Osawa Toshihiko
Laboratory of Food and Biodynamics, Nagoya University Graduate School of Bioagricultural Sciences, Japan.
Adv Exp Med Biol. 2007;595:407-23. doi: 10.1007/978-0-387-46401-5_18.
Curcumin (U1) has a wide spectrum of therapeutic effects such as antitumor and anti-inflammatory effects, including antibacterial, antiviral, antifungal, and antispasmodic activities. By comparison of the structure-activity relationship, tetrahydrocurcumin (THU1), one of the major metabolites, showed the highest antioxidative activity in both in vitro and in vivo systems. U1 has been reported to have the nephroprotective effect to improve creatinine and urea clearance and also protected the chronic renal allograft nephropathy. These beneficial effects have been explained by the protection of oxidative stress and the induction of antioxidative enzymes. The protective effect of THU1 against ferric nitrilotriacetate (Fe-NTA)-induced oxidative renal damage using male ddY mice was greater than that of U1, by monitoring not only radical scavenging activity measured by ESR, and TBARS, 4-HNE-modified protein and 8-OHdG formation but also induction of anioxidative enzymes and detoxification enzymes. THU1 was also expected to improve redox regulation through glutathione and suppress the oxidative stress in diabetic nephropathy and neuropathy. Earlier studies reported that U1 reduced the iron-induced hepatic damage, aflatoxin- and benzo[a]pyrene- induced mutagenicity and hepatocarcinogenecity and also the formation of the DNA adduct by inhibiting cytochrome P450 in the liver. The hepatoprotective role of U1 has been examined using carbone terachloride-induced liver damage in rats and alcoholic liver disease model rats, but not examined using THU1. Our recent data suggests that THU1 is a more promising hepatprotective agent because of its strong induction activity of antioxidant and phase 2-metabolizing enzymes in liver compared to kidney, although more detaied examinations are required.
姜黄素（U1）具有广泛的治疗作用，如抗肿瘤和抗炎作用，包括抗菌、抗病毒、抗真菌和抗痉挛活性。通过比较构效关系，主要代谢产物之一的四氢姜黄素（THU1）在体外和体内系统中均表现出最高的抗氧化活性。据报道，U1具有肾脏保护作用，可改善肌酐和尿素清除率，并对慢性肾移植肾病起到保护作用。这些有益作用可通过氧化应激保护和抗氧化酶的诱导来解释。通过监测不仅通过电子自旋共振（ESR）、硫代巴比妥酸反应物（TBARS）、4-羟基壬烯醛（4-HNE）修饰蛋白和8-羟基脱氧鸟苷（8-OHdG）形成所测量的自由基清除活性，还监测抗氧化酶和解毒酶的诱导，THU1对雄性ddY小鼠铁氰化三乙酸（Fe-NTA）诱导的氧化性肾损伤的保护作用大于U1。THU1还有望通过谷胱甘肽改善氧化还原调节，并抑制糖尿病肾病和神经病变中的氧化应激。早期研究报道，U1可减轻铁诱导的肝损伤、黄曲霉毒素和苯并[a]芘诱导的致突变性和肝癌发生，还可通过抑制肝脏中的细胞色素P450来减少DNA加合物的形成。已在大鼠四氯化碳诱导的肝损伤和酒精性肝病模型大鼠中研究了U1的肝脏保护作用，但未使用THU1进行研究。我们最近的数据表明，由于与肾脏相比，THU1在肝脏中对抗氧化酶和II相代谢酶具有较强的诱导活性，因此它是一种更有前景的肝脏保护剂，尽管还需要更详细的研究。
