POTENTIATION OF THE NGF-MEDIATED NERVE FIBER OUTGROWTH BY GINSENOSIDE Rb1 IN ORGAN CULTURES OF CHICKEN DORSAL ROOT GANGLIA

Saito, Hiroshi; Suda, Kitaru; Thoenen, H.

doi:10.1254/jjp.27.445

Cited by 34 publications

(18 citation statements)

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“…It was reported that ginsenoside Rb1 increased neurite outgrowth in chick dorsal root ganglia neurons and potentiated NGF-induced neurite outgrowth (8,9). We here demonstrated for the first time that protopanaxadiol-type saponins, not only ginsenoside Rb1, stimulated the development of axons and dendrites.…”

Section: Discussionsupporting

confidence: 59%

“…Furthermore, neurites of rat cultured cerebral cortex were extended by ginseng saponins (6). The major ginseng saponins, ginsenosides Rb 1 and Rg 1 , improved spatial learning in normal mice (7), and ginsenoside Rb1 potentiated the nerve growth factor (NGF)-mediated neurite outgrowth of chick dorsal root ganglia (8,9). These findings encouraged us to investigate several Ginseng drugs to search for candidates that can ameliorate dementia.…”

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confidence: 96%

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Axonal and Dendritic Extension by Protopanaxadiol-Type Saponins From Ginseng Drugs in SK-N-SH Cells

Tohda

Matsumoto

Zou

et al. 2002

Japanese Journal of Pharmacology

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ABSTRACT-Extension of axons and dendrites in neurons may compensate for and repair damaged neuronal networks in the dementia brain. To find out drugs capable of regenerating the neuronal network, we focused on several herbal drugs belonging to the genus Panax, kinds of Ginseng, and investigated neurite outgrowth activity of their extracts and compounds. We found that the methanol extracts of Ginseng (root of P. ginseng), Notoginseng (root of P. notoginseng) and Ye-Sanchi in Chinese (rhizome of a relative to P. vietnamensis) increased neurite outgrowth in SK-N-SH cells. The protopanaxadiol-type saponins, ginsenosides Rb 1 and Rb 3 , and notoginsenosides R 4 and Fa isolated from Ye-Sanchi extract extended neurites, while protopanaxatriol-, ocotillol-and oleanane-type saponins had no effect on the neurite outgrowth. The percentage of cells with multipolar neurites and number of varicosities were intensely high in cells treated with the methanol extract of Ye-Sanchi as well as ginsenosides Rb 1 and Rb 3 , and notoginsenosides R 4 and Fa. Both phosphorylated NF-H-expressing neurites and MAP2-expressing ones were extended by treatment with those saponins and the extract. Especially, longer neurites were mainly positive for phosphorylated NF-H. These results suggest that protopanaxadiol-type saponins enhance axonal and dendritic formation activity.Keywords: Ginseng, Protopanaxadiol saponin, Axon, Dendrite, SK-N-SH cell Despite the growing social problem of dementia, there is not yet any drug available for reliable treatment against dementia. Cholinomimetic agents in the form of acetylcholine esterase inhibitors are primarily used in the treatment of dementia patients. These drugs, however, just slow down the progression of dementia rather than actually restoring brain function. Regardless of the type (Alzheimer's or cerebrovascular), dementia is induced by neuronal degeneration and atrophy. Inhibiting the cause of the disease, an accumulation of amyloid b in Alzheimer's brain (1 -3), and attempts for neuroprotection have lately been considered attractive. Such protective measures may reduce progression of dementia, but can not recover severe disfunction of the brain. Therefore, one strategy for achieving an irreversible amelioration of dementia may be reconstruction of synaptic formation in the brain. Although it is difficult to repair neurons or to increase cell number after neurodegeneration in the central nervous system, new synapses could possibly be formed through the activation of remaining immature and mature neurons. Since synaptic formation is based on neurite outgrowth and dendrite and axon maturation, drugs activating these steps could possibly initiate a recovery of brain function.Ginseng, root of Panax ginseng, is the most famous drug in traditional medicine as a tonic and an anti-amnesic agent. It has been reported that significant improvement in learning and memory was observed in brain-damaged rats (4, 5) and aged rats (5) after oral administration of ginseng powder. Furthermore, neurites of rat culture...

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Section: Discussionsupporting

confidence: 59%

mentioning

confidence: 96%

Axonal and Dendritic Extension by Protopanaxadiol-Type Saponins From Ginseng Drugs in SK-N-SH Cells

Tohda

Matsumoto

Zou

et al. 2002

Japanese Journal of Pharmacology

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“…In addition, significant improvement in learning and memory has been observed in brain-damaged rats (Zhao and McDaniel, 1998;Zhong et al, 2000) and aged rats (Zhong et al, 2000) after oral administration of ginseng powder, and the major ginseng saponins, ginsenoside Rb 1 and Rg 1 , are known to improve spatial learning in normal mice (Mook-Jung et al, 2001). With respect to their effects on neuronal cells, it has been shown that neurite outgrowth of rat cultured cerebral cortical neurons is enhanced by crude ginseng saponins (Sugaya et al, 1988), and that ginsenoside Rb 1 potentiates the nerve growth factor (NGF)-mediated neurite outgrowth of chick dorsal root ganglia (Saito et al, 1977;Nishiyama et al, 1994). We have previously studied the neurite outgrowth activity of methanol extracts from seven kinds of Ginseng drugs and 19 constituents isolated from YeSanchi (rhizome of Panax vietnamensis HA et GRUSHV.…”

Section: Introductionmentioning

confidence: 99%

Aβ(25–35)-Induced Memory Impairment, Axonal Atrophy, and Synaptic Loss are Ameliorated by M1, A Metabolite of Protopanaxadiol-Type Saponins

Tohda

Matsumoto

Zou

et al. 2003

Neuropsychopharmacol

142

127

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We previously screened neurite outgrowth activities of several Ginseng drugs in human neuroblastoma, and demonstrated that protopanaxadiol (ppd)-type saponins were active constituents. Since ppd-type saponins are known to be completely metabolized to 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol (M1) by intestinal bacteria when taken orally, M1 and ginsenoside Rb 1 , as a representative of ppd-type saponins, were examined for cognitive disorder. In a mouse model of Alzheimer's disease (AD) by Ab(25-35) i.c.v. injection, impaired spatial memory was recovered by p.o. administration of ginsenoside Rb 1 or M1. Although the expression levels of phosphorylated NF-H and synaptophysin were reduced in the cerebral cortex and the hippocampus of Ab(25-35)-injected mice, their levels in ginsenoside Rb 1 -and M1-treated mice were almost completely recovered up to control levels. Potencies of the effects were not different between ginsenoside Rb 1 and M1 when given orally, suggesting that most of the ginsenoside Rb 1 may be metabolized to M1, and M1 is an active principal of ppd-type saponins for the memory improvement. In cultured rat cortical neurons, M1 showed extension activity of axons, but not dendrites. The axon-specific outgrowth was seen even when neuritic atrophy had already progressed in response to administration of Ab(25-35) as well as in the normal condition. These results suggest that M1 has axonal extension activity in degenerated neurons, and improve memory disorder and synaptic loss induced by . M1 was shown to be effective in vitro and in vivo, indicating that Ginseng drugs containing ppd-type saponins may reactivate neuronal function in AD by p.o. administration.

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“…Ginsenoside Rb1 potentiates the effects of nerve growth factor on nerve fiber outgrowth [32] and increases choline uptake by the brain [33]. Previously, pretreatment of Rb1 (91 lM) had been shown to decrease histamine and LT in allergenactivated lung mast cells [17].…”

Section: Discussionmentioning

confidence: 99%

Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells

Liao

Hou

Wang³

et al. 2006

J Biomed Sci

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SummarySubstance P (SP), a neurotransmitter, may play an important role in neurogenic inflammation. Ginseng has been used extensively in traditional medicine; however, few studies were focused on their anti-allergic effect. Therefore, the effect and mechanism of ginsenoside Rb1 on the SP enhancement of allergic mediators were explored. In this study, SP and dinitrophenyl-bovine serum albumin (DNP-BSA) were used to activate rat basophilic leukemia (RBL)-2H3 cells. The cultured supernatants were assayed for histamine, leukotriene C 4 (LTC 4 ) and interleulin-4 (IL-4) production. The mitogen-activated protein kinases (MAPKs) signaling pathway was determined by Western blotting analysis. We found that IgE/DNP-BSA, SP, ginsenoside Rb1, or MAPK specific inhibitors had no effect on cell viability and cytotoxicity. SP (30 lM) alone, did not induce histamine and LTC 4 release, but it enhanced allergen-induced histamine and LTC 4 release. In addition, SP significantly induced and enhanced allergen-activated IL-4. Ginsenoside Rb1 dosedependently inhibited these effects. SP enhanced the allergen-activated ERK pathway in RBL-2H3 cells, and Rb1 effectively inhibited the ERK pathway activation. Although MAPK specific inhibitors suppressed LTC 4 and IL-4, only U0126 inhibited the SP enhanced histamine release. These results demonstrate that Rb1 dose-dependently inhibited SP enhanced allergen-induced mediator release and its mechanism was through the inhibition of the ERK pathway.

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POTENTIATION OF THE NGF-MEDIATED NERVE FIBER OUTGROWTH BY GINSENOSIDE Rb1 IN ORGAN CULTURES OF CHICKEN DORSAL ROOT GANGLIA

Cited by 34 publications

References 14 publications

Axonal and Dendritic Extension by Protopanaxadiol-Type Saponins From Ginseng Drugs in SK-N-SH Cells

Axonal and Dendritic Extension by Protopanaxadiol-Type Saponins From Ginseng Drugs in SK-N-SH Cells

Aβ(25–35)-Induced Memory Impairment, Axonal Atrophy, and Synaptic Loss are Ameliorated by M1, A Metabolite of Protopanaxadiol-Type Saponins

Enhancement of the release of inflammatory mediators by substance P in rat basophilic leukemia RBL-2H3 cells

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