Table 8.

Cognitive functional enhancement and anti-osteoporotic effect of soybean-derived CGJ.

Model	Strain Used in Fermentation	Action Mode	Reference
Neuroprotection effect
ICR mice	B. subtilis MC31 L. sakei 383	Decreasing the number of dead cells in the granule cell layer of the dentate gyrus; suppressing acetylcholinesterase activity; activating nerve growth factor (NGF) and its receptor signaling pathway, including TrkA high affinity receptor and p75 low affinity receptor; downregulating Bax/Bcl2 and caspase 3 expression; promoting increase in superoxide dismutase activity and decrease in lipid peroxidation	[146]
ICR mice	B. subtilis B. licheniformis	Modulating the gut–microbiome–brain–axis, brain insulin sensitivity, and neuroinflammation by producing bioactive peptides, dietary fiber, poly-γ-glutamic acid (γ-PGA), and isoflavone aglycones	[3]
C57BL/ 6J mice	B. subtilis HCD02 B. amyloliquefaciens EMD17 B. amyloliquefaciens MJ1-4	Inhibiting growth of mouse hippocampal HT22 and human neuroblast-like SHSY5Y cells Reducing the frequency of behavioral dysfunction induced by D-galactose; improving cognitive abnormal function	[3,121]
Raw soybean	B. subtilis	Enhancing tyrosinase inhibitory activity through arbutin production	[124]
Anti-osteoporotic effect
Senescence-accelerated mouse prone 6	B. subtilis	Increasing bone mineral density (BMD) and relative bone length; enhancing osteopontin reactivity; upregulating expression of Alp, Col1a1, Fak, Bmp2/4, Smad1/5/8, and Runx2; downregulating expression of Rnakl and Nfatc1; decreasing Cathepsin K level; increasing osteoprotegerin/Rankl ratio	[35,40]
MC3T3-E1 subclone 4 (CRL-2593) cells	B. subtilis KCTC 12392BP	Suppressing osteoclast formation and increasing cell proliferation, cellular alkaline phosphatase activity, osteocalcin, and calcium deposition by upregulating the ratio of osteoprotegerin/receptor activator of NF-κB ligand; promoting bone health	[36]
Female/male Sprague-Dawley rat	B. subtilis	Preventing bone loss; increasing BMD, bone mineral content (BMC), and trabecular number	[35,147]
Female sham-operated and OVX mice	B. subtilis	Enhancing various isoflavone metabolites, including intact isoflavones, 3-hydroxygenistein, genistein 4′-sulfate, and equol 7-glucuronide → promoting bone health of postmenopausal women	[151]
Male/female Sprague-Dawley rat	B. subtilis	Accumulating total flavonoids, phenolics, and isoflavones; increasing spine BMD and femur BMC; stimulating growth hormone (GH) secretion, which leads to activation of the GH receptor downstream signaling pathway via induction of phosphorylation of Akt and Erk, but not STAT5	[147,148,149]
C57BL/6J mice	B. amyloliquefaciens KCTC11712BP	Increasing BMD through upregulation of bone morphogenic protein 2 (Bmp2) and osteopontin in bone tissues Increasing isoflavone-mediated osteogenesis via the Bmp2 signaling pathway; reducing receptor activator of NF-κB induced by NF-κB inactivation and MAPK dephosphorylation	[150]
Osteoblastic cell line MC3T3-E1	–	Producing vitamin K1 and K2 Stimulating osteoblast mineralization mechanism by elevating transcriptional ratio of osteoprotegerin and the receptor activator of NF-κB ligand	[36,152]