Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells

Publication type:
Journal article
Metadata:
Autoren
Autoren-URL
https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=fis-test-1&SrcAuth=WosAPI&KeyUT=WOS:000451435900029&DestLinkType=FullRecord&DestApp=WOS_CPL
DOI
10.1016/j.phymed.2018.09.202
Externe Identifier
  • Clarivate Analytics Document Solution ID: HB9TN
  • PubMed Identifier: 30466988
ISSN
0944-7113
Zeitschrift
PHYTOMEDICINE
Schlüsselwörter
  • Curcumin
  • Boswellia
  • OPRL1
  • Opioid receptor ORL1
  • Nociception
  • Pain
Paginierung
285 - 299
Datum der Veröffentlichung
2018
Status
Published
Titel
Curcumin downregulates expression of opioid-related nociceptin receptor gene (<i>OPRL1</i>) in isolated neuroglia cells
Sub types
  • Article
Ausgabe der Zeitschrift
50

Data source: Web of Science (Lite)

Other metadata sources:
Autoren
DOI
10.1016/j.phymed.2018.09.202
ISSN
0944-7113
Zeitschrift
Phytomedicine
Sprache
en
Paginierung
285 - 299
Datum der Veröffentlichung
2018
Status
Published
Herausgeber
Elsevier BV
Herausgeber URL
http://dx.doi.org/10.1016/j.phymed.2018.09.202
Datum der Datenerfassung
2020
Titel
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells
Ausgabe der Zeitschrift
50

Data source: Crossref

Abstract
<h4>Background</h4>Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients.<h4>Aim</h4>To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS.<h4>Methods</h4>We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways analysis of the regulated genes.<h4>Results</h4>Treatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1 gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5 encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway.<h4>Conclusion</h4>Here, we report for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks.
Addresses
  • Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Autoren
DOI
10.1016/j.phymed.2018.09.202
eISSN
1618-095X
Externe Identifier
  • PubMed Identifier: 30466988
Funding acknowledgements
  • EuroPharma USA. Sponsor of the of the research: Terry Lemerond, EuroPharma USA Inc.: 2017-01
Open access
false
ISSN
0944-7113
Zeitschrift
Phytomedicine : international journal of phytotherapy and phytopharmacology
Schlüsselwörter
  • Neuroglia
  • Cell Line, Tumor
  • Humans
  • Boswellia
  • Curcumin
  • Receptors, Opioid
  • Analgesics
  • Analgesics, Opioid
  • Narcotic Antagonists
  • Plant Extracts
  • Down-Regulation
  • ADAMTS5 Protein
  • Nociceptin Receptor
Sprache
eng
Medium
Print-Electronic
Online publication date
2018
Paginierung
285 - 299
Datum der Veröffentlichung
2018
Status
Published
Publisher licence
CC BY-NC-ND
Datum der Datenerfassung
2018
Titel
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
50

Data source: Europe PubMed Central

Abstract
BACKGROUND: Curcumin (CC) exerts polyvalent pharmacological actions and multi-target effects, including pain relief and anti-nociceptive activity. In combination with Boswellia serrata extract (BS), curcumin shows greater efficacy in knee osteoarthritis management, presumably due to synergistic interaction of the ingredients. AIM: To elucidate the molecular mechanisms underlying the analgesic activity of curcumin and its synergistic interaction with BS. METHODS: We performed gene expression profiling by transcriptome-wide mRNA sequencing in human T98G neuroglia cells treated with CC (Curamed), BS, and the combination of CC and BS (CC-BS; Curamin), followed by interactive pathways analysis of the regulated genes. RESULTS: Treatment with CC and with CC-BS selectively downregulated opioid-related nociceptin receptor 1 gene (OPRL1) expression by 5.9-fold and 7.2-fold, respectively. No changes were detected in the other canonical opioid receptor genes: OPRK1, OPRD1, and OPRM1. Nociceptin reportedly increases the sensation of pain in supra-spinal pain transduction pathways. Thus, CC and CC-BS may downregulate OPRL1, consequently inhibiting production of the nociception receptor NOP, leading to pain relief. In neuroglia cells, CC and CC-BS inhibited signaling pathways related to opioids, neuropathic pain, neuroinflammation, osteoarthritis, and rheumatoid diseases. CC and CC-BS also downregulated ADAM metallopeptidase gene ADAMTS5 expression by 11.2-fold and 13.5-fold, respectively. ADAMTS5 encodes a peptidase that plays a crucial role in osteoarthritis development via inhibition of a corresponding signaling pathway. CONCLUSION: Here, we report for the first time that CC and CC-BS act as nociceptin receptor antagonists, selectively downregulating opioid-related nociceptin receptor 1 gene (OPRL1) expression, which is associated with pain relief. BS alone did not affect OPRL1 expression, but rather appears to potentiate the effects of CC via multiple mechanisms, including synergistic interactions of molecular networks.
Date of acceptance
2018
Autoren
Autoren-URL
https://www.ncbi.nlm.nih.gov/pubmed/30466988
DOI
10.1016/j.phymed.2018.09.202
eISSN
1618-095X
Zeitschrift
Phytomedicine
Schlüsselwörter
  • Boswellia
  • Curcumin
  • Nociception
  • OPRL1
  • Opioid receptor ORL1
  • Pain
  • ADAMTS5 Protein
  • Analgesics
  • Analgesics, Opioid
  • Boswellia
  • Cell Line, Tumor
  • Curcumin
  • Down-Regulation
  • Humans
  • Narcotic Antagonists
  • Neuroglia
  • Plant Extracts
  • Receptors, Opioid
  • Nociceptin Receptor
Sprache
eng
Country
Germany
Paginierung
285 - 299
PII
S0944-7113(18)30478-1
Datum der Veröffentlichung
2018
Status
Published
Datum, an dem der Datensatz öffentlich gemacht wurde
2019
Titel
Curcumin downregulates expression of opioid-related nociceptin receptor gene (OPRL1) in isolated neuroglia cells.
Sub types
  • Journal Article
Ausgabe der Zeitschrift
50

Data source: PubMed

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