Nakamura Y, Ohto Y, Murakami A, Osawa T, Ohigashi H
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University.
Jpn J Cancer Res. 1998 Apr;89(4):361-70. doi: 10.1111/j.1349-7006.1998.tb00572.x.
The inhibitory effects of curcumin and two tetrahydrocurcuminoids on tumor promoter-induced oxidative stress in vitro and in vivo were investigated. Curcumin, tetrahydrocurcumin (THC) and dihydroxytetrahydrocurcumin (DHTHC) exhibited significant inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced O2-generation in differentiated HL-60 cells. The inhibitory activity of THC was weaker than that of curcumin. This tendency was the inverse of the results of previous studies on in vitro antioxidative activity against lipid peroxidation. The curcuminoids inhibited TPA-induced intracellular peroxide formation in differentiated HL-60 cells. THC exhibited much weaker inhibition of intracellular peroxide formation than curcumin, suggesting that this inhibition might be attributable to the inhibition of O2-generation. The inhibitory effects of curcuminoids on TPA-induced H2O2 formation in female ICR mouse skin were further examined using the double-TPA-application model. Each TPA application induces two distinct biochemical events, 1) recruitment of inflammatory cells to the inflammatory regions and 2) activation of oxidant-producing cells. Double pretreatment of mice with curcuminoids before each TPA treatment significantly suppressed double TPA application-induced H2O2 formation in the mouse skin. Coadministrations of curcumin with either first or second TPA treatment significantly inhibited H2O2 formation. In addition, THC tends to show weaker inhibitory activities than curcumin in bioassays related to tumor promotion, i.e., inhibition of tumor promoter-induced inflammation in mouse skin and Epstein-Barr virus activation. These tendencies were parallel to those in the tumor-suppressive potential of curcumin and THC in mouse skin, as previously reported. Thus, we concluded that curcuminoids significantly suppress TPA-induced oxidative stress via both interference with infiltration of leukocytes into the inflammatory regions and inhibition of their activation.
研究了姜黄素和两种四氢姜黄素类化合物在体外和体内对肿瘤启动子诱导的氧化应激的抑制作用。姜黄素、四氢姜黄素（THC）和二羟基四氢姜黄素（DHTHC）对12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的分化型HL - 60细胞中的O2生成具有显著抑制作用。THC的抑制活性弱于姜黄素。这种趋势与先前关于体外抗脂质过氧化抗氧化活性的研究结果相反。姜黄素类化合物抑制TPA诱导的分化型HL - 60细胞内过氧化物的形成。THC对细胞内过氧化物形成的抑制作用比姜黄素弱得多，表明这种抑制作用可能归因于对O2生成的抑制。使用双TPA应用模型进一步研究了姜黄素类化合物对雌性ICR小鼠皮肤中TPA诱导的H2O2形成的抑制作用。每次TPA应用会引发两个不同的生化事件，1）炎症细胞募集到炎症区域，2）产生活氧细胞的激活。在每次TPA处理前用姜黄素类化合物对小鼠进行双重预处理可显著抑制双TPA应用诱导的小鼠皮肤中H2O2的形成。在第一次或第二次TPA处理时同时给予姜黄素可显著抑制H₂O₂的形成。此外，在与肿瘤促进相关的生物测定中，即抑制小鼠皮肤中肿瘤启动子诱导的炎症和爱泼斯坦 - 巴尔病毒激活方面，THC的抑制活性往往比姜黄素弱。这些趋势与先前报道中姜黄素和THC在小鼠皮肤中的肿瘤抑制潜力的趋势平行。因此，我们得出结论，姜黄素类化合物通过干扰白细胞向炎症区域的浸润及其激活，显著抑制TPA诱导的氧化应激。
