No abstract

Loliolide is a monoterpenoid hydroxylactone found in many algae, including fresh water green algae, Prasiola japonica. To date, loliolide and compounds in P. japonica have not been studied systematically with respect to skin pharmacology. In this study, we investigated oxidative stress-protective and anti-melanogenic effects of loliolide and P. japonica ethanol extract (Pj-EE), known to contain loliolide, in human keratinocyte (HaCaT) cells and mouse melanoma (B16F10) cells. Loliolide suppressed the transcription of genes encoding matrix metalloproteinases (MMPS), which were induced in HaCaT cells by hydrogen peroxide (H2O2) treatment. Loliolide and Pj-EE not only reduced the melanin secretion and content in B16F10 cells but also increased the expression of the antioxidant proteins nuclear factor (erythroid-derived 2)-like 2 (NRF2) and heme oxygenase-1 (HO-1) in HaCaT cells subjected to H2O2 treatment. Furthermore, loliolide and Pj-EE decreased expression of the anti-melanogenic protein microphthalmia-associated transcription factor (MITF) and tyrosinase in B16F10 cells subjected to α-melanocyte-stimulating hormone (α-MSH) treatment. Our findings demonstrate that loliolide and Pj-EE have antioxidant and anti-melanogenic effects on skin.

A new stilbenoid (1) was isolated from the root extract of Polygonum multiflorum together with eight known constituents (2-9). The chemical structure of 1 was established as the 6''-O-monogalloyl ester of (E)-2,3,4',5-beta-tetrahydroxystilbene-2-beta-D-glucopyranoside based on physicochemical and spectroscopic analyses, particularly by NMR spectroscopic data, i.e., COSY, HMQC and HMBC. Compound 1 weakly inhibited acetylcholinesterase in vitro.

Brominated flame retardants (BFRs) are present in many consumer products ranging from fabrics to plastics and electronics. Wide use of flame retardants can pose an environmental hazard, which makes it important to determine the mechanism of their toxicity. In the present study, dose-dependent toxicity of tetrabromobisphenol A (TBBPA), a flame retardant, was examined in male prepubertal rats (postnatal day 18) treated orally with TBBPA at 0, 125, 250 or 500 mg/kg for 30 days. There were no differences in body weight gain between the control and TBBPA-treated groups. However, absolute and relative liver weights were significantly increased in high dose of TBBPA-treated groups. TBBPA treatment led to significant induction of CYP2B1 and constitutive androstane receptor (CAR) expression in the liver. In addition, serum thyroxin (T4) concentration was significantly reduced in the TBBPA treated group. These results indicate that repeated exposure to TBBPA induces drug-metabolising enzymes in rats through the CAR signaling pathway. In particular, TBBPA efficiently produced reactive oxygen species (ROS) through CYP2B1 induction in rats. We measured 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative damage, in the kidney, liver and testes of rats following TBBPA treatment. As expected, TBBPA strongly induced the production of 8-OHdG in the testis and kidney. These observations suggest that TBBPA-induced target organ toxicity may be due to ROS produced by metabolism of TBBPA in Sprague- Dawley rats.

Di(2-ethylhexyl) phthalate (DEHP) used as a common plasticizer additive in the manufacture of plastics, such as polyvinyl chloride (PVC). This study examined the effect of DEHP on steroidogenesis or spermatogenesis in the testes of Sprague-Dawley male rats treated orally with 250, 500, 750 mg/kg over a 30-day period. The expression levels of the steroidogenic-or spermatogenic-related genes were analyzed in the testis using a reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. High doses of DEHP (500 and 750 mg/kg) significantly decreased the testicular sperm counts and daily sperm production (DSP). In addition, serum testosterone levels were significantly lower in the DEHP treatment groups than in the control. The mRNA levels of SR-B1, StAR, PBR and CYP17 increased in a dose-dependent manner. These increases were significant at 500 and 750 mg/kg. In the other hand, the mRNA levels of CYP19 decreased significantly in testes of rats exposed to DEHP 500 and 750 mg/kg. Dose-dependent decreases in Spag4 and LDHA mRNA in the testis were observed after DEHP exposure, while there was a significant decrease in thyroid hormone receptor (TR)α1 protein levels. High doses of DEHP significantly increased the expression of peroxisome proliferator-activated receptor (PPAR)-r and retinoid X receptor (RXR)-α protein but markedly decreased the expression of RXR-r. These results suggest that DEHP exposure can alter the expression of the spermatogenic-or steroidogenic-related genes resulting in a decrease in sperm production in the testis. This study is expected to be helpful in research examining the mechanisms for how DEHP reduces the expression pattern of the genes involved steroid hormone synthesis after chronic exposure to DEHP.