Treatment with Parkinsonia aculeata combats insulin resistance-induced oxidative stress through the increase in PPARγ/CuZn-SOD axis expression in diet-induced obesity mice.

Parkinsonia aculeata L. (Caesalpiniaceae) is a traditional ethnomedicine and has been used for the empiric treatment of hyperglycemia, without scientific background. Mechanistic analyses at molecular level from the antioxidant mechanism observed by P. aculeata are required. Herein the effects of the treatment by hydroethanolic extract partitioned with ethyl acetate of P. aculeata aerial parts (HEPa/EtOAc) in mice fed a high-fat diet that share many obesity phenotypes with humans were evaluated. The animals were treated orally with HEPa/EtOAc (125 and 250 mg/kg/day) and pioglitazone (5 mg/kg/day), for 16 days. After the treatment, HEPa/EtOAc reduced fasting serum glucose and insulin levels, as well as homeostasis model assessment for insulin resistance. In addition, an improvement in glucose intolerance was also observed. Indeed, a reduction in the circulating levels of TNF-α and IL-6 was also observed. Furthermore, at molecular level, it was demonstrated that the HEPa/EtOAc treatment was able to improve these physiological parameters, through the activation of peroxisome proliferator-activated receptor γ (PPARγ) per si, as well as the enhancement of antioxidant mechanism by an increase in PPARγ/Cu(2+), Zn(2+)-superoxide dismutase (CuZn-SOD) axis expression in liver and adipose tissue. In sum, P. aculeata is effective to improve insulin resistance in a mouse model of obesity and this effect seems to involve the antioxidant and anti-inflammatory mechanisms through the increase in PPARγ/CuZn-SOD axis expression.

Parkinsonia aculeata (Caesalpineaceae) improves high-fat diet-induced insulin resistance in mice through the enhancement of insulin signaling and mitochondrial biogenesis.

ETHNOPHARMACOLOGICAL RELEVANCE: The search for natural agents that minimize obesity-associated disorders is receiving special attention. Parkinsonia aculeata L. (Caesalpineaceae) has long been used in Brazil as a hypoglycaemic herbal medicine, without any scientific basis. AIMS OF THE STUDY: In this context, we aimed to use molecular and physiological methods to study the effect of a hydroethanolic extract partitioned with ethyl acetate from the aerial parts of Parkinsonia aculeata (HEPa/EtOAc) on insulin resistance in a mouse model of diet-induced obesity (DIO). MATERIAL AND METHODS: Firstly, C57BL/6J mice were fed either with standard rodent chow diet or a high-fat diet (HFD) for 12 consecutive weeks. Then, the animals were treated with HEPa/EtOAc at two doses (125 and 250mg/kg/day) or metformin (200mg/kg/day) for 16 days. At the end of the experiment, body weight, fat pad weight, fasting serum glucose (FSG), insulin (FSI) and leptin were measured. Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) was also calculated. Glucose, insulin and pyruvate tolerance tests were performed. The expression and phosphorylation of IRß(tyr), Akt(ser473), AMPKα and PGC1α in liver, muscle and adipose tissue were determined by Western blot analyses. RESULTS: Herein we demonstrate for the first time an improvement in insulin resistance following HEPa/EtOAc administration in obese mice, as shown by increased glucose, insulin and pyruvate tolerance, as well as an improvement in FSG, FSI, HOMA-IR and circulating leptin levels, which together are in part due to enhancement of the insulin signaling pathway in its main target tissues. Surprisingly, the increase in activation of the AMPKα-PGC1-α axis by HEPa/EtOAc was similar to that produced by metformin treatment in the liver and muscle tissues. CONCLUSION: In conclusion, P. aculeata appears to be a source of therapeutic agent against obesity-related complications.

Chlorella modulates insulin signaling pathway and prevents high-fat diet-induced insulin resistance in mice.

AIMS: The search for natural agents that minimize obesity-associated disorders is receiving special attention. In this regard, the present study aimed to evaluate the prophylactic effect of Chlorella vulgaris (CV) on body weight, lipid profile, blood glucose and insulin signaling in liver, skeletal muscle and adipose tissue of diet-induced obese mice. MAIN METHODS: Balb/C mice were fed either with standard rodent chow diet or high-fat diet (HFD) and received concomitant treatment with CV for 12 consecutive weeks. Triglyceride, free fatty acid, total cholesterol and fractions of cholesterol were measured using commercial assay. Insulin and leptin levels were determined by enzyme-linked immunosorbent assay (ELISA). Insulin and glucose tolerance tests were performed. The expression and phosphorylation of IRß, IRS-1 and Akt were determined by Western blot analyses. KEY FINDINGS: Herein we demonstrate for the first time in the literature that prevention by CV of high-fat diet-induced insulin resistance in obese mice, as shown by increased glucose and insulin tolerance, is in part due to the improvement in the insulin signaling pathway at its main target tissues, by increasing the phosphorylation levels of proteins such as IR, IRS-1 and Akt. In parallel, the lower phosphorylation levels of IRS-1(ser307) were observed in obese mice. We also found that CV administration prevents high-fat diet-induced dyslipidemia by reducing triglyceride, cholesterol and free fatty acid levels. SIGNIFICANCE: We propose that the modulatory effect of CV treatment preventing the deleterious effects induced by high-fat diet is a good indicator for its use as a prophylactic-therapeutic agent against obesity-related complications.