mangostin and Reperfusion-Injury

The production of reactive oxygen species (ROS) during and after the onset of an ischemic stroke induces neuronal cell death and severely damages brain function. Therefore, reducing ROS by administrating antioxidant compounds is a promising approach to improving ischemic symptoms. Alpha-mangostin (α-M) is an antioxidant compound extracted from the pericarp of the mangosteen fruit. Reportedly, α-M decreases neuronal toxicity in primary rat cerebral cortical neurons. In this study, we investigated the neuroprotective activity of α-M in both in vitro and in vivo assays. Pretreatment with α-M inhibited excessive cellular ROS production after oxygen-glucose deprivation/reoxygenation (OGD/R) in vitro using an SH-SY5Y (human neuroblastoma) cell line. In addition, α-M maintained mitochondrial membrane potential and suppressed mitochondrial-specific ROS production induced by OGD/R. Meanwhile, the low bioavailability of α-M due to its poor water solubility has been an insuperable obstruction impeding extensive investigations of the biological functions of α-M and its medical applications. To overcome this problem, we synthesized a cyclodextrin-based nanoparticle (CDNP) that is known to increase the loading efficiency and binding constant of α-M, compared with cyclodextrins themselves. This nano-formulated α-M (α-M/CDNP) was optimized for an in vivo ischemic stroke model. Our results indicated that α-M/CDNP (25 mg/kg/injection) reduced infarct volume and improved neurological behavior (p = 0.036 and p = 0.046, respectively). These in vivo results suggest that α-M appears to cross the blood-brain barrier (BBB) with the help of a nano-formulation with CDNP. Combining an in vitro BBB model and a physicochemical binding assay between α-M and albumin, it is speculated that α-M released from CDNP would interact with albumin during its prolonged circulation in the blood, and the resultant α-M/albumin complex may cross the BBB through the absorptive-mediated transcytosis pathway. These findings suggest the potential clinical application of α-M in ischemic stroke treatment.

Topics: Animals; Antioxidants; Apoptosis; Brain Ischemia; Cyclodextrins; Glucose; Humans; Ischemic Stroke; Neuroblastoma; Neuroprotective Agents; Oxygen; Rats; Reactive Oxygen Species; Reperfusion Injury

This study was designed to investigate if α-mangostin (α-M), a xanthone present in the pericarp of Garcinia mangostana L., was able to protect against reperfusion injury in Langendorff-reperfused hearts. It was observed that α-M maintains the cardiac mechanical work, diminishes the area of infarct, and prevents the decrease in cardiac ATP and phosphocreatine levels in the reperfused myocardium. The protective effect of this xanthone was associated with reduction of oxidative stress. α-M treatment prevented reperfusion injury-induced protein oxidation (protein carbonyl content), lipid peroxidation (malondialdehyde and 4-hydroxynonenal content), and diminution of glutathione content. In fact, after α-M treatment, the values in these parameters were comparable to those obtained in nonreperfused hearts. In summary, α-M induces a protective effect in postischemic heart associated to the prevention of oxidative stress secondary to reperfusion injury.

Topics: Aldehydes; Animals; Antioxidants; Garcinia mangostana; Glutathione; Heart; Lipid Peroxidation; Male; Malondialdehyde; Myocardium; Oxidative Stress; Phosphocreatine; Plant Extracts; Protective Agents; Rats; Rats, Wistar; Reperfusion Injury; Xanthones