Ji-Ho Park

Publications of Ji-Ho Park

• Dietary silk protein, sericin, improves epidermal hydration with increased levels of filaggrins and free amino acids in NC/Nga mice.

  Authors: Hyunae Kim, Yu-Ji Lim, Ji-Ho Park, Yunhi Cho

  The British journal of nutrition. 01/2012;

  Epidermal hydration is maintained primarily by natural moisturising factors (NMF), of which free amino acids (AA) are major constituents that are generated by filaggrin degradation. To identifyEpidermal hydration is maintained primarily by natural moisturising factors (NMF), of which free amino acids (AA) are major constituents that are generated by filaggrin degradation. To identify dietary sources that may improve skin dryness of atopic dermatitis (AD), we investigated dietary effects of silk proteins, sericin and fibroin, on epidermal levels of hydration, filaggrins and free AA, as well as PPARγ, peptidylarginine deiminase-3 (PAD3) and caspase-14 proteins involved in filaggrin expression and degradation processes. NC/Nga mice, an animal model of AD, were fed a control diet (group CA: atopic control) or diets with 1 % sericin (group S) or fibroin (group F) for 10 weeks. In group S, epidermal levels of hydration, total filaggrins and total free AA, as well as PPARγ, PAD3 and caspase-14, which were reduced in group CA, were increased to higher or similar levels of a normal control group of BALB/c mice (group C). Furthermore, profilaggrin, a precursor with multiple filaggrin repeats, and three repeat intermediates were increased, while two repeat intermediates and filaggrin were decreased in parallel with increased levels of glutamate and serine, major AA of NMF in group S. Despite increased levels of total filaggrins, total free AA, PPARγ and PAD3, epidermal levels of hydration, glutamate, serine and caspase-14 were not increased, but other minor AA of NMF were highly detected in group F. Dietary sericin improves epidermal hydration in parallel with enhancing profilaggrin expression and degradation into free AA that is coupled with elevated levels of PPARγ, PAD3 and caspase-14 proteins.

• Diosgenin from Dioscorea nipponica ameliorates diabetic neuropathy by inducing nerve growth factor.

  Authors: Tong Ho Kang, Eunjung Moon, Bin Na Hong, Sang Zin Choi, Miwon Son, Ji-Ho Park, Sun Yeou Kim

  Biological & pharmaceutical bulletin. 01/2011; 34(9):1493-8.

  Diabetic neuropathy is characterized by axonal degeneration, demyelination, and atrophy in association with failed axonal regeneration, remyelination, and synaptogenesis. Recent reports suggest thatDiabetic neuropathy is characterized by axonal degeneration, demyelination, and atrophy in association with failed axonal regeneration, remyelination, and synaptogenesis. Recent reports suggest that reduced levels of nerve growth factor (NGF) may play a significant role in the pathogenesis of diabetic polyneuropathy. In this study, we investigated the regulation of NGF by steroid diosgenin (DG) in a diabetic neuropathy rodent model. We found that DG, the primary spirostane-type steroid in several Dioscorea species, increased NGF levels in the sciatic nerve of diabetic rats. Additionally, DG increased neurite outgrowth in PC12 cells and enhanced nerve conduction velocities in the diabetic neuropathy mouse model. DG-treated diabetic mice showed reduced disarrangement of the myelin sheath and increased area of myelinated axons by electron microscope studies and exhibited improvement in the damaged axons. Our data further suggest that DG increased the nerve conduction velocity through induction of NGF. Thus, our findings indicate that DG, a major sapogenin obtained from Dioscorea nipponica, reverses functional and ultrastructural changes and induces neural regeneration in a diabetic neuropathy model.

• Anti-inflammatory effects of crocin and crocetin in rat brain microglial cells.

  Authors: Kyong Nyon Nam, Young-Min Park, Hoon-Ji Jung, Jung Yeon Lee, Byung Duk Min, Seong-Uk Park, Woo-Sang Jung, Ki-Ho Cho, Ji-Ho Park, Insug Kang, Joung-Woo Hong, Eunjoo H Lee

  European journal of pharmacology. 12/2010; 648(1-3):110-6.

  Microglial cells play critical roles in the immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of microglia helps in restoring CNSMicroglial cells play critical roles in the immune and inflammatory responses of the central nervous system (CNS). Under pathological conditions, the activation of microglia helps in restoring CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory and neurotoxic factors. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that observed in Alzheimer's and Parkinson's diseases. Crocin and crocetin, found in the fruits of gardenia and in the stigmas of saffron, have been considered for the treatment of various disorders in traditional oriental medicine. Crocin and crocetin have been reported to have diverse pharmacological functions, such as anti-hyperlipidemic, anti-atherosclerotic, and anti-cancer effects. Specifically, the neuroprotective potential of crocetin derivatives has previously been demonstrated. The specific aim of this study was to examine whether crocin or crocetin represses microglial activation. Crocin and crocetin were shown to be effective in the inhibition of LPS-induced nitric oxide (NO) release from cultured rat brain microglial cells. These compounds reduced the LPS-stimulated productions of tumor necrosis factor-α, interleukin-1β, and intracellular reactive oxygen species. The compounds also effectively reduced LPS-elicited NF-κB activation. In addition, crocin reduced NO release from microglia stimulated with interferon-γ and amyloid-β. In organotypic hippocampal slice cultures, both crocin and crocetin blocked the effect of LPS on hippocampal cell death. These results suggest that crocin and crocetin provide neuroprotection by reducing the production of various neurotoxic molecules from activated microglia.

• Inhibition of hexokinase leads to neuroprotection against excitotoxicity in organotypic hippocampal slice culture.

  Authors: Kyung Hee Lee, Ji Ho Park, Ran Won, Hyejung Lee, Taick Sang Nam, Bae Hwan Lee

  Journal of neuroscience research. 11/2010; 89(1):96-107.

  During seizures, glucose concentrations are high in the hippocampus. Mitochondrial hexokinase (HK) catalyzes the first essential step of glucose metabolism and directly couples extramitochondrialDuring seizures, glucose concentrations are high in the hippocampus. Mitochondrial hexokinase (HK) catalyzes the first essential step of glucose metabolism and directly couples extramitochondrial glycolysis to intramitochondrial oxidative phosphorylation. The neuroprotective effects of an HK inhibitor, 3-bromopyruvate (3-BrPA), on kainic acid (KA)-induced excitotoxic injury were investigated. Hippocampal slices were prepared from hippocampi of 6-8-day-old rats using a tissue chopper and placed on a membrane insert. After a treatment with KA (5 μM) for 15 hr, neuronal death was quantified by propidium iodide (PI), cresol violet, and TUNEL staining. KA-induced cell death was significantly prevented by 30 μM 3-BrPA treatment. According to Western blots, the expression level of phospho-Akt increased after 3-BrPA treatment. The induction of long-term potentiation (LTP) at 48 hr after 3-BrPA treatment tended to increase in the CA1 area compared with the KA-only group, but the difference was not significant. Blocking the PI3 kinase/Akt pathway using LY294002 reversed the neuroprotective effect of 3-BrPA. These results suggest that inhibition of HK may play a protective role against neuronal death in KA-induced excitotoxic injury.

• Inhibitory effects of 5-chloroacetyl-2-piperidino-1,3-selenazole, a novel selenium-containing compound, on skin melanin biosynthesis.

  Authors: Eunjoo H Lee, Yu-Ji Lim, Sang Keun Ha, Tong Ho Kang, Mamoru Koketsu, Chulhun Kang, Sun Yeou Kim, Ji-Ho Park

  The Journal of pharmacy and pharmacology. 03/2010; 62(3):352-9.

  Increased production and accumulation of melanin leads to many hyperpigmentation disorders such as melasma, freckles and geriatric pigment spots. Thus, there is a need for the development ofIncreased production and accumulation of melanin leads to many hyperpigmentation disorders such as melasma, freckles and geriatric pigment spots. Thus, there is a need for the development of depigmenting agents. Based on our previous reports, selenium derivatives as anti-melanogenic lead compounds could be very important. The aim of this study was to investigate the depigmenting effect of novel selenium-containing compounds. The inhibitory effects of 5-chloroacetyl-2-piperidino-1,3-selenazole (CS1), a novel selenium-containing compound, on melanogenesis were investigated in B16F10 melanoma cells and cultured brownish guinea pig skin tissue with alpha-melanocyte-stimulating hormone stimulation. We found that CS1 inhibited melanin production in B16F10 cells by suppressing tyrosinase activity and its protein expression. In addition, Western blotting analysis revealed that CS1 suppressed the expression of tyrosinase-related protein (TRP)-1 and TRP-2. Therefore, the depigmenting effect of CS1 might have been due to inhibition of tyrosinase activity and expression of melanogenic enzymes. Furthermore, CS1 had inhibitory effects on melanin biosynthesis of primary cultured skin of brownish guinea pig. The results suggested that CS1 could be a useful candidate for the treatment of skin hyperpigmentation.

• The multi-herbal medicine Gongjin-dan enhances memory and learning tasks via NGF regulation.

  Authors: Eunjung Moon, Youngjin Her, Jung Bok Lee, Ji-Ho Park, Eunjoo H Lee, Sung-Hoon Kim, Myung Sook Oh, Choon-Gon Jang, Sun Yeou Kim

  Neuroscience letters. 09/2009;

  Nerve growth factor (NGF) decreases degeneration of cholinergic neurons, improves memory loss, and increases long-term potentiation and learning tasks. Therefore, NGF mimetics or NGF inducers may beNerve growth factor (NGF) decreases degeneration of cholinergic neurons, improves memory loss, and increases long-term potentiation and learning tasks. Therefore, NGF mimetics or NGF inducers may be important targets for the treatment of various neurodegenerative disorders. Traditionally, Gongjin-dan (GJD) has been used clinically for the treatment of central nervous system disorders. In this study, we examined the effects of GJD on NGF mimetic activity in PC12 cells and the induction of NGF secretion in primary astrocytes. Moreover, we also measured neuron survival by MAP-2 staining in an immobilization stress rat model and induction of long-term potentiation by the MEA system in rat hippocampus slices treated with dexamethasone. The behavioral syndrome by novel object test was also performed in mice. GJD increased neurite outgrowth in PC12 cells and NGF secretion in primary astrocytes. Also, it reduced neuronal cell death and increased long-term potentiation in the rat hippocampus. Moreover, the number of entries, the time spent and the distance moved in the center area of the test region by the mice was increased by oral administration of GJD in comparison with the distance moved over the total area. These data suggest that administration of GJD may improve memory and learning tasks via NGF regulation, and that it may have a potential for multiple function neuroprotection via NGF regulation.

• Inhibitory effects of arbutin on melanin biosynthesis of alpha-melanocyte stimulating hormone-induced hyperpigmentation in cultured brownish guinea pig skin tissues.

  Authors: Yu-Ji Lim, Eunjoo Lee, Tong Kang, Sang Ha, Myung Oh, Seong Kim, Tae-Jin Yoon, Chulhun Kang, Ji-Ho Park, Sun Kim

  Archives of pharmacal research. 04/2009; 32(3):367-373.

  Arbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma orArbutin has been used as a whitening agent in cosmetic products. Melanin, the major pigment that gives color to skin, may be over-produced with sun exposure or in conditions such as melasma or hyperpigmentary diseases. Tyrosinase is a key enzyme that catalyzes melanin synthesis in melanocytes; therefore, inhibitors of the tyrosinase enzyme could be used for cosmetic skin whitening. A recent study has reported that arbutin decreases melanin biosynthesis through the inhibition of tyrosinase activity. However, this inhibitory mechanism of arbutin was not sufficiently demonstrated in skin tissue models. We found that arbutin both inhibits melanin production in B16 cells induced with alpha-MSH and decreases tyrosinase activity in a cell-free system. Furthermore, the hyperpigmentation effects of alpha-MSH were abrogated by the addition of arbutin to brownish guinea pig and human skin tissues. These results suggest that arbutin may be a useful agent for skin whitening.

• Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-kappaB: neuroprotective implications.

  Authors: Kyong Nyon Nam, Min-Sook Son, Ji-Ho Park, Eunjoo H Lee

  Neuropharmacology. 10/2008; 55(5):819-25.

  Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNSMicroglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. Shikonin, a naphthoquinone pigment from the root of Lithospermum erythrorhizon, has long been used as an ointment for wound healing in traditional oriental medicine. Shikonin has been reported to have antibacterial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether shikonin represses microglial activation. In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-alpha, interleukin-1beta, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-alpha and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IkappaB-alpha phosphorylation and NF-kappaB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results suggest that IBS and IVS provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

• Protective effect of apigenin on ovariectomy-induced bone loss in rats.

  Authors: Jeong A Park, Sang Keun Ha, Tong Ho Kang, Myung Sook Oh, Min Hyoung Cho, Soo Yeol Lee, Ji-Ho Park, Sun Yeou Kim

  Life sciences. 07/2008; 82(25-26):1217-23.

  Recent studies have shown that apigenin not only inhibits bone resorption by osteoclasts but also induces osteoclast apoptosis. However, the influence of apigenin on osteoporosis in animals isRecent studies have shown that apigenin not only inhibits bone resorption by osteoclasts but also induces osteoclast apoptosis. However, the influence of apigenin on osteoporosis in animals is relatively unknown. The purpose of this study was to examine the bone-protective effects of apigenin in estrogen-deficient ovariectomized rats. Three-month-old female Sprague-Dawley rats were either sham-operated or ovariectomized and fed AIN-93G diet for 7 weeks to induce bone loss. To confirm bone loss, we used a newly developed non-invasive technique involving zoom-in micro-computed tomography. Apigenin was administered at a dose of 10 mg/kg three times a week for 15 weeks. Our results indicate that apigenin not only increased the mineral content and density of the trabecular bone at the neck of the left femur, but also decreased body weight and dietary consumption. Moreover, our biochemical results indicate that apigenin has a positive effect on bone turnover. The present data suggest that apigenin should be considered for use in the treatment of osteoporosis.

• Effects of Anemarrhena asphodeloides on focal ischemic brain injury induced by middle cerebral artery occlusion in rats.

  Authors: Jin Kyung Oh, Seung Ye Hyun, Hye Rim Oh, Ji Wook Jung, Chan Park, Sun Young Lee, Ji-Ho Park, Sun Yeou Kim, Ki Hoon Kim, Young Kyun Kim, Jong Hoon Ryu

  Biological & pharmaceutical bulletin. 02/2007; 30(1):38-43.

  The preventive effect of Anemarrhena asphodeloides Bunge (Liliaceae), a traditional Chinese medicine, on ischemia-reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was inducedThe preventive effect of Anemarrhena asphodeloides Bunge (Liliaceae), a traditional Chinese medicine, on ischemia-reperfusion-induced brain injury was evaluated in the rat brain. Ischemia was induced by intraluminal occlusion of the right middle cerebral artery for 2 h and reperfusion was continued for 22 h. Water extract of Anemarrhena asphodeloides (WEAA) was orally administered promptly prior to and 2 h after reperfusion. Total infarct volume and edema in the ipsilateral hemispheres of ischemia-reperfusion rats were significantly reduced by treatment with WEAA in a dose-dependent manner (p<0.05). The therapeutic time window of WEAA was 3 h in this ischemia-reperfusion rat model. WEAA also significantly inhibited increased neutrophil infiltration of ischemic brain tissue as estimated by myeloperoxidase (MPO) activity and immunohistochemical analysis. MPO-positive cells were markedly reduced by WEAA administration in striatal and cortical areas. These findings suggest that WEAA plays a crucial protective role in ischemia-induced brain injury, and suggest that WEAA could serve as a lead medicinal herb for the development of neuroprotective agents following transient focal ischemic brain injury.

• In vivo trabecular thickness measurement in cancellous bones: longitudinal rat imaging studies.

  Authors: In Kon Chun, Min Hyoung Cho, Ji-Ho Park, Soo Yeol Lee

  Physiological measurement. 09/2006; 27(8):695-702.

  Using cross-sectional x-ray images taken with zoom-in micro computed tomography (micro-CT), we have measured trabecular thickness in the femoral bones of live rats. Since zoom-in micro-CT is capableUsing cross-sectional x-ray images taken with zoom-in micro computed tomography (micro-CT), we have measured trabecular thickness in the femoral bones of live rats. Since zoom-in micro-CT is capable of high-resolution imaging of a small local region inside a large subject, we were able to measure trabecular thickness in femoral bones without sacrificing the rats. To longitudinally observe the trabecular thickness change caused by ovariectomy-induced osteoporosis, we have taken zoom-in micro-CT images of 15 live Sprague-Dawley rats (group A: 5 ovariectomized rats fed with regular food; group B: 5 ovariectomized rats fed with calcium-deficient food; group C: 5 controls) every other week for 10 weeks. We have observed that the mean trabecular thickness in the femoral bones of groups A and B decreased monotonically down to about 10.7% and 15.5%, respectively, as compared to that of group C, within 12 weeks after the ovariectomy, while the mean trabecular thickness of group C increased about 12.7%. We expect that zoom-in micro-CT can be successfully used in osteoporosis studies in which longitudinal imaging studies are required.

• Observation of the fast response of a magnetic resonance signal to neuronal activity: a snail ganglia study.

  Authors: Tae Seok Park, Sang Yeon Lee, Ji-Ho Park, Min Hyoung Cho, Soo Yeol Lee

  Physiological measurement. 03/2006; 27(2):181-90.

  We observed the response of a magnetic resonance signal to neuronal activity in dissected snail ganglia to investigate faster responding components than the blood oxygenation level dependent (BOLD)We observed the response of a magnetic resonance signal to neuronal activity in dissected snail ganglia to investigate faster responding components than the blood oxygenation level dependent (BOLD) component. To eliminate the BOLD component completely from the magnetic resonance signal, we used dissected snail ganglia which have non-magnetic hemocyanin, other than hemoglobin, as an oxygen carrying protein. To activate the snail ganglia in synchronization with the magnetic resonance signal measurement, we applied 30 Hz electrical stimulation with a pulse width of 2 s to the ganglia just before the 90 degrees RF pulse. The increase of neuronal activity in the snail ganglia after the electrical stimulation was confirmed with extracellular potential recording. The magnetic resonance signal intensity, measured with the volume selection pulse sequence in a 3.0 T MRI, decreased by about 2.97 +/- 1.10% when the ganglia were activated by the electrical stimulation. We think that the MRI signal decrease is partly due to the magnetic field produced by the neuronal current and partly due to the Lorentz force exerted on the neurons when they were firing.

• Cell size-dependent Nogo-A expression in layer V pyramidal neurons of the rat primary somatosensory cortex.

  Authors: Jung-Won Shin, Eun-Sep Shim, Gwang-Ho Hwang, Hyuck-Sang Jung, Ji-Ho Park, Nak-Won Sohn

  Neuroscience letters. 03/2006; 394(2):117-20.

  Nogo-A mRNA and protein are present in the perikarya of neurons in both the intact and injured CNS. The present study focused primarily on Nogo-A protein expression in the primary somatosensoryNogo-A mRNA and protein are present in the perikarya of neurons in both the intact and injured CNS. The present study focused primarily on Nogo-A protein expression in the primary somatosensory cortex of the adult rat. Coronal brain sections were probed with double-immunofluorescent labeling against Nogo-A together with NeuN, RBPC, or MAP-2 for confocal imaging. The sizes of the cell somata in pyramidal neurons and the thicknesses of neurites were measured on the captured confocal images. Nogo-A was expressed in larger pyramidal neurons and thicker neurites in layer V, but not in smaller pyramidal neurons and thinner neurites. Considering the morphological properties and the cell soma size reported in previous studies together with the present data, Nogo-A-positive neurons of layer V appear to be intrinsically bursting neurons that project axons to the subcortical regions. This suggests that intraneuronal Nogo-A may play roles in neurite growth and axonal regeneration of the corticofugal neurons, but not of columnar intrinsic neurons, in layer V of the S1 barrel cortex. Additionally, this study demonstrates a novel result, which is that layer V pyramidal neurons of the S1 barrel cortex exhibit a pattern of cell size-dependent intraneuronal Nogo-A expression.

• Inhibition of tyrosinase activity by N,N-unsubstituted selenourea derivatives.

  Authors: Sang Keun Ha, Mamoru Koketsu, Kunho Lee, Sang Yoon Choi, Ji-Ho Park, Hideharu Ishihara, Sun Yeou Kim

  Biological & pharmaceutical bulletin. 06/2005; 28(5):838-40.

  This study investigated inhibitory effects of N,N-unsubstituted selenourea derivatives on tyrosinase activity. Three types of N,N-unsubstituted selenoureas derivatives exhibited inhibitory effect onThis study investigated inhibitory effects of N,N-unsubstituted selenourea derivatives on tyrosinase activity. Three types of N,N-unsubstituted selenoureas derivatives exhibited inhibitory effect on dopa (3,4-dihydroxyphenylalanine) oxidase activity of mushroom tyrosinase. Compound D at a concentration of 200 microM exhibited 55.5% of inhibition on dopa oxidase activity of mushroom tyrosinase. This inhibitory effect was higher than that of kojic acid (39.4%), a well known tyrosinase inhibitor. Moreover, the compound D identified as a noncompetitive inhibitor by Lineweaver-Burk plot analysis. In addition, compound D also inhibited the melanin production in melan-a cells.

• Effect of nerve cell currents on MRI images in snail ganglia.

  Authors: Tae S Park, Sang Y Lee, Ji-Ho Park, Soo Y Lee

  Neuroreport. 01/2005; 15(18):2783-6.

  We performed extracellular potential recording with dissected snail ganglia inside an MRI scanner to investigate correlation between neuronal activity and MR image intensity. To increase neuronalWe performed extracellular potential recording with dissected snail ganglia inside an MRI scanner to investigate correlation between neuronal activity and MR image intensity. To increase neuronal activity we applied a nitric oxide donor, sodium-nitrosocystein, to the ganglia. The MR image intensity change in the ganglia region is correlated with the neuronal activity and was up to 5.49+/-1.94%. Since the snail has non-magnetic hemocyanins as oxygen carrying protein, it seems that the image intensity change is mainly due to the local magnetic fields produced by the neuronal currents.

• Neuroprotective effect of KR-31378 via KATP channel opening against ischemic insult.

  Authors: Ran Won, Jong-Yoon Lim, Sang Yeon Lee, Ji-Ho Park, Nak-Won Sohn

  Biological & pharmaceutical bulletin. 09/2004; 27(8):1285-8.

  The opening of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on theThe opening of the adenosine triphosphate (ATP)-sensitive potassium (KATP) channel has been proposed as a therapeutic approach for ischemia. Here we examined the opening effect of KR-31378 on the KATP channel using patch clamp recording in neuroblastoma 2a (N2a) cells and investigated the neuroprotective effect of KR-31378 in organotypic hippocampal slice cultures exposed to oxygen/glucose deprivation. The treatment with KR-31378 (10 microM) to N2a cells seemed to induce KATP channel opening in a dose dependent manner. The opening effect of KR-31378 was more significant than that of other known KATP channel openers. Pretreatment with KR-31378 (10 microM) showed a neuroprotective effect in both CA1 and CA3 regions and its effect was attenuated by glibenclamide in a dose dependent manner in both areas. This remarkable neuroprotective effect of KR-31378 seemed to be mediated by the opening of the KATP channel. These results suggest that KR-31378 could be a possible neuroprotective agent against cerebral ischemia.

• Protective effect of apigenin on ovariectomy-induced bone loss in rats

  Authors: Jeong A Park, Sang Keun Ha, Tong Ho Kang, Myung Sook Oh, Min Hyoung Cho, Soo Yeol Lee, Ji-Ho Park, Sun Yeou Kim

  Life Sciences.

  Recent studies have shown that apigenin not only inhibits bone resorption by osteoclasts but also induces osteoclast apoptosis. However, the influence of apigenin on osteoporosis in animals isRecent studies have shown that apigenin not only inhibits bone resorption by osteoclasts but also induces osteoclast apoptosis. However, the influence of apigenin on osteoporosis in animals is relatively unknown. The purpose of this study was to examine the bone-protective effects of apigenin in estrogen-deficient ovariectomized rats.Three-month-old female Sprague–Dawley rats were either sham-operated or ovariectomized and fed AIN-93G diet for 7 weeks to induce bone loss. To confirm bone loss, we used a newly developed non-invasive technique involving zoom-in micro-computed tomography. Apigenin was administered at a dose of 10 mg/kg three times a week for 15 weeks. Our results indicate that apigenin not only increased the mineral content and density of the trabecular bone at the neck of the left femur, but also decreased body weight and dietary consumption. Moreover, our biochemical results indicate that apigenin has a positive effect on bone turnover. The present data suggest that apigenin should be considered for use in the treatment of osteoporosis.

• Shikonins attenuate microglial inflammatory responses by inhibition of ERK, Akt, and NF-κB: neuroprotective implications

  Authors: Kyong Nyon Nam, Min-Sook Son, Ji-Ho Park, Eunjoo H. Lee

  Neuropharmacology.

  Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNSMicroglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. Shikonin, a naphthoquinone pigment from the root of Lithospermum erythrorhizon, has long been used as an ointment for wound healing in traditional oriental medicine. Shikonin has been reported to have antibacterial, antitumor, and anti-inflammatory effects. The aim of this study was to examine whether shikonin represses microglial activation. In a study of shikonin and five of its derivatives, isobutyrylshikonin (IBS) and isovalerylshikonin (IVS) were the most effective at inhibiting LPS-induced nitric oxide (NO) release from microglial cells. Reverse transcriptase real-time PCR analysis revealed that pretreatment of rat brain microglia with IBS and IVS attenuated the LPS-induced expression of mRNAs encoding inducible NO synthase, tumor necrosis factor (TNF)-α, interleukin-1β, and cyclooxygenase-2. In rat brain microglia, IBS and IVS reduced the LPS-stimulated production of TNF-α and prostaglandin E2. In addition, IBS and IVS significantly decreased LPS-induced IκB-α phosphorylation and NF-κB DNA binding activity, as well as the phosphorylation of the ERK1/2 and Akt signaling proteins. In organotypic hippocampal slice cultures, propidium iodide staining revealed prominent cell death in the hippocampal layer after 72 h of LPS treatment. Both IBS and IVS clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results suggest that IBS and IVS provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

• Apigenin inhibits the production of NO and PGE2 in microglia and inhibits neuronal cell death in a middle cerebral artery occlusion-induced focal ischemia mice model.

  Authors: Sang Keun Ha, Pyeongjae Lee, Jeong A Park, Hye Rim Oh, Sang Yeon Lee, Ji-Ho Park, Eunjoo H Lee, Jong Hoon Ryu, Kang Ro Lee, Sun Yeou Kim

  Neurochemistry international. 52(4-5):878-86.

  Flavonoids have been intensively studied on their pharmacological activities such as anti-cancer, anti-oxidant and anti-inflammation. However, little is known about their neuroprotective effects.Flavonoids have been intensively studied on their pharmacological activities such as anti-cancer, anti-oxidant and anti-inflammation. However, little is known about their neuroprotective effects. Recent studies suggest that inflammation mediated by microglia may play a role in neurodegenerative diseases. In this study, we evaluated the anti-inflammatory effect of various flavonoid compounds by using BV-2, a murine microglia cell line. Of the compounds that were evaluated, apigenin inhibited the production of nitric oxide and prostaglandin E(2) by suppressing the expression of inducible nitric oxide synthase and cyclooxygenase-2 protein, respectively. Moreover, apigenin suppressed p38 mitogen-activated protein kinase (MAPK), c-Jun N-terminal kinase (JNK) phosphorylation without affecting the activity of extracellular signal-regulated kinase (ERK). Apigenin was also found to protect neuronal cells from injury in middle cerebral artery occlusion.