Wenpeng Dong

Neuroprotective effect of osthole against acute ischemic stroke on middle cerebral ischemia occlusion in rats

Osthole, a natural coumarin derivative, has taken considerable attention because of its diverse pharmacological functions. It has been reported to be useful in the treatment of chronic cerebral hypoperfusion and neuronal damage. In the present study, we examined the neuroprotective effect of osthole and its potential mechanisms against acute ischemic stroke induced by middle cerebral artery occlusion (MCAO) in rats. The rats were pretreated with osthole 10, 20 and 40 mg/kg 30 min before MCAO. The neuroprotective effect of osthole against acute ischemic stroke was evaluated by neurological deficit score (NDS), dry-wet weight and 2,3,5-triphenyltetrazolium chloride (TTC) staining. The contents of malondialdehyde (MDA) and glutathione (GSH), activity of myeloperoxidase (MPO) and the level of interleukin (IL)-1β and IL-8 after 2h of MCAO in rats were detected to investigate its anti-oxidative action and anti-inflammatory property. Pretreatment with osthole significantly increased in GSH, and decreased the volume of infarction, NDS, edema, MDA, MPO, IL-1β and IL-8 compared with rats in the MCAO group at 24h after MCAO. The study suggests the neuroprotective effect of osthole in the MCAO model of rats. The anti-oxidative action and anti-inflammatory property of osthole may contribute to a beneficial effect against stroke.

Resveratrol attenuates ischemic brain damage in the delayed phase after stroke and induces messenger RNA and protein express for angiogenic factors.

BACKGROUND It has been reported recently that resveratrol preconditioning can protect the brain from ischemia-reperfusion injury. However, it was unclear whether resveratrol administration after stroke was beneficial to the delayed phases after focal cerebral ischemia injury. This study investigated the effects and possible protective mechanism of resveratrol on the delayed phase after focal cerebral ischemia injury in mice. METHODS Mice were randomly assigned to five groups according to the time of administration of resveratrol. Control group mice received a corresponding volume of saline solution (0.9% NaCl) containing 20% hydroxypropyl h-cyclodextrin by gavage and were exposed to middle cerebral artery (MCA) occlusion and reperfusion injury. The treatment groups received resveratrol (50 mg/kg/d, gavage) until day 7. Ischemia group mice received their first dose 5 minutes before MCA ischemia, reperfusion group mice received their first dose 5 minutes before MCA reperfusion, first-day, group mice received their first dose 24 hours after MCA reperfusion, and third-day group mice received their first dose at 72 hours after MCA reperfusion. Brain injury was evaluated by triphenyltetrazolium chloride staining and neurologic examination 7 days after reperfusion. The microvascular cell number was examined with immunohistochemistry staining. Effect of resveratrol on matrix metalloproteinase-2 (MMP-2) and vascular endothelial growth factor (VEGF) gene expression was investigated with reverse transcriptase-polymerase chain reaction and Western blot. RESULTS The mean neurologic scores and infarct volumes of the ischemia and reperfusion groups were lower than that of the control group at 7 days after MCA reperfusion (P < .05). Immunohistochemistry staining showed significantly less reduction in the number of microvessels in the cortical area of mice of the ischemia and reperfusion groups compared with controls. The ischemic hemispheres of the ischemia and reperfusion groups showed significantly (P < .05) elevated levels of protein of MMP-2 and VEGF. CONCLUSIONS Resveratrol administration by gavage provided an important neuroprotective effect on focal cerebral ischemic injury in the delayed phase. The elevated MMP-2 and VEGF levels might be important in the neuroprotective effect of resveratrol administration by inducing angiogenesis.

Cell death‐inducing DFF45‐like effector, a lipid droplet‐associated protein, might be involved in the differentiation of human adipocytes

Cell death‐inducing DFF45‐like effector (CIDE) family proteins, including cell death‐inducing DFF45‐like effector A (CIDEA), cell death‐inducing DFF45‐like effector B (CIDEB) and cell death‐inducing DFF45‐like effector C (CIDEC) [fat‐specific protein of 27 kDa in rodent (FSP27) in rodents], were originally identified by their sequence homology to the N‐terminal region of DNA fragmentation factor DFF40/45. Recent reports have revealed that CIDE family proteins play important roles in lipid metabolism. Several studies involving knockdown mice revealed that FSP27 is a lipid droplet‐targeting protein that can promote the formation of lipid droplets. However, the detailed roles of human CIDEC in the differentiation of human adipocytes remain unknown. In the present study, we found that the expression of CIDEC increased during the differentiation of fetal adipose tissues, but decreased during the de‐differentiation of adipocytic tumors, suggesting that the expression of CIDEC should be positively correlated with the differentiation of adipocytes. Furthermore, we verified that human CIDEC was localized on the surface of lipid droplets. Using human primary pre‐adipocytes, we confirmed that the expression of CIDEC was elevated during the differentiation of pre‐adipocytes, and knockdown of CIDEC in human primary pre‐adipocytes resulted in differentiation defects. These data demonstrate that CIDEC is essential for the differentiation of adipose tissue. Together with regulating adipocyte lipid metabolism, CIDEC should be a potential target for regulating adipocyte differentiation and reducing fat cell mass.

Resveratrol prevents hepatic steatosis induced by hepatitis C virus core protein

Hepatitis C virus (HCV) core protein plays an important role in the development of hepatic steatosis in patients with chronic HCV infection. Treatment of C57BL/6 mice infected with HCV core recombinant adenoviruses with resveratrol significantly decreased hepatic triacylglycerols (TAG) while the serum TAG level was unaffected. RT-PCR and Western blotting showed that HCV core protein attenuated the expression of Sirt1 and PPAR-α, which would be reversed by resveratrol. This was also confirmed in primary mouse hepatic cells infected with HCV core protein expressing adenovirus. Thus, resveratrol may prevent against hepatic steatosis by blocking the inhibited expression of Sirt1 and PPAR-α induced by HCV core protein.

Cell death-inducing DFF45-like effector b (Cideb) is present in pancreatic beta-cells and involved in palmitate induced beta-cell apoptosis

Excessive accumulation of long‐chain fatty acids in the pancreatic islets is associated with beta cell dysfunction and ultimately contributes to the pathogenesis of type 2 diabetes. It has been well proved that the cell death‐inducing DFF45‐like effector b (Cideb) is involved in cell apoptosis and lipid metabolism. However, the expression and function of Cideb in endocrine pancreas remain to be investigated.