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The aim of this study is to evaluate the changes in soy isoflavones and peptides in soy milk after lactic acid bacterial fermentation, and explore the positive effects of fermented soy milk on an oxidative aging mouse model induced with D-galactose. We found that free soybean isoflavones and peptides increased after soy milk was fermented by Lactobacillus fermentum CQPC04. The in vivo results indicated that L. fermentum CQPC04-fermented soy milk enhanced the organ index of the liver and spleen, and improved the pathological morphology of the liver, spleen, and skin. L. fermentum CQPC04-fermented soy milk increased the enzymatic activity of glutathione peroxidase (GSH-Px), total superoxide dismutase (T-SOD), and catalase (CAT), increased glutathione (GSH), but decreased the levels of nitric oxide (NO) and malondialdehyde (MDA) in serum, liver, and brain tissues of oxidative aging mice. The above mentioned fermented soy milk also increased the levels of collagen I (Col I), hyaluronic acid (HA), and collagen III (Col III), and decreased the levels of advanced glycation End products (AGEs) and hydrogen peroxide (H2O2). The RT-qPCR results showed that L. fermentum CQPC04-fermented soy milk upregulated the mRNA expression of nuclear factor erythroid 2?related factor (Nrf2), heme oxygenase-1 (HMOX1), quinone oxido-reductase 1 (Nqo1), neuronal nitric oxide synthase (NOS1), endothelial nitric oxide synthase (NOS3), Cu/Zn–superoxide dismutase (Cu/Zn-SOD), Mn–superoxide dismutase (Mn-SOD), and CAT, but downregulated the expression of inducible nitric oxide synthase (NOS2) and glutamate cysteine ligase modifier subunit (Gclm) in liver and spleen tissues. Lastly, the fermented soy milk also increased the gene expression of Cu/Zn-SOD, Mn-SOD, CAT, GSH-Px, matrix metalloproteinases 1 (TIMP1), and matrix metalloproteinases 2 (TIMP2), and decreased the expression of matrix metalloproteinase 2 (MMP2) and matrix metalloproteinase 9 (MMP9) in skin tissue. In conclusion, L. fermentum CQPC04-fermented soy milk was able to satisfactorily delay oxidative aging effects, and its mechanism may be related to the increase in free soy isoflavones and peptides.

After soymilk fermented by L. plantarum HFY09, the bound soybean isoflavones content was reduced, but free soybean isoflavones and peptides increased. In vivo results show that L. plantarum HFY09-fermented soymilk increased the T-SOD, MDA, GSH-Px, GSH, CAT, and NO in the serum, liver, and brain tissues of mice. The aforementioned soymilk also increased the Col I and hyaluronic acid, and reduced the contents of Col III, H2O2, and AGEs in the skin. L. plantarum HFY09-fermented soymilk upregulated Nrf2, HO-1, NOS1, NOS3, SOD1, SOD2, CAT, Nqol, Gclm expression in the liver and the spleen, reduced the NOS2 expression, and upregulated SOD1 SOD2, CAT, GSH-Px, TIMP1, and TIMP2 expression in skin, downregulated MMP3, and MMP9 expression. These results show that L. plantarum HFY09-fermented soymilk could effectively alleviate aging in D-galactose-induced aging mice, the mechanism may be related to the activation of Nrf2 signaling pathway by soy isoflavone aglycone and small molecule peptides.