Peripheral Analgesic Effect and Possible Mechanisms of Ferulic Acid

Year 2019, Volume: 9 Issue: 3, 385 - 392, 25.09.2019

Merve Kaşık Hazal Eken Rana Arslan , Nurcan Bektas

https://doi.org/10.31020/mutftd.587236

Cited By: 1

Abstract

Ferulic acid is a bioactive phenolic compound that is
found intensely in plants used in traditional medicine such as Ferula assa-foetida L.. The analgesic effect of various medicinal plants
has been associated with its constituent, ferulic acid. However, there are
limited number of studies about mechanism of its analgesic action. The aim of
this study was to evaluate the contribution of NO/cGMP/PKG/K_ATP
pathway in peripheral analgesic effect of ferulic acid by acetic acid-induced
(0.6 % acetic acid, i.p.) writhing
test in mice. For this purpose, following the determination of the analgesic
effect of ferulic acid at the doses of 20, 40, 80 and 160 mg/kg (p.o.), NO precursor 100 mg/kg L-arginine
(i.p.), nitric oxide synthase
inhibitor 30 mg/kg L-NAME (i.p.),
guanylate cyclase inhibitor 20 mg/kg methylene blue (i.p.) and K_ATP channel blocker 10 mg/kg glibenclamide (i.p.) were administered separately prior
to ferulic acid treatment at the dose effective for clarifying the mechanism of
action. Reduction in the number of writhes was evaluated as peripheral
analgesic activity. Ferulic acid significantly decreased the number of writhes
at the doses of 40, 80 and 160 mg/kg. 80 mg/kg ferulic acid and 100 mg/kg
acetyl salicylic acid demonstrated similar efficacy. L-arginine and methylene
blue relatively reversed the reduction in the number of writhes caused by
ferulic acid at 80 mg/kg, whereas L-NAME did not. Glibenclamide pre-treatment
significantly inhibited analgesic effect induced by ferulic acid. The results
of the study indicate that ferulic acid has peripheral analgesic activity and
it is mediated predominantly by activation of K_ATP channels and
partially by cGMP. In conclusion, findings of this study demonstrate that
ferulic acid may provide an advantage in K_ATP channel-targeted
management of pain.

Keywords

Ferulic acid, Nitric oxide, Guanylate cyclase, KATP channels, Pain

Supporting Institution

Anadolu University

Project Number

1802S034

Thanks

This article is based on the M.Sc. degree thesis of Merve KASIK and supported financially by Anadolu University Research Foundation (Eskisehir, Turkey), Project no: 1802S034. The authors declare no conflict of interest, financial or otherwise.

Ferulik Asitin Periferik Analjezik Etkisi ve Olası Mekanizmaları

Abstract

Ferulik asit, Ferula
assa-foetida L.. gibi geleneksel
tıpta kullanılan bitkilerin içerisinde yoğun olarak yer alan biyoaktif bir
fenolik bileşiktir. Çeşitli tıbbi bitkilerin analjezik etkileri içerdiği
ferulik asit ile ilişkilendirilmektedir. Fakat, analjezik etkinin mekanizmasına
ilişkin çalışmalar sınırlı sayıdadır. Bu çalışmada farelerde % 0.6 asetik asit,
i.p., injeksiyonu ile indüklenen
kıvranma testinde ferulik asitin periferal analjezik etkisine NO/sGMP/PKG/K_ATP
yolağının katılımının araştırılması amaçlandı. Bu amaçla ferulik asitin 20, 40,
80 ve 160 mg/kg (p.o.) dozlarda
oluşturduğu analjezik etkinin belirlenmesini takiben, etki mekanizmasının
aydınlatılması için etkili bulunan dozda uygulanan ferulik asit öncesi ayrı
ayrı, NO prekürsörü 100 mg/kg L-arjinin (i.p.),
nitrik oksit sentaz inhibitörü 30 mg/kg L-NAME (i.p.), guanilat siklaz inhibitörü 20 mg/kg metilen mavisi (i.p.) ve K_ATP kanal blokörü
10 mg/kg glibenklamid (i.p.)
kullanıldı. Kıvranma sayısındaki azalma analjezik aktivite olarak
değerlendirildi. 40, 80 ve 160 mg/kg dozlarda ferulik asitin kıvranma
sayılarını anlamlı olarak azalttığı gözlendi. 80 mg/kg ferulik asit ve 100
mg/kg asetil salisilik asitin birbirine yakın seviyelerde etkinlik gösterdiği
belirlendi. 80 mg/kg ferulik asitin neden olduğu kıvranma sayısındaki azalmayı;
L-arjinin ve metilen mavisinin göreceli olarak geri çevirdiği, L-NAME’nin ise
geri çeviremediği gözlendi. Glibenklamid ön-uygulaması ise ferulik asit ile
indüklenen bu azalmayı anlamlı bir şekilde önledi. Çalışma bulguları ferulik
asitin periferal analjezik etkinliğe sahip olduğunu ve bu etkinliğe sGMP’nin
kısmen fakat K_ATP kanalları aktivasyonunun daha baskın olarak
katılımının olduğunu göstermektedir. Sonuç olarak, bu çalışma ferulik asitin
ağrının K_ATP kanalları hedefli tedavisinde avantaj sağlayabileceğini
ortaya koymaktadır.   

Keywords

Ferulik asit, Nitrik oksit, Guanilat siklaz, KATP kanalları, Ağrı

Project Number

1802S034

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