Impaired mitochondrial function and reduced viability in bone marrow cells of obese mice.

Bone marrow cells (BMCs) are the main type of cells used for transplantation therapies. Obesity, a major world health problem, has been demonstrated to affect various tissues, including bone marrow. This could compromise the success of such therapies. One of the main mechanisms underlying the pathogenesis of obesity is mitochondrial dysfunction, and recent data have suggested an important role for mitochondrial metabolism in the regulation of stem cell proliferation and differentiation. Since the potential use of BMCs for clinical therapies depends on their viability and capacity to proliferate and/or differentiate properly, the analysis of mitochondrial function and cell viability could be important approaches for evaluating BMC quality in the context of obesity. We therefore compared BMCs from a control group (CG) and an obese group (OG) of mice and evaluated their mitochondrial function, proliferation capacity, apoptosis, and levels of proteins involved in energy metabolism. BMCs from OG had increased apoptosis and decreased proliferation rates compared with CG. Mitochondrial respiratory capacity, biogenesis, and the coupling between oxidative phosphorylation and ATP synthesis were significantly decreased in OG compared with CG, in correlation with increased levels of uncoupling protein 2 and reduced peroxisome proliferator-activated receptor-coactivator 1α content. OG also had decreased amounts of the glucose transporter GLUT-1 and insulin receptor (IRß). Thus, Western-diet-induced obesity leads to mitochondrial dysfunction and reduced proliferative capacity in BMCs, changes that, in turn, might compromise the success of therapies utilizing these cells.

Pterodon pubescens seed extract induces the cell cycle arrest of leukemic cells by deregulating cyclin D1 and E2 mRNA levels.

Plant-derived compounds are important sources of effective anti-cancer agents. Pterodon pubescens is a native Brazilian plant popularly known for its anti-inflammatory and anti-arthritic effects. The ethanolic extract of its seeds (EEPp) is a viscous, brown and fragrant oil containing geranylgeraniol, farnesol, naphthalene, dimethyldodecatrienol and vouacapan diterpene derivatives, in addition to other compounds. This study investigated the in vitro anti-leukemic properties of EEPp using the resistant human leukemia cell line K562. The EEPp anti-proliferative effect was demonstrated by the inhibition of DNA synthesis and cell growth, and the induction of cell cycle arrest in the G(1) phase. Furthermore, cyclin E2 mRNA levels were down-regulated, while those of cyclin D1 were up-regulated. An EEPp anti-leukemic effect may have also triggered apoptosis, as it increased the number of shrunken cells and phosphatidylserine cell membrane exposure. These observations suggest that EEPp deregulates cyclin D1 and E2 expression, inducing cell cycle arrest and apoptosis of leukemic cells.

Immunosuppressive effects of Echinodorus macrophyllus aqueous extract.

Echinodorus macrophyllus is a medicinal plant, popularly known in Brazil as "chapéu de couro", used to treat rheumatic diseases, which are usually characterized by exacerbated T and B lymphocyte response. We have evaluated the effects of the aqueous extract of Echinodorus macrophyllus (AEEm) on these cell functions, proliferation, and nitric oxide production. Mice treated orally for 7 days with AEEm had inhibited B cell antibody production (0.5mg/kg b.w.) and delayed type hypersensitivity (0.5 and 5mg/kg b.w.) mediated by T cells, reducing subcutaneous tissue leukocyte infiltration. AEEm inhibited, in vitro, NO production by stimulating J774 cells in a dose-dependent manner, with no cytotoxicity. We have demonstrated, for the first time, its immunosuppressive effect. This immunosuppressive effect supports a potential therapeutic use of AEEm to control exacerbated humoral and/or cellular immune response, as in autoimmune rheumatic diseases. However, it is important to be cautious about its indiscriminate popular use to avoid side effects, mainly in immunodeficiency diseases.

Antinociceptive properties of ethanolic extract and fractions of Pterodon pubescens Benth. seeds.

We have previously demonstrated that the hydroalcoholic extract from Pterodon pubescens Benth. seeds (sucupira branca, Leguminosae) exhibits anti-arthritic activity and that its oleaginous extract (OEP) and PF1 fraction exhibit acute and topic anti-edematogenic activities. In this work, we studied the antinociceptive activity of OEP and its fractions on the acetic acid-induced abdominal constriction and formalin assays in SW male mice. OEP was obtained by ethanol extraction and its four fractions by sequential liquid-liquid extraction. PF2 GC/MS profile indicated it contains furane diterpenes derivatives of vouacapan and non-vouacapan compounds. The antinociceptive properties were demonstrated to OEP and predominantly to PF1 and PF2 by the writhing test. In the formalin assay, PF1 inhibited both phases and PF2 inhibited mainly the late one. Then, PF1 and PF2 seemed to present antinociceptive effects by different mechanisms, peripheral and/or central inhibitory ones, and showed maximum antinociceptive properties with very low doses, providing a rationale for its popular use in pain disorders.