Antinociceptive actions of honokiol and magnolol on glutamatergic and inflammatory pain

Abstract

The antinociceptive effects of honokiol and magnolol, two major bioactive constituents of the bark of Magnolia officinalis, were investigated on animal paw licking responses and thermal hyperalgesia induced by glutamate receptor agonists including glutamate, N-methyl-D-aspartate (NMDA), and metabotropic glutamate 5 receptor (mGluR5) activator (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as inflammatory mediators such as substance P and prostaglandin E2 (PGE2) in mice. The actions of honokiol and magnolol on glutamate-induced c-Fos expression in the spinal cord dorsal horn were also examined. Our data showed that honokiol and magnolol blocked glutamate-, substance P- and PGE2-induced inflammatory pain with similar potency and efficacy. Consistently, honokiol and magnolol significantly decreased glutamate-induced c-Fos protein expression in superficial (I-II) laminae of the L4-L5 lumbar dorsal horn. However, honokiol was more selective than magnolol for inhibition of NMDA-induced licking behavioral and thermal hyperalgesia. In contrast, magnolol was more potent to block CHPG-mediated thermal hyperalgesia. These results demonstrate that honokiol and magnolol effectively decreased the inflammatory pain. Furthermore, their different potency on inhibition of nociception provoked by NMDA receptor and mGluR5 activation should be considered.

Simultaneous determination of liquiritin, hesperidin, and glycyrrhizin by HPLC-photodiode array detection and the anti-inflammatory effect of Pyungwi-san

“…However, there are unclear the active compounds of Atracylodis Rhizoma and Zizyphi Fructus in anti-inflammatory effects. Magnolol and 6-gingerol are reported the major ingredients of Magnoliae Cortex (Lin et al, , 2009) and Zingiberis Rhizoma (Funk et al, 2009;Lee et al, 2009), respectively. The major ingredients in Glycyrrhizae Radix are glycyrrhizin and liquiritin, these were shown to have anti-inflammatory effects (Kim et al, 2006;Yoshida et al, 2007;Menegazzi et al, 2008;Jayaprakasam et al, 2009;Schröfelbauer et al, 2009).…”

Protective and Restorative Effects of Magnolol on Neurotoxicity in Mice with 6-Hydroxydopamine-Induced Hemiparkinsonism

“…Consistently, magnolol can inhibit cation signals stimulated by excitatory amino acid, leading to an increase in seizure threshold [9] . Moreover, our studies further demonstrated that magnolol and its isomer could attenuate inflammatory and glutamatergic pain in animal models [8,10] . Thus, the ability of magnolol to ameliorate neurotoxicity may be attributed to its antioxidative and anti-inflammatory activities.…”

“…The symptomatic relief of PD has been attributed to the relative compensation of glutamate hyperactivity, because apomorphine has been shown to enhance extracellular glutamate levels in the striatum of 6-OHDA-lesioned animals [36] . Importantly, our previous studies have demonstrated that magnolol can antagonize glutamate-and NMDA-induced cation dysregulation, neuronal damage, seizures, as well as nociception [7,9,10] . Thus it is suggested that the protective and restorative effects of subchronic magnolol on apomorphine-induced rotational behavior may be due to blockade of glutamatergic signaling after dopamine denervation in 6-OHDA-lesioned mice.…”

Antinociceptive activity and chemical composition of Wei–Chang–An–Wan extracts

“…Anthraquinone derivatives including aloe-emodin, rhein and sennosides also showed anti-inflammatory effects (Ma et al, 2009). Magnolol and honokiol also inhibited the second phase in the formalin test by inhibition of glutamate receptors and suppression of inflammatory mediators including PGE2 (Lee et al, 2011;Li et al, 2007;Lin et al, 2009). It was reported that the compounds exhibited the effects by synergy like three compounds of rhein, magnolol and naringenin exerted combined anti-inflammatory effect in a tradition Chinese formula (Tseng et al, 2006).…”