Ethnopharmacological relevance: The endemic Brazilian medicinal plants of the genus Terminalia (Combretaceae), popularly known as capita tilde o, comprising the similar species Terminalia phaeocarpa Eichler and Terminalia argentea, are traditionally and indistinguishably used in the country to treat diabetes.Aim of the study: The present work investigated the effect of 28 days of treatment with the crude ethanolic extract (CEE) and its derived ethyl acetate fraction (EAF) from T. phaeocarpa leaves in a mice model of diabetes.Materials and methods: Streptozotocin-nicotinamide-fructose diabetic model was used to evaluate the antidiabetic activity of 28 days of treatment with the CEE and EAF from the leaves of T. phaeocarpa and metformin as a positive control. Serum levels of total cholesterol, triglycerides, uric acid, ALP, AST, and ALT were measured with specific commercial kits and glucose with a strip glucometer. The thiobarbituric acid method measured the liver MDA level, while a colorimetric assay measured the GSH level and PTP1B activity. A UPLC-DAD profile was obtained to identify the main polyphenolic compound in the EAF.Results: Treatment with CEE and EAF reduced plasma glucose in diabetic mice. At the end of the treatment, the plasma glucose level was significantly lower in EAF-treated (100 mg/kg) diabetic mice (106.1 +/- 13.7 mg/dL) than those treated with 100 mg/kg CEE (175.2 +/- 20.9 mg/dL), both significantly lower than untreated diabetic mice (350.4 +/- 28.1 mg/dL). The serum levels of total cholesterol, triglycerides, uric acid, ALP, AST, and ALT were significantly reduced in diabetic mice treated with CEE and EAF. In the livers of diabetic mice, the treat-ment with CEE and EAF reduced MDA levels and the activity of the enzyme PTP1B (96.9 +/- 3.7%, 113.8 +/- 2.8%, and 134.8 +/- 4.6% for CEE-, EAF-treated, and untreated diabetic mice, respectively). Galloylpunicalagin was the main polyphenol observed in the EAF of T. phaeocarpa.Conclusion: The present results demonstrate the significant antidiabetic effect of CEE and EAF of T. phaeocarpa and their reduction on the markers of liver dysfunction in diabetic mice. Moreover, the antidiabetic activity of T. phaeocarpa might be associated with lowering the augmented activity of the PTP1B enzyme in the liver of diabetic mice.

Abstract Hancornia speciosa is a medicinal species traditionally used in Brazilian folk medicine to treat a variety of conditions. Compounds isolated from the leaves, bark, and trunk of this plant have shown therapeutic properties, but only recently have the fruits of H. speciosa been explored for potential pharmacological applications. The present study investigated the effects of an ethanolic extract from the fruits, fractions, and compounds thereof in bone resorbing cells. Primary osteoclast cultures from bone marrow cells and osteoclasts derived from a monocyte/macrophage cell line, RAW 264.7, were incubated with different concentrations of the ethanolic extract, ethyl acetate fraction, water fraction, quinic acid, and L-(+)-bornesitol. In RAW 264.7 cell cultures, quinic acid significantly reduced osteoclast formation. In bone marrow cell-derived osteoclasts, the ethyl acetate fraction induced a decrease in the number of osteoclasts, promoting a remarkable reduction in the mean area of those cells and in their resorption activity. The compounds quinic acid and bornesitol also affected bone marrow cell-derived osteoclasts. In both cell cultures, the substances tested did not affect cell viability/proliferation. In conclusion, components extracted from H. speciosa fruit affected the cells responsible for bone resorption, making them promising tools for interference in osteoclastogenesis.

Sphingosine-1-phosphate (S1P) is an important sphingolipid derived from plasma membrane and has a known role in productive phase of inflammation, but its role in neutrophil survival and resolution phase of inflammation is unknown. Here, we investigated the effects of inhibition of S1P receptors and the blockade of S1P synthesis in BALB/c mice and human neutrophils. S1P and S1PR1-3 receptors expression were increased in cells from the pleural cavity stimulated with LPS. Using different antagonists of S1PRs and inhibitors of different steps of the metabolic pathway of S1P production, we show that S1P and its receptors are involved in regulating neutrophil survival and resolution of inflammation in the pleural cavity. Given the role of the S1P-S1PR axis in resolution of inflammation, we sought to identify whether blockade at different levels of the sphingosine-1-phosphate synthesis pathway could affect neutrophil survival in vitro. Inhibitors of the S1P pathway were also able to induce human neutrophil apoptosis. In addition, blockade of S1P synthesis or its receptor facilitated the efferocytosis of apoptotic neutrophil. Taken together, our data demonstrate a fundamental role for S1P in regulating the outcome of inflammatory responses, and position S1P-S1PR axis as a potential target for treatment of neutrophilic inflammation.