Erythroxylum cuneatum regulates the cell adaptation through the ERK 1/2 signalling in addictive morphine-induced cell line
Introduction: Chronic treatment of morphine stimulates prolonged activation of the µ-opioid receptor, causes the stimulation of cellular adaptation through ERK 1/2 pathway. The abrupt termination of chronic morphine was observed to cause withdrawal activity through the same pathway. The alkaloi...
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| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
2020
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| Subjects: | |
| Online Access: | http://eprints.unisza.edu.my/7304/1/FH02-FP-20-44226.pdf http://eprints.unisza.edu.my/7304/ |
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| Summary: | Introduction: Chronic treatment of morphine stimulates
prolonged activation of the µ-opioid receptor, causes
the stimulation of cellular adaptation through ERK 1/2
pathway. The abrupt termination of chronic morphine was
observed to cause withdrawal activity through the same
pathway. The alkaloid extract of Erythroxylum cuneatum
was proposed to have anti-withdrawal properties against
morphine, regardless of lacking information on the
cellular adaptation. Objectives: The in vitro study, using
the neuroblastoma cell line; SK-N-SH, was designed
to observe the morphine withdrawal activities in the
cellular adaptation perspective against the plant extract
and methadone. Materials and Methods: To achieve
the objective, the cells were pre-treated with morphine.
Meanwhile, to observe the antagonistic activity, the
cells were co-treated with morphine and plant extract
or morphine with methadone. The protein expression of respective proteins for cellular adaptation; mitogenactivated protein (MAP)/extracellular signal-regulated
(ERK) kinase 1/2 (MEK 1/2), extracellular signal-regulated
kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA),
protein kinases C (PKC), were obtained from western blot
technique. Results: The finding showed pre-treated cell
with morphine expressed higher content of MEK 1/2, ERK
2, PKA and PKC, as compared to co-treatment of morphine.
In regards, the co-treatment and post-treatment of
methadone and extract of E. cuneatum were evaluated to
normalise the changes affected by morphine, comparable
to the control group. Conclusion: E. cuneatum was
postulated to have anti-withdrawal property mimicking
the methadone and react on the same pathway with
methadone and morphine observed through antagonistic
activity. E. cuneatum was suggested to normalise the effect
of chronic morphine via ERK 1/2 signalling pathway. |
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