title: Antidepressant-like effects of ginsenosides: A comparison of ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K, and 20(S)-protopanaxadiol in mice models of despair.
abstract: Ginsenoside Rb3 has been proved to have antidepressant-like effects, which possesses 1 xylose and 3 glucose moieties with 20(S)-protopanaxadiol (PPD) as the aglycone. However, it is commonly accepted that orally ingested ginsenosides can be deglycosylated or partially deglycosylated into active derivatives by the intestinal bacteria. To identify potential antidepressant drug candidates, we compared the antidepressant-like activities between ginsenoside Rb3 and its four deglycosylated derivatives, Rg3, Rh2, compound K (C-K), and PPD. Effects of acute (1-day), short chronic (7-days), and longer chronic treatments (14-days) with these ginsenosides (50 and 100mg/kg, p.o.) on the behavioral changes in the forced swim test (FST), tail suspension test (TST) and open field test were investigated. Serum corticosterone and adrenocorticotropic hormone (ACTH) levels and mouse brain monoamine neurotransmitters 5-HT, NA and DA levels were measured using commercially available competitive enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, C-K showed antidepressant-like activities similar to that of Rb3, and Rg3 displayed antidepressant-like effects at lower dosage and faster time, indicating it has better effects than Rb3, whereas Rh2 and PPD failed to show any effect. Our results also showed, unlike the positive control fluoxetine, Rb3, Rg3 and C-K significantly increased the NA levels in the brain regions of mice exposed to FST but did not affect the 5-HT and DA levels. Moreover, treatment with Rg3 could reverse swim stress-induced increased levels of serum ACTH and corticosterone. These results suggest that C-K and Rg3 are the active deglycosylated derivatives, especially the latter compound, which is more potent than Rb3 and exerts antidepressant-like effects by regulating NA, ACTH and corticosterone levels.
authors.affiliation: School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang 524048, China. Electronic address: zhanghualin303@163.com.
authors.forename: Hualin
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Neurology Department, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510655, China. Electronic address: Zhongli605@126.com.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.affiliation: School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang 524048, China.
authors.forename: Zhongliu
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Chemistry and Chemical Engineering, Lingnan Normal University, Zhanjiang 524048, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Yang
authors.affiliation: Guangdong Medical Laboratory Animal Center, Guangzhou 528248, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Guangdong Medical Laboratory Animal Center, Guangzhou 528248, China.
authors.forename: Caixia
authors.initials: C
authors.lastname: Lou
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D036145:Ginsenosides / Q000494:pharmacology*; D019417:Hindlimb Suspension / Q000523:psychology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D018377:Neurotransmitter Agents / Q000378:metabolism; D012502:Sapogenins / Q000494:pharmacology*; D013550:Swimming / Q000523:psychology
chemical_list: D000324:Adrenocorticotropic Hormone; D000928:Antidepressive Agents; D003345:Corticosterone; D036145:Ginsenosides; D018377:Neurotransmitter Agents; D012502:Sapogenins; C044463:ginsenoside Rb3; C055305:ginsenoside Rh2; C112772:ginsenoside compound K; C062916:protopanaxadiol
keywords: Antidepressant; Ginsenoside; HPA; Mice; Monoamine neurotransmitters