Jung Wha Kim

Associations between serotonin transporter gene (SLC6A4) methylation and clinical characteristics and cortical thickness in children with ADHD.

BACKGROUND Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable psychiatric disorder. Additionally, environmental factors such as perinatal stress and early adversities contribute to the occurrence and severity of ADHD. Recently, DNA methylation has emerged as a mechanism that potentially mediates gene-environmental interaction effects in the aetiology and phenomenology of psychiatric disorders. Here, we investigated whether serotonin transporter gene (SLC6A4) methylation patterns were associated with clinical characteristics and regional cortical thickness in children with ADHD. METHOD In 102 children with ADHD (age 6-15 years), the methylation status of the SLC6A4 promoter was measured. Brain magnetic resonance imaging was obtained and ADHD symptoms were evaluated. RESULTS A higher methylation status of the SLC6A4 promoter was significantly associated with worse clinical presentations (more hyperactive-impulsive symptoms and more commission errors). Additionally, a negative correlation was observed between SLC6A4 methylation levels and cortical thickness values in the right occipito-temporal regions. CONCLUSIONS Our results suggest that the SLC6A4 methylation status may be associated with certain symptoms of ADHD, such as behavioural disinhibition, and related brain changes. Future studies that use a larger sample size and a control group are required to corroborate these results.

Hepatoprotective constituents of Firmiana simplex stem bark against ethanol insult to primary rat hepatocytes

Background: Ethanol causes hepatic cellular damage by alterations in biological functions. This study evaluated the hepatoprotective potential of the methanolic extract originating from Firmiana simplex (Sterculiaceae) stem bark against the ethanol-induced hepatotoxicity in rat primary hepatocytes. Materials and Methods: The extract of F. simplex stem bark was successively fractionated into n-hexane, chloroform, ethyl acetate (EtOAc), and n-butanol. Column chromatography with silica gel and sephadex LH-20 was used to isolate the EtOAc fraction. Rat primary hepatocytes were cultured to study the hepatoprotective activity of isolated substances against ethanol-induced toxicity. Intracellular reactive oxygen species (ROS) levels, the antioxidant activities of glutathione reductase (GR) and glutathione peroxidase (GSH-PX) enzymes, and the GSH content were measured to examine the antioxidative property of the isolated compounds. Results: Two flavonoid glycosides, quercitrin (1) and tamarixetin 3-O-rhamnopyranoside (2), were isolated from the active EtOAc fraction. Compound 1 significantly protected rat primary hepatocytes against ethanol-induced oxidative stress by reducing the intracellular ROS level and preserving antioxidative defense systems such as GR, GSH-PX, and total GSH. Conclusion: This is the first report on the hepatoprotective activities of the extract of F. simplex. The EtOAc fraction of F. simplex stem bark and its major constituent quercitrin (1) could function as hepatoprotective agents to attenuate the development of alcoholic liver disease.

Prickly Pear Cactus (Opuntia ficus indica var. saboten) Protects Against Stress-Induced Acute Gastric Lesions in Rats

The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSMs gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

Chemical constituents isolated from Disporum viridescens leaves and their inhibitory effect on nitric oxide production in BV2 microglial cells.

Excessive NO (nitric oxide) has been associated with the pathogenesis of various neurodegenerative diseases including Alzheimers disease (AD). In our screening system using LPS-activated BV2 microglial cells, the methanolic extract of Disporum viridescens leaves was found to have significant NO inhibitory activity. Bioactivity-guided isolation yielded a new phenylpropanoid characterized as 4-ally-2,6-dimethoxyphenyl 1-O-β-D-apiofuranosyl (1→6)-β-D-glucopyranoside (12) with 21 known compounds from the leaves of D. viridescens. Among them, compounds 2 and 4 significantly inhibited NO production. Thus, we further elucidated the anti-inflammatory mechanism of these lignans. Especially, compound 4 inhibited the expression of both inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) through the suppression of the MAPK signaling pathway. Taken together, the anti-inflammatory activities of the active constituents isolated from D. viridescens leaves could have therapeutic potential against neurodegenerative diseases.

No significant association between the alpha-2A-adrenergic receptor gene and treatment response in combined or inattentive subtypes of attention-deficit hyperactivity disorder.

INTRODUCTION Given the shortage of pharmacogenetic studies on treatment response according to subtype of attention-deficit hyperactivity disorder (ADHD), we investigated the associations between the MspI and DraI polymorphisms of the alpha-2 A-adrenergic receptor gene (ADRA2A) and treatment response to methylphenidate according to subtype of ADHD. METHODS We enrolled 115 medication-naïve children with ADHD into an open label 8-week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical -Global Impression (CGI), ADHD rating scale, and Continuous Performance Test (CPT) pre- and post-treatment. RESULTS There was no statistically significant association between the MspI or DraI genotypes and the relative frequency of CGI-improvement (CGI-I) 1 or 2 status among any of the groups (all types of ADHD, ADHD-C, or ADHD-I). However, among the children with ADHD-C, those subjects with the C/C genotype at the ADRA2A DraI polymorphism tended to have a CGI-I 1 or 2 status post-treatment (OR=4.45, p=0.045). DISCUSSION The results of this study do not support the association between the the MspI or DraI genotypes and treatment response to methylphenidate in ADHD. However, our results -suggest that subtypes might influence pharmacogenetic results in ADHD.·available online at http://www.thieme-connect.de/ejournals/toc/pharmaco.

Catechin-Bound Ceanothane-Type Triterpenoid Derivatives from the Roots of Zizyphus jujuba

Three unprecedented ceanothane-type triterpenoids, ent-epicatechinoceanothic acid A (1), ent-epicatechinoceanothic acid B (2), and epicatechino-3-deoxyceanothetric acid A (3), containing C-C bond linkages with catechin moieties, were isolated from the roots of Zizyphus jujuba. Their chemical structures, including absolute configurations, were established by spectroscopic analysis and calculation of their ECD spectra. A possible biogenetic pathway for C-C bond formation between the catechin and the triterpenoid moieties is presented. Compound 1 was evaluated for its antiproliferative activity on HSC-T6 hepatic stellate cells.

Lignans from Opuntia ficus-indica seeds protect rat primary hepatocytes and HepG2 cells against ethanol-induced oxidative stress

Bioactivity-guided isolation of Opuntia ficus-indica (Cactaceae) seeds against ethanol-treated primary rat hepatocytes yielded six lignan compounds. Among the isolates, furofuran lignans 4−6, significantly protected rat hepatocytes against ethanol-induced oxidative stress by reducing intracellular reactive oxygen species levels, preserving antioxidative defense enzyme activities, and maintaining the glutathione content. Moreover, 4 dose-dependently induced the heme oxygenase-1 expression in HepG2 cells.

Hepatoprotective flavonoids in Opuntia ficus-indica fruits by reducing oxidative stress in primary rat hepatocytes

Background: Liver disorder was associated with alcohol consumption caused by hepatic cellular damages. Opuntia ficus-indica fruit extracts (OFIEs), which contain betalain pigments and polyphenols including flavonoids, have been introduced as reducing hangover symptoms and liver protective activity. Objective: To evaluate hepatoprotective activity of OFIEs and isolated compounds by high-speed countercurrent chromatography (HSCCC). Materials and Methods: The extract of O. ficus-indica fruits was fractionated into methylene chloride and n-butanol. The n-butanol fraction was isolated by HSCCC separation (methylene chloride-methanol-n-butanol-water, 5:4:3:5, v/v/v/v). The hepatoprotective activity of OFIEs and isolated compounds was evaluated on rat primary hepatocytes against ethanol-induced toxicity. Antioxidative parameters such as glutathione reductase and glutathione peroxidase (GSH-Px) enzymes and the GSH content were measured. Results: Two flavonoids, quercetin 3-O-methyl ester (1) and (+)-taxifolin, and two flavonoid glycosides, isorhamnetin 3-O-β-d-glucoside (3) and narcissin (4), were isolated from the n-butanol fraction by HSCCC separation. Among them, compound 2 significantly protected rat primary hepatocytes against ethanol exposure by preserving antioxidative properties of GR and GSH-Px. Conclusions: OFIEs and (+)-taxifolin were suggested to reduce hepatic damage by alcoholic oxidative stress.