Copaifera spp. are Amazonian species widely studied and whose oleoresins are used by local people for various medicinal purposes. However, a detailed study of the activity of the main phytochemical components of these oleoresins remains to be done. Here, we studied the cytotoxicity and in vitro anti-inflammatory effects of six diterpene acids: copalic, 3-hydroxy-copalic, 3-acetoxy-copalic, hardwickiic, kolavic-15-metyl ester, and kaurenoic, isolated from the oleoresins of Copaifera spp. The diterpenes did not show cytotoxicity in normal cell lines, nor did they show significant changes in viability of tumoral line cells. The 3-hydroxy-copalic was able to inhibit the enzyme tyrosinase (64% ± 1.5%) at 250 µM. The kolavic-15-metyl ester at 200 µM showed high inhibitory effect on lipoxygenase (89.5% ± 1.2%). Among the diterpenes tested, only kaurenoic and copalic acids showed significant hemolytic activities with 61.7% and 38.4% at 100 µM, respectively. In addition, it was observed that only the copalic acid (98.5% ± 1.3%) and hardwickiic acid (92.7% ± 4.9%) at 100 mM inhibited nitric oxide production in macrophages activated by lipopolysaccharide. In this assay, the diterpenes did not inhibit tumor necrosis factor-α production. The acids inhibited the production of IL-6, 3-acetoxy-copalic (23.8% ± 8.2%), kaurenoic (11.2% ± 5.7%), kolavic-15-methyl ester (17.3% ± 4.2%), and copalic (4.2% ± 1.8%), respectively, at 25 µM. The kaurenoic, 3-acetoxy-copalic and copalic acids increased IL-10 production. This study may provide a basis for future studies on the therapeutic role of diterpenic acids in treating acute injuries such as inflammation or skin disorders.

Background: The oil-resin of Eperua oleifera Ducke has been used in popular medicine similarly to the copaiba oil (Copaifera spp.). Objective: This study aimed to investigate the effects of the acid fraction of E. oleifera oil-resin (AFEOR) on cell proliferation, collagen production in human fibroblasts, inhibition of metalloproteinases, and cytotoxicity against tumor cell lines. Materials and Methods: Acid fraction of E. oleifera was fractionated in the ion exchange column chromatography. Cytotoxicity and genotoxicity were evaluated by Alamar Blue^® and Cometa assay. The inhibition of metalloproteinases was performed by zymography and Western blotting. Results: The predominant acidic diterpenes in the AFEOR were copalic and hardwickiic acids. AFEOR caused morphology alteration and decrease of proliferation at concentrations higher than 5 μg/mL. It also caused significant collagen proliferation in fibroblasts. It showed cytotoxicity against tumoral and nontumoral cell lines, with IC₅₀values ranging from 13 to 50 μg/mL, and a hemolytic activity with an IC₅₀value of 38.29 μg/mL. AFEOR inhibited collagenase activity, with an IC₅₀value of 46.64 μg/mL, and matrix metalloproteinase-2 (MMP)-2 and MMP-9 in HaCaT cells or MMP-1 expression in MRC-5 cells. AFEOR induced genotoxicity in MRC-5 cells with a DNA damage index between 40% and 60% when compared to the negative controls (0%–20%). Conclusion: For the first time, biological activities from oil-resin E. oleifera demonstrated ratifying somehow its popular use. Abbreviations used: AFEOR: Eperua oleifera oil-resin.

Introduction: Guarana (Paullinia cupana) is a native Amazonian fruit and, due to its medicinal properties, stands out as one of the most promising species of Brazilian flora. Known for its invigorating and stimulating action, this species produces phenolic compounds responsible for its biological activities, which are of great interest to the phytocosmetic industry, in the preparation of anti-aging creams, for example. In this study, the antimicrobial, antioxidant, photoprotective and cytotoxic activities of extracts obtained from guarana seeds were evaluated. Methods: Guarana seeds were obtained in Maués, Amazonas state, Brazil and, after drying, the seeds were ground in a knife mill. P. cupana seed extracts were obtained by the depletion method using hexane, dichloromethane and ethanol as solvents. Antioxidant activity assays were performed to determine the ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH•). To assess the sun protection factor (SPF), Mansur's spectrophotometric method was used. For the analysis of antimicrobial activity, the microplate dilution technique was used against strains of Escherichia coli, Pseudomonas aeruginosa and Candida albicans. To evaluate the toxicity of the extracts, the lethal concentration of 50% of the population of the microcrustacean Artemia salina was determined. The cytotoxic effect of the extracts against human colorectal carcinoma cells (HCT 116) was also evaluated using the Alamar Blue test. Results: The ethanolic extract from guarana seeds showed SPF value of 249.10 and a critical wavelength number (λc) of 383 nm, when evaluated at a concentration of 0.1% (m/m). The ethanolic extract also showed antioxidant activity, and a 50% efficient concentration (EC50) of 647 μg mL-1. The dichloromethane extract was active against E. coli and P. aeruginosa, with a minimum inhibitory concentration (MIC) of 20 mg mL-1 for both bacteria, and a MIC of 2.0 mg mL-1 for the yeast. This extract did not show toxicity against A. salina (LD50> 1 mg mL-1). The ethanolic and hexane extracts, however, presented low toxicity to the microcrustacean. On the other hand, none of the evaluated extracts inhibited the proliferation of HCT116 cells, showing no cytotoxicity. Conclusion: P. cupana seeds have an important therapeutic value due to the presence of substances with antioxidant, antibiotic and photoprotective activities, though with low cytotoxicity, which allows their use as functional additives in phytocosmetics, as well as in the development of possible phytotherapeutic products.