Donghyuck Bae

Inhaled essential oil from Chamaecyparis obtuse ameliorates the impairments of cognitive function induced by injection of β-amyloid in rats.

Context: Chamaecyparis obtusa Sieb. & Zucc., Endlicher (Cupressaceae) forest bathing or aromatherapy has been shown in various studies to have biological functions such as anticancer, antiallergies, antiinflammatory, and antioxidant activity. However, no reports exist on the pharmacological or biological activities of the essential oil of C. obtusa (EOCO) or its effects on central nervous system. Objective: The aggregation and formation of β-amyloid peptides (Aβ) into fibrils are central events in the pathogenesis of Alzheimer’s disease (AD), and overproduction and aggregation of Aβ into oligomers have been known to trigger neurotoxicity. In this study, we investigated the effects of inhaled EOCO on cognitive function and neuronal apoptosis in rats intrahippocampally injected with Aβ. Materials and methods: To model AD, 4 μg of aggregated Aβ was injected into the hippocampus. To test the effects of EOCO, behavioral performance in the Morris water maze was tested 4 days after injection. After behavioral testing, brain sections were prepared for TTC staining and TUNEL assay. Results: Inhaled EOCO protected spatial learning and memory from the impairments induced by Aβ1–40 injection. In addition, the behavioral deficits accompanying Aβ1–40-induced AD were attenuated by inhalation of EOCO. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly inhibited in rats treated with Aβ1–40 and EOCO compared to rats treated only with Aβ1–40. Discussion and conclusion: EOCO suppressed both AD-related neuronal cell apoptosis and AD-related dysfunction of the memory system. Thus, the results of this study support EOCO as a candidate drug for the treatment of AD.

Hepatoprotective effects of aqueous extracts from leaves of Dendropanax morbifera leveille against alcohol-induced hepatotoxicity in rats and in vitro anti-oxidant effects

Protective effects of Dendropanax morbifera Lev. leaves (DM) against alcohol-induced liver injury in rat hepatocytes, and rats were investigated. Cell viability increased, and normally elevated intracellular reactive oxygen species (ROS) levels were reduced in cells treated with water extracts of DM (DMW) before ethanol treatment, compared with cells treated with 200 mM ethanol. DMW administration with ethanol resulted in prevention of ethanol-induced hepatotoxicity due to reductions of serum aspartate aminotransferase and alanine aminotransferase levels. DMW supplementation reduced formation of malondialdehyde, and inhibited reductions of hepatic glutathione, catalase, glutathione-S-transferase, glutathione reductase, and glutathione peroxidase levels, compared with rats administered ethanol, and suppressed expression of cytochrome P-450 2E1 that was elevated by ethanol administration. DMW reduced blood ethanol concentrations, and enhanced alcohol dehydrogenase and alcohol dehydrogenase activities that are typically decreased by ethanol administration, compared with ethanol-administered rats. DM exerted hepatoprotective effects against alcoholinduced hepatocyte injury.

Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

Tetradecanol reduces EL-4 T cell growth by the down regulation of NF-κB mediated IL-2 secretion

Abstract Tetradecanol is a straight‐chain saturated fatty alcohol purified from Dendropanax morbifera leaves. We found that tetradecanol (30 &mgr;M) reduced specifically the growth of T cells such as EL‐4 T cell and isolated murine CD4+ T cells. In this study, we investigated the effects of tetradecanol on the regulation of interlukin‐2 (IL‐2), a potent T cell growth factor. Tetradecanol significantly inhibited IL‐2 secretion in EL‐4 T cells activated with phorbol 12‐myristate 13‐acetate (PMA) plus ionomycin (Io) and also in isolated murine CD4+ T cells activated with anti‐CD3 and anti‐CD28 antibodies. Next, we examined the effect of tetradecanol on the transcriptional activity related to IL‐2 production in T cells. Tetradecanol decreased PMA/Io‐induced promoter activity of NF‐&kgr;B in EL‐4 T cells, but did not show any significant effects on the promoters of activator protein 1 (AP‐1) and nuclear factor of activated T cells (NF‐AT). Tetradecanol inhibited I&kgr;B&agr; degradation and nuclear translocation of NF‐&kgr;B subunit, p65 in PMA/Io–activated EL‐4 T cells. These results suggest that tetradecanol might have immunosuppressive effects on T cell mediated disorders. Using a chronic allergic contact dermatitis model induced by repeated application of oxazolone, we showed that tetradecanol reduced ear thickness induced by oxazolone.

Cynanchum wilfordii Ameliorates Testosterone-Induced Benign Prostatic Hyperplasia by Regulating 5α-Reductase and Androgen Receptor Activities in a Rat Model

Benign prostatic hyperplasia (BPH) is characterized by uncontrolled proliferation of the prostate gland. Cynanchum wilfordii has been reported to improve sexual behavior in male rats. In this study, we investigated the protective effect of an aqueous extract of C. wilfordii (CWW) against BPH development in a testosterone-induced BPH rat model. The rats were divided into the following six groups: sham/vehicle; BPH/vehicle; BPH/finasteride; and three CWW doses (50, 100, and 200 mg/kg). After a 4-week treatment with CWW, the rats were euthanized at scheduled times, and their prostates were weighed, followed by a histopathological examination. Prostate growth inhibition rates in rats administered CWW 50, 100, and 200 mg/kg were 54.5%, 51.8%, and 50.1%, respectively. The BPH/CWW group showed decreased serum testosterone and dihydrotestosterone (DHT) levels compared to the BPH/vehicle group. Furthermore, the BPH/CWW group showed reduced prostate testosterone and DHT levels compared to the BPH/vehicle group. Mechanistically, the reverse transcription-polymerase chain reaction revealed downregulated mRNA expression levels of the androgen receptor, 5α-reductase, and B-cell lymphoma-2 (Bcl-2) in the BPH/CWW200 group compared with those in the testosterone-induced groups. In conclusion, these findings show the effectiveness of CWW in slowing the progression of testosterone-induced BPH in rats.

Antiobesity Effects of Unripe Rubus coreanus Miquel and Its Constituents: An In Vitro and In Vivo Characterization of the Underlying Mechanism.

Background. The objective of the present study was to perform a bioguided fractionation of unripe Rubus coreanus Miquel (uRC) and evaluate the lipid accumulation system involvement in its antiobesity activity as well as study the uRC mechanism of action. Results. After the fractionation, the BuOH fraction of uRC (uRCB) was the most active fraction, suppressing the differentiation of 3T3-L1 adipocytes in a dose-dependent manner. Moreover, after an oral administration for 8 weeks in HFD-induced obese mice, uRCB (10 and 50 mg/kg/day) produced a significant decrease in body weight, food efficiency ratio, adipose tissue weight and LDL-cholesterol, serum glucose, TC, and TG levels. Similarly, uRCB significantly suppressed the elevated mRNA levels of PPARγ in the adipose tissue in vivo. Next, we investigated the antiobesity effects of ellagic acid, erycibelline, 5-hydroxy-2-pyridinemethanol, m-hydroxyphenylglycine, and 4-hydroxycoumarin isolated from uRCB. Without affecting cell viability, five bioactive compounds decreased the lipid accumulation in the 3T3-L1 cells and the mRNA expression levels of key adipogenic genes such as PPARγ, C/EBPα, SREBP-1c, ACC, and FAS. Conclusion. These results suggest that uRC and its five bioactive compounds may be a useful therapeutic agent for body weight control by downregulating adipogenesis and lipogenesis.

Neuroprotective effects of Eriobotrya japonica and Salvia miltiorrhiza Bunge in in vitro and in vivo models

We previously reported that Eriobotrya japonica (EJ) improves the cognitive dysfunction caused by amyloid-β (Aβ) peptide injection. Here, we further examined the possible neuroprotective effects and the combined ameliorating effects of EJ and Salvia miltiorrhiza Bunge (SM) in various in vitro and in vivo models. We confirmed the combined effects of a mixture of 5% ethanol extract from EJ leaves (EJE) and water extract from SM roots (SMW) on Aβ1–42-induced toxicity in an in vitro model. Treatment with the mixture (1:1) of EJ and SM (Mix) produced significantly better protection of cells from Aβ-induced toxicity and more strongly suppressed caspase-3 activity compared to treatment with EJE or SMW alone. Additionally, EJE, SMW, and Mix attenuated CoCl2-induced hypoxic damage and corticosterone-induced impairment in SH-SY5Y cells. To examine the combined effects of EJE and SMW in in vivo models, behavioral performance in the Morris water maze was tested two days after injection of Aβ1–42. Administration of Mix provided significantly more protection of spatial learning and memory against the impairments induced by Aβ1–42 injection than did administration of EJE or SMW alone. Additionally, the behavioral deficits that accompanied Aβ-induced memory impairment were attenuated to a greater extent by the administration of the mixture. Furthermore, acetylcholinesterase (AChE) activity and neuronal apoptosis were significantly more inhibited in rats treated with Aβ and the mixture than in rats treated with Aβ1–42 alone. Thus, the results of this study indicate that the mixture of EJ and SM has combined effects that are neuroprotective against Aβ1–42-induced neuronal toxicity.

Vaccinium bracteatum Leaf Extract Reverses Chronic Restraint Stress-Induced Depression-Like Behavior in Mice: Regulation of Hypothalamic-Pituitary-Adrenal Axis, Serotonin Turnover Systems, and ERK/Akt Phosphorylation

The leaves of Vaccinium bracteatum Thunb. are a source of traditional herbal medicines found in East Asia. The present study aimed to evaluate the mechanisms underlying the antidepressant-like effects of water extract of V. bracteatum Thunb. leaves (VBLW) in a mouse model of chronic restraint stress (CRS) and to identify the possible molecular in vitro mechanisms of the neuroprotective effects. The CRS-exposed mice were orally administered VBLW (100 and 200 mg/kg) daily for 21 days consecutively. The behavioral effects of VBLW were assessed through the forced swim test (FST) and the open field test (OFT). The levels of serum corticosterone (CORT), corticotropin releasing hormone (CRH), and adrenocorticotropin hormone (ACTH), brain monoamines, such as serotonin, dopamine, and norepinephrine, and serotonin turnover by tryptophan hydroxylase 2 (TPH2), serotonin reuptake (SERT), and monoamine oxidase A (MAO-A) were evaluated, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway. CRS-exposed mice treated with VBLW (100 and 200 mg/kg) showed significantly reduced immobility time and increased swimming and climbing times in the FST, and increased locomotor activity in the OFT. Moreover, CRS mice treated with VBLW exhibited significantly decreased CORT and ACTH, but enhanced brain monoamine neurotransmitters. In addition, CRS mice treated with VBLW had dramatically decreased protein levels of MAO-A and SERT, but increased TPH2 protein levels in the hippocampus and the PFC. Similarly, VBLW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and the PFC. Furthermore, VBLW showed neuroprotective effects via increased CREB phosphorylation in CORT-induced cell injury that were mediated through the ERK/Akt/mTOR signaling pathways. These results suggested that the antidepressant-like effects of VBLW might be mediated by the regulation of the HPA axis, glucocorticoids, and serotonin turnover, such as TPH2, SERT, and MAO-A, as well as the concentration of monoamine neurotransmitters, and the activities of ERK and Akt phosphorylation, which were possibly associated with neuroprotective effects.

Effect of Aqueous Extract of Dendropanax morbifera Leaf on Sexual Behavior in Male Rats

Sexual function in an important of the quality of life and subjective well-being in humans. Successful treatment of sexual dysfunction may improve not only sexual relationships, but also overall quality of life. The objective of this study was to determine the effects of Dendropanax morbifera (DM) Lev. leaf extracts on sexual behavior and testosterone levels in male rats. Three different doses of DM (50, 100, and 200 mg/kg/day) were administered orally for 28 days. On day 28 (final day of the sample treatment period) and day 42 (after 2 weeks of sample withdrawal period following 28 days of sample treatment), serum testosterone levels and sexual behavior of rats were determined, including mount frequency (MF), intromission frequency, mount latency (ML, the time from introduction of the female to the male to the first mount), intromission latency (IL), and post-ejaculatory interval (PEI). ML significantly reduced, whereas MF increased in the DM group. The DM group also had a reduced PEI. The oral administration of DM significantly increased serum testosterone levels compared with those in the control group. The results of this study demonstrate that an aqueous extract of DM represents a useful natural resource for the management of sexual function.

Multifunctional antistress effects of standardized aqueous extracts from Hippophae rhamnoides L.

ABSTRACT This study aims to screen and identify the multi-mechanism antistress effects of an extract of Hippophae rhamnoides L. (HR) leaves on corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activity tests (in vitro), electric foot shock and forced swimming tests (FSTs) (in vivo), and tests for hippocampal CORT and monoamine levels (ex vivo), in search of active principles and underlying mechanisms of action. We confirmed that the water extract of HR (HRW) and various ethanol extracts of HR confer protective effects against CORT-induced impairments in SH-SY5Y cells and antagonistic effects on NMDA receptors and the 5-HT6 receptor by using primary cultured rat hippocampal neurons and a stable 5-HT6 receptor-expressing cell line, respectively. In addition, we confirmed the antistress effects of HRW in an electric foot shock stress model in mice and explored the underlying mechanisms of its action. We observed that HRW treatment significantly reversed the reduction in immobility times and increased climbing times in FSTs induced by electric foot shocks in the stress model. The levels of CORT, dopamine, and norepinephrine were increased, and the level of serotonin in the hippocampus was decreased in the electric foot shock stress model. The standardized HRW effectively restored abnormal CORT and monoamine levels in the hippocampus that were induced by stress. The results of the present study demonstrate that the standardized HRW produces novel multifunctional antistress effects.