The high prevalence of diabetes and obesity encourages research for the development of α-glucosidase inhibitors from natural sources. This study evaluated the activity of fractions obtained from Protium spruceanum branches. Anti-α-glucosidase activity was investigated in vitro using 4-nitrophenyl-α-D-glucopyranoside as the substrate, while free-radical scavenging activity was evaluated by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2’-azinobis-3-ethylbenzotiazoline-6-sulfonic acid (ABTS) assays. Furthermore, a model of oxidative stress promoted by H2O2 in fibroblasts was employed, and cell viability was determined by sulforhodamine B. Fractions inhibited α-glucosidase activity effectively, highlighting the hydromethanolic fraction (HMF). Quercitrin, isolated from the HMF, was identified by spectroscopy and quantified by a validated high performance liquid chromatography with diode array detector (HPLC-DAD) method and exhibited free radical scavenging activity comparable to the HMF. However, this flavonoid showed low anti-α-glucosidase effect, suggesting a synergism effect among several components of the HMF. This proposal is also supported by the docking results obtained by PyRx software. The compounds present in the HMF showed a noncompetitive inhibition at the in silico simulation. Finally, the HMF also protected fibroblasts against cell death induced by oxidative stress. This is the first evidence of the capacity of P. spruceanum branches to inhibit α-glucosidase activity and to counteract oxidative stress. These results encourage the use of this Brazilian plant against hyperglycemia-correlated diseases.

ABSTRACT The metabolism of ethanol occurs mainly in the liver, promoting increase of reactive oxygen species and nitrogen, leading to redox imbalance. Therefore, antioxidants can be seen as an alternative to reestablish the oxidizing/reducing equilibrium. The aim of this study was to evaluate the antioxidant and hepatoprotective effect of aqueous extract of Baccharis trimera (Less.) DC., Asteraceae, in a model of hepatotoxicity induced by ethanol. The extract was characterized and in vitro tests were conducted in HepG2 cells. It was evaluated the cells viability exposed to aqueous extract for 24 h, ability to scavenging the radical DPPH, besides the production of reactive oxygen species and nitric oxide, and the influence on the transcriptional activity of transcription factor Nrf2 (12 and 24 h) after exposure to 200 mM ethanol. The results showed that aqueous extract was non-cytotoxic in any concentration tested; moreover, it was observed a decrease in ROS and NO production, also promoting the transcriptional activity of Nrf2. In vivo, we pretreatment male rats Fisher with 600 mg/kg of aqueous extract and 1 h later 5 ml/kg of absolute ethanol was administrated. After two days of treatment, the animals were euthanized and lipid profile, hepatic and renal functions, antioxidant status and oxidative damage were evaluated. The treatment with extract improved liver function and lipid profile, reflecting the reduction of lipid microvesicules in the liver. It also promoted an increase of glutathione peroxidase activity, decrease of oxidative damage and MMP-2 activity. These results, analyzed together, suggest the hepatoprotective effect of B. trimera aqueous extract.

Lupeol, a triterpene frequently found in Asteraceae plant species, showed moderate to low activity in different strains of Plasmodium falciparum, the most virulent malaria etiological agents. In this work, lupeol was isolated from Parahancornia fasciculata, a plant that is used to treat malaria in the Amazonia region. In the search of more activity lupeol derivatives, five new 1,2,3-triazole hybrid molecules were synthetized by copper-catalyzed azide-alkyne cycloaddition. The antiplasmodial activity of the semi-synthetic compounds were evaluated by the lactate dehydrogenase assay; the lupeol propargyl ether was the only one to disclosing increased activity (half maximal inhibitory concentration-IC50-62.0 ± 1.92 µmol L-1) in relation to lupeol (IC50 117.00 µmol L-1). Therefore, this work revealed a new class of interesting lupeol derivatives that can be obtained by linking electron donors to the hydroxy group at C-3.

We herein report the synthesis of hybrid kauranoid molecules of type 1,2,3-triazole-1,4-disubstituted aiming to improve the antimalarial activity of kaurenoic and xylopic acids. The CuI-catalyzed cycloaddition of azides and kauranoid terminal alkynes was explored as a hybridization strategy. Kauranoid terminal alkynes were prepared from kaurenoic and xylopic acids that were isolated from Wedelia paludosa D. C. (Asteraceae) and Xylopia frutescens Aubl. (Annonaceae). A total of 15 kauranoid derivatives, including nine new triazoles, were obtained and five out of these were more active than the original diterpenes. Interestingly, an increased activity was observed for a kauranoid propargyl ether. Interaction between ent-kaurane diterpene derivatives and Ca2+-ATPase (PfATP6) was investigated. Synthesis of diterpene derivatives emerges as a possible route to be explored in the quest of potentially new inhibitors of PfATP6.

Pectolinarina, uma flavona heterosídica, foi isolada do extrato etanólico das folhas de Distictella elongata (Vahl) Urb., além de uma mistura de ácidos ursólico, pomólico e oleanólico, além de β-sitosterol. Suas estruturas foram estabelecidas com base em análise espectral (RMN de 1H e 13C 1D e 2D) em comparação com a literatura. Esta é a primeira vez em que se relata a ocorrência deste flavonoide em uma espécies da família Bignoniaceae.

Pectolinarin, a flavone heteroside, was isolated from Distictella elongata (Vahl) Urb. leaves ethanol extract, along with a mixture of ursolic, pomolic and oleanolic acids, besides β-sitosterol. Their structures were established on the basis of spectral analysis (1H and 13C NMR, 1D and 2D) and they were compared with literature. This is the first report on the occurrence of this flavonoid in a species of the Bignoniaceae family.

Wedelia paludosa D.C. (Asteraceae) é uma planta ornamental facilmente encontrada em várias regiões do Brasil, principalmente nos estados de Santa Catarina, São Paulo, Minas Gerais, Bahia e Pernambuco. Objetivando descobrir novas substâncias citotóxicas a partir desta espécie, o extrato hidrometanólico de W. paludosa (HME) e as frações diclorometânica (FD) e aquosa (FA) resultantes de sua partição em CH2Cl2-H2O foram avaliados utilizando-se o bioensaio em Artemia salina. A fração diclorometânica (FD) apresentou a maior atividade citotóxica (CL50 = 140,6 μg/mL), e sua análise por cromatografia líquida de alta eficiência empregando-se fase reversa (FR-CLAE) revelou os ácidos caurenóico (1, 6,22 ± 0,23%) e grandiflorênico (2, 3,22 ± 0,31%) como constituintes majoritários. As amostras HME (CL50 = 980 μg/mL), FD (CLC50 = 140,6 μg/mL), 1 (CL50 = 15,9 μg/mL) e 2 (CL50 = 29,8 μg/mL) foram citotóxicas contra A. salina, enquanto que a fração aquosa (FA, CL50 >> 1000 μg/mL) mostrou-se inativa. Conclui-se que a citotoxidade observada para HME e FD pode ser atribuída à presença dos ácidos caurenóico (1) e grandiflorênico (2) nestes extratos.

Wedelia paludosa D.C. (Asteraceae) is an ornamental species occurring in many regions of Brazil. Aiming to find new cytotoxic compounds, the hydromethanol extract of W. paludosa (HME), as well as the dichloromethane (DF) and water (WF) fractions resulting from its partition, were submitted to the brine shrimp lethality bioassay (BSLB) in order to evaluate their cytotoxicity. Dichloromethane fraction (DF) was shown to be the most cytotoxic fraction (LC50 = 140.6 μg/mL), and its analysis by reversed phase high performance liquid chromatography (RP-HPLC) revealed ent-kaurenoic (1, 6.22 ± 0.23%) and grandiflorenic (2, 3.22 ± 0.31%) acids as important constituents. HME (LC50 = 980 μg/mL), DF (LC50 = 140.6 μg/mL), 1 (LC50 = 15.9 μg/mL) and 2 (LC50 = 29.8 μg/mL) were found to be cytotoxic, while the water fraction (WF, LC50 >> 1000 μg/mL) was inactive. As conclusion, the cytotoxicity observed for HME and DF is mainly due to the presence of 1 and 2 in their constitution.