Abstract

BACKGROUND Magnolol has been demonstrated to exhibit anti-inflammatory and antioxidant properties. The Nrf2/HO-1 pathway is associated with cellular antioxidant and anti-inflammatory responses. Thus, we investigated the role of magnolol in the development of spinal cord injury (SCI) and whether its function is mediated by the Nrf2/HO-1 pathway. METHODS SCI was established in a T9 clip-compression animal model. Locomotor function and pain tolerance in SCI rats were evaluated using the open-field test, along with the assessment of the average Von Frey threshold and average tail flick response time. Hematoxylin and eosin staining and Luxol Fast Blue staining were carried out to determine histopathological alterations. The levels of malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were measured to detect oxidative stress. The levels of tumor necrosis factor-α, interleukin-1β, and monocyte chemoattractant protein-1 were measured to detect inflammation. Microglial and astrocytic activation and polarization were examined by immunofluorescence staining and reverse transcription quantitative polymerase chain reaction (RT-qPCR). The levels of pathway-related proteins were measured by western blotting and RT-qPCR. RESULTS Magnolol enhanced the locomotor function and mitigated the spinal cord impairment in rats with SCI. The pain tolerance in the SCI rat model was enhanced by magnolol treatment. Magnolol alleviated oxidative stress damage, decreased the activation of microglia and astrocytes, and promoted M2 and A2 polarization. Moreover, magnolol enhanced the activation of Nrf2/HO-1 in the injured spinal cords. CONCLUSION Magnolol alleviates oxidative stress damage by regulating the activation and polarization of microglia and astrocytes through the Nrf2/HO-1 pathway in SCI rats.