Alleviative effect of fucoxanthin-containing extract from brown seaweed Laminaria japonica on renal tubular cell apoptosis through upregulating Na+/H+ exchanger NHE1 in chronic kidney disease mice

Ethnopharmacological relevance: 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. Materials and methods: The fucoxanthin-containing brown seaweed extract (LIE) 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. Results: LIE 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. LIE also upregulated peroxisome proliferator-activated receptor alpha (PPAR alpha). PPAR alpha 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 PPARa knockout mice. The inhibitory effect of LJE on apoptosis also reduced renal tubulointerstitial fibrosis and improved renal function in CKD mice. Conclusion We demonstrated that LIE inhibits renal apoptosis via NHE1 upregulation. The anti-apoptotic effect of LIE also improves renal function in CKD mice. Therefore, fucoxanthin-containing brown seaweed may have a therapeutic potential for CKD patients.