Division of Nephrology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Nephrology, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan.
J Ethnopharmacol. 2018 Oct 5;224:391-399. doi: 10.1016/j.jep.2018.06.023. Epub 2018 Jun 18.
Brown seaweed is a common food for Asians, and the bioactive ingredient fucoxanthin exerts anti-apoptotic activities in several cell types. Renal tubular cell apoptosis is one of the common cellular events leading to renal fibrosis and chronic kidney disease (CKD). However, the influence of fucoxanthin-containing brown seaweed extract on CKD is still unknown. We intended to evaluate the inhibitory effect of fucoxanthin-containing extract from brown seaweed on renal apoptosis under CKD condition and its molecular mechanism.
The fucoxanthin-containing brown seaweed extract (LJE) was prepared from Laminaria japonica. We investigated how LJE influences on both doxorubicin-treated rat renal tubular cells (NRK-52E) and the renal symptoms of nephrectomy-induced CKD mice.
LJE inhibited doxorubicin-induced apoptosis and upregulated Na/H exchanger isoform 1 (NHE1) expression in NRK-52E cells, which were blocked by the NHE1 inhibitor cariporide. LJE also upregulated peroxisome proliferator-activated receptor alpha (PPARα). PPARα siRNA transfection inhibited LJE-induced NHE1 expression and anti-apoptotic effect. In CKD mice, LJE increased NHE1 expression in renal tubules and reduced apoptotic renal tubular cells, but not in PPARα knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice.
We demonstrated that LJE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LJE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.
民族药理学相关性：褐藻是亚洲人的常见食物，其生物活性成分岩藻黄质在几种细胞类型中具有抗细胞凋亡作用。肾小管细胞凋亡是导致肾纤维化和慢性肾脏病（CKD）的常见细胞事件之一。然而，含岩藻黄质的褐藻提取物对 CKD 的影响尚不清楚。我们旨在评估含岩藻黄质的褐藻提取物对 CKD 条件下肾脏细胞凋亡的抑制作用及其分子机制。
材料和方法：从裙带菜中提取含岩藻黄质的褐藻提取物（LJE）。我们研究了 LJE 如何影响多柔比星处理的大鼠肾小管细胞（NRK-52E）和肾切除诱导的 CKD 小鼠的肾脏症状。
结果：LJE 抑制多柔比星诱导的 NRK-52E 细胞凋亡，并上调钠/氢交换体 1（NHE1）的表达，该作用被 NHE1 抑制剂 cariporide 阻断。LJE 还上调过氧化物酶体增殖物激活受体α（PPARα）。PPARα siRNA 转染抑制 LJE 诱导的 NHE1 表达和抗细胞凋亡作用。在 CKD 小鼠中，LJE 增加了肾小管中的 NHE1 表达并减少了凋亡的肾小管细胞，但在 PPARα 敲除小鼠中则没有。LJE 对细胞凋亡的抑制作用也减少了 CKD 小鼠的肾小管间质纤维化并改善了肾功能。
结论：我们证明 LJE 通过上调 NHE1 抑制肾脏细胞凋亡。LJE 的抗凋亡作用也改善了 CKD 小鼠的肾功能。因此，含岩藻黄质的褐藻可能对 CKD 患者具有治疗潜力。
