fraxin and Reperfusion-Injury

Inflammation and oxidative stress are associated with the pathogenesis of cerebral ischemia-reperfusion (I/R) injury. Fraxin, one of the primary active ingredients of Cortex Fraxini, may have potent anti-inflammatory activity. This study intended to investigate the function and mechanism of fraxin in a middle cerebral artery occlusion (MCAO) model.. A middle cerebral artery occlusion (MCAO) rat model was engineered. Both in-vivo and in-vitro models were dealt with Fraxin. The profiles of inflammation-concerned cytokines, proteins and oxidative stress factors were determined by RT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA), and neuronal apoptosis and reactive oxygen species (ROS) levels were measured. The neurological functions of rats were evaluated by Morris water maze and modified neurological severity scores (mNSS).. The data revealed that fraxin abated the OGD/R-mediated release of inflammatory and oxidative stress mediators, enhanced "M2″-like BV2 microglia polarization, and mitigated HT22 cell apoptosis. Mechanistically, fraxin boosted PPAR-γ expression, activated the Nrf2/HO-1 pathway, and suppressed NF-κB, IKK-β，p38 MAPK, ERK1/2 and Keap1 in a dose-dependent manner. Furthermore, attenuating PPAR-γ through pharmacological treatment with GW9662 (a PPAR-γ antagonist) mainly weakened the neuroprotective and anti-inflammatory functions of fraxin.. Fraxin could considerably ameliorate cerebral I/R damage by repressing oxidative stress, inflammatory response, and cell apoptosis through abrogating the PPARγ/ NF-κB pathway.

Topics: Animals; Anti-Inflammatory Agents; Brain Ischemia; Coumarins; Infarction, Middle Cerebral Artery; Inflammation; Kelch-Like ECH-Associated Protein 1; Neuroinflammatory Diseases; NF-E2-Related Factor 2; NF-kappa B; Oxidative Stress; PPAR gamma; Rats; Reperfusion Injury; Signal Transduction

Kidney ischemia reperfusion (IR) injury is an important health problem resulting in acute kidney failure. The oxidative stress and inflammatory process are the underlying mechanisms of IR injury. It has been purposed in this study to research the possible protective effects of fraxin on kidney injury induced by IR.. 32 Sprague Dawley male rats were divided into 4 groups. The groups were organized as follows; sham, IR, IR + fraxin 10 mg/kg, and IR + 50 mg/kg fraxin groups. Some oxidant, antioxidant and inflammatory parameters were evaluated in kidney tissues removed at the end of our experimental study.. It was detected that the oxidant and proinflammatory markers increased and antioxidant parameters decreased in IR group but the results significantly reversed in treatment groups compared to IR group. And also, 8-OHdG, NF-κB, HAVCR1 immunopositivities were at severe levels and these results attenuated in IR fraxin + 10 mg/kg, and IR + fraxin 50 mg/kg groups.. These presented results have shown that fraxin performed protective effects against kidney injury induced by IR.

Topics: Acute Kidney Injury; Animals; Antioxidants; Coumarins; Disease Models, Animal; Kidney; Male; Malondialdehyde; Peroxidase; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Superoxide Dismutase