Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Division of Nephrology and Hypertension, 1124 W Carson St, Torrance, CA 90502, USA.
BMC Complement Altern Med. 2010 Nov 12;10:67. doi: 10.1186/1472-6882-10-67.
Curcumin has anti-inflammatory, anti-oxidant, and anti-proliferative properties, and depending upon the experimental circumstances, may be pro- or anti-apoptotic. Many of these biological actions could ameliorate diabetic nephropathy.
METHODS/DESIGN: Mouse podocytes, cultured in basal or high glucose conditions, underwent acute exposure to curcumin. Western blots for p38-MAPK, COX-2 and cleaved caspase-3; isoelectric focusing for HSP25 phosphorylation; and DNase I assays for F- to G- actin cleavage were performed for in vitro analyses. In vivo studies examined the effects of dietary curcumin on the development of diabetic nephropathy in streptozotocin (Stz)-induced diabetes in DBA2J mice. Urinary albumin to creatinine ratios were obtained, high performance liquid chromatography was performed for urinary curcuminoid measurements, and Western blots for p38-MAPK and total HSP25 were performed.
Curcumin enhanced the phosphorylation of both p38MAPK and downstream HSP25; inhibited COX-2; induced a trend towards attenuation of F- to G-actin cleavage; and dramatically inhibited the activation of caspase-3 in vitro. In curcumin-treated DBA2J mice with Stz-diabetes, HPLC measurements confirmed the presence of urinary curcuminoid. Nevertheless, dietary provision of curcumin either before or after the induction of diabetes failed to attenuate albuminuria.
Apart from species, strain, early differences in glycemic control, and/or dosing effects, the failure to modulate albuminuria may have been due to a decrement in renal HSP25 or stimulation of the 12/15 lipoxygenase pathway in DBA2J mice fed curcumin. In addition, these studies suggest that timed urine collections may be useful for monitoring curcumin dosing and renal pharmacodynamic effects.
姜黄素具有抗炎、抗氧化和抗增殖特性，根据实验情况，可能具有促凋亡或抗凋亡作用。这些生物学作用中的许多都可以改善糖尿病肾病。
方法/设计：在基础或高糖条件下培养的小鼠足细胞，急性暴露于姜黄素。进行 Western blot 检测 p38-MAPK、COX-2 和 cleaved caspase-3；等电聚焦检测 HSP25 磷酸化；DNase I 测定 F-肌动蛋白到 G-肌动蛋白的切割，进行体外分析。体内研究检查了膳食姜黄素对链脲佐菌素（Stz）诱导的 DBA2J 小鼠糖尿病肾病发展的影响。获得尿白蛋白与肌酐比值，进行高效液相色谱法测量尿姜黄素含量，并进行 Western blot 检测 p38-MAPK 和总 HSP25。
姜黄素增强了 p38MAPK 和下游 HSP25 的磷酸化；抑制 COX-2；诱导 F-肌动蛋白到 G-肌动蛋白切割的趋势减弱；并显著抑制了体外 caspase-3 的激活。在 Stz 糖尿病的 DBA2J 小鼠中，HPLC 测量证实存在尿姜黄素。然而，膳食提供的姜黄素无论是在糖尿病诱导之前还是之后，都未能减轻蛋白尿。
除了物种、品系、血糖控制早期差异和/或给药效果外，未能调节蛋白尿可能是由于 DBA2J 小鼠给予姜黄素后肾脏 HSP25 减少或 12/15 脂氧合酶途径的刺激所致。此外，这些研究表明，定时尿液收集可能有助于监测姜黄素的给药和肾脏药效学效应。
