Leopoldia comosa prevents metabolic disorders in rats with high-fat diet-induced obesity.

PURPOSE: Obesity is the main feature of a complex illness known as metabolic syndrome. Anti-obesogenic therapies are often associated with side effects and represent a high cost in conventional pharmacological approaches. New strategies based on natural remedies are under continuous investigation. Leopoldia comosa (L.) Parl. (L. comosa) is a spontaneous plant with diuretic, anti-inflammatory and antioxidant properties. Recently, a hypoglycemic activity mediated by inhibition of carbohydrate digestion has been identified. The aim of this study was to evaluate the effects of a diet supplemented with L. comosa extracts on a rat model of diet-induced obesity. METHODS: Leopoldia comosa bulb extracts were obtained using a dynamic extractor. Phytochemical properties and in vitro determination of the antioxidant activity and of the inhibitory effects on lipase and pancreatic amylase were performed. Rats were fed (12 weeks) a standard diet, or a high-fat diet (HFD), or an HFD plus L. comosa (20 or 60 mg/die) extracts. The metabolic and anthropometric parameters were recorded. RESULTS: Results indicated that L. comosa inhibited lipase and pancreatic amylase activities. In vivo data showed that the supplementation with both doses of L. comosa extracts counteracted the HFD-dependent effects. It reduced body weight, abdominal obesity and dyslipidemia, and improved glucose tolerance with a reduction of lipidic tissue hypertrophy and liver steatosis, as compared to HFD-fed rat. In liver, L. comosa reduced protein expression levels of PEPCK and G6Pase. CONCLUSION: We suggest that L. comosa extracts prevent obesity-dependent metabolic disorders. This paves the way for their therapeutic application as a natural anti-obesity drug.

A selenoprotein T-derived peptide protects the heart against ischaemia/reperfusion injury through inhibition of apoptosis and oxidative stress.

AIM: Selenoprotein T (SelT or SELENOT) is a novel thioredoxin-like enzyme whose genetic ablation in mice results in early embryonic lethality. SelT exerts an essential cytoprotective action during development and after injury through its redox-active catalytic site. This study aimed to determine the expression and regulation of SelT in the mammalian heart in normal and pathological conditions and to evaluate the cardioprotective effect of a SelT-derived peptide, SelT43-52(PSELT) encompassing the redox motif which is key to its function, against ischaemia/reperfusion(I/R) injury. METHODS: We used the isolated Langendorff rat heart model and different analyses by immunohistochemistry, Western blot and ELISA. RESULTS: We found that SelT expression is very abundant in embryo but is undetectable in adult heart. However, SelT expression was tremendously increased after I/R. PSELT (5 nmol/L) was able to induce pharmacological post-conditioning cardioprotection as evidenced by a significant recovery of contractility (dLVP) and reduction of infarct size (IS), without changes in cardiac contracture (LVEDP). In contrast, a control peptide lacking the redox site did not confer cardioprotection. Immunoblot analysis showed that PSELT-dependent cardioprotection is accompanied by a significant increase in phosphorylated Akt, Erk-1/2 and Gsk3α-ß, and a decrement of p38MAPK. PSELT inhibited the pro-apoptotic factors Bax, caspase 3 and cytochrome c and stimulated the anti-apoptotic factor Bcl-2. Furthermore, PSELT significantly reduced several markers of I/R-induced oxidative and nitrosative stress. CONCLUSION: These results unravel the role of SelT as a cardiac modulator and identify PSELT as an effective pharmacological post-conditioning agent able to protect the heart after ischaemic injury.

Phoenixin-14: detection and novel physiological implications in cardiac modulation and cardioprotection.

Phoenixin-14 (PNX) is a newly identified peptide co-expressed in the hypothalamus with the anorexic and cardioactive Nesfatin-1. Like Nesfatin-1, PNX is able to cross the blood-brain barrier and this suggests a role in peripheral modulation. Preliminary mass spectrography data indicate that, in addition to the hypothalamus, PNX is present in the mammalian heart. This study aimed to quantify PNX expression in the rat heart, and to evaluate whether the peptide influences the myocardial function under basal condition and in the presence of ischemia/reperfusion (I/R). By ELISA the presence of PNX was detected in both hypothalamus and heart. In plasma of normal, but not of obese rats, the peptide concentrations increased after meal. Exposure of the isolated and Langendorff perfused rat heart to exogenous PNX induces a reduction of contractility and relaxation, without effects on coronary pressure and heart rate. As revealed by immunoblotting, these effects were accompanied by an increase of Erk1/2, Akt and eNOS phosphorylation. PNX (EC50 dose), administered after ischemia, induced post-conditioning-like cardioprotection. This was revealed by a smaller infarct size and a better systolic recovery with respect to those detected on hearts exposed to I/R alone. The peptide also activates the cardioprotective RISK and SAFE cascades and inhibits apoptosis. These effects were also observed in the heart of obese rats. Our data provide a first evidence on the peripheral activity of PNX and on its direct cardiomodulatory and cardioprotective role under both normal conditions and in the presence of metabolic disorders.