Biological Activities and Cytotoxicity of Diterpenes from Copaifera spp. Oleoresins

Abstract

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.

Copaiba Oil Influences Ventral Hernia Repair With Vicryl® Mesh?

“…Although with effects on the modulation of the inflammatory response, the copaiba oil did not show a change in the repair of the healing process. There was almost no effect when compared to other studies where this oil was supplied prophylactically 16 19 .…”

Copaifera of the Neotropics: A Review of the Phytochemistry and Pharmacology

“…The oleoresins of several Copaifera species have been shown to be rich sources of clerodane, kaurane, and labdane triterpenoids ( Figure 1 , Figure 2 and Figure 3 , Table 2 ). In particular, C. langsdorffii resin is composed of biologically active copalic acid [ 70 , 71 ] and kaurenoic acid [ 72 , 73 , 74 ]. C. multijuga [ 74 ] and C. paupera [ 75 ] resins are also good sources of copalic acid.…”

“…Copalic acid, isolated from C. langsdorffii , showed in vitro cytotoxicity on MO59J human glioblastoma cells and HeLa human cervical adenocarcinoma cells with IC 50 of 68.3 and 44.0 μg/mL, respectively [ 71 ]. Kaurenoic acid has demonstrated cytotoxicity against several human tumor cell lines, including CEM leukemia, MCF-7 breast tumor, HCT-8 colon tumor [ 73 ], AGP01 gastric tumor, and SF-295 glioblastoma [ 74 ]. Growth inhibition of AGP01 and SF-295 cells was also demonstrated by 3β-alepterolic acid and 3β-alepterolic acid acetate [ 73 ].…”

An Overview of Biotransformation and Toxicity of Diterpenes

“…Diterpenes have been identified as active compounds in several medicinal plants showing remarkable biological activities [ 4 , 11 , 12 , 13 , 14 ]. Paclitaxel and ingenol-3-angelate are examples of important anti-cancer drugs [ 4 ] and forskolin, salvinorin A, triptolide, carnosic acid and ginkgolide B are prominent compounds showing cardioprotective, analgesic, anti-inflammatory, antioxidant and inhibitor of platelet activating-factor effects, respectively [ 4 ].…”