Discovery of vinyl sulfones as a novel class of neuroprotective agents toward Parkinson's disease therapy.

Although the etiology of Parkinson's disease (PD) remains elusive, recent studies suggest that oxidative stress contributes to the cascade leading to dopaminergic (DAergic) neurodegeneration. The Nrf2 signaling is the main pathway responsible for cellular defense system against oxidative stress. Nrf2 is a transcription factor that regulates environmental stress response by inducing expression of antioxidant enzyme genes. We have synthesized novel vinyl sulfone derivatives. They exhibited a broad range of activities in inducing HO-1, whose gene expression is under the control of Nrf2. Among them, compound 12g was confirmed to activate Nrf2 and induce expression of the Nrf2-dependent antioxidant enzymes NQO1, GCLC, GLCM, and HO-1, at both mRNA and protein levels in DAergic neuronal cells. This was accompanied by protection of DAergic neurons in both in vitro and MPTP-induced in vivo models of PD. In addition, compound 12g effectively resulted in attenuation of the PD-associated behavioral deficits in the mouse model.

Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet.

Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.

Inhibitory activities of anthraquinones from Rubia akane on phosphatase regenerating liver-3.

The methanolic extract of the roots of Rubia akane (Rubiaceae) was found to show inhibitory activity on phosphatase of regenerating liver-3 (PRL-3). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of two anthraquinone compounds, 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone-3-O-(6'-O-acetyl)-α-rhamnosyl(1→2)-ß-glucoside and 2-methyl-1,3,6-trihydroxy-9,10-anthraquinone, as inhibitors on PRL-3. These compounds inhibited PRL-3 in a dose-dependent manner with IC50 values of 5.2 and 1.3 µg/mL, respectively.

Ethanol extract and saponin of Platycodon grandiflorum ameliorate scopolamine-induced amnesia in mice.

This study was carried out to examine the effects of ethanol extract (EXPG) and saponin (SAP) from Platycodon grandiflorum on scopolamine-induced amnesia in mice. Fifty male ICR mice were assigned to five groups--normal (normal diet + saline), control (normal diet + scopolamine), EXPG 0.2% (normal diet + 0.2% EXPG + scopolamine), EXPG 0.5% (normal diet + 0.5% EXPG + scopolamine), and SAP 0.02% (normal diet + 0.02% SAP + scopolamine)--and fed each diet ad libitum. After 4 weeks of feeding the appropriate diet, scopolamine (1 mg/kg, i.p.) was given to mice 45 minutes before the passive avoidance and Morris water maze tasks. Both the EXPG groups and the SAP group exhibited significant amelioration of scopolamine-induced amnesia as measured in both the passive avoidance task and the Morris water maze task. Moreover, acetylcholinesterase (AChE) activity and the levels of thiobarbituric acid-reactive substance (TBARS) in the serum and brain of the EXPG groups were lower than those of the control group. These results suggest that EXPG may improve the cognitive deficit caused by scopolamine and that these effects might be due to EXPG mediated by inhibition of AChE activity and inhibition of TBARS.

Farnesyl protein transferase and tumor cell growth inhibitory activities of lipiferolide isolated from Liriodendron tulipifera.

The methanolic extract of the leaves of Liriodendron tulipifera was found to show inhibitory activity towards farnesyl protein transferase (FPTase). Bioassay-guided fractionation of the methanolic extract resulted in the isolation of lipiferolide, an inhibitor of FPTase. This compound inhibited the FPTase activity in a dose-dependent manner, and showed cell growth inhibitory activity against several tumor cells.