The Investigation of the Protective Effect of the Ethanol Extract from Brown Seaweed Laminaria Japonica on Chronic Kidney Disease and Its Molecular Mechanism

Chronic kidney disease (CKD) is a common illness that is becoming a global public health problem. CKD shares a common appearance of glomerulosclerosis, vascular sclerosis and tubulointerstitial fibrosis. Progressive nephron loss results mainly from stress-induced cell death (i.e. apoptosis) in a glomerulus and a tubule. Severe nephron loss is accompanied by renal fibrosis, vascular rarefaction, and chronic inflammation. Recent studies have found that apoptosis is one of the common cellular events leading to renal fibrosis. Prevention of stress-induced apoptosis will be beneficial for the treatment of CKD patients. Brown seaweeds has been used by Asians as food and medicine for a long time. Traditional Chinese pharmacopoeias, such as Shennong's Herbal and Bencao Gangmu, record that brown seaweeds are used to treat edema. Because edema is a symptom of kidney diseases, brown seaweeds are potentially beneficial for the treatment of CKD. Fucoxanthin is a major marine carotenoid, found in the photosynthetic organs of edible brown seaweeds. Recently, fucoxanthin has been found to prevent neuronal apoptosis via the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. The PI3K/Akt pathway can be activated by peroxisome proliferator-activated receptor α (PPARα)-mediated Na+/H+ exchanger NHE1 upregulation to exerts an anti-apoptotic effect in renal tubular cells. Therefore, the brown seaweed extracts containing fucoxanthin is potential to prevent renal cell apoptosis and improve CKD progression. But fucoxanthin is very unstable, increasing the difficulty of the application. Recently, it has been found that extracts of brown algae extracted with alcohol are rich in high stable fucoxanthin (> 10%). The influence of fucoxanthin-containing brown seaweed extracts on the PPARα/NHE1 signal pathway and CKD is worth studying. In the present study, we investigated the influence of the extracts from Laminaria japonica, one of the most abundant brown seaweeds in the Asian-Pacific region, on doxorubicin-treated renal tubular cells and the renal symptoms of nephrectomy-induced CKD mice. The protective mechanism of the brown seaweed extract was also revealed. The specific aims of this project are listed as below:1. To clarify the protective effect of the brown seaweed extract on rat renal tubular cells.2. To analyze the role of PPARα and NHE1 in the protective effect of the brown seaweed extract.3. To evaluate the differences between the signal transduction of the brown seaweed extract and fucoxanthin.4. To detect the influence of the brown seaweed extract on renal injury in a CKD mouse model.5. To determine the role of NHE1 in the protective effect of the brown seaweed in a CKD mouse model.6. To clarify the combined effect of the anti-apoptotic effect of the brown seaweed extract and the anti-fibrotic effect of fucoidan in a CKD mouse model.The investigation the protective effect of fucoxanthin-containing brown seaweed extract will provides a new therapeutic agent for CKD patients.