Erythroxylum cuneatum Prevented Cellular Adaptation in Morphineinduced Neuroblastoma Cells

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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).

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:22

Enthalten in:

Central nervous system agents in medicinal chemistry - 22(2022), 2 vom: 16., Seite 108-117

Sprache:

Englisch

Beteiligte Personen:

Suliman, Noor Azuin [VerfasserIn]
Moklas, Mohamad Aris Mohd [VerfasserIn]
Taib, Che Norma Mat [VerfasserIn]
Hidayat Baharuldin, Mohamad Taufik [VerfasserIn]
Chiroma, Musa Samaila [VerfasserIn]

Links:

Volltext

Themen:

μ-opioid receptor
76I7G6D29C
Analgesics, Opioid
Anti-addiction
Cellular adaptation
Chronic morphine
Erythroxylum cuneatum
Human neuroblastoma cell line (SK-N-SH)
Journal Article
Methadone
Morphine
UC6VBE7V1Z

Anmerkungen:

Date Completed 16.09.2022

Date Revised 19.09.2022

published: Print

Citation Status MEDLINE

doi:

10.2174/1871524922666220516151121

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM341017108