Honokiol-Rich Magnolia officinalis Bark Extract Attenuates Trauma-Induced Neuropathic Pain

Neuropathic pain (NP) affects about 8% of the general population. Current analgesic therapies have limited efficacy, making NP one of the most difficult to treat pain conditions. Evidence indicates that excessive oxidative stress can contribute to the onset of chronic NP and several natural antioxidant compounds have shown promising efficacy in NP models. Thus, this study aimed to investigate the pain-relieving activity of honokiol (HNK)-rich standardized extract of Magnolia officinalis Rehder & E. Wilson bark (MOE), well known for its antioxidant and anti-inflammatory properties, in the spared nerve injury (SNI) model. The molecular mechanisms and efficacy toward neuroinflammation were investigated in spinal cord samples from SNI mice and LPS-stimulated BV2 microglia cells. MOE and HNK showed antioxidant activity. MOE (30 mg/kg p.o.) produced an antiallodynic effect in SNI mice in the absence of locomotor impairment, reduced spinal p-p38, p-JNK1, iNOS, p-p65, IL-1ß, and Nrf2 overexpression, increased IL-10 and MBP levels and attenuated the Notch signaling pathway by reducing Jagged1 and NEXT. These effects were prevented by the CB1 antagonist AM251. HNK reduced the proinflammatory response of LPS-stimulated BV2 and reduced Jagged1 overexpression. MOE and HNK, by modulating oxidative and proinflammatory responses, might represent interesting candidates for NP management.