Spondias purpurea L. Bark Extract Protects against Oxidative Stress and Reduces Hypercholesterolemia in Mice Fed High-Fat Diet.

Oxidative stress plays a key role in the initiation and progression of metabolic diseases, including obesity. Preventing the accumulation of reactive oxygen species and oxidative damage to macromolecules is a beneficial strategy for reducing comorbidities associated with obesity. Fruits from the Spondias genus are known for their antioxidant activity, but they are not available year-round due to their seasonality. In this context, we investigated the antioxidant activity and identified the chemical constituents of the aqueous extract of the stem bark of Spondias purpurea L. (EBSp). Additionally, we evaluated the effect of EBSp consumption on metabolic parameters in mice with obesity induced by a high-fat diet. Chemical analyses revealed 19 annotated compounds from EBSp, including flavan-3-ols, proanthocyanidins, methoxylated coumarin, and gallic and ellagic acids, besides other phenolic compounds. In vitro, EBSp showed antioxidant activity through the scavenging of the free radicals and the protection of macromolecules against oxidative damage. Cellular assays revealed that EBSp reduced the levels of malondialdehyde produced by erythrocytes exposed to the oxidizing agent AAPH. Flow cytometry studies showed that EBSp reduced reactive oxygen species levels in human peripheral blood mononuclear cells treated with hydrogen peroxide. Obese mice treated with EBSp (400 mg.kg-1) for 60 days showed reduced levels of malondialdehyde in the heart, liver, kidneys, and nervous system. The total cholesterol levels in mice treated with EBSp reached levels similar to those after treatment with the drug simvastatin. Together, the results show that the combination of the different phenolic compounds in S. purpurea L. bark promotes antioxidant effects in vitro and in vivo, resulting in cytoprotection in the context of oxidative stress associated with obesity and a reduction in hypercholesterolemia. From a clinical perspective, the reduction in oxidative stress in obese individuals contributes to the reduction in the emergence of comorbidities associated with this metabolic syndrome.

Arginine increases growth hormone gene expression in rat pituitary and GH3 cells.

The effect of arginine (Arg) and Ornitargin (OT) [a compound containing the aminoacids Arg, citrulline (Cit) and ornithine (Orn)] administration upon growth hormone (GH) gene expression was studied both in vivo and in vitro (hemipituitaries and GH3 cells) by Northern blot analysis. For in vivo studies, adult male Wistar rats were anesthetized, subjected to i.v. infusion of 200 microl of 150 mM NaCl (control group), Arg (15 or 150 mg) or OT (15 mg of Arg, 1 mg of Cit and 4 mg of Orn) at a rate of 20 microl/min, and killed 50 min thereafter. For the in vitro studies, hemipituitaries or GH3 cells were incubated in 1 ml of appropriate medium containing Arg (15 or 150 mg) or OT (15 mg of Arg, 1 mg of Cit and 4 mg of Orn) for 60 min. The pituitaries of the in vivo and in vitro studies and GH3 cells were subsequently processed for RNA extraction. Total RNA was subjected to electrophoresis in agarose (1%)/formaldehyde gel, transferred to a nylon membrane and subjected to hybridization with a rat GH (32)P-cDNA, and (32)P-18S rRNA probe to correct for the variability in RNA loading. After autoradiography of the membrane, the abundance of GH mRNA and 18S rRNA bands was quantified by densitometry. The in vivo study demonstrated that Arg and OT infusion induced a 2.3-fold increase in GH mRNA expression, which could result from the Arg-mediated inhibition of somatostatin release. In addition, in vitro Arg, but not OT, induced GH gene expression in hemipituitaries and GH3 cells, indicating that the aminoacid can act per se at the pituitary somatotrope level. In conclusion, our data show for the first time that arginine stimulates GH gene expression in parallel to its recognized GH-releasing activity.