**1. Introduction**

Chronic kidney disease has become a significant public health concern. Nephrotic syndrome (NS) is a special type of chronic kidney disease, which could be caused by a variety of factors. It is characterized by heavy proteinuria (more than 3.5 g/d), hypoalbuminemia, and edema [1]. Affected patients without effective treatment will in time develop end-stage renal disease. The adriamycin-induced nephrotic syndrome, which was first reported by Bertani et al. in 1982, is a classical nephrotic syndrome model [2]. Adriamycin is a quinone-containing anthracycline antibiotic and can be reduced to a semiquinone radical by metabolism in the kidney. The latter reacts with oxygen to produce reactive oxygen, inducing lipid peroxidation in the glomerular epithelial cells and destruction of the structure and function of the filtration membrane, and leading to progressive and irreversible proteinuria, hypoalbuminemia and hyperlipidemia [3]. An acute adriamycin-induced nephropathy model is induced by a single tail vein injection of 5–7.5 mg/kg adriamycin. This model, similar to human minimal change nephrotic syndrome, has been well characterized as an experimental model for nephrotic syndrome [4].

Treatment of nephrotic syndrome can slow its progression to end-stage renal disease. However, the therapies of nephrotic syndrome remain limited [5]. Many clinical and experimental studies have shown that the pathogenesis of nephrotic syndrome is associated with immune dysfunction. Immunosuppressive treatment, including corticosteroids, is the first-line treatment for nephrotic syndrome [6]. However, steroid resistance or steroid dependence is very common and frequently causes immune dysfunction and complicated infection, leading to end-stage renal failure [7]. Therefore identification of effective and less toxic therapeutic interventions for nephrotic syndrome remains to be an important issue.

The brown seaweed, *Saccharina japonica*, is a common seafood in China and Japan. It was documented as a traditional herb in traditional Chinese medicine for over a thousand years. The hot-water decoction of *S. japonica* is orally administered solely or combined with other herb extracts, and used for treatment of edema, a symptom of renal disease. Based on its therapeutic effect, our previous studies revealed that fucoidan, the water-soluble sulfated fucose-containing polysaccharide from *S. japonica*, was the main active component to treat edema. Fucoidan from *S. japonica* had renoprotective effect on chronic renal failure, diabetic nephropathy and acute kidney disease [8–11]. Nephrotic syndrome is a special type of chronic kidney disease, whether fucoidan have protective effect on nephrotic syndrome is still unclear.

As reviewed by Berteau and Mulloy [12], algal fucoidan represents a rather heterogeneous group of sulfated polysaccharides with complex and heterogeneous structures devoid of regularity. The structure of fucoidan extracted from *S. japonica* was much more complicated [13]. Its backbone was primarily consisted of (1→3)-linked-α-L-fucopyranose residues and a few (1→4)-α-L-fucopyranose linkages. The branch points were at C-4 of 3-linked -<sup>α</sup>-L-fucopyranose residues by β-D-galactopyranose unites or at C-2 of 3-linked -<sup>α</sup>-L-fucopyranose residues by non-reducing terminal fucose units. Sulfate groups occupied at position C-4 or C-2, sometimes C-2, 4 to fucose residues, and C-3 and/or C-4 to galactose residues. Besides fucose, fucoidan from *S. japonica* also contains minor galactose, mannose, glucose, rhamnose, and xylose. Fucoidans have been reported to have diverse bioactivities, such as antioxidant [14], anti-inflammatory [15], reno-protective [8], antitumor [16], and anticoagulant [17] activities. The molecular weight has been demonstrated to play an important role in the biological activities of polysaccharides. Comparing with unfractioned heparin, low-molecular-weight heparin has improved bio-availability, a longer half-life, and more predictable dose response, which make their use increasing common in the treatment and prophylaxis [18]. The relationship between molecular weight and bioactivities of fucoidan was reported in recent years. A low-molecular-weight fucan fraction extracted from the brown seaweed *Ascophyllum nodosum* exhibited dose-related venous antithrombotic activity [19]. A high level of inhibitory activity on complement can be achieved with low-molecular-weight fucoidan molecules [20]. If fucoidans with different molecular weight have a different effect on nephrotic syndrome still needs investigation.

In this study, we isolated a fucoidan from *S. japonica* and prepared its depolymerized fragment by oxidant degradation. The effect of fucoidan and its depolymerized fragment on adriamycin-induced nephrotic syndrome were investigated in a rat model.
