Inhibition of Intestinal Motility by the Putative BKCa Channel Opener LDD175

Ike Campomayor dela Peña,정재훈,Seo Young Yoon,이금선,Geum Seon Lee,Chul-Seung Park,김용철 대한약학회 2009 Archives of Pharmacal Research Vol.32 No.3

LDD175 (4-chloro-7-trifluoromethyl-10H-benzo[4,5]furo[3,2-b]indole-1-carboxylic acid) is a benzofuroindole compound characterized previously as a potent opener of the large conductance calcium activated (BKCa) channels. Activators of the BKCa channels are potential therapies for smooth muscle hyperactivity disorders. The present study investigates the influence of LDD175 on the mechanical activity of the ileum smooth muscle. LDD175 inhibited spontaneous contractions of the ileum in a concentration-dependent manner (pEC50=5.9 ± 0.1) (Emax=96 ± 1.0% at 100 μM, n=3). It also remarkably inhibited contractions due to acetylcholine (ACh) (pEC50=5.3 ± 0.1)(Emax=97.7 ± 2.3%, n=6) and electrical field stimulation (EFS) (pEC50=5.5 ± 0.1) (Emax=83.3 ± 6.0%, n=6). In strips precontracted by 20 mM KCl, LDD175 significantly reduced the contractions yielding a pEC50 of 6.1 ± 0.1 and Emax of 96.6 ± 0.9%, (n=6). In 60 mM KCl, a concentration-dependent inhibition was observed with respective pEC50 and Emax values of 4.1 ± 0.1 and 50.8 ± 5.0% (n=3). BKCa channel blockers iberiotoxin (IbTX) and tetraethylammonium chloride (TEA, 1 mM) attenuated the relaxative effect of LDD175 but not barium chloride (BaCl2), and glibenclamide (KIR and KATP channel blockers, respectively). These data demonstrate the antispasmodic activity of LDD175 attributable to the potentiation of the BKCa channels.

Is the Anti-stress Effect of Vitamin C Related to Adrenal Gland Function in Rat?

최지영,Ike Campomayor dela Peña,Seo Young YOON,Tae Sun Woo,Yoon Jung Choi,정재훈,Gu Yong Yu,신찬영,Jong Hoon RYU,이용수 한국식품과학회 2011 Food Science and Biotechnology Vol.20 No.2

The aim of this study was to investigate whether vitamin C influences the stress response system of the adrenal gland. Adrenalectomized (ADX) rats and non-ADX rats were administered vitamin C and were subjected to electroshock stress (ES) for 5 days. After loading the final stress, stress-related behaviors and corticosterone (CORT), vitamin C, and adrenocorticotropin-releasing hormone (ACTH) levels in the blood were measured. Vitamin C supplementation decreased CORT levels in non-ADX rats. Stress decreased the mean value of rearing frequency in both non-ADX and ADX rats, while vitamin C partially enhanced it only in non-ADX. Vitamin C supplementation decreased mean ACTH level in both groups. It also significantly decreased freezing time increased by stress. Lastly, vitamin C motivated both groups to cross over an electric field more frequently as compared to their respective control groups. These results suggest that the alleviating effect of vitamin C on stress-related rearing behavior was exerted via modulation of CORT, but its effect on freezing behavior may be attributed to corticotropinreleasing hormone (CRH) or ACTH.

A Simple Behavioral Paradigm to Measure Impulsive Behavior in an Animal Model of Attention Deficit Hyperactivity Disorder (ADHD) of the Spontaneously Hypertensive Rats

( 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.

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.

Red Ginseng Supplementation More Effectively Alleviates Psychological than Physical Fatigue

Ji Young Choi,Tae Sun Woo,Seo Young Yoon,Ike Campomayor dela Pena,Yoon Jung Choi,Hyung Seok Ahn,Yong Soo Lee,Gu Yong Yu,Jae Hoon Cheong 고려인삼학회 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±4℃) 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.

Comparative triple-color FISH mapping in eleven Senna species using rDNA and telomeric repeat probes

Thi Hong Nguyen,Nomar Espinosa Waminal,이도신,Remnyl Joyce Pellerin,Thanh Dat Ta,Nicole Bon Campomayor,Byung Yong Kang,김현희 한국원예학회 2021 Horticulture, Environment, and Biotechnology Vol.62 No.6

Senna is a diverse and paraphyletic genus in the subfamily Caesalpinioideae (Fabaceae Lindl.) comprising various speciesof industrial and medicinal value. To date, the genome-based taxonomic relationship among several Senna species remainsenigmatic. Cytogenetic information is invaluable in deciphering phylogenetic relationships and evolutionary history. However,insuffi cient chromosomal research for many Senna species impedes comparative cytotaxonomic analyses aimed at understandingtheir genomic evolution. To provide additional Senna -related molecular cytogenetic information, we karyotyped11 Senna species by employing triple-color fl uorescence in situ hybridization using 5S rDNA, 45S rDNA, and Arabidopsisthaliana -type telomeric pre-labeled oligonucleotide probes. Chromosome numbers were predominantly 2 n = 28, but 2 n = 22( S. marilandica ) and 2 n = 24 ( S. unifl ora ) were also observed. While most species revealed only one interstitial 5S rDNAlocus, except for S. unifl ora which has two loci, a range of one to three 45S rDNA loci were detected at distal chromosomalregions. Additionally, we observed a hemizygous 45S rDNA locus in S. auriculata . In addition to chromosome termini,weak signals for telomeric repeats were found in interstitial regions in S. hirsuta, S. corymbosa , and S. alexandrina . Thesecytogenetic data can be integrated with molecular phylogenetic data for more comprehensive Senna cytotaxonomic analyses.

Vitamin C Supplementation Alleviates Electroshock Stress but not Restraint Stress in ICR Mice

Ji Young Choi,Yoon Jung Choi,신찬영,Jong Hoon Ryu,Gu Yong Yu,정재훈,Ike Campomayor dela Peña,Seo Young Yoon,Geum Seon Lee 한국식품과학회 2010 Food Science and Biotechnology Vol.19 No.1

The aim of this study was to investigate what kind of stress vitamin C could alleviate. Experiments were performed using male ICR mice. Vitamin C (1, 5, 25, and 100 mg/kg) was administered orally daily for 7 days without stress and then were given for 5 days with electroshock (ES) or restraint stress (RS). After loading final stress, we recorded stress-related behaviors and measured the levels of blood corticosterone. Vitamin C supplementation (25 and 100 mg/kg) partially blocked stress-related behaviors such as freezing, smelling,burrowing, facewashing, and grooming. It decreased also staying time in closed arms. Stress responses induced by ES but not immobility were also significantly alleviated by vitamin C. Vitamin C (25 and 100 mg/kg) decreased corticosterone level increased by ES. Swimming time in cold water (8±2℃) was not changed by vitamin C, but crossing frequency in the electric field was increased by vitamin C (25 mg/kg). These results suggest that vitamin C supplementation can prevent damages or diseases induced by stress, especially psychological stress.

4-F-PCP, a Novel PCP Analog Ameliorates the Depressive-Like Behavior of Chronic Social Defeat Stress Mice via NMDA Receptor Antagonism

( Darlene Mae D. Ortiz ),( Mikyung Kim ),( Hyun Jun Lee ),( Chrislean Jun Botanas ),( Raly James Perez Custodio ),( Leandro Val Sayson ),( Nicole Bon Campomayor ),( Chaeyeon Lee ),( Yong Sup Lee ),( J 한국응용약물학회 2023 Biomolecules & Therapeutics(구 응용약물학회지) Vol.31 No.2

Major depressive disorder is a leading cause of disability in more than 280 million people worldwide. Monoamine-based antidepressants are currently used to treat depression, but delays in treatment effects and lack of responses are major reasons for the need to develop faster and more efficient antidepressants. Studies show that ketamine (KET), a PCP analog, produces antidepressant effects within a few hours of administration that lasts up to a week. However, the use of KET has raised concerns about side effects, as well as the risk of abuse. 4 -F-PCP analog is a novel PCP analog that is also an NMDA receptor antagonist, structurally similar to KET, and might potentially elicit similar antidepressant effects, however, there has been no study on this subject yet. Herein, we investigate whether 4-F-PCP displays antidepressant effects and explored their potential therapeutic mechanisms. 4-F-PCP at 3 and 10 mg/kg doses showed antidepressant-like effects and repeated treatments maintained its effects. Furthermore, treatment with 4-F-PCP rescued the decreased expression of proteins most likely involved in depression and synaptic plasticity. Changes in the excitatory amino acid transporters (EAAT2, EAAT3, EAAT4) were also seen following drug treatment. Lastly, we assessed the possible side effects of 4-F-PCP after long-term treatment (up to 21 days). Results show that 4-F-PCP at 3 mg/kg dose did not alter the cognitive function of mice. Overall, current findings provide significant implications for future research not only with PCP analogs but also on the next generation of different types of antidepressants.