This study investigated the neuroprotective effects of heat-killed Lactiplantibacillus plantarum SMF398 and SMF470 isolated from kimchi. To indirectly reflect gut–brain axis-related intercellular interactions, conditioned medium (CM) derived from HT-29 cells treated with heat-killed L. plantarum was applied to SH-SY5Y neuronal cells. CM from SMF398 and SMF470 significantly increased cell viability under H2O2-induced oxidative stress (p<0.05), indicating protective effects against oxidative damage. Furthermore, both CMs attenuated 1-methyl-4-phenylpyridinium(MPP⁺)-induced neurotoxicity in SH-SY5Y cells. Treatment with SMF398-CM and SMF470-CM significantly suppressed the MPP⁺-induced upregulation of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), reduced the Bax/Bcl-2 ratio, and increased brain-derived neurotrophic factor (BDNF) expression (p<0.05). These findings suggest that heat-killed L. plantarum may exert neuroprotective effects through intestinal cell-mediated interactions associated with anti-inflammatory, anti-apoptotic, and neurotrophic mechanisms. These results suggest the potential application of kimchi-derived heat-killed L. plantarum in neuroprotection.
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