Effect of OM-853, a Cerebral Metabolic Ameliorator, on Ambulatory Activity and Passive and Active Avoidance Responses in Mice and Mongolian Gerbils

Watano, Tomokazu; Nakazawa, Ken; Obama, Tomoko; Mori, Mayumi; Inoue, Kazuhide; Fujimori, Kannosuke; Takanaka, Akira

doi:10.1254/jjp.61.351

Cited by 7 publications

(2 citation statements)

References 38 publications

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“…Oxyindole alkaloids such as rhynchophylline, isorhynchophylline, corynoxeine and isocorynoxeine, and the indole alkaloid hirsutine have vasodilative and Ca 2 -channel-blocking activity in isolated rat thoracic aorta (Yamahara et al 1987;Yano et al 1991;Horie et al 1992). Hirsuteine, an indole alkaloid, non-competitively antagonizes nicotineevoked dopamine release by blocking ion permeation through nicotinic receptor-channel complexes in rat pheochromocytoma PC12 cells (Watano et al 1993). Alkaloids obtained from Uncaria sinensis, for example geissoschizine methyl ether, corynantheine and dihydrocorynantheine, reduced spe-ci®c [ 3 H]5-hydroxytryptamine binding to membrane preparations from rat brain (Kanatani et al 1985).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats

Shimada

Goto

Itoh

et al. 1999

Journal of Pharmacy and Pharmacology

154

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We have previously shown that an aqueous extract of the hooks and stems of Uncaria sinensis (Oliv.) Havil., Uncariae Uncus Cum Ramulusis, protects against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx. Because it is not known which components of Uncaria sinensis are active, in this study we have evaluated, by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) staining, the neuroprotective effects of the oxyindole alkaloids corynoxeine, rhynchophylline, isorhynchophylline and isocorynoxeine, and the indole alkaloids geissoschizine methyl ether, hirsuteine and hirsutine, isolated from the hooks and stems of Uncaria sinensis, on glutamate-induced cell death. We also investigated the inhibitory effects of the compounds on 45Ca2+ influx in cultured rat cerebellar granule cells. Cell viability evaluated by the MTT assay was significantly increased by application of rhynchophylline (10(-3) M), isorhynchophylline (10(-4)-10(-3) M), isocorynoxeine (10(-4)-10(-3) M), hirsuteine (10(-4)-3 x 10(-4) M) or hirsutine (10(-4)-3 x 10(-4) M) compared with exposure to glutamate only, with the effect of isorhynchophylline being the strongest. The increased 45Ca2+ influx into cells induced by glutamate was significantly inhibited by administration of rhynchophylline (10(-3) M), isorhynchophylline (3 x 10(-4)-10(-3) M), isocorynoxeine (3 x 10(-4)-10(-3) M), geissoschizine methyl ether (10(-3) M), hirsuteine (3 x 10(-4)-10(-3) M) or hirsutine (3 x 10(-4)-10(-3) M). These results suggest that oxyindole alkaloids such as isorhynchophylline, isocorynoxeine and rhynchophylline and indole alkaloids such as hirsuteine and hirsutine are the active components of the hooks and stems of Uncaria sinensis which protect against glutamate-induced neuronal death in cultured cerebellar granule cells by inhibition of Ca2+ influx.

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Section: Discussionmentioning

confidence: 99%

Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats

Shimada

Goto

Itoh

et al. 1999

Journal of Pharmacy and Pharmacology

154

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“…For example, Salviae miltiorrhizae radix, a Korean herbal medicine, increases dopamine release from PC12 cells [10]. On the other hand, hirsuteine, a compound isolated from a Japanese herb of the Uncaria genus, antagonizes the nicotine-evoked secretion of dopamine [11]. In addition, extracts of ginseng, a component of rikkunshito, suppress the gene expression of enzymes involved in dopamine and norepinephrine synthesis in PC12 cells [12].…”

Section: Introductionmentioning

confidence: 99%

Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito

Nagamura¹,

Terawaki

Uezono³

et al. 2014

BMC Complement Altern Med

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BackgroundRikkunshito is a traditional Japanese herbal medicine that is used to treat appetite loss associated with cancer and other disorders. The formulation contains various constituents that influence cell signaling, and rikkunshito may accordingly affect human homeostasis through multiple regulatory pathways, including those governed by the endocrine system. We investigated the actions of rikkunshito on catecholamine release from PC12 cells, an adrenal chromaffin cell line.MethodsThe actions of rikkunshito on PC12 cells were evaluated by measuring intracellular cAMP levels, tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP) mRNA expression levels, and catecholamine levels in the culture medium. The transcriptional activation of VIP gene by rikkunshito was assessed by using a VIP promoter-driven reporter gene assay.ResultsRikkunshito dose-dependently enhanced forskolin-induced elevations in cAMP in PC12 cells, and also increased the gene expression of TH and VIP. The transcriptional activation of VIP gene by rikkunshito was confirmed. Norepinephrine and dopamine secretion into the culture medium of PC12 cells were also dose-dependently augmented by rikkunshito and/or forskolin, but experiments with a protein kinase C (PKC) activator and a phosphodiesterase inhibitor revealed that the effects of rikkunshito were not simply due to the modulation of PKC or phosphodiesterase activity.ConclusionsThese findings suggest that rikkunshito enhances the release of catecholamines by a novel mechanism involving cAMP.

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Modes of Action of Defensive Secondary Metabolites

Wink

Schimmer

2018

Annual Plant Reviews Online

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Effect of OM-853, a Cerebral Metabolic Ameliorator, on Ambulatory Activity and Passive and Active Avoidance Responses in Mice and Mongolian Gerbils

Cited by 7 publications

References 38 publications

Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats

Evaluation of the Protective Effects of Alkaloids Isolated from the Hooks and Stems of Uncaria sinensis on Glutamate-induced Neuronal Death in Cultured Cerebellar Granule Cells from Rats

Enhancement of catecholamine release from PC12 cells by the traditional Japanese medicine, rikkunshito

Modes of Action of Defensive Secondary Metabolites

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