**Table 2.**

*Clinical studies for lipid metabolism improvements of* β*-conglycinin.*

consumption of legumes was significantly associated with lower risks of CKD, with an HR of 0.83 [95% CI, 0.72; 0.95] for high versus low intakes [36]. Soy protein, which is representative of legumes, has been reported to suppress the progression of DN [37, 38]. The effects of soy protein on DN/CKD in clinical trials are summarized in **Table 3** [39–43].

Kidney disease patients are carefully monitored for protein intake, and restricted protein intake according to the progression of their condition by doctors and nutritionists. However, there are some reports showing that mild protein restriction does not suppress the progression of kidney disease [44–46]. Therefore, it is necessary to consider not only the quantity but also the quality of protein. Legumes, including soy protein, can be regarded as very significant proteins to help treat nephropathy.


*Note:* ↓ *sign represents decrease, after supplement of soy protein. Fasting plasma glucose [FPG]; total-cholesterol (Total-C); low-density lipoprotein cholesterol (LDL-C); C-reactive protein [CRP], blood urea nitrogen (BUN).*

#### **Table 3.**

*Summary of clinical studies by soy protein for CKD.*

*Soybean and Other Legume Proteins Exhibit Beneficial Physiological Effects on Metabolic… DOI: http://dx.doi.org/10.5772/intechopen.99955*

#### **2.3 Anti-inflammatory roles of soy protein and peptides**

Inflammation can occur when infectious microorganisms such as bacteria, viruses, and fungi invade the body and circulate in the blood, and/or when they enter certain tissues [47, 48]. Inflammation can also occur during the course of pathologies such as tissue damage, cell death, cancer, ischemia, and degeneration [49–51].

There are reports of the anti-inflammatory effects of soy protein and its hydrolysate peptides [52]. Among them, lunasin is considered one of the most studied bioactive peptides. Since its discovery in soybean twenty years ago, many researchers around the world have focused their studies on demonstrating the chemo preventive and chemotherapeutic activity of lunasin [53–55]. Lunasin is a 44 amino acid peptide isolated from soy that has three domains implicated in anticancer activity: an RGD motif [Arg-Gly-Asp], a helical domain with a sequence conserved in chromatin binding proteins [Glu-Lys-His-Ile-Met-Glu-Lys-Ile], and a poly-aspartic acid tail [56]. Lunacin has been reported to have unique antioxidant, anti-inflammatory, and anti-cancer properties, and to play an important role in the regulation of cholesterol biosynthesis in the body [57]. Lunacin has potential as a dietary supplement by its high bioavailability and thermal stability.

Trypsin digests of soy proteins revealed that the sequence MITLAIPVNKPGR was able to stimulate phagocytosis in leukocytes. This peptide derived from β-conglycinin was named "Soymetide". The Met at its N-terminus was essential for its activity [58]. Four residues of the C-terminal residues of Soymetide-13 could be removed to form Soymetide-9 [MITLAIPVN], which had the highest activity. In these 9 residues [Soymetide-9], Soymetide-4 [MITL] is the minimal sequence required for its activity [58].

Soy protein with or without isoflavones was shown to reduce oxidative stress and have anti-inflammatory properties by inhibiting nuclear factor-kappa B [NF-κB] and blocking the secretion of pro-inflammatory cytokines in model rats and mouse. In clinical study by subjects with end-stage renal disease and healthy women over 70 years of age, their oxidative stress and inflammatory symptom were reduced [59]. The bioactive peptides RQRK and VIK were produced by digestion with pepsin and pancreatin from soy milk. These peptides inhibited lipopolysaccharide-induced inflammation in murine macrophages and the production of nitric oxide, interleukin [I])-1, nitric oxide synthase, and cyclooxygenase-2 [60].

Inflammatory bowel disease [IBD] is an intractable disease that causes inflammation of the gastrointestinal tract. Ulcerative colitis and Crohn's disease are the two major pathologies of IBD [61]. Ulcerative colitis is a non-specific inflammatory disorder that causes ulcers and erosion, primarily in the colonic mucosa. Young et al. revealed that soy peptides were effective in preventing dextran sulphate sodium[(DSS)-induced colitis in pigs [62]. The soy-derived tripeptide Val-Pro-Tyr [VPY] has been reported that anti-inflammatory effects in Caco-2 and THP-1 macrophages and inhibition of the secretion of IL-8 and TNF-α in a DSS-induced colitis model mouse [63]. They suggested that tripeptide VPY from soy peptides may be promising for the treatment of IBD.

Insulin resistance and diabetes has revealed to relate closely between nutrient excess and activation of the innate immune system in most organs pertinent to energy homeostasis by the research for a mechanism linking the pathogenesis of obesity over the past two decades [64–66]. Inflammation has been revealed to occur as a consequence of obesity, and to play a causative role in generating insulin resistance, defective insulin secretion [i.e., MetS), and disruption of other aspects of energy homeostasis by recent many studies. It has been reported that the suppressive effect of soy protein on the progression of CKD/DN, which is highly

related to MetS, is also exerted by the anti-inflammatory effect in renal tubules [67]. From such a close relationship between MetS and inflammation, it is easy to predict that the beneficial effect of soy protein on MetS may be due to its antiinflammatory effect.
