Morphine dependence is attenuated by red ginseng extract and ginsenosides Rh2, Rg3, and compound K

Taddesse Yayeh, Kyunghwa Yun, Soyong Jang, Seikwan Oh

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13 Scopus citations


Background: Red ginseng and ginsenosides have shown plethoric effects against various ailments. However, little is known regarding the effect of red ginseng on morphine-induced dependence and tolerance. We therefore investigated the effect of red ginseng extract (RGE) and biotransformed ginsenosides Rh2, Rg3, and compound K on morphine-induced dependence in mice and rats. Methods: While mice were pretreated with RGE and then morphine was injected intraperitoneally, rats were infused with ginsenosides and morphine intracranially for 7 days. Naloxone-induced morphine withdrawal syndrome was estimated and conditioned place preference test was performed for physical and psychological dependence, respectively. Western blotting was used to measure protein expressions. Results: Whereas RGE inhibited the number of naloxone-precipitated jumps and reduced conditioned place preference score, it restored the level of glutathione in mice. Likewise, ginsenosides Rh2, Rg3, and compound K attenuated morphine-dependent behavioral patterns such as teeth chattering, grooming, wet-dog shake, and escape behavior in rats. Moreover, activated N-methyl-D-aspartate acid receptor subunit 1 and extracellular signal-regulated kinase in the frontal cortex of rats, and cultured cortical neurons from mice were downregulated by ginsenosides Rh2, Rg3, and compound K despite their differential effects. Conclusion: RGE and biotransformed ginsenosides could be considered as potential therapeutic agents against morphine-induced dependence.

Original languageEnglish
Pages (from-to)445-452
Number of pages8
JournalJournal of Ginseng Research
Issue number4
StatePublished - 1 Oct 2016

Bibliographical note

Publisher Copyright:
© 2016, The Korean Society of Ginseng, Published by Elsevier.


  • Biotransformation
  • Ginsenosides
  • Morphine dependence
  • Red ginseng extract


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