Magnolin Inhibits Paclitaxel-Induced Cold Allodynia and ERK1/2 Activation in Mice

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of anti-cancer drugs. The main symptoms often include sensory disturbances and neuropathic pain, and currently there is no effective treatment for this condition. This study aimed to investigate the suppressive effects of magnolin, an extracellular signal-regulated kinase (ERK) inhibitor substance derived from a 95% EtOH extract of the seeds of Magnolia denudata, on the symptoms of CIPN. A taxol-based anti-cancer drug paclitaxel (PTX) was repeatedly injected (2 mg/kg/day, total 8 mg/kg) into mice to induce CIPN. A neuropathic pain symptom was assessed using a cold allodynia test that scores behaviors of licking and shaking paw after plantar administration of acetone drop. Magnolin was administered intraperitoneally (0.1, 1, or 10 mg/kg) and behavioral changes to acetone drop were measured. The effect of magnolin administration on ERK expression in the dorsal root ganglion (DRG) was investigated using western blot analysis. The results showed that the repeated injections of PTX induced cold allodynia in mice. Magnolin administration exerted an analgesic effect on the PTX-induced cold allodynia and inhibited the ERK phosphorylation in the DRG. These results suggest that magnolin could be developed as an alternative treatment to suppress paclitaxel-induced neuropathic pain symptoms.

Machine learning-based evaluation of spontaneous pain and analgesics from cellular calcium signals in the mouse primary somatosensory cortex using explainable features

“…However, after repeated doses twice daily for 4 days, a significant analgesic effect was observed ( Figure 6C ). The results observed following the initial injection of magnolin suggest a discrepancy in its analgesic effectiveness between evoked and spontaneous pain (Cao et al, 2012 ; Kim N. et al, 2023 ). These results lead us to suggest that it would be more appropriate to test repeated dosing of magnolin in clinical trials.…”

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

“…In addition to the antioxidant activity, honokiol (HNK) displayed anti-inflammatory action in primary cultures of microglia and astrocytes stimulated by LPS, as demonstrated by the inhibition of expression of pro-inflammatory mediators, such as IL-6, IL-1β, iNOS, and TNF-α [ 22 ] and showed antinociceptive activity in inflammatory pain models [ 23 ]. Furthermore, a recent study showed the efficacy of magnolin, a neolignan obtained from the flower buds of Magnolia denudata , in attenuating paclitaxel-induced cold allodynia [ 24 ], In the effort to identify new potential therapies for NP, the purpose of our research was to evaluate the analgesic activity of an HNK-rich standardized extract of Magnolia officinalis Rehder & E. Wilson bark (MOE) in an animal model of neuropathic pain. The underlying molecular mechanisms of MOE and HNK were investigated in vitro.…”