Merve KAŞIK, Hazal EKEN, Rana ARSLAN, Nurcan BEKTAŞ

Ferulik Asitin Periferik Analjezik Etkisi ve Olası Mekanizmaları

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/KATP 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 KATP 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 KATP kanalları aktivasyonunun daha baskın olarak katılımının olduğunu göstermektedir. Sonuç olarak, bu çalışma ferulik asitin ağrının KATP kanalları hedefli tedavisinde avantaj sağlayabileceğini ortaya koymaktadır.

Anahtar Kelimeler:

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

Peripheral Analgesic Effect and Possible Mechanisms of Ferulic Acid

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/KATP 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 KATP 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 KATP channels and partially by cGMP. In conclusion, findings of this study demonstrate that ferulic acid may provide an advantage in KATP channel-targeted management of pain.

Keywords:

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

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