<i>Magnolia officinalis</i> and neuronal mitochondrial dysfunction: a potential therapeutic approach for aging or chemotherapy-induced peripheral neuropathy

Abstract Objectives Peripheral neuropathy caused by aging and chemotherapy significantly reduces quality of life. Magnolia officinalis (MAGO), a traditional Chinese medicinal plant, is renowned for its anti-inflammatory, antioxidant, and anticancer properties. However, its effects on aging- and chemotherapy-induced peripheral neuropathy remain poorly understood. Therefore, this study aimed to investigate the impact of MAGO on peripheral neuropathy induced by aging or chemotherapy at the cellular level. Methods PC12 cell lines were used to establish models of D-galactose (D-gal)-induced aging and cisplatin-induced peripheral neuropathy. Cells in these models were treated with MAGO at concentrations of 5 µM or 10 µM. The effects of MAGO were evaluated by assessing cell viability, immunocytochemistry, RT-PCR, and mitochondrial function through measurement of mitochondrial membrane potential. Results MAGO treatment significantly improved cell viability in both D-gal-induced aging (5 µM: 82.2 ± 1.3 %; 10 µM: 78.9 ± 1.0 %) and cisplatin-induced peripheral neuropathy (CIPN5 µM: 74.7 ± 0.3 %; 10 µM: 70.3 ± 0.2 %) model cells. Treatment with MAGO significantly alleviated cellular viability in D-gal-induced aging (5 µM; 82.2 ± 1.3 or 10 µM; 78.9 ± 1.0) or cisplatin-induced peripheral neuropathy (5 µM; 74.7 ± 0.3 or 10 µM; 70.3 ± 0.2) model cells. Treatment with MAGO (5 µM) significantly prevented the upregulation of the apoptosis marker caspase-3 (Cas-3) and mitochondrial uncoupling protein 3 (UCP3), as determined by immunostaining and subsequent quantification. The analysis showed that the elevated levels of these two proteins in the model cells were effectively reduced following MAGO treatment. Additionally, the expression of a mitofusin 1 (MFN1), a key gene involved in mitochondrial function, was also restored in the treated groups. This recovery was consistent with the observed improvement in mitochondrial membrane potential, suggesting a protective role of MAGO in maintaining mitochondrial integrity. Conclusions Overall, our data suggest that MAGO has potential in reducing aging-related cellular damage and chemotherapy-induced neuropathy by modulating apoptosis and mitochondrial dysfunction.