Previous studies have demonstrated the crosstalk between inflammation and AMPK signaling (Lyons and Roche, 2018). Inflammatory stimuli reduce AMPK phosphorylation in nutrient-rich conditions (Yang et al., 2010). As a downstream target of AMPK, SIRT1 can be suppressed by oxidative stress in addition to inflammation (Ota et al., 2012). These findings may explain the downregulation of AMPK/SIRT1 signaling in 2VO, which is characterized by inflammation and oxidative stress. However, activated AMPK upregulates the level of nicotinamide adenosine dinucleotide to enhance SIRT1 activity and subsequent deacetylation of the RelA/p65 subunit, resulting in inhibition of NF-κB nuclear entry and subsequent inflammation (Ashburner et al., 2001; Yeung et al., 2004; Lee et al., 2009; Salminen et al., 2011; Kauppinen et al., 2013). The regulatory mechanism responsible for the crosstalk between inflammation and AMPK/SIRT1 signaling has not been elucidated. However, in the present study, low levels of nuclear NF-κB and its downstream target TNF-α were associated with the upregulation of the AMPK/SIRT1 pathway in NBP-treated rats. Thus, NBP may function as a regulator between inflammation and AMPK/SIRT1 signaling. Given the crucial impact of inflammation on oligodendrocyte death and demyelination and the finding that AMPK/SIRT1 signaling promotes remyelination and neuroprotection (Elbaz et al., 2018; Dembic et al., 2019; Houshmand et al., 2019), we speculate that the molecular basis for the neuroprotective effect of NBP involves the upregulation of the AMPK/SIRT1 and downregulation of the STAT3/NF-κB pathway. We also observed the opposite trend for these two pathways, suggesting that they cross regulate in VD.