de S Vargas Fabiano, D O de Almeida Patrícia, Aranha Elenn Suzany P, de A Boleti Ana Paula, Newton Peter, de Vasconcellos Marne C, Junior Valdir F Veiga, Lima Emerson S
Chemistry Department, Federal University of Amazonas, Av. Gal. Rodrigo Octávio, 6.200, Japiim, Manaus-AM 69080-900, Brazil.
Faculty of Pharmaceutical Sciences, Federal University of Amazonas, Manaus, Av. Gal. Rodrigo Octávio, 6.200, Japiim, Manaus-AM 69080-900, Brazil.
Molecules. 2015 Apr 9;20(4):6194-210. doi: 10.3390/molecules20046194.
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.
古巴乳香属植物是亚马逊地区的物种，已得到广泛研究，其油树脂被当地人用于多种药用目的。然而，对这些油树脂主要植物化学成分的活性仍有待进行详细研究。在此，我们研究了从古巴乳香属植物油树脂中分离出的六种二萜酸的细胞毒性和体外抗炎作用：古巴树脂酸、3-羟基-古巴树脂酸、3-乙酰氧基-古巴树脂酸、哈德威克酸、科拉维酸-15-甲酯和贝壳杉烯酸。这些二萜在正常细胞系中未显示出细胞毒性，在肿瘤细胞系的活力方面也未显示出显著变化。3-羟基-古巴树脂酸在250μM时能够抑制酪氨酸酶（64%±1.5%）。200μM的科拉维酸-15-甲酯对脂氧合酶显示出高抑制作用（89.5%±1.2%）。在所测试的二萜中，只有贝壳杉烯酸和古巴树脂酸在100μM时分别显示出显著的溶血活性，溶血率为61.7%和38.4%。此外，观察到只有100mM的古巴树脂酸（98.5%±1.3%）和哈德威克酸（92.7%±4.9%）抑制脂多糖激活的巨噬细胞中一氧化氮的产生。在该试验中，二萜未抑制肿瘤坏死因子-α的产生。这些酸分别在25μM时抑制白细胞介素-6的产生，3-乙酰氧基-古巴树脂酸（23.8%±8.2%）、贝壳杉烯酸（11.2%±5.7%）、科拉维酸-15-甲酯（17.3%±4.2%）和古巴树脂酸（4.2%±1.8%）。贝壳杉烯酸、3-乙酰氧基-古巴树脂酸和古巴树脂酸增加白细胞介素-10的产生。本研究可为未来关于二萜酸在治疗炎症或皮肤疾病等急性损伤中的治疗作用的研究提供依据。
