Anti-stress effects of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol in immobilized mice.
Panax ginseng C.A. MEYER (Araliaceae), which contains ginsenosides as its main components, has been shown to have various biological effects, including anti-inflammatory, anxiolytic, anti-stress, and anti-tumor effects. Orally administered ginsenoside Rb1 and Re are metabolized to 20(S)-protopanaxadiol (PPD) and compound K via ginsenoside Rd and 20(S)-protopanaxatriol (PPT) and ginsenoside Rh1 via ginsenoside Rg1 by gut microbiota, respectively. Therefore, we investigated the anti-stress effects of these metabolites, PPD and PPT, by measuring their anxiolytic and anti-inflammatory effects in immobilized mice. Treatment with PPD and PPT prior to immobilization stress increased the time spent in open arms and open arm entries in the elevated plus-maze (EPM) test. The anxiolytic effects of PPD (10 mg/kg) and PPT (10 mg/kg) were comparable to that of buspirone (1 mg/kg). This observed anxiolytic effect of PPD was significantly blocked by flumazenil or bicuculline, and the effect of PPT was blocked by WAY-100635. Treatment with PPD also potently suppressed immobilization stress-induced serum levels of corticosterone and interleukin (IL)-6 by the enzyme-linked immunosorbent assay. However, PPT treatment did not suppress them. Based on these findings, PPD and PPT may exhibit the anxiolytic effect via γ-aminobutyrateA (GABAA) receptor(s) and serotonergic receptor(s), respectively, and PPD may have an anti-inflammatory effect that is more potent than that of PPT.
Department of Life and Nanopharmaceutical Sciences, College of Pharmacy, Kyung Hee University.
Hyun A
HA
Oh
Dae-Eung
DE
Kim
Hyuck Jai
HJ
Choi
Nam Jae
NJ
Kim
Dong-Hyun
DH
Kim
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001640:Bicuculline / Q000494:pharmacology; D003345:Corticosterone / Q000097:blood; D005442:Flumazenil / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008813:Mice, Inbred ICR; D010879:Piperazines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D012149:Restraint, Physical; D012502:Sapogenins / Q000494:pharmacology / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000097:blood / Q000188:drug therapy*
D014151:Anti-Anxiety Agents; D000893:Anti-Inflammatory Agents; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D015850:Interleukin-6; D010879:Piperazines; D011725:Pyridines; D011963:Receptors, GABA-A; D011985:Receptors, Serotonin; D012502:Sapogenins; D012702:Serotonin Antagonists; C081552:protopanaxatriol; D005442:Flumazenil; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; C062916:protopanaxadiol; D003345:Corticosterone; D001640:Bicuculline