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Graphical abstract Abstract Phytomodulatory proteins from the latex of the medicinal plant Calotropis procera has been shown to be implicated in many pharmacological properties. However there is no current information about their activity on glucose metabolism, although the latex is used in folk medicine for treating diabetes. In this study the phytomodulatory proteins (LP) from C. procera latex were assessed on glycemic homeostasis. Control animals received a single intravenous dose (5 mg/kg) of LP or saline solution (CTL). Four hours after treatment, the animals were euthanized and their livers were excised for analysis by western blot and RT-PCR AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase (PEPCK) and tumor necrosis factor alpha (TNF-α). In vivo tests of intraperitoneal tolerance to insulin, glucose and pyruvate were also performed, and the effect of LP administration on fed glycemia was studied followed by blood analysis to determine serum insulin levels. Treatment with LP reduced glycemia two hours after glucose administration (LP: 87.2 ± 3.70 mg/dL versus CTL: 115.6 ± 8.73 mg/dL). However, there was no change in insulin secretion (CTL: 14.16 ± 0.68 mUI/mL and LP: 14.96 ± 0.55 mUI/mL). LP improved the insulin sensitivity, represented by a superior glucose decay constant during an insulin tolerance test (kITT) (4.17 ± 0.94%/min) compared to the CTL group (0.82 ± 0.72%/min), and also improved glucose tolerance at 30 min (105.2 ± 12.4 mg/dL versus 154.2 ± 18.51 mg/dL), while it decreased hepatic glucose production at 15 and 30 min (LP: 75.5 ± 9.31 and 52.5 ± 12.05 mg/dL compared to the CTL: 79.0 ± 3.02 and 84.5 ± 7.49 mg/dL). Furthermore, there was a significant inhibition of gene expression of PEPCK (LP: 0.66 ± 0.06 UA and CTL: 1.14 ± 0.22 UA) and an increase of phosphorylated AMPK (LP: 1.342 ± 0.21 UA versus CTL: 0.402 ± 0.09 UA). These findings confirm the effect of LP on glycemic control and suggest LP may be useful in diabetes treatment. However, the pharmacological mechanism of LP in PEPCK modulation still needs more clarification. [ABSTRACT FROM AUTHOR]

• Chronic high doses of Decanoate Nandrolone increase reactive oxygen species production in the retroperitoneal adipose tissue. • Chronic high doses of Decanoate Nandrolone lower antioxidant enzymatic activity and decrease total reduced thiol. • Chronic high doses of Decanoate Nandrolone lead to protein oxidative damage in the retroperitoneal adipose tissue. • The oxidative stress in the adipose tissue was established together with an increasing of TNF-α, IL-1β and IL-6 local levels. The non-therapeutic use of the androgenic anabolic steroid Nandrolone Decanoate is popular due to its effects on physical performance and body composition, especially for its lipolytic and anabolic effects associated. However, high doses of such drugs are often associated with a series of pathologies related to unbalanced redox homeostasis, which, in turn, can be linked to inflammation. The oxidative stress onset could deregulate the secretion of cytokines, evidencing a dysfunctional adipocyte. Thus, the aim of this study was to investigate the effect of supraphysiological doses of Nandrolone Decanoate on redox homeostasis of retroperitoneal fatpad of male rats and its relationship with cytokines-based inflammatory signaling. Hydrogen peroxide production was assessed in the retroperitoneal fat pad of adult male rats which received either 10 mg kg of Nandrolone Decanoate or only a vehicle. Also, catalase, superoxide dismutase and glutathione peroxidase activities were measured, together with total reduced thiols and protein carbonylation, as well as IL-1β, TNF-α, and IL-6 local levels. High doses of Nandrolone Decanoate caused an increase in the hydrogen peroxide production, together with lower activities of the antioxidant enzymes and lower levels of total reduced thiol. There were also higher protein carbonylation and greater levels of IL-1β, TNF-α, and IL-6 in the treated group compared to control group. Therefore, it was possible to verify that high doses of Nandrolone Decanoate cause oxidative stress and induce higher inflammatory signaling in retroperitoneal fat pad of male rats. [ABSTRACT FROM AUTHOR]