Noor Azuin Suliman, M. Moklas, C. N. M. Taib, Mohamad Taufik Hidayat Baharuldin, S. M. Chiroma
{"title":"Erythroxylum cuneatum prevented cellular adaptation in morphine-induced neuroblastoma cells.","authors":"Noor Azuin Suliman, M. Moklas, C. N. M. Taib, Mohamad Taufik Hidayat Baharuldin, S. M. Chiroma","doi":"10.2174/1871524922666220516151121","DOIUrl":null,"url":null,"abstract":"BACKGROUND\nChronic morphine stimulates prolonged stimulation of opioid receptors, especially µ-opioid subtype (MOR), which in turn signals cellular adaptation. However, the sudden termination of morphine after chronic intake causes withdrawal syndrome.\n\n\nOBJECTIVES\nHence, this study was designed to find an alternative treatment for the morphine withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum), done on morphine-exposed neuroblastoma cell lines.\n\n\nMETHODS\nSK-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 h. The pre-treatment design was carried out by exposing the cells to morphine for 24 h, followed by 24 h exposures to E. cuneatum or methadone. The cytosolic fraction was collected and run for protein expression involved in cellular adaptation; mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signal-regulated kinase 2 (ERK 2), cAMP-dependent protein kinase (PKA) and protein kinases C (PKC).\n\n\nRESULTS\nThe 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.\n\n\nCONCLUSION\nE. cuneatum exerted anti-addiction properties by lowering the levels of cellular adaptation proteins, and its effects are comparable to that of methadone (an established anti-addiction drug).","PeriodicalId":9799,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Central nervous system agents in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/1871524922666220516151121","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"Psychology","Score":null,"Total":0}
引用次数: 1
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 morphine after chronic intake causes withdrawal syndrome.
OBJECTIVES
Hence, this study was designed to find an alternative treatment for the morphine withdrawal using the alkaloid leaf extract of Erythroxylum cuneatum (E. cuneatum), done on 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 h. The pre-treatment design was carried out by exposing the cells to morphine for 24 h, followed by 24 h exposures to E. cuneatum or methadone. The cytosolic fraction was collected and run for protein expression involved in cellular adaptation; mitogen-activated protein (MAP)/extracellular signal-regulated (ERK) kinase 1/2 (MEK 1/2), extracellular signal-regulated 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, and its effects are comparable to that of methadone (an established anti-addiction drug).
期刊介绍:
Central Nervous System Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new central nervous system agents. Containing a series of timely in-depth reviews written by leaders in the field covering a range of current topics, Central Nervous System Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in the field.