Sains Malaysiana 48(8)(2019): 1619–1625

http://dx.doi.org/10.17576/jsm-2019-4808-07

Inhibitory Effects of Melicope ptelefoliaExtract on Compound Action Potentials in Frog Sciatic Nerves and Its Possible Mechanism of Action

(Kesan Perencat Ekstrak Melicope ptelefoliapada Potensi Tindakan Sebatian dalam Saraf Skiatik Katak dan Tindakan Mekanisme Kemungkinan)

JASMINE SIEW MIN CHIA, AMMAR IZZATI AMIR RAMADAN, FARIHAH HANANI GHAZALI, SIONG JIUN WONG, MOHD ROSLAN SULAIMAN, TENGKU AZAM SHAH TENGKU MOHAMAD, MOHD KHAIRI HUSSAIN & ENOCH KUMAR PERIMAL*

Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor Darul Ehsan, Malaysia

Received: 17 May 2018/Accepted: 15 May 2019

ABSTRACT

Melicope ptelefolia is a medicinal plant from the Rutaceae, also known as 'tenggek burung' in Malaysia. Traditionally, natives ingest M. ptelefolia to treat a wide range of illnesses. This study aimed to investigate the effects of M. ptelefolia aqueous extract (MPAE) on compound action potentials (CAPs) in frog sciatic nerves and its mechanism involving the opioid receptors. The effects of MPAE on CAPs in frog sciatic nerves were examined using the AD Instrument Nerve Chamber. The frog sciatic nerves were dissected from the lumbar plexus to the knee of the frog and placed in Ringer's solution. Three treatment groups with different dosages (1, 3 and 10 mg/mL) of MPAE, including negative (vehicle) and positive control group (3 mg/mL of morphine) were tested on the frog sciatic nerves by placing them in a nerve organ chamber. Following this, the involvement of opioid receptors in the effects of MPAE on CAPs was investigated by using naloxone hydrochloride as a non-selective opioid receptor antagonist. Our results showed that the peak amplitudes of CAPs were significantly (p<0.001) reduced when treated with MPAE (3 and 10 mg/mL) in frog sciatic nerves. The MPAE-induced CAPs inhibition was reversed when pre-treated with naloxone, suggesting the involvement of the opioidergic system. These results indicated the modulatory action of MPAE on nerve conduction, which may provide important leads in the development of new therapeutic drugs through the involvement of opioid receptors.

Keywords: Compound action potential; frog sciatic nerves; opioidergic; opioid receptors; Melicope ptelefolia

ABSTRAK

Melicope ptelefolia adalah sejenis tumbuhan ubatan daripada Rutaceae, juga dikenali sebagai ' tenggek burung' di Malaysia. Secara tradisinya, penduduk pribumi menggunakanM. ptelefolia untuk merawat pelbagai jenis penyakit. Kajian ini bertujuan untuk mengkaji kesan ekstrak akuasM. ptelefolia (MPAE) terhadap potensi tindakan sebatian (CAPs) dalam saraf skiatik katak dan mekanisme yang melibatkan reseptor opioid. Kesan MPAE pada CAPs saraf skiatik dikaji menggunakan AD Instrument Nerve Chamber. Saraf skiatik katak dibedah dari pleksus lumbar ke lutut katak dan diletakkan di dalam larutan Ringer. Sebanyak tiga kumpulan rawatan dengan dos yang berbeza (1, 3 dan 10 mg/mL) MPAE, dengan kumpulan kawalan negatif (pembawa) dan positif (3 mg/mL morfin) diuji pada saraf skiatik katak dengan meletakkannya dalam ruang organ saraf. Berikutan itu, penglibatan reseptor opioid dalam mekanisme MPAE menghalang CAP telah dikaji dengan menggunakan nalokson hidroklorida sebagai antagonis reseptor opioid yang tidak memilih. Hasil kajian kami menunjukkan bahawa puncak amplitud potensi tindakan sebatian telah berkurang dengan ketara (p<0.001) apabila dirawat dengan ekstrak akuaM. ptelefolia (3 dan 10 mg/mL) dalam saraf skiatik katak. Perencatan CAPs yang disebabkan oleh MPAE dibalikkan apabila saraf skiatik menerima pra-rawatan dengan nalokson mencadangkan penglibatan sistem opioidergik. Hasil kajian ini menunjukkan tindakan modulasi MPAE pada pengaliran saraf yang dapat memberikan petunjuk yang penting dalam perkembangan dadah terapeutik baru melalui penglibatan reseptor opioid.

Kata kunci: Melicope ptelefolia; opioidergik; potensi tindakan sebatian; reseptor opioid; saraf skiatik katak

REFERENCES

Al-Hasani, R. & Bruchas, M.R. 2011. Molecular mechanisms of opioid receptor-dependent signaling and behavior. Anesthesiology 115(6): 1363-1381.

Bogatov, N.M., Grigoryan, L.R., Ponetaeva, E.G. & Sinisyn, A.S. 2014. Calculation of action potential propagation in nerve fiber. Progress in Biophysics & Molecular Biology 114(3): 170-174.

Fields, H.L., Emson, P.C., Leigh, B.K., Gilbert, R.F. & Iversen, L.L. 1980. Multiple opiate receptor sites on primary afferent fibres. Nature 284(5754): 351-353.

Gissen, A.J., Gugino, L.D., Datta, S., Miller, J. & Covino, B.G. 1987. Effects of fentanyl and sufentanil on peripheral mammalian nerves. Anesthesia & Analgesia 66(12): 1272- 1276.

Güven, M., Mert, T. & Günay, I. 2005. Effects of tramadol on nerve action potentials in rat: Comparisons with benzocaine and lidocaine. International Journal of Neuroscience 115(3): 339-349.

Jaffe, R.A. & Rowe, M.A. 1996. A comparison of the local anesthetic effects of meperidine, fentanyl, and sufentanil on dorsal root axons. Anesthesia & Analgesia 83(4): 776-781.

Jurna, I. & Grossman, W. 1977. The effect of morphine on mammalian nerve fibres. European Journal of Pharmacology 44(4): 339-348.

Karim, A., Shahrim, M., Nasouddin, S.S., Othman, M., Mohd Adzahan, N., Hussin, S.R. & Shaari, K. 2011. Consumers knowledge and perception towards Melicope ptelefolia(Daun Tenggek Burung): A preliminary qualitative study. International Food Research Journal 18(4): 1481-1488.

Katsuki, R., Fujita, T., Koga, A., Liu, T., Nakatsuka, T., Nakashima, M. & Kumamoto, E. 2006. Tramadol, but not its major metabolite (mono - O - demethyl tramadol) depresses compound action potentials in frog sciatic nerves. British Journal of Pharmacology 149(3): 319-327.

Kosugi, T., Mizuta, K., Fujita, T., Nakashima, M. & Kumamoto, E. 2010. High concentrations of dexmedetomidine inhibit compound action potentials in frog sciatic nerves without alpha(2) adrenoceptor activation. British Journal of Pharmacology 160(7): 1662-1676.

Li, J. 2015. Molecular regulators of nerve conduction - Lessons from inherited neuropathies and rodent genetic models. Experimental Neurology 267: 209-218.

Mizuta, K., Fujita, T., Nakatsuka, T. & Kumamoto, E. 2008. Inhibitory effects of opioids on compound action potentials in frog sciatic nerves and their chemical structures. Life Sciences 83(5): 198-207.

Pandey, A.K. & Deshpande, S.B. 2012. Bisphenol A depresses compound action potential of frog sciatic nerve in vitro involving Ca(2+)-dependent mechanisms. Neuroscience Letters 517(2): 128-132.

Sandkühler, J. 2000. Learning and memory in pain pathways. Pain 88(2): 113-118.

Sulaiman, M.R., Mohd Padzil, A., Shaari, K., Khalid, S., Shaik Mossadeq, W.M., Mohamad, A.S., Ahmad, S., Akira, A., Israf, D. & Lajis, N. 2010. Antinociceptive activity of Melicope ptelefoliaethanolic extract in experimental animals. Journal of Biomedicine & Biotechnology 2010: 937642.

Uemura, Y., Fujita, T., Ohtsubo, S., Hirakawa, N., Sakaguchi, Y. & Kumamoto, E. 2014. Effects of various antiepileptics used to alleviate neuropathic pain on compound action potential in frog sciatic nerves: Comparison with those of local anesthetics. BioMed Research International 2014: 5402389.

Yao, L.H., Yu, H.M., Xiong, Q.P., Sun, W., Xu, Y.L., Meng, W., Li, Y.P., Liu, X.P. & Yuan, C.H. 2015. Cordycepin decreases compound action potential conduction of frog sciatic nerve in vitro involving Ca(2+)-dependent mechanisms. Neural Plasticity 2015: 927817.

*Corresponding author; email: enoch@upm.edu.my