• Proceedings of the Ginseng society Conference
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• 1988.08a
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• pp.151-155
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• 1988

The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins(SP), protopanaxadiol saponins (PD), and protopanaxatriol saponins(PT) on the development of morphine-induced tolerance and physical dependence in mice. The study also sought to determine the hepatic glutathione contents. which are closely related to the degree of detoxification of mine the effects of GS on morphine 6-dehydrogenase, which catalyzes the production of morphinone from morphine, and the roles of spinal descendign inhibitory systems in the production of antagonism. The results of the present study showed that GS, PD and PT administered orally inhibited the development of morphine induced tolerance and dependence. GS. PD and PT inhibited the reduction of hepatic glutathione concentration in mice treated chronically with morphine and the activity of morphine 6-dehydrogenase, and the activation of spinal descending inhibitory systems was inhibited by GS. So we hypothesized that the results were partially due to the dual action of the test drugs, the inhibition of morphinone production and the activated formation of morphinone-glutathinone conjugation, and the inhibition of the activatin of apinal descending inhibitory systems and the others.

• Korean Journal of Pharmacognosy
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• v.25 no.2
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• pp.160-166
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• 1994

The possible mechanisms of ginseng saponins on the inhibition of the development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. The administration of morphine causes a reduction of non-protein sulfhydryl contents in the liver, because morphinone metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine. In addition, ginseng saponins inhibited the reduction of non-protein sulfhydryl levels by increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.304-304
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• 1994

The possible mechanisms of ginseng saponins on the inhibition of development of morphine tolerance and physical dependence were investigated in the aspects of morphine metabolism by morphine 6-dehydrogenase. Administration of morphine causes a reduction of non-protein sulfhydryl contents in liver, because morphinone is metabolized from morphine by morphine 6-dehydrogenase conjugates with sulfhydryl compounds. However, ginseng saponins inhibited the activity of morphine 6-dehydrogenase which catalized the production of morphinone from morphine. In addition, ginseng' saponins inhibited the reduction of non-protein sulfhydryl levels by Increasing the level of hepatic glutathione. These results suggest that the dual action of the above plays an important role in the inhibition of development of morphine tolerance and physical dependence. On the other hand, it was observed that less polar components of ginseng saponins with parent structures were more active components in vitro.

• Journal of Ginseng Research
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• v.14 no.2
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• pp.178-186
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• 1990

The analgesic effect of morphine was antagonized and the development of tolerance was suppressed by the modification of the neurologic function in the animals treated with ginseng saponins The activation of the spinal descending inhibitory systems as well as the supraspinal structures by the administration of morphine was inhibited in the animals treated with ginseng saponine intracerebrally or intrathecally. The development of morphine tolerance and dependence, and the abrupt expression of naloxone inducted abstinence syndrom were also inhibited by ginsenoside Rb1, Rb2, Rg1 and Re. These results suggest that ginsenoside Rbl, Hbs, Rgl and Re are the bioactive components of panax ginseng on the inhibition of the development of morphine tolerance and dependence, and the inhibition of abrupt abstinence sindrome. In addition, further research on the minor components of Pnnnxkinsenl should be investigated. A single or daily treatment with ginseng saponins did not induce any appreciable changes in the brain in level of monoamines at the variolls time intervals and at the various day intervals, respectively. The inhibitory or facilitated effects of ginseng saponins on electrically evoked contractions in guinea pig ileum ($\mu$-receptor) and mouse vats deferens ($\delta$-receptor) were not mediated through opioid receptors. The antagonism of a $\chi$ receptor agonist, U-50, 488H was also not mediated through opioid receptors in the animals treated with ginseng saponins, but mediated through serotonergic mechanisms. Ginseng saponins inhibited morphine 6-dehydrogenase which catalyzed the production of morphinone from morphine, and increased hepatic glutathione contents for the detoxication of morphinone. This result suggests that the dual action of the above plays an important role in the inhibition of the development of morphine tolerance and dependence.

• YAKHAK HOEJI
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• v.32 no.6
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• pp.377-385
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• 1988

The biologically active component of licoris(Glycyrrhizae Radix L.) is considered to be glycyrrhetinic acid, an aglycone of glycyrrhizin, on the basis of chemical and pharmacological studies. The present study was undertaken to investigate the effect of glycyrrhetinic acid on the hepatic morphine-6-dehydrogenase activity, which catalize morphine to morphinone. Morphine-6-dehydrogenase was further purified by centrifugation, $(NH_4)_2SO_4$ fractionation, sephadex G-100, hydroxyapatite column. Hepatic morphine-6-dehydrogenase activity was significantly decreased by the treatment of glycyrrhetinic acid. When effect of glycyrrhetinic acid on the hepatic morphine-6-dehydrogenase was investigated in vitro, it was powerfully inhibited the enzyme activity with dose-dependent manner. From the above results, glycyrrhetinic acid inhibits hepatic morphine-6-dehydrogenase activity and decreases the morphine induced harmful side effects.

• Proceedings of the Ginseng society Conference
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• 1987.06a
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• pp.38-46
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• 1987

The present study was undertaken to determine the inhibitory effects of orally administered ginseng saponins (GS), protopanaxadiol saponins(PD) and protopanaxatriol saponins(PT) on the development of morphine induced tolerance and physical dependence in mice, and to determine the increases in the loss of morphine tolerance and dependence. The study also sought to determine the hepatic glutathione contents, which are closely related to the degree of detoxication of morphinone, a novel metabolite of morphine, and the effects of ginseng saponins on morphine 6-dehydrogenase. The results of the present study showed that GS, PD and PT administered orally inhibited the development of morphine-induced tolerance and dependence. GS, PD and PT, however, increased the loss of morphine tolerance and dependence. GS, PD and PT inhibited the reduction of hepatic glutathione concentration in mice treated chronically with morphine, and the activity of morphine 6-dehydrogenase. So we hypothesized that these results were partially due to the dual action of the test drugs, the inhibition of morphine production and the activation in morphine-glutathione conjugation due to the increased glutathione level for detoxication.

• Archives of Pharmacal Research
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• v.28 no.9
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• pp.995-1001
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• 2005

Morphine-induced analgesia has been shown to be antagonized by ginseng total saponins (GTS), which also inhibit the development of analgesic tolerance to and physical dependence on morphine. GTS is involved in both of these processes by inhibiting morphine-6-dehydrogenase, which catalyzes the synthesis of morphinone from morphine, and by increasing the level of hepatic glutathione, which participates in the toxicity response. Thus, the dual actions of ginseng are associated with the detoxification of morphine. In addition, the inhibitory or facilitated effects of GTS on electrically evoked contractions in guinea pig ileum (I-L-receptors) and mouse vas deferens $(\delta-receptors)$ are not mediated through opioid receptors, suggesting the involvement of non-opioid mechanisms. GTS also attenuates hyperactivity, reverse tolerance (behavioral sensitization), and conditioned place preference induced by psychotropic agents, such as methamphetamine, cocaine, and morphine. These effects of GTS may be attributed to complex pharmacological actions between dopamine receptors and a serotonergic/adenosine $A_{2A}1\delta-opioid$ receptor complex. Ginsenosides also attenuate the morphine-induced cAMP signaling pathway. Together, the results suggest that GTS may be useful in the prevention and therapy of the behavioral side effects induced by psychotropic agents.