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J Ginseng Res. 2016 Oct;40(4):445-452. Epub 2016 Aug 21.

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

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Department of Molecular Medicine, School of Medicine, Ewha Womans University, Seoul, Korea.



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.


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.


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.


RGE and biotransformed ginsenosides could be considered as potential therapeutic agents against morphine-induced dependence.


biotransformation; ginsenosides; morphine dependence; red ginseng extract

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