흰쥐의 손상된 뇌조직에서의 유전자 발현 변화에 대한 홍화(紅花) 추출물 투여의 작용

김부여,임세현,이금산,김형우,임지연,조수인,Kim, Bu-Yeo,Limb, Se-Hyun,Lee, Guem-San,Kim, Hyung-Woo,Lim, Chi-Yeon,Cho, Su-In 대한한방내과학회 2010 大韓韓方內科學會誌 Vol.31 No.4

Objectives : The source is from the flower of Carthamus tinctorius L., family Compositae. It is used in clinical medicine to promote blood circulation, remove blood stasis, promote menstruation and alleviate pain. In the present study, we investigated the genome wide analysis of Carthami Flos on the intra-cranial hemorrhage(ICH) model. Methods : ICH in rat was induced by injection of collagenase type IV and Carthami Flos extract(CFe) was administered orally. The molecular profile of cerebral hemorrhage in rat brain tissue was measured using microarray technique to identify up- or down- regulated genes in brain tissue. Results : Expression profile showed that diverse genes were up- or down-regulated by ICH induction. Administration of CFe restored the expression level of some of altered genes by ICH to normal expressional level. Interestingly, these recovered genes by CFe were involved in the same biological pathways which were significantly activated or suppressed by ICH. Conclusion : The above results might explain the therapeutic mechanism of CFe on ICH. Further, by analyzing interaction network, core genes was identified which could be key molecular targets of CFe against ICH.

Concurrent progress of reprogramming and gene correction to overcome therapeutic limitation of mutant ALK2-iPSC

김부여,정상균,이서영,이소민,권은정,안현준,김장환,정선구 생화학분자생물학회 2016 Experimental and molecular medicine Vol.48 No.-

Fibrodysplasia ossificans progressiva (FOP) syndrome is caused by mutation of the gene ACVR1, encoding a constitutive active bone morphogenetic protein type I receptor (also called ALK2) to induce heterotopic ossification in the patient. To genetically correct it, we attempted to generate the mutant ALK2-iPSCs (mALK2-iPSCs) from FOP-human dermal fibroblasts. However, the mALK2 leads to inhibitory pluripotency maintenance, or impaired clonogenic potential after single-cell dissociation as an inevitable step, which applies gene-correction tools to induced pluripotent stem cells (iPSCs). Thus, current iPSC-based gene therapy approach reveals a limitation that is not readily applicable to iPSCs with ALK2 mutation. Here we developed a simplified one-step procedure by simultaneously introducing reprogramming and gene-editing components into human fibroblasts derived from patient with FOP syndrome, and genetically treated it. The mixtures of reprogramming and gene-editing components are composed of reprogramming episomal vectors, CRISPR/Cas9-expressing vectors and single-stranded oligodeoxynucleotide harboring normal base to correct ALK2 c.617G4A. The one-step-mediated ALK2 gene-corrected iPSCs restored global gene expression pattern, as well as mineralization to the extent of normal iPSCs. This procedure not only helps save time, labor and costs but also opens up a new paradigm that is beyond the current application of gene-editing methodologies, which is hampered by inhibitory pluripotency-maintenance requirements, or vulnerability of single-cell-dissociated iPSCs.

조각자(?角刺)가 악성흑색종 세포주에 미치는 영향

김부여,임세현,이병호,임지연,김용성,조수인,Kim, Bu-Yeo,Lim, Se-Hyun,Lee, Byoung-Ho,Lim, Chi-Yeon,Kim, Yong-Seong,Cho, Su-In 대한한방안이비인후피부과학회 2009 한방안이비인후피부과학회지 Vol.22 No.3

Glenditsia spina (GS) can resolve carbuncle, relive swelling, dispel wind and destroy parasites. For these reasons, GS has been widely used as dermatologic agent clinically. In this study, the specific pathways of anti-proliferative effect of GS on human derived melanoma cells were identified. The molecular profile was measured using microarray technique to identify up- or down-regulated genes in SK-MEL-2 cell line. Pathway analysis was done by listing percentage of pathway involvement, and the represented pathways were obtained from KEGG. The transcription factor binding sequences were obtained by Transfac database. By the promoter analysis, up-regulated genes by GS were mainly associated with MAPK, Regulation of actin cytoskeleton, Wnt, Focal adhesion and Long term potentiation pathway. Down-regulated genes by GS were mainly associated with MAPK and Antigen processing and presentation pathway. And some of the transcription factors like Sp1 and NF-Y in up-regulated genes and Oct-1 in down-regulated genes by GS also identified.

Apigetrin from Scutellaria baicalensis Georgi Inhibits Neuroinflammation in BV-2 Microglia and Exerts Neuroprotective Effect in HT22 Hippocampal Cells

임혜선,김온순,김부여,정수진 한국식품영양과학회 2016 Journal of medicinal food Vol.19 No.11

Apigetrin is a flavonoid isolated from various herbal medicines such as Scutellaria baicalensis Georgi, Matricaria chamomilla, Stachys tibetica Vatke, and Teucrium gnaphalodes. In the present study, we investigated the inhibitory effects of apigetrin on neuroinflammation using the BV-2 microglia cell line. Our data revealed that apigetrin significantly reduced secretion and mRNA expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-a) and interleukin-6 (IL-6), in lipopolysaccharide (LPS)-stimulated BV-2 mouse microglia. Apigetrin also significantly decreased LPS-mediated production of prostaglandin E2 (PGE2) level and nitric oxide (NO) production as well as expression of cyclooxygenase 2 (COX-2) and inducible nitric oxide synthase (iNOS) in BV-2 cells. In addition, apigetrin suppressed nuclear expression of nuclear factor kappa B (NF-κB) in LPS-stimulated BV-2 cells. Furthermore, apigetrin significantly impaired reactive oxygen species (ROS) generation and enhanced expression of antioxidant enzymes, hempxygenase 1 (HO-1) and nuclear factor-like 2 (Nrf2), in BV-2 cells. Apigetrin also increased 2,2'-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity, indicating antioxidative activity of apigetrin. Moreover, we found that apigetrin inhibited hydrogen peroxide (H2O2)-induced cell death in HT22 hippocampal cells. Overall, our findings indicate that apigetrin has inhibitory effects on neuroinflammation as well as antioxidation and neuroprotection, suggesting the potential prophylactic activity for neurodegenerative diseases through the inter-regulation of neuroinflammation, oxidative stress, and neuronal injury.

유전자발현 패턴에 의한 간암환자의 생존 및 재발예측에 관한 연구

박명진,김부여,박선후,한철주,김상범,정숙향,염영일,이제근,김창민,서경석,최동욱,이기호 한국간담췌외과학회 2005 한국간담췌외과학회 학술대회지 Vol.2005 No.3

지모(知母) 추출물이 MCF-7 세포의 생존율에 미치는 영향

김형우,김부여,조수진,조수인,Kim, Hyung-Woo,Kim, Bu-Yeo,Cho, Su-Jin,Cho, Su-In 대한한방내과학회 2007 大韓韓方內科學會誌 Vol.28 No.3

Objectives : This study was carried out to investigate anti-proliferative effects on MCF-7 human breast cancer cells of Anemarrhenae Rhizoma (AR) extract. Breast cancer is the most common disease in Korean women. Despite remarkable improvements in treatment strategies against various cancers during the past 40 years. breast cancer still remains as one of the main causes of cancer mortality among women the whole world over. Methods : Be investigated the effects of AR on cytotoxicity of MCF-7 human breast cancer cells in various extract conditions (n-hexane, ethyl acetate, butanol and water fraction). Results : The extract of Anemarrhenae Rhjzoma inhibits the proliferation of MCF-7 cells in a dose dependent manner. Especially. the ethyl acetate fraction of Anemarrhenae Rhizoma showed specific Cytotoxicity on MCF-7 cells. Conclusions : In conclusion. it can be concluded that Anemarrhenae Rhizoma extract has an anti-proliferative effect on MCF-7 human breast cancer cells. Especially. the ethyl acetate fraction is most effective to inhibit proliferation of MCF-7 cells.

소엽(蘇葉) 추출물이 백서(白鼠)의 뇌허혈에 미치는 효과

김형우,김부여,조수진,정현우,조수인,Kim, Hyung-Woo,Kim, Bu-Yeo,Cho, Su-Jin,Jeong, Hyun-Woo,Cho, Su-In 대한한방내과학회 2007 大韓韓方內科學會誌 Vol.28 No.3

Objectives : Folium perillae (FP) can relieve superficial pathogenic factors to dissipate cold and promote the circulation of qi and regulate the function of the stomach and is often used for interior qi-stagnation. We hypothesized that FP could rescue cerebral ischemia in rats. Methods : The present study was carried out to investigate the effects of FP on cerebral ischemia in terms of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP) in rats. Finally, lactate dehydrogenase (LDH) release was investigated, too. Results : In this study, treatment with FP elevated rCBF and MABP levels in dose-dependent manner. Pre-treatment with indomethacin, an inhibitor of cyclooxygenase, inhibited rCBF increase induced by FP effectively. However, FP did not affect stability during cerebral reperfusion. Finally, FP significantly inhibited LD H activity in vitro Conclusions : These results suggest that FP is useful to treat patient with diseases related to cerebral ischemia, because FP can increase rCBF and MABP.

Anti-thrombotic Effects of Modified Jeho-tang using a FeCl3-induced Carotid Arterial Thrombosis Model

방지혜,이기모,김부여,이정화,이인선,전원경 대한한의학회 2013 대한한의학회지 Vol.34 No.2

Objectives: The aim of this study was to examine the antithrombotic effects of the four herbal ingredients (Mume Fructus, MF; Santali Albi Lignum, SAL; Amomi Tsao-Ko Fructus, ATF; and Amomi Fructus, AF) of modified Jeho-tang (MJHT) in a ferric chloride (FeCl3)-induced carotid arterial thrombosis model. Methods: Thirty minutes prior to a 35% FeCl3 application, Sprague-Dawley (SD) rats were injected with saline, MF, SAL, ATF or AF (100 mg/kg, intraperitoneal injection), respectively. The effect of the MJHT ingredients was examined for time to occlusion (TTO) and thrombus weight (TW) in a FeCl3-induced thrombosis model. Histological analysis was performed to examine the effect of the MJHT ingredients on collagen fiber damage using hematoxylin & eosin and Masson’s trichrome staining. Results: Compared with vehicle treatment, MF, SAL and ATF treatment delayed TTO (vehicle, 8.11 ± 0.60 min; MF, 16.67 ± 1.03 min; SAL, 17.50 ± 1.52 min and ATF, 13.33 ± 1.21 min; P < 0.001) and inhibited thrombus formation (vehicle, 0.79 ± 0.03 mg/mm; MF, 0.61 ± 0.07 mg/mm; SAL, 0.57 ± 0.03 mg/mm and ATF, 0.72 ± 0.02 mg/mm; P < 0.001). In addition, each herbal ingredient of MJHT except for AF prevented the collagen fiber damage induced by a 35% FeCl3 application. These results indicate that the MJHT ingredients MF ≥ SAL 〉ATF 〉AF possess antithrombotic activity in a FeCl3-induced carotid arterial thrombosis. Conclusions: Altogether, these results are the first evidence that the MJHT ingredients MF, SAL and ATF have the ability to prevent vascular damage and thrombus formation in FeCl3-induced carotid arterial thrombosis.

Licorice Pretreatment Protects Against Brain Damage Induced by Middle Cerebral Artery Occlusion in Mice

임치연,임세현,이병호,김부여,조수인 한국식품영양과학회 2018 Journal of medicinal food Vol.21 No.5

Licorice is extracted from the roots of plants in the Glycyrrhiza genus, especially Glycyrrhiza uralensis in China and Korea. It has several pharmacological activities, including neuro-protective, anti-fungal, and anti-cariogenic effects. Ischemia/reperfusion-induced brain injury is a leading cause of adult disability and death; thus, the identification of anti-apoptotic, neuro-protective therapeutic agents is viewed as an attractive drug development strategy. Infarct volumes and the expression of several apoptosis-related proteins, including Bcl-xL, Bcl-2, caspase-8, and caspase-9, were evaluated by western blotting in the brains of mice subjected to middle cerebral artery occlusion (MCAO). Three consecutive days of oral pretreatment with the methanol extract of licorice (GRex) significantly reduced infarct volumes 24 h after MCAO. In addition, GRex effectively inhibited the activation of caspase-9 by upregulating protein expression of Bcl-xL and Bcl-2. The neuro-protective effect of licorice was due to its regulation of apoptosis-related proteins. These data suggest that licorice could be a potential candidate for the treatment of ischemia-induced brain damage.

팔정산(八正散) 약침(藥鍼) 및 복강(腹腔) 주입 병용 시술이 글리세롤로 유발된 토끼의 급성 신부전에 미치는 영향

임지연,김민호,이금산,김형우,김부여,윤여충,조수인,Lim, Chi-Yeon,Kim, Min-Ho,Lee, Geum-San,Kim, Hyung-Woo,Kim, Bu-Yeo,Yun, Yeo-Choong,Cho, Su-In 대한약침학회 2010 Journal of pharmacopuncture Vol.13 No.3

Purpose: The present study was carried out to determine if Paljeong-san extract (PJS) treatment exerts beneficial effect against the glycerol-induced acute renal failure in rabbits. Material and Method: PJS was selected in the basis of invigorating kidney which can eliminate pathogens. Rabbits were treated with PJS pharmacopuncture on Shin-shu ($BL_{23}$) point for 5 days right after the injection of 50% concentration of glycerol ($5m{\ell}/kg$ body weight). Results and Conclusions: Glycerol injection caused an increase in serum creatinine and BUN level and urine glucose secretion, which were accompanied by a reduction in GFR. PJS Pharmacopuncture treatment combined with peritoneal injection showed beneficial effect on glycerol-induced acute renal failure by inhibition of serum creatinine increase and GFR decrease.