Cardamonin Modulates Neuropathic Pain through the Possible Involvement of Serotonergic 5-HT1A Receptor Pathway in CCI-Induced Neuropathic Pain Mice Model.

Nur Khalisah Kaswan,Enoch Kumar Perimal,Noor Aishah Binti Mohammed Izham,Tengku Azam Shah Tengku Mohamad,Mohd Roslan Sulaiman

doi:10.3390/molecules26123677

Abstract

Cardamonin, a naturally occurring chalcone isolated from Alpinia species has shown to possess strong anti-inflammatory and anti-nociceptive activities. Previous studies have demonstrated that cardamonin exerts antihyperalgesic and antiallodynic properties in chronic constriction injury (CCI)-induced neuropathic pain animal model. However, the mechanisms underlying cardamonin’s effect have yet to be fully understood. The present study aims to investigate the involvement of the serotonergic system in cardamonin induced antihyperalgesic and antiallodynic effects in CCI-induced neuropathic pain mice model. The neuropathic pain symptoms in the CCI mice model were assessed using Hargreaves Plantar test and von-Frey filament test on day 14 post-surgery. Central depletion of serotonin along the descending serotonergic pathway was done using ρ-chlorophenylalanine (PCPA, 100 mg/kg, i.p.), an inhibitor of serotonin synthesis for four consecutive days before cardamonin treatment, and was found to reverse the antihyperalgesic and antiallodynic effect produced by cardamonin. Pretreatment of the mice with several 5-HT receptor subtypes antagonists: methiothepin (5-HT1/6/77 receptor antagonist, 0.1 mg/kg), WAY 100635 (5-HT1A receptor antagonist, 1 mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5 mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3 mg/kg), and ondansetron (5-HT3 receptor antagonist, 0.5 mg/kg) were shown to abolish the effect of cardamonin induced antihyperalgesic and antiallodynic effects. Further evaluation of the 5-HT1A receptor subtype protein expressions reveals that cardamonin significantly upregulated its expression in the brainstem and spinal cord. Our results suggest that the serotonergic pathway is essential for cardamonin to exert its antineuropathic effect in CCI mice through the involvement of the 5-HT1A receptor subtype in the central nervous system.

Highlights

IntroductionCardamonin (20 , 40 -dihydroxy-60 -methoxychalcone) is a naturally derived chalcone that can be found widely in the fruit and rhizomes of Alpinia species [1,2]
The present study reveals that cardamonin involves the serotonergic pathway to exhibit antineuropathic in constriction injury (CCI)-induced neuropathic pain mice model
Our present findings indicate that serotonergic inhibitory pathway is important for cardamonin to exhibit antihyperalgesic and antiallodynic effects in the CCI-induced neuropathic pain mice model use in this study

Summary

Introduction

Cardamonin (20 , 40 -dihydroxy-60 -methoxychalcone) is a naturally derived chalcone that can be found widely in the fruit and rhizomes of Alpinia species [1,2]. It has been identified for its beneficial properties towards human health primarily because of its multitargeting properties [3,4]. The significant role of cardamonin as anti-inflammatory [5,6], antinociceptive [7], antioxidant [8], anticancer, and antiproliferative [9,10] agent has gained remarkable interest to further understand its effect as a potential therapy for other noncommunicable diseases. We have reported that cardamonin exerts both antihyperalgesic and antiallodynic effects in neuropathic pain mice model [11]

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Conclusion