Yu Zhou

Astrocyte inflammation activation is an important cause that hinders the recovery of motor function after cerebral ischemia. However, its molecular mechanism has not yet been clearly clarified. The peroxisome proliferator-activated receptor α (PPARα) is a ligand-activated nuclear transcriptional factor. This study aims to further clarify the role of PPARα in astrocyte inflammation activation after cerebral ischemia and to explore the underlying mechanism. Astrocyte activation was induced in an in vivo model by transient middle cerebral artery occlusion (tMCAO) in mice. The in vitro model was induced by an oxygen-glucose deprivation/reoxygenation (OGD/R) in a primary culture of mouse astrocyte. PPARα-deficient mice were used to observe the effects of PPARα on astrocyte activation and autophagic flux. Our results showed that PPARα was mainly expressed in activated astrocytes during the chronic phase of brain ischemia and PPARα dysfunction promoted astrocyte inflammatory activation. After cerebral ischemia, the expressions of LC3-II/I and p62 both increased. Autophagic vesicle accumulation was observed by electron microscopy in astrocytes, and the block of autophagic flux was indicated by an mRFP-GFP-LC3 adenovirus infection assay. A PPARα deficit aggravated the autophagic flux block, while PPARα activation preserved the lysosome function and restored autophagic flux in astrocytes after OGD/R. The autophagic flux blocker bafilomycin A1 and chloroquine antagonized the effect of the PPARα agonist on astrocyte activation inhibition. This study identifies a potentially novel function of PPARα in astrocyte autophagic flux and suggests a therapeutic target for the prevention and treatment of chronic brain ischemic injury.

Moringa oleifera, also known as horseradish tree or drumstick tree, has strong antioxidant properties. In the present study, we investigated the potential effect of Moringa oleifera stem extract (MOSE) on cataract formation induced by oxidative stress in cultured mouse lenses. Mouse lenses cultured in vitro were pretreated with MOSE (0.5 and 1 mg/mL) for 24 h. Then, 1 mM hydrogen peroxide was added, and mouse lenses were cultured for a further 24 h. The medium was then changed to normal culture medium. After 48 h, lens opacification, reactive oxygen species (ROS) generation, reduced glutathione (GSH) content, and activities of superoxide dismutase (SOD) and catalase (CAT) were measured in lens tissues. In addition, the protein expression of peroxisome proliferator-activated receptor alpha (PPARα), a nuclear receptor with potential benefits to improve vision-threatening eye diseases, was assayed. MOSE (1 mg/mL) alleviated lens opacification, reduced ROS generation, increased GSH content, and elevated SOD and CAT activities in cultured lenses. Moreover, MOSE upregulated the expressions of SOD, CAT, and PPARα. This study showed that MOSE alleviates oxidative stress-induced cataract formation, and the mechanism of the effect is mainly related to its improvement of the endogenous antioxidant system in the lens.

Oxidative stress is an important cause of skin injury induced by UVB radiation. The present study was to investigate the protective effects of the Moringa oleifera stem extract (MSE) on solar ultraviolet B (UVB)-induced skin injury in mice and hydrogen peroxide (H2O2) induced cellular oxidative stress injury in human keratinocytes (HaCaT cells). As the important role of peroxisome proliferator-activated receptor alpha (PPARα) in the redox balance of the skin, the effect of MSE on PPARα activation was also evaluated. Our results indicate that MSE dose-dependently activate PPARα by a dual-luciferase reporter assay. Topical treatment with 6% MSE markedly alleviated UVB-induced oxidative stress injury especially in the epidermis of the mouse skin. In HaCaT cells, we found that MSE (100-400 μg/mL) protected the cell against oxidative stress injury and this effect is related to its activation of PPARα. Finally high-performance liquid chromatography (HPLC) assay confirmed that the main flavonoid compositions in MSE were rutin, luteolin and quercetin. Molecular docking study further indicated that rutin may be the activate component to activate PPARα. These results confirmed that the protective effects of MSE are mediated by its antioxidative potential resulting from its direct activation of PPARα in skin keratinocytes.