Protective Effects of Natrii Sulfas on Cerebral Focal Ischemia Induced by MCAO in Rats.

Sohn, Youngjoo,Kang, Ho Chang,Kim, Kon Sik,Park, Sun-Min,Sohn, Nak-Won,Jung, Hyuk-Sang,Kim, Sung-Hoon Institute for Advanced Research in Asian Science a 2009 The American journal of Chinese medicine Vol.37 No.2

<P>This study examined the effect of Natrii sulfas, a treatment for stroke patients suffering constipation in Oriental medicine, on the physiological indices and brain edema of rats. Brain edema was induced by a middle cerebral artery occlusion (MCAO), Natrii sulfas was administered after the MCAO. At 3, 6, 15, 24, and 48 hours after reperfusion, the physiological indices such as the fecal weight, urine volume and water content in the stools were assessed. The edema index was measured 48 hours after reperfusion. At 48 hours, the expressions of iNOS, MMP9, VEGF, GFAP, Bax, Bcl-2, c-Fos, and HSP72 positive astrocytes were observed on the brain tissues by immunohistochemistry. Natrii sulfas significantly improved the decrease in fecal weight, urine volume and water content in the stool caused by the ischemic insult (p < 0.05) and attenuated the brain edema caused by the ischemia insult (p < 0.05). Natrii sulfas significantly down-regulated iNOS and MMP9 expressions and attenuated the astrocyte swelling due to brain edema in the penumbra of the cerebral cortex of MCAO rats. Natrii sulfas reduced the excess Bax and HSP72 expressions in ischemic brain, which was statistically significant in the penumbra of the cerebral cortex but not in the caudate putamen. These results suggest Natrii sulfas has a protective effect on ischemia-induced brain edema and improves the physiological symptoms.</P>

Ginsenoside Rg1 Attenuates Neuroinflammation Following Systemic Lipopolysaccharide Treatment in Mice

( Jung Won Shin ),( Sun Ho Ma ),( Ju Won Lee ),( Dong Kyu Kim ),( Kyu Ho Do ),( Nak Won Sohn ) 대한본초학회 2013 大韓本草學會誌 Vol.28 No.6

Objectives: Neuroinflammation is characterized by microglial activation and the expression of major inflammatory mediators. The present study investigated the inhibitory effect of ginsenoside Rg1 (GRg1), a principle active ingredient in Panax ginseng, on pro-inflammatory cytokines and microglial activation induced by systemic lipopolysaccharide (LPS) treatment in the mouse brain tissue. Methods : Varying doses of GRg1 was orally administered (10, 20, and 30 mg/kg) 1 h before the LPS injection (3 mg/kg, intraperitoneally). The mRNA expression of pro-inflammatory cytokines in the brain tissue was measured using the quantitative real-time PCR method at 4 h after the LPS injection, Microglial activation was evaluated using western blotting and immunohistochemistry against ionized calcium binding adaptor molecule 1 (Iba1) in the brain tissue. Cyclooxigenase-2 (COX-2) expressions also observed using western blotting and immunohistochemistry at 4 h after the LPS injection, In addition, double-immunofluorescent labeling of tumor necrosis factor-α (TNF-α) and COX-2 with microglia and neurons was processed in the brain tissue. Results : GRg1 (30 mg/kg) significantly attenuated the upregulation of TNF-α, interleukin (IL)-1β and IL-6 mRNA in the brain tissue at 4 h after LPS injection. Morphological activation and Iba1 protein expression of microglia induced by systemic LPS injection were reduced by the GRg1 (30 mg/kg) treatment. Upregulation of COX-2 protein expression in the brain tissue was also attenuated by the GRg1 (30 mg/kg) treatment. Conclusion : The results suggest that GRg1 is effective in the early stage of neuroinflammation which causes neurodegenerative diseases.

a-Asarone Ameliorates Memory Deficit in Lipopolysaccharide-Treated Mice via Suppression of Pro-Inflammatory Cytokines and Microglial Activation

( Jung Won Shin ),( Young Jin Cheong ),( Yong Mo Koo ),( Soo Yong Kim ),( Chung Ku Noh ),( Young Ha Son ),( Chul Hun Kang ),( Nak Won Sohn ) 한국응용약물학회 2014 Biomolecules & Therapeutics(구 응용약물학회지) Vol.22 No.1

a-Asarone exhibits a number of pharmacological actions including neuroprotective, anti-oxidative, anticonvulsive, and cognitive enhancing action. The present study investigated the effects of a-asarone on pro-inflammatory cytokines mRNA, microglial activation, and neuronal damage in the hippocampus and on learning and memory deficits in systemic lipopolysaccharide (LPS)- treated C57BL/6 mice. Varying doses of a-asarone was orally administered (7.5, 15, or 30 mg/kg) once a day for 3 days before the LPS (3 mg/kg) injection. a-Asarone significantly reduced TNF-a and IL-1b mRNA at 4 and 24 hours after the LPS injection at dose of 30 mg/kg. At 24 hours after the LPS injection, the loss of CA1 neurons, the increase of TUNEL-labeled cells, and the up-regulation of BACE1 expression in the hippocampus were attenuated by 30 mg/kg of a-asarone treatment. a-Asarone signifi- cantly reduced Iba1 protein expression in the hippocampal tissue at a dose of 30 mg/kg. a-Asarone did not reduce the number of Iba1-expressing microglia on immunohistochemistry but the average cell size and percentage areas of Iba1-expressing microglia in the hippocampus were significantly decreased by 30 mg/kg of a-asarone treatment. In the Morris water maze test, a-asarone significantly prolonged the swimming time spent in the target and peri-target zones. a-Asarone also significantly increased the number of target heading and memory score in the Morris water maze. The results suggest that inhibition of pro-inflammatory cytokines and microglial activation in the hippocampus by a-asarone may be one of the mechanisms for the a-asarone-mediated ameliorating effect on memory deficits.

구척(狗脊)이 흰쥐의 척수압박에 의한 신경세포 손상에 미치는 영향

박원상 ( Won Sang Park ),김은석 ( Eun Seok Kim ),신정원 ( Jung Won Shin ),김범회 ( Bum Hoi Kim ),김성준 ( Seong Joon Kim ),강희 ( Hee Kang ),손낙원 ( Nak Won Sohn ) 한방재활의학과학회 2010 한방재활의학과학회지 Vol.20 No.2

Objectives: This study was performed to evaluate the effects of root of Cibotii rhizoma(CR) ethanol extract on the tissue and neuronal damage of the spinal cord injury(SCI). Methods :SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. CR was orally given once a day for 7 days after SCI. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue(LFB) histochemistry. HSP72(as neuronal damage marker), MAP2(as nerve fiber degeneration marker), c-Fos(immediate early gene), and Bax(pro-apoptotic molecule) expressions were examined using immuno-histochemistry. Individual immuno-positive cells expressing HSP72, MAP2, c-Fos and Bax were observed on the damaged level and the upper thoracic and lower lumbar spinal segments. Results :1. CR reduced degeneration of nerve fibers and motor neuron shrinkage in the ventral horn of the lower lumbar spinal segment, but generally it did not seem to ameliorate the tissue injury following SCI. 2. CR reduced demyelination in the ventral and lateral funiculus of the lower lumbar spinal segment. 3. CR reduced HSP72 expression on the neurons in the peri-central canal gray matter adjacent to the damaged region. 4. CR strengthened MAP2 expression on the motor neurons in the ventral horn and on nerve fibers in the lateral funiculus of the lower lumbar spinal segment. 5. CR reduced c-Fos positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. 6. CR reduced Bax positive cells in the peri-lesion and the dorsal horn of the damaged level and in the ventral horn of the lower lumbar spinal segment. Conclusions :These results suggest that CR plays an inhibitory role against secondary neuronal damage and nerve fiber degeneration following SCI.

천마(天麻)가 뇌조직출혈(腦組織出血) 흰쥐의 뇌부종(腦浮腫)과 Aquaporins 발현에 미치는 영향

손낙원 ( Nak Won Sohn ),이주용 ( Ju Yong Lee ),구자승 ( Ja Seung Ku ),이동은 ( Dong Eun Lee ),신정원 ( Jung Won Shin ),김성준 ( Seung Joon Kim ) 대한본초학회 2010 大韓本草學會誌 Vol.25 No.4

Objectives: This study aimed at evaluation of the effects of Gastrodiae Rhizoma on brain edema and aquaporin water channel expressions in the brain. Methods: Brain edema following intracerebral hemorrhage (ICH) was induced by the stereotaxic intrastriatal injection of bacterial collagenase type VII in Sprague-Dawley rats. Then ethanol extract of Gastrodiae rhizoma was treated once a day for 3 days. Brain edema % and water contents, and cell size of neurons in the cerebral cortex were examined. Immuno-histochemistry was processed for AQP4, AQP1, and AQP9 expressions in the brain sections and area % of immuno-labeling was analyzed with image analysis. Results: 1. Ethanol extract of Gastrodiae Rhizoma reduced brain edema of ICH induced rats significantly. 2. Ethanol extract of Gastrodiae Rhizoma reduced excessive brain tissue water contents of ICH induced rats significantly. 3. Ethanol extract of Gastrodiae Rhizoma reduced cellular edema of neurons in cerebral cortex of ICH induced rats significantly. 4. Ethanol extract of Gastrodiae Rhizoma reduced AQP4 immuno-positive area % in cerebral cortex and external capsule of ICH induced rat brain significantly. 5. Ethanol extract of Gastrodiae Rhizoma reduced AQP9 immuno-positive area % in glia limitans externa of ICH induced rat brain significantly. Conclusions: These results suggest that Gastrodiae Rhizoma reveals protective effects against brain edema and cytotoxic edema of neurons by means of down-regulation of AQP4 expression in the brain.

쌍화탕이 흰쥐의 간 및 근육 Glycogen함량에 미치는 영향에 대한 조직화학적 연구

손낙원 ( Nak Won Sohn ) 대한본초학회 1994 大韓本草學會誌 Vol.9 No.1

흥화가 Cholesterol식이에 의한 토끼의 죽상동맥경화증에 미치는 조직학적 연구

박낙진(PARK Nak Jin),손낙원(SOHN Nak Won),이학인(LEE Hak In) 대한체질인류학회 1998 해부·생물인류학 (Anat Biol Anthropol) Vol.11 No.1

홍화 (Flos Carthaml) 가 cholesterol 식이에 의한 토끼의 죽상동맥경화증에 미치는 영향을 조직학적으로 관찰하기 위하여 토끼에 4% cholesterol 사료와 4% cholestet 이 및 4% 홍화 건조분말 사료를 각각 하루에 토끼체중 lkg 당 약 100g 씩 12 주간 투여한 후 대동맥 속막에 형성된 죽종의 변화를 관찰하였다. 홍화의 동시투여가 대동맥 속막에 점액단백질을 억제하여 죽종의 형성을 억제하는 작용이 있는 것으로 관찰되었으며, 대동맥 중간막의 탄력섬유가 손상을 감소시킴으로써 섬유를 사이 간격이 넓어져서 지질침착이 촉진되는 것을 방어하는 역할을 하고, 아교섬유 성상의 변화도 감소시킨 것으로 관찰되었다. 이러한 결과로 보아, 아직 그 작용기전에 대하여는 머 연구되어야 할것이나, 홍화가 고지혈증에 의한 동맥벽의 지질침착 방지에 효능이 있는 것으로 생각된다.

Ginsenoside Rg1 Attenuates Neuroinflammation Following Systemic Lipopolysaccharide Treatment in Mice

Shin, Jung-Won,Ma, Sun-Ho,Lee, Ju-Won,Kim, Dong-Kyu,Do, Kyuho,Sohn, Nak-Won The Korea Association of Herbology 2013 大韓本草學會誌 Vol.28 No.6

Objectives : Neuroinflammation is characterized by microglial activation and the expression of major inflammatory mediators. The present study investigated the inhibitory effect of ginsenoside Rg1 ($GRg_1$), a principle active ingredient in Panax ginseng, on pro-inflammatory cytokines and microglial activation induced by systemic lipopolysaccharide (LPS) treatment in the mouse brain tissue. Methods : Varying doses of $GRg_1$ was orally administered (10, 20, and 30 mg/kg) 1 h before the LPS injection (3 mg/kg, intraperitoneally). The mRNA expression of pro-inflammatory cytokines in the brain tissue was measured using the quantitative real-time PCR method at 4 h after the LPS injection, Microglial activation was evaluated using western blotting and immunohistochemistry against ionized calcium binding adaptor molecule 1 (Iba1) in the brain tissue. Cyclooxigenase-2 (COX-2) expressions also observed using western blotting and immunohistochemistry at 4 h after the LPS injection, In addition, double-immunofluorescent labeling of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and COX-2 with microglia and neurons was processed in the brain tissue. Results : $GRg_1$ (30 mg/kg) significantly attenuated the upregulation of TNF-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 mRNA in the brain tissue at 4 h after LPS injection. Morphological activation and Iba1 protein expression of microglia induced by systemic LPS injection were reduced by the $GRg_1$ (30 mg/kg) treatment. Upregulation of COX-2 protein expression in the brain tissue was also attenuated by the $GRg_1$ (30 mg/kg) treatment. Conclusion : The results suggest that $GRg_1$ is effective in the early stage of neuroinflammation which causes neurodegenerative diseases.

Effect of Guibi-tang on Neuronal Apoptosis and Cognitive Impairment Induced by Beta Amyloid in Mice

Lee Ju-Won,Cho Dong-Guk,Cho Woo-Sung,Ahn Hyung-Gyu,Lee Hyun-Joon,Shin Jung-Won,Sohn Nak-Won 대한한의학회 2014 대한한의학회지 Vol.35 No.4

황련해독탕(黃連解毒湯)이 척수 압박손상 흰쥐의 운동기능 장애에 미치는 영향

성주원 ( Ju Won Seong ),반효정 ( Hyo Jung Bahn ),김성준 ( Seong Joon Kim ),김기역 ( Ki Yuk Kim ),신정원 ( Jung Won Shin ),강희 ( Hee Kang ),손낙원 ( Nak Won Sohn ) 한방재활의학과학회 2010 한방재활의학과학회지 Vol.20 No.4

Objectives :This study was performed to evaluate the effects of Hwangryunhaedok-tang(Huanglianjiedu-tang; HHT) water extract on locomotor dysfunction induced by spinal cord injury(SCI) in rats. Methods :SCI was induced by mechanical contusion following laminectomy of 10th thoracic vertebra in Sprague-Dawley rats. HHT was orally given once a day for 14 days after SCI. Neurological behavior was examined with the Basso-Beattie-Bresnahan locomotor rating scale. Tissue damage and nerve fiber degeneration were examined with cresyl violet and luxol fast blue staining. Using immunohistochemistry, cellular damage to neurons and nerve fibers were examined against Bax and MAP-2. As inflammatory response markers, iNOS and COX-2 expressions were also examined. Results :1. HHT ameliorated the locomotor dysfunction of the SCI-induced rats. 2. HHT attenuated the reduction of motor neurons in the ventral horn of the SCI-induced rat spinal cord. 3. HHT significantly reduced the number of Bax positive cells in the peri-lesion of the SCI-induced rat spinal cord. 4. HHT attenuated the reduction of MAP-2 positive cells in the peri-lesion of the SCI-induced rat spinal cord. 3. HHT significantly reduced the number of iNOS and COX-2 positive cells in the peri-lesion of the SCI-induced rat spinal cord. Conclusions :These results suggest that HHT improves the locomotor dysfunction of SCI by protecting motor neurons from cell death through anti-inflammatory effect.