Confirmation of the anxiolytic-like effect of dihydrohonokiol following behavioural and biochemical assessments

Abstract

Previous studies in this laboratory revealed that dihydrohonokiol-B (DHH-B; 3'-(2 propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol), a partially reduced derivative of honokiol, was an effective anxiolytic-like agent in mice at an oral dose of 0.04 mg kg(-1), and at higher doses, when evaluated by the elevated plus-maze test. The aim of this study was to further confirm the anxiolytic-like effect of DHH-B using an additional behavioural procedure (Vogel's conflict test in mice) and a biochemical assessment (in-vitro determination of muscimol-stimulated 36Cl- uptake into mouse cortical synaptoneurosomes). As in earlier experiments, DHH-B (0.04-1 mg kg(-1), p.o.) was shown to prolong the time spent in the open-sided arms of the elevated plus-maze in a dose-dependent manner. Moreover, in the Vogel's conflict test, DHH-B (5 mg kg(-1), p.o.) significantly increased punished water intake. In tests with mouse cerebral cortical synaptoneurosomes, 10 and 30 microM of DHH-B significantly increased 36Cl- influx in the absence of muscimol. In the presence of 25 microM muscimol, the addition of 1 microM DHH-B led to significant enhancement of 36Cl- uptake, while 30 microM DHH-B was required to further stimulate the 36Cl- uptake induced by 250 microM muscimol. The results of these studies confirm that DHH-B is a potent anxiolytic-like agent and that GABA(A) receptor-gated Cl(-)-channel complex is involved in the anxiolytic-like efficacy of DHH-B.

A comparison of chlordiazepoxide, bretazenil, L838,417 and zolpidem in a validated mouse Vogel conflict test

“…Classical benzodiazepines reduce conflict behaviour in rats in the VCT, as measured by an increase in water intake in the presence of shock delivery (Millan and Brocco 2003;Loiseau et al 2003;Griebel et al 1999Griebel et al , 2002Sorbera et al 2001;Flores and Pellon 2000;Nazar et al 1997;Brocco et al 1990). Although similar effects of benzodiazepines have been shown in mice in the VCT, this species has not been routinely used (Liao et al 2003;Maruyama et al 2001;van Gaalen and Steckler 2000;Umezu 1995Umezu , 1999Kuribara et al 1989Kuribara et al , 1990. However, the simplicity of the original VCT in rats and the increased use of transgenic mice in anxiety research (Anagnostopoulos et al 2001) suggest that conditioned mouse models of anxiety are needed to give a more complete picture of the anxiety phenotype of genetically modified mice.…”

“…Similarly, the effect of drugs on pain threshold may be difficult to transfer from, for example, the tail-flick test to the VCT context (Millan and Brocco 2003). For these reasons, we have not concentrated exhaustively on obviating all potential confounding variables, although some are inherently addressed by the pharmacological agents tested as well as by previous studies (Liao et al 2003;Maruyama et al 2001;van Gaalen and Steckler 2000;Umezu 1995Umezu , 1999Kuribara et al 1989Kuribara et al , 1990.…”

4-O-methylhonokiol attenuated β-amyloid-induced memory impairment through reduction of oxidative damages via inactivation of p38 MAP kinase

“…Intravenous pre-treatment or post-treatment of honokiol at a concentration of 0.1 and 1.0 μm/kg significantly decreased the neutrophil infiltration and oxidative damages in the infracted infected brains [24]. It was found that dihydrohonokiol-B [3′-(2 propenyl)-5-propyl-(1,1′-biphenyl)-2,4′-diol], a partially reduced derivative of honokiol, was an effective anxiolytic-like agent in mice at an oral dose of 0.04-1 mg kg −1 [62]. Oral treatment of 0.2 mg/kg honokiol for seven days showed a similar anxiolytic effect with a single treatment of 1 mg kg −1 diazepam in mice [29].…”

Honokiol Potentiates Pentobarbital-Induced Sleeping Behaviors through GABAAReceptor Cl-Channel Activation

“…Recent evidence indicated that honokiol possessed the neuroprotective eects, and some of these studies suggest that the amelioration of neurotoxicity by honokiol may be attributed to the anti-oxidative and anti-inammatory actions through, at least in part, limiting lipid peroxidation and reducing neutrophil activation/inltration during ischemia and heatstroke (Sheu et al, 2008;Fukuyama et al, 2002). Laboratory studies also revealed that a partially reduced derivative of honokiol, dihydrohonokiol-B (DHH-B; 3'-(2 propenyl)-5-propyl-(1,1'-biphenyl)-2,4'-diol), was also an effective anxiolytic-like agent in mice (Maruyama et al, 2001). Another possible mechanism for honokiol-mediated neuroprotective effects is thought blockade of glutamate and N-methyl-D-aspartic acid (NMDA) activated excitotoxicity and disruption of ionic homeostasis on various CNS injuries (Lin et al, 2005).…”