Acacetin alleviates neuroinflammation and oxidative stress injury via the Nrf2/HO-1 pathway in a mouse model of spinal cord injury

Spinal cord injury (SCI) is a severe central nervous system disease, which may cause serious locomotor deficit. Acacetin is a flavone that possesses antioxidant and anti-inflammatory effects in different human diseases. The main purpose of this study was to explore whether acacetin ameliorates SCI in mice. A model of SCI was established in C57BL/6 mice. The Basso Mouse Scale (BMS) score, BMS subscore, mechanical hypersensitivity, and thermal hypersensitivity of mice were tested for determining the motor function. Immunofluorescence staining was utilized to detect NeuN, GFAP, and Iba-1 levels in spinal cord tissues. ELISA was utilized to assess the contents of proinflammatory factors such as interleukin (IL)-1β, IL-18, and tumor necrosis factor-Alpha (TNF-α) in spinal cord tissues. The levels of oxidative stress markers, reactive oxygen species, thiobarbituric acid-reactive substances, superoxide dismutase, catalase, glutathione peroxidase, and glutathione were detected using their corresponding kits. Western blot was employed for estimating the levels of heme oxygenase 1 (HO-1), nuclear factor E2-related factor 2 (Nrf2), and Kelch-like ECH-Associated protein 1 (Keap-1). In this study, acacetin treatment recovered the motor function in SCI mice. Acacetin improved neuron integrity and repressed glial cell activation in the spinal cord tissues of SCI mice. Furthermore, acacetin administration reduced the SCI-induced high concentrations of IL-1β, IL-18, and TNF-α, as well as inhibited oxidative stress in SCI mice. Moreover, acacetin activated HO-1/Nrf2 pathway in SCI mice. The neuroprotective effects of acacetin against SCI were reversed by Nrf2 inhibitor. Overall, acacetin alleviated neuroinflammation and oxidative stress injury by activating the Nrf2/HO-1 signaling pathway in the mouse models of SCI.

Duke Scholars

Author Xin Zhang Anesthesiology