Celastrus paniculatus seed fractions attenuate DMSO-induced neurotoxicity through mitochondrial protection and BDNF-mediated neurite growth

Celastrus paniculatus (CP) seed extract has been reported to exert neuroprotective effects, partially through glycogen synthase kinase-3 beta (GSK-3β) modulation. However, its effects on mitochondrial function and neuronal integrity remain poorly characterized. This study investigated the neuroprotective potential of CP fractions by measuring cell viability, mitochondrial membrane potential (ΔΨm), neurite morphology, and BDNF expression in a DMSO-induced SH-SY5Y cell model of neuron toxicity. SH-SY5Y cells were exposed to 10% DMSO for 3 h, followed by 24-h treatment with CP fractions (F2–F7). Cell viability, ΔΨm, neurite morphology, and BDNF expression were evaluated using an MTT assay, JC-1 staining, βIII-tubulin immunofluorescence, and Western blot, respectively. F4–F7 fractions effectively restored cell viability after DMSO-induced cytotoxicity. ΔΨm was significantly recovered, as indicated by increased red/green fluorescence ratio. F5–F7 fractions improved neurite length and neurite outgrowth, as evidenced by increased longest neurite length and the percentage of neurite-bearing cells. Time-lapse imaging confirmed F7-induced dynamic neurite elongation, showing progressive sprouting at 4 h and neurite extension by 6 h after treatment. Moreover, F4–F7 fractions significantly restored BDNF expression from the ~ 60% of control levels caused by DMSO. These results show that CP fractions with medium to high polarity (F5–F7) help shield neurons from damage caused by DMSO by maintaining mitochondrial health and triggering BDNF-related neurite changes. This indicates they could serve as natural neuroprotectants targeting mitochondria.