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Graphical abstract Highlights • Moringa oleifera Stem Extracts (MSE) protected HaCaT cells against H 2 O 2 exposure induced oxidative stress injury. • Topical treatment with MSE alleviated UVB-induced epidemic oxidative stress injury. • The protective effects of MSE are mediated by enhancement of antioxidant defense systems and activation of PPARα in skin keratinocytes. Abstract Oxidative stress is an important cause of skin injury induced by UVB radiation. Moringa oleifera also known as horseradish tree or drumstick tree, have multiple nutraceutical or pharmacological functions. However, whether Moringa oleifera protects skin against oxidative stress injury remains unknown. To investigate the effects of the ethanol extract of Moringa oleifera stem (MSE) on skin oxidative stress injury and its molecular mechanism, we first determined the effect of MSE on epidermal oxidative stress injury induced by H 2 O 2 in keratinocytes (HaCaT cells) and by UVB-radiation in mice. Then we investigated the effect of MSE on the enhancement of antioxidant system and activation of PPARα in vitro and in vivo. Furthermore, the flavonoids compositions in MSE were assayed by high-performance liquid chromatography (HPLC), and then molecular docking study was used to assess the major component in MSE to activate PPARα. Our results indicate that MSE (100–400 μg/mL) protected the epidemic cell against oxidative stress injury in vitro and topical treatment with MSE cream (6%) inhibit UVB-induced oxidative stress injury in the epidermis of the mouse skin. PPARα activation is involved in the protective effect of MSE. HPLC assay and molecular docking study indicated that rutin might be the main component in MSE to activate PPARα. These results confirm that MSE exerts the protective effect on oxidative stress induced skin keratinocytes injury. Moreover, the protective effect of MSE is mediated by enhancement of antioxidant defense systems and activation of PPARα in skin keratinocytes. [ABSTRACT FROM AUTHOR]

Propane-2-sulfonic acid octadec-9-enyl-amide (N15), an analogue of oleoylethanolamide (OEA), is a novel PPARα/γ dual agonist. Our previous studies verified the positive effects of OEA on the acute and delayed stages of cerebral ischemia. However, it is not clear whether N15 is effective against ischemic cerebral injury. In the present study, male Kunming mice were subjected to middle cerebral artery occlusion (MCAO). To evaluate its preventive effects, N15 (50, 100 or 200 mg/kg, ip ) was administered for 3 days before ischemia. To evaluate its therapeutic effects, N15 (200 mg/kg, ip ) was administered 1 h before reperfusion or 0, 1, 2 or 4 h after reperfusion. Neurological deficit scores, infarct volume and the degree of brain oedema were determined at 24 h after reperfusion. Blood brain barrier (BBB) disruption was evaluated by Evans blue (EB) and FITC-dextran leakages at 6 h after reperfusion. The activation/inflammatory responses of microglia/macrophages were detected using immunohistochemistry and western blot. N15 pretreatment improved neurological dysfunction, reduced infarct volume and alleviated brain oedema in a dose-dependent manner; the most effective dose was 200 mg/kg. The therapeutic time window was within 2 h after reperfusion. N15 treatment preserved the BBB integrity and suppressed the activation of microglia/macrophages. N15 inhibited inflammatory cytokine expression not only in MCAO mice but also in lipopolysaccharide (LPS)-stimulated BV-2 microglial cells. Additionally, N15 markedly decreased the phosphorylation levels of NF-κBp65, STAT3, and ERK1/2 both in vivo and in vitro . Furthermore, the PPARα antagonist MK886 or PPARγ antagonist T0070907 respectively partly abolished the anti-inflammatory effects of N15 in vitro . Our findings demonstrated that N15 can exert neuroprotective effects against cerebral ischemic insult. Moreover, the neuroprotective effects of N15 on cerebral ischemia may be attributed to its anti-inflammatory properties, at least in part, by enhancing PPARα/γ dual signaling and inhibiting the activation of the NF-κB, STAT3, and ERK1/2 signaling pathways. These findings suggest that N15 may be a potential therapeutic choice for the prevention and treatment of ischemic stroke. [ABSTRACT FROM AUTHOR]

Abstract: Oleoylethanolamide (OEA) is a high-affinity agonist of peroxisome proliferator-activated receptor α (PPARα) which may act as an endogenous neuroprotective factor. However, it is not clear whether orally administered OEA is effective against ischemic brain injury. In our study, transient focal cerebral ischemia was induced by middle cerebral artery occlusion for 90 min followed by reperfusion. To evaluate its preventive effects, OEA (10, 20 or 40mg/kg, ig) was administered for 3 days before ischemia. To evaluate its therapeutic effects, OEA (40mg/kg, ig) was administered at 0.5 or 1h before reperfusion or at 0 or 1h after reperfusion. In some experiments, the PPARα antagonist MK886 (10mg/kg, ig) was administered 0.5h before OEA. Neurological deficit score, infarct volume and brain edema degree were determined at 24h after reperfusion. Blood–brain barrier (BBB) disruption was evaluated by Evans blue (EB) leakage at 6h after reperfusion. Real-time RT-PCR and western blot were performed to detect PPARα mRNA and protein expression. Oral OEA pretreatment improved neurological dysfunction reduced infarct volume and alleviated brain edema in a dose-dependent manner; the most effective dose was 40mg/kg. The therapeutic time is within 1h after reperfusion. OEA also increased PPARα mRNA and protein expression in the ischemic brain. The PPARα antagonist MK886 abolished the protective effects of OEA. In conclusion, our results indicate that orally administered OEA protects against acute cerebral ischemic injury in mice, at least in part by activating PPARα. [Copyright &y& Elsevier]