Açaí (Euterpe oleracea Mart.) presents anti-neuroinflammatory capacity in LPS-activated microglia cells.

INTRODUCTION: Neuropsychiatric diseases are responsible for one of the highest burden of morbidity and mortality worldwide. These illnesses include schizophrenia, bipolar disorder, and major depression. Individuals affected by these diseases may present mitochondrial dysfunction and oxidative stress. Additionally, patients also have increased peripheral and neural chronic inflammation. The Brazilian fruit, açaí, has been demonstrated to be a neuroprotective agent through its recovery of mitochondrial complex I activity. This extract has previously shown anti-inflammatory effects in inflammatory cells. However, there is a lack of understanding of potential anti-neuroinflammatory mechanisms, such as cell cycle involvement. OBJECTIVE: The objective of this study is to evaluate the anti-neuroinflammatory potential of an açaí extract in lipopolysaccharide-activated BV-2 microglia cells. METHODS: Açaí extract was produced and characterized through high performance liquid chromatography. Following açaí extraction and characterization, BV-2 microglia cells were activated with LPS and a dose-response curve was generated to select the most effective açaí dose to reduce cellular proliferation. This dose was then used to assess reactive oxygen species (ROS) production, double-strand DNA release, cell cycle modulation, and cytokine and caspase protein expression. RESULTS: Characterization of the açaí extract revealed 10 bioactive molecules. The extract reduced cellular proliferation, ROS production, and reduced pro-inflammatory cytokines and caspase 1 protein expression under 1 µg/mL in LPS-activated BV-2 microglia cells but had no effect on double strand DNA release. Additionally, açaí treatment caused cell cycle arrest, specifically within synthesis and G2/Mitosis phases. CONCLUSION: These results suggest that the freeze-dried hydroalcoholic açaí extract presents high anti-neuroinflammatory potential.

Uncaria tomentosa extract alters the catabolism of adenine nucleotides and expression of ecto-5'-nucleotidase/CD73 and P2X7 and A1 receptors in the MDA-MB-231 cell line.

ETHOPHARMACOLOGICAL RELEVANCE: Uncaria tomentosa (Willd.) DC. (Rubiaceae) (Ut), also known as cat's claw, is a woody liana widely spread throughout the Amazon rainforest of Central and South America, containing many chemical constituents such as oxindole alkaloids, which are responsible for various biological activities. Since ancient times, the indigenous people of Peru have used it as a bark infusion for the treatment of a wide range of health problems gastric ulcers, arthritis and rheumatism. Recently, Ut is distributed worldwide and used as an immunomodulatory and anti-inflammatory herbal remedy. Additionally, U. tomentosa also has antitumural activity. However, little is known about the action of U. tomentosa on the purinergic system mechanisms, which is involved in tumor progression. AIM OF THE STUDY: Considering the pharmacological properties of U. tomentosa, we sought to evaluate the hydroalcoholic extract U tomentosa is able to influence the purinergic system in breast cancer cells, MDA-MB-231. Through the activity and expression of ectonucleotidases (NTPDase - CD39; Ecto-5'-nucleotidase - CD73) and purinergic repceptores (P2X7 and A1). MATERIALS AND METHODS: A hydroalcoholic extract was prepared in two concentrations, 250 and 500µg/mL. (Ut250; Ut500). The effect of these concentrations on the activity and expression of ectonucleotidases, as well as on the density of purinergic receptors were investigated in MDA-MB-231 breast cancer cells. Cells were treated with the hydroalcoholic extract of Uncaria tomentosa and/or doxorubicin (Doxo 1µM; Ut250+Doxo; Ut500+Doxo) for 24h. RESULTS: Although the results were not significant for the hydrolysis of the ATP, they presented an increase in the ADP hydrolysis in the Ut500+Doxo group when compared to the control group. Additionally, the activity of 5'-nucleotidase was inhibited in all groups when compared with the untreated group of cells. Inhibition of the enzyme was more evident in groups with U. tomentosa per se. The expression of CD39 was increased in the Ut250 and Ut250+Doxo groups when compared to the control group. No changes were found in the CD73 expression. Furthermore, a reduction in the density of the P2X7 receptor in all treated groups was detected. On the other hand, the density of the A1 receptor increased in all groups compared to the control group, with the exception of the Ut500+Doxo group. CONCLUSION: Therefore, we conclude that hydroalcoholic extract of U. tomentosa may be responsible for the reduction of adenosine levels in the extracellular medium, which accelerates tumor progression. Interestingly, the dysregulation of A1 and P2X7 receptors in the MDA-MB-231 cells exacerbate the proliferation of this cells and U. tomentosa treatment may be stimulate the antitumor activity of adenosine A1 receptor and control the P2X7 effects. Our study demonstrates the significant participation of purinergic pathway in the regulation of MDA-MB-231 progression; additionally, U. tomentosa treatment alone or combined with chemotherapy may favor the action of doxorubicin.