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Pena, Ike Dela,Yoon, Seo Young,Kim, Hee Jin,Park, Sejin,Hong, Eun Young,Ryu, Jong Hoon,Park, Il Ho,Cheong, Jae Hoon The Korean Society of Ginseng 2014 Journal of Ginseng Research Vol.38 No.1
Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25-200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamine-induced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.
Ike Dela PENA,June Bryan dela Pen˜a,김붕년,한덕현,노민수,정재훈 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5
Attention-deficit/hyperactivity disorder (ADHD),the most commonly diagnosed neurobehavioral disorder ofchildhood, is usually treated with psychostimulants (e.g.,amphetamine). Little is known about the neuronal and behavioralconsequences of chronic amphetamine use or abuse inindividuals with ADHD. Of all ADHD animal models, thespontaneously hypertensive rat (SHR) is the most validated andwidely used. Here, we analyzed striatal transcriptomes inamphetamine-pretreated SHRs (5 mg/kg, i.p. for 7 days [twicedaily]), which showed a conditioned place preference to andself-administration of amphetamine. Microarray analysesrevealed increased mRNA expression of 55 genes ([1.65-foldincrease), while 17 genes were downregulated (\0.6-fold) inthe striatum of SHRs. The main functional categories overrepresentedamong the differentially expressed genes in thestriatum include those involved in transcription (e.g., Cebpb,Per2), genes associated with angiogenesis (e.g., Kdr, Klf5), celladhesion (e.g., Col11a1, Ctgf), apoptosis (e.g., Nfkbia, Perp)and neuronal development (e.g., Egr2, Nr4a3). In conclusion,we dissected the striatal transcriptional responses to the reinforcingeffects of repeated amphetamine treatment in the SHRmodel ofADHD. Future studies should determine the influenceof these altered transcripts on amphetamine reinforcement inamphetamine-treated SHRs, and the clinical relevance of thepresent findings with regard to amphetamine use/abuse inADHD individuals.
Ike Dela PENA,정재훈,한덕현,김붕년 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.4
Methylphenidate is the most prescribed stimulantmedication for attention-deficit/hyperactivity disorder(ADHD). Despite the well documented clinical benefits ofthe drug, several questions remain unanswered concerningthe effects of extended methylphenidate use (e.g. canmethylphenidate be abused by ADHD patients? doesrepeated methylphenidate treatment produce addiction?). Preclinical studies can help address the long-term safety ofclinical treatments, moreover animal studies providevaluable information on the details of drug actions. Thespontaneously hypertensive rat (SHR), bred from normotensiveWistar Kyoto rat strain, is considered as the bestvalidated and the most widely used animal model ofADHD. We reviewed the findings of research reports thatinvestigated the abuse and dependence liability of methylphenidatein SHR. In particular, we surveyed the studieswhich investigated the effects of methylphenidate pretreatmenton subsequent methylphenidate-induced conditionedplace preference or self-administration for they maygive insights into the abuse or dependence liability of longtermmethylphenidate treatment in ADHD.
Ike dela Pena,Seo Young Yoon,Hee Jin Kim,Sejin Park,Eun Young Hong,Jong Hoon Ryu,Il Ho Park,Jae Hoon Cheong 고려인삼학회 2014 Journal of Ginseng Research Vol.38 No.1
Background: Although ginsenosides such as Rg1, Rb1 and Rg3 have shown promise as potential nutraceuticals for cognitive impairment, their use has been limited due to high production cost and low potency. In particular, the process of extracting pure Rg3 from ginseng is laborious and expensive. Methods: We described the methods in preparing ginseol k-g3, an Rg3-enriched fraction, and evaluated its effects on scopolamine-induced memory impairment in mice. Results: Ginseol k-g3 (25e200 mg/kg) significantly reversed scopolamine-induced cognitive impairment in the passive avoidance, but not in Y-maze testing. Ginseol k-g3 (50 and 200 mg/kg) improved escape latency in training trials and increased swimming times within the target zone of the Morris water maze. The effect of ginseol k-g3 on the water maze task was more potent than that of Rg3 or Red ginseng. Acute or subchronic (6 d) treatment of ginseol k-g3 did not alter normal locomotor activity of mice in an open field. Ginseol k-g3 did not inhibit acetylcholinesterase activity, unlike donezepil, an acetylcholinesterase inhibitor. Rg3 enrichment through the ginseol k-g3 fraction enhanced the efficacy of Rg3 in scopolamineinduced memory impairment in mice as demonstrated in the Morris water maze task. Conclusion: The effects of ginseol k-g3 in ameliorating scopolamine-induced memory impairment in the passive avoidance and Morris water maze tests indicate its specific influence on reference or long-term memory. The mechanism underlying the reversal of scopolamine-induced amnesia by ginseol k-g3 is not yet known, but is not related to anticholinesterase-like activity.
윤서영,Ike Dela PENA,김성목,Tae Sun Woo,신찬영,손건호,박해일,이용수,류종훈,Mingli Jin,Kyeong-Man KIM,정재훈 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.1
In previous studies we have demonstrated thatthe c-aminobutryic acid-A (GABA-A) receptor antagonistoroxylin A has an awakening effect and it also repressesADHD-like behaviors (hyperactivity, impulsivity andinattention) in the spontaneously hypertensive rat (SHR)model of attention-deficit hyperactivity disorder (ADHD). We hypothesized that the effects of oroxylin A wereexerted via the GABA-A receptor given the important roleof the GABAergic system in ADHD. However, it is possiblethat aside from the GABAergic system, oroxylin Amay influence other systems especially those implicated inADHD (e.g. DAergic, etc.). To test this hypothesis, weevaluated the effects of GABA agonist, or dopamine (DA)antagonist in oroxylin A-induced alleviation of ADHD-likebehaviors in SHR. SHR showed inattention and impulsivityas measured by the Y-maze and the electro-foot shockaversive water drinking tests, respectively. Oroxylin Asignificantly improved these behaviors, furthermore, itseffect on SHR impulsivity was attenuated by haloperidol, aDA antagonist, but not by baicalein, an agonist of theGABA-A receptor. In vitro studies showed that oroxylin Ainhibited DA uptake similar to methylphenidate, a dopaminetransporter blocker, but did not influence norepinephrineuptake unlike atomoxetine, a selective NEreuptake inhibitor. Collectively, the present findings suggestthat oroxylin A improves ADHD-like behaviors inSHR via enhancement of DA neurotransmission and notmodulation of GABA pathway as previously reported. Importantly, the present study indicates the potential therapeuticvalue of oroxylin A in the treatment of ADHD.
( Pitna Kim ),( In Ha Choi ),( Ike Campomayor Dela Pena ),( Hee Jin Kim ),( Kyung Ja Kwon ),( Jin Hee Park ),( Seol Heui Han ),( Jong Hoon Ryu ),( Jae Hoon Cheong ),( Chan Young Shin ) 한국응용약물학회 2012 Biomolecules & Therapeutics(구 응용약물학회지) Vol.20 No.1
Impulsiveness is an important component of many psychiatric disorders including Attention-deficit/hyperactivity disorder (ADHD). Although the neurobiological basis of ADHD is unresolved, behavioral tests in animal models have become indispensable tools for improving our understanding of this disorder. In the punishment/extinction paradigm, impulsivity is shown by subjects that persevere with responding despite punishment or unrewarded responses. Exploiting this principle, we developed a new behavioral test that would evaluate impulsivity in the most validated animal model of ADHD of the Spontaneously Hypertensive rat (SHR) as compared with the normotensive control strain, the Wistar Kyoto rat (WKY). In this paradigm we call the Electro-Foot Shock aversive water Drinking test (EFSDT), water-deprived rats should pass over an electrified quadrant of the EFSDT apparatus to drink water. We reasoned that impulsive animals show increased frequency to drink water even with the presentation of an aversive consequence (electro-shock). Through this assay, we showed that the SHR was more impulsive than the WKY as it demonstrated more drinking attempts and drinking frequency. Methylphenidate, the most widely used ADHD medication, significantly reduced drinking frequency of both SHR and WKY in the EFSDT. Thus, the present assay may be considered as another behavioral tool to measure impulsivity in animal disease models, especially in the context of ADHD.
Anticonvulsant Effect of Artemisia capillaris Herba in Mice
( Tae Seon Woo ),( Seo Young Yoon ),( Ike Campomayor Dela Pena ),( Ji Young Choi ),( Hye Lim Lee ),( Yoon Jung Choi ),( Yong Soo Lee ),( Jong Hoon Ryu ),( Jae Sue Choi ),( Jae Hoon Cheong ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.3
In the present study, the anticonvulsant effects of Artemisia capillaris Herba (AC) and its major constituent, esculetin (ECT), were tested and the mechanism studied. Locomotion, Myorelaxation, motor coordination and electroshock seizure experiment were conducted in mice. To identify the anticonvulsant mechanism effect of this drug, chemical-induced seizure in mice and the ionic movement in neuroblastoma cells were also observed. The ethanol extract of AC was orally administered to mice 30 min. prior to testing and ECT was intraperitoneally injected. AC and ECT treatment did not change locomotor activities as well as activities on the rota-rod, which indicates that they did not cause a sedative and myorelaxation effect. AC and ECT treatment increased threshold of convulsion induced by electroshock. AC treatment also inhibited convulsion induced by pentylenetetrazole. In the case of strychnine however, only high dose of AC treatment inhibited convulsion. AC and ECT treatment increased the Cl- influx into the intracellular area in a dose-dependent manner. On the other hand, bicuculline, a GABA antagonist, inhibited the Cl- influx induced by AC and ECT. These results indicate that ECT induces the anticonvulsive effect of AC extract through the GABAergic neuron.
( Jae Hoon Cheong ),( Chan Young Shin ),( Ike C. Dela Pena ),( Hyung Seok Ahn ) 한국응용약물학회 2011 Biomolecules & Therapeutics(구 응용약물학회지) Vol.19 No.1
Repeated administration of addictive drugs causes cellular and molecular changes believed to be the mechanism of pro-addictive behaviors. Neuroadaptations also take place with repeated administration of amphetamine, methylphenidate and atomoxetine, drugs for Attention Deficit Hyperactivity Disorders (ADHD), and it is speculated that these changes may serve as markers to demonstrate the dependence liability of these therapies. In this review, we enumerate the neuroadaptive changes in molecules associated with neuronal signaling and plasticity, as well as neuronal morphology wrought by repeated administration of ADHD medications. We provide the current perspective on the dependence liability of these therapies, and also suggest of some factors that need to be considered in future investigations, so that what is drawn from animal studies would be better consolidated with those known clinically.
Red Ginseng Supplementation More Effectively Alleviates Psychological than Physical Fatigue
Choi, Ji-Young,Woo, Tae-Sun,Yoon, Seo-Young,Dela Pena, Ike Campomayor,Choi, Yoon-Jung,Ahn, Hyung-Seok,Lee, Yong-Soo,Yu, Gu-Yong,Cheong, Jae-Hoon The Korean Society of Ginseng 2011 Journal of Ginseng Research Vol.35 No.3
Red ginseng (RG, the extract of Panax ginseng Meyer) has various biological and psychological activities and may also alleviate fatigue-related disorders. The present study was undertaken to evaluate what kind of fatigue red ginseng alleviate. Animals were orally administered with 50, 100, 200, 400 mg/kg of RG for 7 days. Before experiments were performed. Physiological stress (swimming, rotarod, and wire test) are behavioral parameters used to represent physical fatigue. Restraint stress and electric field test to a certain degree, induce psychological fatigue in animals. Plasma concentration of lactate and corticosterone (CORT) were also measured after these behavioral assays. RG supplementation (100 mg/kg) increased movement duration and rearing frequency of restrainted mice in comparison with control. 100 and 200 mg/kg of RG increased swimming time in cold water ($8{\pm}4^{\circ}C$) while at 100 mg/kg, RG increased electric field crossing over frequencies. 50, 100 and 200 mg/kg RG prolonged running time on the rotarod and at 100 mg/kg, it increased balancing time on the wire. RG at those doses also reduced falling frequencies. RG supplementation decreased plasma CORT levels, which was increased by stress. Lactate levels were not significantly altered. These results suggest that RG supplementation can alleviate more the damages induced by psychological than physical fatigue.