies of some mouse models of behavioral impairments. The results obtained suggested that SAT extract exerted anti-depression-like effects in the forced swim test, which may be mediated by the up-regulated expression of brain-derived neurotrophic factor (BDNF) in the hippocampus. They may also be mediated by the enhanced phosphorylation of the cAMP response element-binding protein (CREB) via the mitogen-activated protein kinase (MAPK) cascade and Ca/calmodulin-dependent protein kinase II (CaMK II) cascade, a downstream signaling cascade of the N-methyl-D-aspartate (NMDA) receptor. These results indicate that the extract of SAT has potential as a new remedial medicine in the treatment of depression-like behavior.

In recent years, drug-induced photosensitivity as a side effect has been an increasing problem. To examine the effectiveness of broadspectrum sunscreens in preventing the disease, we quantitatively assessed efficiency of some sunscreens in suppressing the photosensitized reactions with sparfloxacin, a fluoroquinolone antibacterial agent. Some broad-spectrum sunscreens suppressed sparfloxacin-photosensitized formation of strand-breakage in plasmid pBR322 DNA. The present findings suggest that the use of broad-spectrum sunscreens contributes to the prevention of drug-induced photosensitivity. In addition, the suppressive effects showed a linear relation with the effective UV-A quanta absorbed by the tested sunscreens independent of the product types and manufacturers. Therefore, we propose that the indication of UV-A absorption spectrum in addition to PA classification (protection grade of UV-A) as factors for assessing for the ability of sunscreens to prevent drug-induced photosensitivity. An in vitro method to assess quantitatively the effectiveness of broad-spectrum sunscreens in preventing druginduced photosensitivity was also presented.