| Summary: | <i>Astragalus membranaceus</i> (AM) has been used for anti-oxidative, anti-inflammatory, anti-cancer, and immunomodulatory activities. In this study, we confirmed that the anti-oxidative and anti-inflammatory effects of AM were enhanced after it was fermented by <i>Lactiplantibacillus plantarum</i>. The anti-oxidative effect was measured by 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical levels, total phenolic contents (TPC), reducing power, and H<sub>2</sub>O<sub>2</sub> levels. AM-LP MG5145 and MG5276 showed higher free radical scavenging activity than AM-NF (51.22%). In addition, AM-LP MG5145 and MG5276 showed higher TPC (49.11 mg GAE/mL), reducing power (OD<sub>700</sub> = 0.37), and H<sub>2</sub>O<sub>2</sub> (1.71 µM) than AM-NF. The calycosin contents determined to AM-NF (17.24 ng/mL), AM-LP MG5145 (139.94 ng/mL), and MG5276 (351.01 ng/mL) using UPLC-ESI-MS/MS. Anti-inflammatory effects were analyzed by investigating the inhibitory effects of fermented AM on cytotoxicity, NO production, and mRNA expression of COX-2, iNOS, NF-κB, and TNF-α in LPS-induced RAW 264.7 cells. AM-LP MG5145 and MG5276 showed no cytotoxicity. AM-LP MG5145 (50.86%) and MG5276 (51.66%) inhibited NO production in LPS-induced RAW 264.7 cells. Moreover, AM-LP MG5145 and MG5276 downregulated macrophage iNOS, COX2, TNF-α, and NF-κB expression. In conclusion, <i>A. membranaceus</i> fermented by <i>L. plantarum</i> MG5145 and MG5276 can be used in cosmetics and health foods as natural antioxidant compounds.
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