A Comprehensive Description of the Anatomy and Histochemistry of Psychotria capillacea (Müll. Arg.) Standl. and an Investigation into Its Anti-Inflammatory Effects in Mice and Role in Scopolamine-Induced Memory Impairment.

Species of the genus Psychotria are used in popular medicine for pain, inflammatory symptoms, and mental disorders. Psychotria capillacea (Müll. Arg.) Standl. (Rubiaceae) is commonly known as coffee and some scientific studies have demonstrated its therapeutic potential. The goal of this study was to investigate the anti-inflammatory and neuroprotective effects, and acetylcholinesterase (AChE) inhibitory activity of a methanolic extract obtained from leaves of P. capillacea (MEPC), as well as the micromorphology and histochemistry of the leaves and stems of this plant. In addition, the MEPC was analyzed by UHPLC-MS/MS and the alkaloidal fraction (AF) obtained from the MEPC was tested in a mouse model of inflammation. MEPC contained three indole alkaloids, one sesquiterpene (megastigmane-type) and two terpene lactones. MEPC (3, 30 and 100 mg/kg) and AF (3 and 30 mg/kg) were evaluated in inflammation models and significantly inhibited edema at 2 h and 4 h, mechanical hyperalgesia after 4 h and the response to cold 3 h and 4 h after carrageenan injection. Scopolamine significantly increased the escape latency, and reduced the swimming time and number of crossings in the target quadrant and distance, while MEPC (3, 30 and 100 mg/kg), due to its neuroprotective actions, reversed these effects. AChE activity was significantly decreased in the cerebral cortex (52 ± 3%) and hippocampus (60 ± 3%), after MEPC administration. Moreover, micromorphological and histochemical information was presented, to aid in species identification and quality control of P. capillacea. The results of this study demonstrated that P. capillacea is an anti-inflammatory and antihyperalgesic agent that can treat acute disease and enhance memory functions in mouse models.

Acrocomia aculeata associated with doxorubicin: cardioprotection and anticancer activity.

Doxorubicin (Dox) is a chemotherapeutic agent widely used in the clinic, whose side effects include cardiotoxicity, associated with decreased antioxidant defenses and increased oxidative stress. The association of Dox with natural antioxidants can extend its use if not interfering with its pharmacological potential. In this study, we aimed to understand the effects and mechanisms of the aqueous extract of Acrocomia aculeata leaves (EA-Aa) in cancer cells and the co-treatment with Dox, in in vitro and in vivo models. It was found that EA-Aa showed a relevant decrease in the viability of cancer cells (K562 and MCF-7) and increased apoptosis and death. The Dox cytotoxic effect in co-treatment with EA-Aa was increased in cancer cells. The therapeutic association also promoted a change in cell death, leading to a higher rate of apoptosis compared to the Dox group, which induced necrosis. In addition, in non-cancer cells, EA-Aa enhanced red blood cell (RBC) redox state with lower hemolysis and malondialdehyde (MDA) content and had no in vitro nor in vivo toxicity. Furthermore, EA-Aa showed antioxidant protection against Dox-induced cytotoxicity in H9c2 cells (cardiomyoblast), partially mediated by the NRF2 pathway. In vivo, EA-Aa treatment showed a relevant decrease in MDA levels in the heart, kidney, and brain, evaluated in C57Bl/6 mice induced to cardiotoxicity by Dox. Together, our results proved the effectiveness of EA-Aa in potentiating Dox anticancer effects, with antioxidant and cardioprotective activity, suggesting EA-Aa as a potential Dox pharmacological adjuvant.

Acrocomia aculeata (Jacq.) Lodd. ex Mart. Leaves Increase SIRT1 Levels and Improve Stress Resistance.

Oxidative stress is a metabolic disorder linked with several chronic diseases, and this condition can be improved by natural antioxidants. The fruit pulp of the palm Acrocomia aculeata (Jacq.) Lodd. ex Mart. is widely used in the treatment of various illnesses, but as far as we know, there are no reports regarding the properties of its leaves. Thus, we aimed to evaluate the antioxidant activity of A. aculeata leaf extracts obtained with water (EA-Aa), ethanol (EE-Aa), and methanol (EM-Aa) solvents. The extracts were chemically characterized, and their antioxidant activity was assessed through the scavenging of the free radicals DPPH and ABTS. EE-Aa and EM-Aa showed the highest amounts of phenolic compounds and free radical scavenging activity. However, EA-Aa was more efficient to protect human erythrocytes against AAPH-induced hemolysis and lipid peroxidation. Thus, we further show the antioxidant effect of EA-Aa in preventing AAPH-induced protein oxidation, H2O2-induced DNA fragmentation, and ROS generation in Cos-7 cells. Increased levels of Sirt1, catalase, and activation of ERK and Nrf2 were observed in Cos-7 treated with EA-Aa. We also verify increased survival in nematodes C. elegans, when induced to the oxidative condition by Juglone. Therefore, our results showed a typical chemical composition of plants for all extracts, but the diversity of compounds presented in EA-Aa is involved in the lower toxicity and antioxidant properties provided to the macromolecules tested, proteins, DNA, and lipids. This protective effect also proven in Cos-7 and in C. elegans was probably due to the activation of the Sirt1/Nrf2 pathway. Altogether, the low toxicity and the antioxidant properties of EA-Aa showed in all the experimental models support its further use in the treatment of oxidative stress-related diseases.

Guazuma ulmifolia Lam. Decreases Oxidative Stress in Blood Cells and Prevents Doxorubicin-Induced Cardiotoxicity.

Doxorubicin (DOX) is an efficient chemotherapeutic agent, but its clinical application is limited by its cardiotoxicity associated with increased oxidative stress. Thus, the combination of DOX and antioxidants has been encouraged. In this study, we evaluated (I) the chemical composition and antioxidant capacity of aqueous extracts from Guazuma ulmifolia stem bark (GUEsb) and leaves (GUEl) in 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging, 2,2'-azobis(2-amidinopropane) dihydrochloride- (AAPH-) or DOX-induced lipid peroxidation inhibition in human blood cells, and intracellular reactive oxygen species (ROS) quantification using the fluorescent probe dichloro-dihydro-fluorescein diacetate (DCFH-DA) in K562 erythroleukemia cells incubated with GUEsb and stimulated with hydrogen peroxide; (II) the viability of K562 cells and human leukocytes treated with GUEsb in the absence or presence of DOX using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay; (III) the acute toxicity of GUEsb; and (IV) the cardioprotective effect of GUEsb in C57Bl/6 mice treated with DOX. The chemical composition indicated the presence of flavan-3-ol derivatives and condensed tannins in GUEsb and glycosylated flavonoids in GUEl. GUEsb and GUEl showed free-radical scavenging antioxidant activity, antihemolytic activity, and AAPH- as well as DOX-induced malondialdehyde content reduction in human erythrocytes. Based on its higher antioxidant potential, GUEsb was selected and subsequently showed intracellular ROS reduction without impairing the chemotherapeutic activity of DOX in K562 cells or inducing leukocyte cell death, but protected them against DOX-induced cell death. Yet, GUEsb did not show in vivo acute toxicity, and it prevented MDA generation in the cardiac tissue of DOX-treated mice, thus demonstrating its cardioprotective effect. Taken together, the results show that GUEsb and GUEl are natural alternatives to treat diseases associated with oxidative stress and that, in particular, GUEsb may play an adjuvant role in DOX chemotherapy.

Antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea.

Diabetes has emerged as one of the largest global epidemics; it is estimated that by 2035, there will be 592 million diabetic people in the world. Brazilian biodiversity and the knowledge of traditional peoples have contributed to the treatment of several diseases, including diabetes. Apis mellifera bee tea is used by indigenous Brazilians to treat diabetes, and this traditional knowledge needs to be recorded and studied.The objective of this study was to record the use and to evaluate the antioxidant, antihyperglycemic, and antidiabetic activity of Apis mellifera bee tea, which is used by the Guarani and Kaiowá indigenous people for the treatment of diabetes. Semi-structured interviews were performed with Guarani and Kaiowá ethnic indigenous people from the State of Mato Grosso do Sul, Brazil, seeking to identify the animal species used for medicinal purposes. For the experimental procedures, tea prepared with macerated Apis mellifera bees was used. In vitro assays were performed to evaluate antioxidant activity; direct free radical scavenging, protection against oxidative hemolysis, lipid peroxidation were evaluated in human erythrocytes and potential in inhibiting the formation of advanced glycation end products (AGEs). In vivo, normoglycemic Swiss male mice treated with Apis mellifera tea (AmT) were subjected to the oral glucose tolerance test and compared with control and metformin-treated groups. Diet-induced diabetic mice were treated for 21 days with AmT and evaluated for glycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes. During interviews, the indigenous people described the use of Apis mellifera bee tea for the treatment of diabetes. In in vitro assays, AmT showed direct antioxidant activity and reduced oxidative hemolysis and malondialdehyde generation in human erythrocytes. The AmT inhibited the formation of AGEs by albumin-fructose pathways and methylglyoxal products. In vivo, after oral glucose overload, normoglycemic mice treated with AmT had reduced hyperglycemia at all times evaluated up to 180 min. AmT also reduced hyperglycemia and malondialdehyde levels in the blood, liver, nervous system, and eyes of diabetic mice to similar levels as those in metformin-treated mice and normoglycemic controls. In summary, Apis mellifera bee tea showed antioxidant, antihyperglycemic, and antidiabetic activity, which provides support for the therapeutic application of Guarani and Kaiowá indigenous knowledge.