Title:Erythroxylum cuneatum Prevented Cellular Adaptation in Morphineinduced
Neuroblastoma Cells
Volume: 22
Issue: 2
Author(s): Noor Azuin Suliman, Mohamad Aris Mohd Moklas*, Che Norma Mat Taib, Mohamad Taufik Hidayat Baharuldin and Musa Samaila Chiroma
Affiliation:
- Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra
Malaysia, 43400 Serdang, Malaysia
Keywords:
Erythroxylum cuneatum, chronic morphine, cellular adaptation, anti-addiction, methadone, μ-opioid receptor, human neuroblastoma cell line (SK-N-SH).
Abstract:
Background: Chronic morphine stimulates prolonged stimulation of opioid receptors,
especially μ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the
sudden termination of the use of morphine after chronic intake causes the withdrawal syndrome.
Objectives: Hence, this study was designed to find an alternative treatment for morphine
withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum) for the
treatment of morphine-exposed neuroblastoma cell lines.
Methods: SK-N-SH, a commercialised neuroblastoma cell line, was used in two separate study
designs; the antagonistic and pre-treatment of morphine. The antagonistic treatment was conducted
through concurrent exposure of the cells to morphine and E. cuneatum or morphine and methadone
for 24 hrs. The pre-treatment design was carried out by exposing the cells to morphine for 24 hrs,
followed by 24 hrs exposure to E. cuneatum or methadone. The cytosolic fraction was collected
and assessed for proteins expression involved in cellular adaptation, including mitogen-activated
protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signalregulated
kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA) and protein kinases C (PKC).
Results: The antagonistic treatment showed the normal level of MEK 1/2, ERK 2, PKA and PKC
by the combination treatment of morphine and E. cuneatum, comparable to the combination of
morphine and methadone. Neuroblastoma cells exposed to morphine pre-treatment expressed a
high level of MEK 1/2, ERK 2, PKA and PKC, while the treatments with E. cuneatum and methadone
normalised the expression of the cellular adaptation proteins.
Conclusion: E. cuneatum exerted anti-addiction properties by lowering the levels of cellular adaptation
proteins it’s effects is comparable to that of methadone (an established anti-addiction drug).
