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Yoshio Kase - One of the best experts on this subject based on the ideXlab platform.
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Effects of 17 Atractylodes Lancea rhizome-, Glycyrrhiza-, and Uncaria hook-derived components on glutamate-induced PC12 cell death.
2014Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio KaseAbstract:Survival rates in groups treated with 2.5 mM glutamate (Glu) or Glu+various components were evaluated 24 h after the addition of Glu to the medium at a fixed concentration of 10 µM. Control (Ctrl) did not contain glutamate. Abbreviations: Atractylodes Lancea rhizome (ALR), Glycyrrhiza (GR), Uncaria hook (UH), β-Eudesmol (EM), liquiritinapioside (LQA), liquiritin (LQ), liquiritigenin (LQG), isoliquiritin (ILQ), isoliquiritigenin (ILQG), glycyrrhizic acid (GL), 18β-glycyrrhetinic acid (GA), glycycoumarin (GC), isoRhynchophylline (IRP), Rhynchophylline (RP), isocorynoxeine (ICX), corynoxeine (CX), geissoschizine methyl ether (GM), hirsuteine (HTE), hirsutine (HIR), and procyanidin B1 (PCB1). Each data calculated as a percentage of the control represents as the mean ± S.E.M. (n = 6). ***P
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simultaneous quantitative analyses of indole and oxindole alkaloids of uncaria hook in rat plasma and brain after oral administration of the traditional japanese medicine yokukansan using high performance liquid chromatography with tandem mass spectr
Biomedical Chromatography, 2013Co-Authors: Hirotaka Kushida, Yasushi Ikarashi, Masahiro Tabuchi, Miwako Fukutake, Takao Katsuhara, Hiroaki Nishimura, Masanao Kanitani, Yoshio KaseAbstract:Uncaria Hook (UH) alkaloids are involved in the beneficial effects of Yokukansan. However, the pharmacokinetics of UH alkaloids after oral administration of Yokukansan has not yet been sufficiently investigated. Therefore, we developed and validated a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of seven UH alkaloids (corynoxeine, isocorynoxeine, Rhynchophylline, isoRhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether) in rat plasma and brain. After protein precipitation with acetonitrile, chromatographic separation was performed using an Ascentis Express RP-amide column, with gradient elution with 0.2% formic acid and acetonitrile at 0.3 mL/min. All analytes in the plasma and brain showed good linearity over a wide concentration range (r > 0.995). Intra-day and inter-day variations of each constituent were 8.6 and 8.0% or less in the plasma, and 14.9 and 15.0% or less in the brain, respectively. The validated LC/MS/MS method was applied in the pharmacokinetic studies of UH alkaloids after oral administration of Yokukansan to rats. In the plasma, Rhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether were detected, but only geissoschizine methyl ether was detected in the brain. These results suggest that geissoschizine methyl ether is an important constituent of the pharmacological effects of Yokukansan.
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Effects of Geissoschizine Methyl Ether, an Indole Alkaloid in Uncaria Hook, a Constituent of Yokukansan, on Human Recombinant Serotonin_7 Receptor
Cellular and Molecular Neurobiology, 2013Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Akinori Nishi, Sachiko Imamura, Hitomi Kanno, Yoshio KaseAbstract:Effects of seven alkaloids, geissoschizine methyl ether (GM), hirsutine, hirsuteine, Rhynchophylline, isoRhynchophylline, corynoxeine and isocorynoxeine, in Uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin_7 (5-HT_7) receptor were investigated using Chinese hamster ovary (CHO) cell membranes and human embryonic kidney 293 (HEK293) cells stably expressing the human recombinant 5-HT_7 receptor. A competitive binding assay using CHO membranes showed that GM (IC_50 = 0.034 μM) more strongly inhibited the binding of the radioligand [^3H] LSD to 5-HT_7 receptor than the other alkaloids, suggesting that GM is bound to 5-HT_7 receptor. Agonistic/antagonistic effects of GM (1–50 μM) on the receptor were evaluated by measuring intracellular cAMP levels in HEK239 cells. GM (IC_50 = 6.0 μM) inhibited 5-HT-induced cAMP production in a concentration-dependent manner, as well as the specific 5-HT_7 receptor antagonist SB-269970 (0.1–1 μM). However, GM did not induce intracellular cAMP production as 5-HT did. These results suggest that GM has an antagonistic effect on 5-HT_7 receptor.
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Isoliquiritigenin is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan
Cellular and Molecular Neurobiology, 2011Co-Authors: Zenji Kawakami, Yasushi Ikarashi, Yoshio KaseAbstract:Effects of a traditional Japanese medicine, yokukansan, which is composed of seven medicinal herbs, on glutamate-induced cell death were examined using primary cultured rat cortical neurons. Yokukansan (10–300 μg/ml) inhibited the 100 μM glutamate-induced neuronal death in a concentration-dependent manner. Among seven constituent herbs, higher potency of protection was found in Uncaria thorn (UT) and Glycyrrhiza root (GR). A similar neuroprotective effect was found in four components (geissoschizine methyl ether, hirsuteine, hirsutine, and Rhynchophylline) in UT and four components (glycycoumarin, isoliquiritigenin, liquiritin, and 18β-glycyrrhetinic acid) in GR. In the NMDA receptor binding and receptor-linked Ca^2+ influx assays, only isoliquiritigenin bound to NMDA receptors and inhibited the glutamate-induced increase in Ca^2+ influx. Glycycoumarin and 18β-glycyrrhetinic acid bound to NMDA receptors, but did not inhibit the Ca^2+ influx. The four UT-derived components did not bind to NMDA receptors. The present results suggest that neuroprotective components (isoliquiritigenin, glycycoumarin, liquiritin, and 18β-glycyrrhetinic acid in GR and geissoschizine methyl ether, hirsuteine, hirsutine, and Rhynchophylline in UT) are contained in yokukansan, and isoliquiritigenin, which is one of them, is a novel NMDA receptor antagonist.
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The blood-brain barrier permeability of geissoschizine methyl ether in Uncaria hook, a galenical constituent of the traditional Japanese medicine yokukansan.
Cellular and molecular neurobiology, 2011Co-Authors: Sachiko Imamura, Takuji Yamaguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Akinori Nishi, Masahiro Tabuchi, Hitomi Kanno, Hirotaka Kushida, Yoshio KaseAbstract:Geissoschizine methyl ether (GM) in Uncaria hook, a galenical constituent of yokukansan is thought to be one of active components in the psychotropic effect of yokukansan, a traditional Japanese medicine (kampo medicine). However, there is no data on the blood–brain barrier (BBB) permeability of Uncaria hook-derived alkaloids containing GM. In this study, we investigated the BBB permeability of seven Uncaria hook alkaloids (GM, isocorynoxeine, isoRhynchophylline, hirsuteine, hirsutine, Rhynchophylline, and corynoxeine) using in vivo and in vitro methods. In the in vivo experiment, seven alkaloids in the plasma and brain of rats orally administered with yokukansan were measured by liquid chromatography–mass spectroscopy/mass spectrometric multiple reaction monitoring assay. In the in vitro experiment, the BBB permeability of seven alkaloids were examined using the BBB model composed of co-culture of endothelial cells, pericytes, and astrocytes. In the in vivo study, six components containing GM but not isocorynoxeine were detected in the plasma, and three (GM, hirsuteine, and corynoxeine) of components were detected in the brain. The in vitro BBB permeability data indicated that seven alkaloids were able to cross brain endothelial cells in culture conditions and that the BBB permeability of GM was higher than those of the other six alkaloids. These results suggest that target ingredient GM in yokukansan administered orally is absorbed into the blood and then reaches the brain through the BBB. This evidence further supports the possibility that GM is an active component in the psychotropic effect of yokukansan.
Yuqiang Wang - One of the best experts on this subject based on the ideXlab platform.
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neuroprotection against mpp induced cytotoxicity through the activation of pi3 k akt gsk3β mef2d signaling pathway by Rhynchophylline the major tetracyclic oxindole alkaloid isolated from uncaria rhynchophylla
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.
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Neuroprotection Against MPP+-Induced Cytotoxicity Through the Activation of PI3-K/Akt/GSK3β/MEF2D Signaling Pathway by Rhynchophylline, the Major Tetracyclic Oxindole Alkaloid Isolated From Uncaria rhynchophylla.
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.
Shengquan Hu - One of the best experts on this subject based on the ideXlab platform.
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neuroprotection against mpp induced cytotoxicity through the activation of pi3 k akt gsk3β mef2d signaling pathway by Rhynchophylline the major tetracyclic oxindole alkaloid isolated from uncaria rhynchophylla
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.
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Neuroprotection Against MPP+-Induced Cytotoxicity Through the Activation of PI3-K/Akt/GSK3β/MEF2D Signaling Pathway by Rhynchophylline, the Major Tetracyclic Oxindole Alkaloid Isolated From Uncaria rhynchophylla.
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.
Yasushi Ikarashi - One of the best experts on this subject based on the ideXlab platform.
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Properties, Pharmacology, and Pharmacokinetics of Active Indole and Oxindole Alkaloids in Uncaria Hook
'Frontiers Media SA', 2021Co-Authors: Hirotaka Kushida, Takashi Matsumoto, Yasushi IkarashiAbstract:Uncaria Hook (UH) is a dry stem with hook of Ucaria plant and is contained in Traditional Japanese and Chinese medicine such as yokukansan, yokukansankachimpihange, chotosan, Gouteng-Baitouweng, and Tianma-Gouteng Yin. UH contains active indole and oxindole alkaloids and has the therapeutic effects on ailments of the cardiovascular and central nervous systems. The recent advances of analytical technology led to reports of detailed pharmacokinetics of UH alkaloids. These observations of pharmacokinetics are extremely important for understanding the treatment’s pharmacological activity, efficacy, and safety. This review describes properties, pharmacology, and the recently accumulated pharmacokinetic findings of UH alkaloids, and discusses challenges and future prospects. UH contains major indole and oxindole alkaloids such as corynoxeine, isocorynoxeine, Rhynchophylline, isoRhynchophylline, hirsuteine, hirsutine, and geissoschizine methyl ether (GM). These alkaloids exert neuroprotective effects against Alzheimer’s disease, Parkinson’s disease, and depression, and the mechanisms of these effects include anti-oxidant, anti-inflammatory, and neuromodulatory activities. Among the UH alkaloids, GM exhibits comparatively potent pharmacological activity (e.g., agonist activity at 5-HT1A receptors). UH alkaloids are absorbed into the blood circulation and rapidly eliminated when orally administered. UH alkaloids are predominantly metabolized by Cytochrome P450 (CYP) and converted into various metabolites, including oxidized and demethylated forms. Regarding GM metabolism by CYPs, a gender-dependent difference is observed in rats but not in humans. Several alkaloids are detected in the brain after passing through the blood–brain barrier in rats upon orally administered. GM is uniformly distributed in the brain and binds to various channels and receptors such as the 5-HT receptor. By reviewing the pharmacokinetics of UH alkaloids, challenges were found, such as differences in pharmacokinetics between pure drug and crude drug products administration, food-influenced absorption, metabolite excretion profile, and intestinal tissue metabolism of UH alkaloids. This review will provide readers with a better understanding of the pharmacokinetics of UH alkaloids and their future challenges, and will be helpful for further research on UH alkaloids and crude drug products containing UH
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Effects of 17 Atractylodes Lancea rhizome-, Glycyrrhiza-, and Uncaria hook-derived components on glutamate-induced PC12 cell death.
2014Co-Authors: Hitomi Kanno, Zenji Kawakami, Kazushige Mizoguchi, Yasushi Ikarashi, Yoshio KaseAbstract:Survival rates in groups treated with 2.5 mM glutamate (Glu) or Glu+various components were evaluated 24 h after the addition of Glu to the medium at a fixed concentration of 10 µM. Control (Ctrl) did not contain glutamate. Abbreviations: Atractylodes Lancea rhizome (ALR), Glycyrrhiza (GR), Uncaria hook (UH), β-Eudesmol (EM), liquiritinapioside (LQA), liquiritin (LQ), liquiritigenin (LQG), isoliquiritin (ILQ), isoliquiritigenin (ILQG), glycyrrhizic acid (GL), 18β-glycyrrhetinic acid (GA), glycycoumarin (GC), isoRhynchophylline (IRP), Rhynchophylline (RP), isocorynoxeine (ICX), corynoxeine (CX), geissoschizine methyl ether (GM), hirsuteine (HTE), hirsutine (HIR), and procyanidin B1 (PCB1). Each data calculated as a percentage of the control represents as the mean ± S.E.M. (n = 6). ***P
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simultaneous quantitative analyses of indole and oxindole alkaloids of uncaria hook in rat plasma and brain after oral administration of the traditional japanese medicine yokukansan using high performance liquid chromatography with tandem mass spectr
Biomedical Chromatography, 2013Co-Authors: Hirotaka Kushida, Yasushi Ikarashi, Masahiro Tabuchi, Miwako Fukutake, Takao Katsuhara, Hiroaki Nishimura, Masanao Kanitani, Yoshio KaseAbstract:Uncaria Hook (UH) alkaloids are involved in the beneficial effects of Yokukansan. However, the pharmacokinetics of UH alkaloids after oral administration of Yokukansan has not yet been sufficiently investigated. Therefore, we developed and validated a sensitive and specific high-performance liquid chromatography with tandem mass spectrometry (LC/MS/MS) method for the simultaneous quantitation of seven UH alkaloids (corynoxeine, isocorynoxeine, Rhynchophylline, isoRhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether) in rat plasma and brain. After protein precipitation with acetonitrile, chromatographic separation was performed using an Ascentis Express RP-amide column, with gradient elution with 0.2% formic acid and acetonitrile at 0.3 mL/min. All analytes in the plasma and brain showed good linearity over a wide concentration range (r > 0.995). Intra-day and inter-day variations of each constituent were 8.6 and 8.0% or less in the plasma, and 14.9 and 15.0% or less in the brain, respectively. The validated LC/MS/MS method was applied in the pharmacokinetic studies of UH alkaloids after oral administration of Yokukansan to rats. In the plasma, Rhynchophylline, hirsutine, hirsuteine and geissoschizine methyl ether were detected, but only geissoschizine methyl ether was detected in the brain. These results suggest that geissoschizine methyl ether is an important constituent of the pharmacological effects of Yokukansan.
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Effects of Geissoschizine Methyl Ether, an Indole Alkaloid in Uncaria Hook, a Constituent of Yokukansan, on Human Recombinant Serotonin_7 Receptor
Cellular and Molecular Neurobiology, 2013Co-Authors: Toshiyuki Ueki, Kazushige Mizoguchi, Kyoji Sekiguchi, Yasushi Ikarashi, Akinori Nishi, Sachiko Imamura, Hitomi Kanno, Yoshio KaseAbstract:Effects of seven alkaloids, geissoschizine methyl ether (GM), hirsutine, hirsuteine, Rhynchophylline, isoRhynchophylline, corynoxeine and isocorynoxeine, in Uncaria hook, a constituent of the kampo medicine yokukansan, on serotonin_7 (5-HT_7) receptor were investigated using Chinese hamster ovary (CHO) cell membranes and human embryonic kidney 293 (HEK293) cells stably expressing the human recombinant 5-HT_7 receptor. A competitive binding assay using CHO membranes showed that GM (IC_50 = 0.034 μM) more strongly inhibited the binding of the radioligand [^3H] LSD to 5-HT_7 receptor than the other alkaloids, suggesting that GM is bound to 5-HT_7 receptor. Agonistic/antagonistic effects of GM (1–50 μM) on the receptor were evaluated by measuring intracellular cAMP levels in HEK239 cells. GM (IC_50 = 6.0 μM) inhibited 5-HT-induced cAMP production in a concentration-dependent manner, as well as the specific 5-HT_7 receptor antagonist SB-269970 (0.1–1 μM). However, GM did not induce intracellular cAMP production as 5-HT did. These results suggest that GM has an antagonistic effect on 5-HT_7 receptor.
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Isoliquiritigenin is a Novel NMDA Receptor Antagonist in Kampo Medicine Yokukansan
Cellular and Molecular Neurobiology, 2011Co-Authors: Zenji Kawakami, Yasushi Ikarashi, Yoshio KaseAbstract:Effects of a traditional Japanese medicine, yokukansan, which is composed of seven medicinal herbs, on glutamate-induced cell death were examined using primary cultured rat cortical neurons. Yokukansan (10–300 μg/ml) inhibited the 100 μM glutamate-induced neuronal death in a concentration-dependent manner. Among seven constituent herbs, higher potency of protection was found in Uncaria thorn (UT) and Glycyrrhiza root (GR). A similar neuroprotective effect was found in four components (geissoschizine methyl ether, hirsuteine, hirsutine, and Rhynchophylline) in UT and four components (glycycoumarin, isoliquiritigenin, liquiritin, and 18β-glycyrrhetinic acid) in GR. In the NMDA receptor binding and receptor-linked Ca^2+ influx assays, only isoliquiritigenin bound to NMDA receptors and inhibited the glutamate-induced increase in Ca^2+ influx. Glycycoumarin and 18β-glycyrrhetinic acid bound to NMDA receptors, but did not inhibit the Ca^2+ influx. The four UT-derived components did not bind to NMDA receptors. The present results suggest that neuroprotective components (isoliquiritigenin, glycycoumarin, liquiritin, and 18β-glycyrrhetinic acid in GR and geissoschizine methyl ether, hirsuteine, hirsutine, and Rhynchophylline in UT) are contained in yokukansan, and isoliquiritigenin, which is one of them, is a novel NMDA receptor antagonist.
Haitao Li - One of the best experts on this subject based on the ideXlab platform.
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neuroprotection against mpp induced cytotoxicity through the activation of pi3 k akt gsk3β mef2d signaling pathway by Rhynchophylline the major tetracyclic oxindole alkaloid isolated from uncaria rhynchophylla
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.
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Neuroprotection Against MPP+-Induced Cytotoxicity Through the Activation of PI3-K/Akt/GSK3β/MEF2D Signaling Pathway by Rhynchophylline, the Major Tetracyclic Oxindole Alkaloid Isolated From Uncaria rhynchophylla.
Frontiers in Pharmacology, 2018Co-Authors: Shengquan Hu, Haitao Li, Yuqiang WangAbstract:Rhynchophylline is a major tetracyclic oxindole alkaloid in Uncaria rhynchophylla, which has been extensively used as traditional herb medicine for the prevention of convulsions and hypertension. However, there is still little evidence about the neuroprotective effects of Rhynchophylline for Parkinson’s disease (PD), a neurodegenerative condition currently without any effective cure. In this present study, the neuroprotective molecular mechanisms of Rhynchophylline were investigated in a cellular model associated with PD. It is shown that Rhynchophylline (10-50 µM) greatly prevented neurotoxicity caused by 1-methyl-4-phenylpyridinium ion (MPP+) in primary cerebellar granule neurons, as evidenced by the promotion of cell viability as well as the reversal of dysregulated protein expression of Bax/Bcl-2 ratio. Very encouragingly, we found that Rhynchophylline markedly enhanced the activity of the transcription factor myocyte enhancer factor 2D (MEF2D) at both basal and pathological conditions using luciferase reporter gene assay, and reversed the inhibition of MEF2D caused by MPP+. Additionally, pharmacological inhibition of PI3-Kinase or short hairpin RNA-mediated gene down-regulation of MEF2D abrogated the protection provided by Rhynchophylline. Furthermore, Western blot analysis revealed that Rhynchophylline could potentiate PI3-K/Akt to attenuate GSK3β (the MEF2D inhibitor) in response to MPP+ insult. In conclusion, Rhynchophylline inhibits MPP+-triggered neurotoxicity by stimulating MEF2D via activating PI3-K/Akt/GSK3β cascade. Rhynchophylline is served as a novel MEF2D enhancer and might be a potential candidate for further preclinical study in the prevention of PD.