Institute of Health Science, College of Health Science, Korea University, Seoul 136-703, Republic of Korea.
J Ethnopharmacol. 2010 Oct 5;131(3):567-74. doi: 10.1016/j.jep.2010.07.039. Epub 2010 Jul 24.
The aqueous extract of Terminalia chebular fruits was reported to have anti-hyperglycemia and anti-diabetic complication effects. The present study therefore investigated the protective mechanism of chebulic acid, a phenolcarboxylic acid compound isolated from the ripe fruits of Terminalia chebula against advanced glycation endproducts (AGEs)-induced endothelial cell dysfunction.
To investigate the protective mechanism of chebulic acid against vascular endothelial dysfunction human umbilical vein endothelial cells (HUVEC) were treated with chebulic acid in the presence/absence of glyceraldehyde-related AGEs (glycer-AGEs).
HUVEC incubated with 100 μg/ml of glycer-AGEs had significantly enhanced reactive oxygen species formation, whereas the treatment of chebulic acid dose-dependently reduced glycer-AGE-induced formation to 108.2 ± 1.9% for 25 μM versus 137.8 ± 1.1% for glycer-AGEs treated alone. The transendothelial electrical resistance (TER) value of the glycer-AGEs group was dramatically decreased to 76.9 ± 2.2% compared to the control, whereas chebulic acid treatment prevented glycer-AGE-induced TER change with a value of 91.3 ± 5.3%. The incubation of confluent HUVEC with 100 μg/ml of glycer-AGEs for 24h remarkably increased the adhesion of human monocytic THP-1 cells compared to non-stimulated HUVEC. These increases in HUVEC adhesiveness were dose-dependently reduced by chebulic acid.
The present study shows the effects of chebulic acid against the progression of AGE-induced endothelial cell dysfunction suggesting that this compound may constitute a promising intervention agent against diabetic vascular complications.
诃子果实的水提物具有降血糖和防治糖尿病并发症的作用。本研究因此调查了从诃子果实中分离得到的酚羧酸化合物诃子酸对晚期糖基化终产物（AGEs）诱导的内皮细胞功能障碍的保护机制。
为了研究诃子酸对血管内皮功能障碍的保护机制，用诃子酸处理人脐静脉内皮细胞（HUVEC），同时存在/不存在甘油醛相关 AGEs（甘油-AGEs）。
孵育 100μg/ml 甘油-AGEs 的 HUVEC 显著增强活性氧（ROS）的形成，而诃子酸处理呈剂量依赖性地将甘油-AGE 诱导的形成减少至 25μM 时为 108.2±1.9%，而单独用甘油-AGEs 处理时为 137.8±1.1%。甘油-AGEs 组的跨内皮电阻（TER）值显著下降至 76.9±2.2%，与对照组相比，而诃子酸处理可防止甘油-AGE 诱导的 TER 变化，TER 值为 91.3±5.3%。用 100μg/ml 的甘油-AGEs 孵育 24h 后，与未刺激的 HUVEC 相比，人单核细胞 THP-1 细胞在融合的 HUVEC 上的黏附显著增加。诃子酸可显著降低这种 HUVEC 黏附性的增加。
本研究表明诃子酸对 AGE 诱导的内皮细胞功能障碍的进展有抑制作用，提示该化合物可能是一种有前途的防治糖尿病血管并发症的干预剂。
