Consumption of soybean-based fermented foods offers many physiological effects to consumers. Soybean-based food products are generally main or side dishes in China, Japan, and Korea [22,24,25]. Recently, soybean-based food products have been introduced in diet among western communities [78, 113]. The isoflavones and peptides in soybean-based fermented foods are responsible for offering therapeutic activities [13, 20, 28, 44, 97]. Consumption of soybean-based food products are recognized for the reduction of occurrence or severity of several diseases and offer modest health benefits [13, 20, 28, 44, 97, 113]. The therapeutic activities (such as: anti-obesity, anti-angiotensin converting enzyme activity, anti-oxidation activity, anti-microbial activity and anti-cancer activity) have been offered by soybean-based fermented foods and peptides are discussed in this section (Figure 1.11).

Biological activities, provided by different types of soybean-based fermented food products

FIGURE1.11 Biological activities, provided by different types of soybean-based fermented food products.

Source: Self-developed with concepts from Refs. [5, 13, 20, 28, 44, 97, 113].


Obesity or overweight is strongly correlated with the consumption of high caloric food, dyslipidemia (accumulations of triglyceride and cholesterol in systems and organs) and diabetes. It is also related to heredity [8, 48]. lack of physical movement, endocrine disorders and medications. If obesity- associated disorders are not considered as serious issue, it can lead to life- threatening situations [114, 119].


Soybean-derived peptides have activity on nerves system. The p-subunit of soybean protein p-conglycmin contains the sequence Thr-Pro-Phe-Val (an opioid peptide with morphine-like activity). Three peptides (such as: Thr-Pro-Phe-Val-Val, Thr-Pro-Phe-Val-Val-Asn, and Thr-Pro-Phe-Val-Val- Asn-Ala) with anxiolytic activity have been identified. These peptides can suppress the urge of food intake and small intestinal transit. Furthermore, Thr-Pro-Phe-Val-Val has influence on oral food intake, blood glucose and triglyceride levels. Similarly, p-conglycinin-derived peptide (Val-Arg-Ile- Arg-Leu-Leu-Gln-Arg-Phe-Asn-Lys-Arg-Ser) can suppress the urge for food intake and gastric emptying [5, 92].


The soybean-derived bioactive peptides can reduce the risk of dyslipidemia (accumulation of cholesterol and triglycerides. Their accumulations are recognized as one of the causes of obesity [3, 8, 45, 114, 117].

Soybean-derived peptides can reduce lipid synthesis and lipid accumulation through versatile mechanisms. Following peptides have been identified for biochemical activities [33, 51, 82, 92], such as:

  • • Reduce lipoprotein lipase activity;
  • • Lower activity of fatty acids synthase;
  • • Suppress the oxidative stress;
  • • Reduce the growth of preadipocytes;
  • • Reduce the activities of sterol regulatory element-binding proteins- lc, peroxisome proliferator-activated receptor gamma and fatty acid synthase several di-peptides (such as: Lys-Ala, Val-Lys, and Ser-Tyr [34], tri-peptide Pro-Gly-Pro [92], tetra-peptide Leu-Pro-Tyr-Pro

[51]) and long-chain peptide (such as: Leu-Pro-Tyr-Pro-Arg [92], Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Ile-Ala-Val-Pro-Thr-Gly-Val-Ala [51,92]).

In Figure 1.12, biochemical mechanisms of anti-dyslipidemic activity due to soybean-derived peptides are presented.

Biochemical mechanisms of anti-dyslipidemic activity offered by soybean- derived peptides

FIGURE 1.12 Biochemical mechanisms of anti-dyslipidemic activity offered by soybean- derived peptides.

Source: Self-developed with concepts from Refs. [5,51, 82, 92].


Several soybean-derived peptides have anti-diabetic activity in addition to their anti-obesity activity [48, 59, 75]. Soybean-derived peptides (such as: Leu-Pro-Tyr-Pro, Iso-Ala-Val-Pro-Gly-Glu-Val-ala, and Iso-Ala-Val-Pro- Thr-Gly-Val-Ala) help glucose metabolism by supporting glucose uptake in liver cells by activation of glucose transporters (GLUT 1 and GLUT 4) [5]. The peptide, Iso-Ala-Val-Pro-Tlir-Gly-Val-Ala, inhibits activity of dipeptidyl peptidase IV that is responsible for hydrolysis of peptide hormone glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide [52]. Furthermore, soybean-derived peptides can suppress the activity of a-glucosidase that is located at brush border of the enterocytes of jejunum in small intestine. It is a key enzyme for producing monosaccharide and then- absorption on the gut-wall.

Inhibition of a-glucosidase activity affects secretion and activity of glucagon-like protein-1. Therefore, it can suppress postprandial hyperglycemia [5]. Soybean-derived peptides control the diabetes by controlling appetite through regulating the hormones, such as: ghrelin, CCK, and peptide YY [59, 75, 92]. Also, soybean-derived peptides can protect pancreas and its activity from inflammation and oxidative stress [5]. It has been reported that soybean-based fermented food products (such as: natto [106], chungkook- jang [38, 46, 47], and tauchi [21]) were able to reduce the risks of diabetes in humans and mouse models. In Figure 1.13, biochemical mechanisms of anti-diabetic activity due to soybean-derived peptides are presented.

Biochemical mechanisms of anti-diabetic activity offered by soybean-derived peptides

FIGURE 1.13 Biochemical mechanisms of anti-diabetic activity offered by soybean-derived peptides.

Source: Self-developed with concepts from Refs. [5, 59, 75,92].


Due to presence of an angiotensin-converting enzyme (ACE) in soybean products, Angiotensin-I is converted to Angiotensin-II in the rennin-angio- tensin pathway, which promotes vasoconstriction and high blood pressure (BP). Also, ACE supports the transformation of bradykinin into inactive metabolites [17].

Several di-peptides (such as: Ala-Trp, Gly-Trp, Ala-Tyr, Ser-Tyr, Gly-Tyr, Ala-Phe, Val-Pro, Ala-Ile, and Val-Gly [73]) and tri-peptides (such as: Val-Pro-Pro, Ile-Pro-Pro, Ala-Phe-His, Ile-Phe-Leu, Ile-Phe-Tyr, Leu-Phe- Tyr, His-His-Leu [5, 92]) with angiotensine converting inhibitory activity have been identified in several soybean-based fermented food products

[15,67,114]. Furthermore, the angiotensin-converting inhibitory activity of several long-chain peptides (e.g.: Ala-Asp-Phe-Val-Leu-Asp-Asn-Glu-Gly- Asn-Phe-Leu-Glu-AsnGly-Gly-Thr-Tyr-Tyr-Ile, Phe-Phe-Tyr-Tyr, Tyr-Val- Val-Phe-Lys, and Lle-Pro-Pro-Gly-Val-Pro-Try-Trp-Thr) in soybean-based fermented foods have been investigated [92]. In peptide chain, presence of Val, Ala, lie at the N-terminal end and Pro at the C-terminal end have been recognized for potential of ACE inhibitory activity [5]. Figure 1.14 shows biochemical mechanisms of vasodilation and vasoconstriction that are offered by soybean-derived peptides.

Biochemical mechanisms of vasodilation and vasoconstriction offered by soybean-derived peptides

FIGURE 1.14 Biochemical mechanisms of vasodilation and vasoconstriction offered by soybean-derived peptides.

Source: Self-developed with concepts from Refs. [5,43, 62, 93, 94].


Antioxidants help to protect cells against oxidative stress. Free radicals (such as: reactive oxygen species-peroxides, superoxide, hydroxyl radical, singlet oxygen, and alpha-oxygen) and reactive nitrogen species (nitric oxide) as metabolic byproducts are produced due to unhealthy lifestyle, smoking, high alcohol consumption, over stress, inflammation, suffering with chronic metabolic disease. Their generation and accumulation are cause of oxidative damage of cell organelles, including DNA. Antioxidants operate by triggering and neutralizing free radicals in cell through (a) donating electron and (b) activation of transcription factor DAF-16 [5, 27].

Soybean-derived bioactive peptides playas anti-oxidants in damaged or unhealthy cells that are under oxidative stress. As antioxidants, isoflavones, and lunasin may suppress risk of cancer by inhibiting DNA damage [5]. Genistein among all of soybean isoflavones might support the synthesis and activity of antioxidant enzyme superoxide dismutase (SOD), which inhibit accumulations and activities of free radicals [92]. Due to enzymatic hydrolysis of soy protein, more R-groups in peptide chain are exposed, which offer free radical scavenging. The C- or N-terminal end amino acids in bioactive peptide sequence donate electrons to free radicals and neutralize the activity of reactive oxygen species and protect the cells and tissues from oxidative damage [23, 92]. Anti-oxidation activity in several soybean-based fermented food products (such as: soy milk [101], gochujang [116], kinema [68], soy sauce [69], dauclii [111], and kanjang [96]) have been validated. Figure 1.15 indicates biochemical mechanisms of anti-oxidation activity that are being offered by soybean-derived peptides.

Biochemical mechanism of anti-oxidation activity of soybean-derived peptides. Source

FIGURE1.15 Biochemical mechanism of anti-oxidation activity of soybean-derived peptides. Source: Self-developed with concepts from Refs. [5, 27, 92].


Multidrug-resistant mechanisms by chemically synthesized antimicrobial compounds are [35, 115] are:

  • • Genetic modifications, such as: (i) mutational resistance; and (ii) horizontal gene transfer;
  • • Mechanistic based modifications, such as: (i) partially modifications in the antibiotic molecule; (ii) decrease antibiotic penetration and efflux; (iii) changes in target sites; and (iv) global cell adaptations.

Bioactive peptides display anti-bacterial, anti-viral, anti-fungal, and/ or anti-parasitic activities. They often play a major role in imiate immunity [83]. Some soybean-based peptides offer anti-microbial activities. Similar to the anti-microbial mechanism of antibiotics, anti-bacterial peptides do not inhibit bacterial peptidoglycan synthesis or genetic transformation. Instead, they bind with membrane proteins and create complex as a primary step in the antimicrobial mechanism [115]. They make pores in cell layer/membrane from cellular items (cell organelles) and are leaked to abiotic phase [107,109]. It has been reported that the anti-bacterial mechanism of soybean-derived peptide is detergent-like. Phospholipids in cellular membrane, teichoic acid and lipoteichoic acids in peptidoglycans of Gram-positive bacteria participate in electrostatic interaction with functional groups of peptides from soybean [63]. Interaction between anti-bacterial peptides with cytoplasmic membrane frequently lead to lipid segregation in cell membrane, which affects membrane permeability, inhibits cell division and leads to delocalization of essential membrane proteins [115]. It was reported that the level of binding of peptides with bacterial cell membrane depends on the sequence and concentration of antimicrobial peptides and nature of the bacterial cell membrane [88].

Anti-microbial activity of conglycinin- and glycinin-derived peptides has been proven against both Gram-negative and Gram-positive bacteria [109]. Dhayakaran et al. [14] found that soybean-based peptides (such as: pro-gly- thr-ala-val-phe-lys and iso-lys-ala-phe-lys-glu-ala-thr-lys-val-asp-lys-val-val- val-luc-try-thr-ala) have significant effects against Listeria monocytogenes and Pseudomonas aeruginosa [14]. Anti-bacterial activity of tempeh [70] and miso [79] have been proven. Figure 1.16 shows the biochemical mechanism of anti-microbial activity, offered by soybean-derived peptides.

Biochemical mechanism of anti-microbial activity, offered by soybean-derived peptides

FIGURE 1.16 Biochemical mechanism of anti-microbial activity, offered by soybean-derived peptides.

Source: Self-developed with concepts from Refs. [88,115].


Cancer is partially related to activation of pro-inflainniatory agents, prooxidant, and immunosuppressive mechanisms that are prone to growth of tissues in an abnormal way and often formation of tumor [4, 60, 65]. Several research studies have shown that some soybean-derived peptides offer anticancer activity [11, 39, 40, 53, 84]. Mainly two peptides (known as lunasin [12, 60, 65, 81, 84] and Bowman-Birk inhibitor [19, 64, 99]) have shown to have anti-cancer properties.

Bowman-Birk inhibitor suppresses reactive-oxygen-species induced mitochondrial damage after proteasomal inhibition and angiogenesis [19, 64, 99]. Amino acid sequence in lunasin peptide is almost similar to Bowman-Birk inhibitor. Structurally, lunasin is 43 amino acid having nine aspartic acid residues at the C-tenninal end with a cell adhesion motif preceding to it. Tri-peptide RGD (Arg-Gly-Asp) from the sequence helps its binding with the non-acetylated H3 and H4 histones to prevent then acetylation and anti-carcinogenic activity [65, 84]. It has been reported that Bowman-Birk inhibitor has a role in the protection of lunasin from gastrointestinal degradation [12, 85].

Soybean-derived peptide has anti-cancer and anti-oxidation activities [12, 60, 64]. Presence of small amount of free radicals in tissues increases the risk of cell damage in DNA, which leads to increase the risks of cancer [27]. Soybean-based fermented food products (such as: soy sauce, natto, etc.), increase the activity of natural killer cells and cytokine regulation [65]. Soybean-derived peptides (such as: lunasin) and other similar peptides inhibit inflammation in lipopolysaccharide- induced macrophages. It suppresses the nuclear factor-kappa-B formation pathway. Furthermore, it has been proven that peptide (with molecular weight 5 kDa) may inhibit the formation of most potent pro-inflammatory markers, including formations and expressions of interleukin-6, nuclear factor-kappa B, nitric oxide, cyclooxygenase-2, nitric oxide synthase (NOS), nuclear translocation, and p50 nuclear translocation [60, 65]. The research study has been attempted to prove the potentiality of soybean isoflavones to the suppression of breast cancer [92], due to soybean-based foods [119]. Soy isoflavone supplementation reduces the increase of the concentration of serum prostate-specific antigen (PSA) along with growth of tumor in prostate and cancer in patients [121].

The biochemical activities of different soybean-based fermented food products are presented in Table 1.1.

Soybean-Based Food

Microorganism Used

Biological Activities



B. natto 09516



Temp eh

R. microspores



E.faecium LMG 19827, E.faecium LMG 19828



Soy sauce


[39, 53]

A. sojae

Angiotensin-converting enzyme inhibitory


Angiotensin-converting enzyme inhibitory





[2, 37, 72]

Dou chi

B. subtilis natto, B. sttbtilis B1

Angiotensin-converting enzyme inhibitory


A. oryzae, M. wutungkiao

Angiotensin-converting enzyme inhibitory


A. egypticus



A. otyzae




Lactococcus sp. GM005




B. subtilis



Soy yogurt

Lb. delbrueckii LB 1466, S', thennophilus St 1342, Lb. acidophilus LAFTI L10. B. lactis LAFTI B94. Lb. para case! LAFTI L26

Angiotensin-converting enzyme inhibitory



B. lichenifonnis SCD 111067P



B. subtilis CSY 191




A. otyzae



B. amyloliquefaciens FSE-68




B. subtilis CSY 191



Soybean-Based Food

Microorganism Used

Biological Activities


B. subtilis SCB3

Angiotensin-converting enzyme inhibitory




A. oiyzae BCRC 30222, Л. sojae BCRC 30103,

A. awamori, R. azygospous 31158, Rhizopus sp. No. 2





[69. 96]






B. amyloliquefaciens CJ 3-27 (KCCM 11317P),



B. amyloliquefaciens CJ 14-6 (KCCM 1171 SP),

A. oiyzae CJ 1354 (KCCM 11300Р)



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