A Toxicological Study of HangAmDan-B in Mice

유화승,이효재,김정선,윤정원,Grace H. Lee,이연월,조종관 사단법인약침학회 2011 Journal of Acupuncture & Meridian Studies Vol.4 No.1

The aim of the study was to define the toxicity of HangAmDan-B (HAD-B) in mice over the short and long term. HAD-B was studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. Doses used in 1 week single oral dose toxicity tests were 0, 0.2, 1, 5, and 25 g/kg/day and those of repeated toxicity test were 0, 0.04, 0.2, 1, and 2 g/kg/day. Blood and urine samples were assayed and their morphology observed. Numerical data were compared using Mann-Whitney U test and analysis of variance. Significantly decreased red blood cell levels in mice from S2-HAD-B, S3-HAD-B, S4-HAD-B, and S5-HAD-B groups were observed in single oral dose toxicity tests. Hemoglobin, hematocrit,and mean cell hemoglobin values in mice from the S4-HAD-B and S5-HAD-B groups were also significantly decreased. No mortalities or significant differences in all factors were observed during the dosing period of the repeated dose toxicity test. Administering 2 g/kg/day of HAD-B in mice over a 5-week period showed no significant hematological changes. However, risk of anemia with more than 5 g/kg/day administration of HAD-B was found. In general, HAD-B appears to be safe and nontoxic, and a no observed adverse effect level in mice was established at 2 g/kg/day. This data serves as satisfactory preclinical evidence for the safety of HAD-B should a future clinical trial for HAD-B be launched. Further studies are required to confirm these safety results and to carry out a safety trial in humans.

Changes of Serum VEGF and b-FGF in 26 Patients with Breast Cancer after Treatment with Hang-Am-Dan (HAD), an Antiangiogenic Botanical Prescription

Yoo Hwa Seung,Lee Nam Heon,Cho Jung Hyo,Lee Yeon Weol,Son Chang Gue,Kang Wee Chang,Cho Chong Kwan The Society of Korean Medicine 2005 대한한의학회지 Vol.26 No.4

Objectives: Recently, angiogenesis has gained an increasing interest as a prognostic factor in breast cancer. In this study we aimed to assess the anti angiogenic effects of HAD, a botanical anticancer remedy which has been prescribed in Daejeon University Oriental Hospital in Korea, on patients with breast carcinoma by measuring the serum vascular endothelial growth factor (VEGF), basic fibroblast growth factor (b-FGF) and platelets levels. Methods: The study included 26 consecutive breast cancer patients (mean age$\pm$standard deviation: 47.5$\pm$8.7 years) with stage II to IV disease who were treated with HAD (mean duration $\pm$ standard deviation: 264.5$\pm$121.6 days). In addition to routine laboratory and staging procedures, serum VEGF, b-FGF levels and platelet counts were determined as antiangiogenic markers. The antiangiogenic effects of HAD were evaluated by analyzing the differences between the values of the antiangiogenic markers before and after the treatment with HAD. Results: Serum b-FGF concentrations were significantly reduced after the treatment with HAD (P=0.042). Serum VEGF concentrations were found to have a somewhat decreasing change, though the change was not statistically significant (P=0.229). Platelet counts had little changes (P=O.80). Conclusions: It is supposed that HAD has effects on decreasing the serum b-FGF levels related with the clinical outcome of breast cancer patients.

Galectin-3-independent Down-regulation of GABABR1 due to Treatment with Korean Herbal Extract HAD-B Reduces Proliferation of Human Colon Cancer Cells

Kyung-Hee Kim,Yong-Kyun Kwon,Chong-Kwan Cho,이연월,Byong-Chul Yoo,So-Hyun Lee,Sang-Geun Jang,Hwa-Seong Yoo 대한약침학회 2012 Journal of pharmacopuncture Vol.15 No.3

Objectives: Many efforts have shown multi-oncologic roles of galectin-3 for cell proliferation, angiogenesis, and apoptosis. However, the mechanisms by which galectin-3 is involved in cell proliferation are not yet fully understood, especially in human colon cancer cells. Methods: To cluster genes showing positively or negatively correlated expression with galectin-3, we employed human colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4and SNU-C5 in high-throughput gene expression profiling. Gene and protein expression levels were determined by using real-time quantitative polymerase chain reaction (PCR) and western blot analysis, respectively. The proliferation rate of human colon cancer cells was measured by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT)assay. Results: Expression of γ-aminobutyric acid B receptor 1(GABABR1) showed a positive correlation with galectin-3 at both the transcriptional and the translational levels. Downregulation of galectin-3 decreased not only GABABR1expression but also the proliferation rate of human colon cancer cells. However, Korean herbal extract, HangAmDan-B (HAD-B), decreased expression of GABABR1 without any expressional change of galectin-3, and offset γ-aminobutyric acid (GABA)-enhanced human colon cancer cell proliferation. Conclusions: Our present study confirmed that GABABR1expression was regulated by galectin-3. HAD-B induced galectin-3-independent down-regulation of GABABR1, which resulted in a decreased proliferation of human colon cancer cells. The therapeutic effect of HAD-B for the treatment of human colon cancer needs to be further validated.

Galectin-3-independent Down-regulation of GABABR1 due to Treatment with Korean Herbal Extract HAD-B Reduces Proliferation of Human Colon Cancer Cells

Kim, Kyung-Hee,Kwon, Yong-Kyun,Cho, Chong-Kwan,Lee, Yeon-Weol,Lee, So-Hyun,Jang, Sang-Geun,Yoo, Byong-Chul,Yoo, Hwa-Seong KOREAN PHARMACOPUNCTURE INSTITUTE 2012 Journal of pharmacopuncture Vol.15 No.3

Objectives: Many efforts have shown multi-oncologic roles of galectin-3 for cell proliferation, angiogenesis, and apoptosis. However, the mechanisms by which galectin-3 is involved in cell proliferation are not yet fully understood, especially in human colon cancer cells. Methods: To cluster genes showing positively or negatively correlated expression with galectin-3, we employed human colon cancer cell lines, SNU-61, SNU-81, SNU-769B, SNU-C4 and SNU-C5 in high-throughput gene expression profiling. Gene and protein expression levels were determined by using real-time quantitative polymerase chain reaction (PCR) and western blot analysis, respectively. The proliferation rate of human colon cancer cells was measured by using a 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Results: Expression of ${\gamma}$-aminobutyric acid B receptor 1 (GABABR1) showed a positive correlation with galectin-3 at both the transcriptional and the translational levels. Down-regulation of galectin-3 decreased not only GABABR1 expression but also the proliferation rate of human colon cancer cells. However, Korean herbal extract, HangAmDan-B (HAD-B), decreased expression of GABABR1 without any expressional change of galectin-3, and offset ${\gamma}$-aminobutyric acid (GABA)-enhanced human colon cancer cell proliferation. Conclusions: Our present study confirmed that GABABR1 expression was regulated by galectin-3. HAD-B induced galectin-3-independent down-regulation of GABABR1, which resulted in a decreased proliferation of human colon cancer cells. The therapeutic effect of HAD-B for the treatment of human colon cancer needs to be further validated.

Mitochondrial Dysfunction of Immortalized Human Adipose Tissue-Derived Mesenchymal Stromal Cells from Patients with Parkinson’s Disease

문효은,박성섭,전범석,김한준,김동규,황재하,김인경,백승렬,손진희,유승현,심정희,김경희,하지영,박형우,허용석,윤승희,백선하,손형진 한국뇌신경과학회 2013 Experimental Neurobiology Vol.22 No.4

Mitochondrial dysfunction in dopaminergic neurons of patients with idiopathic and familial Parkinson’s disease (PD) is well knownalthough the underlying mechanism is not clear. We established a homogeneous population of human adipose tissue-derivedmesenchymal stromal cells (hAD-MSCs) from human adult patients with early-onset hereditary familial Parkin-defect PD as wellas late-onset idiopathic PD by immortalizing cells with the hTERT gene to better understand the underlying mechanism of PD. The hAD-MSCs from patients with idiopathic PD were designated as “PD”, from patients with Parkin-defect PD as “Parkin” andfrom patients with pituitary adenomas as “non-PD” in short. The pGRN145 plasmid containing hTERT was introduced to establishtelomerase immortalized cells. The established hTERT-immortalized cell lines showed chromosomal aneuploidy sustained stably overtwo-years. The morphological study of mitochondria in the primary and immortalized hAD-MSCs showed that the mitochondriaof the non-PD were normal; however, those of the PD and Parkin were gradually damaged. A striking decrease in mitochondrialcomplex I, II, and IV activities was observed in the hTERT-immortalized cells from the patients with idiopathic and Parkin-defectPD. Comparative Western blot analyses were performed to investigate the expressions of PD specific marker proteins in the hTERT-immortalized cell lines. This study suggests that the hTERT-immortalized hAD-MSC cell lines established from patients withidiopathic and familial Parkin-defect PD could be good cellular models to evaluate mitochondrial dysfunction to better understandthe pathogenesis of PD and to develop early diagnostic markers and effective therapy targets for the treatment of PD.

Human Adipose Tissue-Derived Mesenchymal Stem Cells 배양 시 효율적인 Extracellular Matrix의 증명

민선옥(Seon Ok Min),이상우(Sang Woo Lee),최새별(Sae Byeol Choi),김경식(Kyung Sik Kim) 한국간담췌외과학회 2009 한국간담췌외과학회지 Vol.13 No.4

Purpose: Human mesenchymal stem cells (hMSCs) have the potency for self-renewal and differentiation into various kinds of cells. The hMSCs are obtained from the various tissues, including adipose tissue, bone marrow and cord blood. The extracellular matrix (ECM) is an important factor that affects cell adherence, growth, migration, apoptosis and differentiation both in vitro and vivo. The adipose-derived mesenchymal stem cells (AD-MSCs) have CD29 (integrin) on the cell surface, which is the receptor for fibronectin. The aim of this study is to validate the efficacy of ECM, and especially fibronectin, for cell expansion. Methods: The AD-MSCs were obtained from the abdominal fat of humans. These cells were seeded onto culture plates coated with fibronectin-Human (FN) and plates without ECM (control). The cells were incubated for 3 passages and the cellular morphology was simultaneously observed with microscopy. CCK-8 assay was performed to compare the proliferation ability in each condition at the same passage. Immunocytochemistry staining for integrin-beta1 was performed to observe the cell to cell interaction. Results: The hAD-MSCs in the FN-coated and non-coated plates exhibited cytoplasm staining for integrin-beta1. In all the cultures, extended fibroblastic-shaped cells that turned into rhomboid cells were most frequently observed. The cell growth rates for the non coated culture plate were lower than those for the FN coated plates. After 72 hour culture under the different coated concentrations of FN and the non coated condition (control), the control group had a lower growth rate. In the culture with a FN coated plate, a significant change was observed as compared with that of the control group. We observed an increase in cell proliferation, with a maximum of 140%, on the FN coated plate by performing CCK-8 assay. In comparison, integrin β1 on the cells was more expressed in the FN-coated plates than that in the non-coated plates. Conclusion: The cell morphology can be changed faster in the FN coated culture plates than that in the non coated culture plates. Because proliferation and adhesion with FN can enhance the expansion, the culture within a FN coated plate is needed to encourage hAD-MSCs to proliferate in vitro.

비소세포성 폐암에서 Gefitinib과 삼칠충초정을 병용 투약하여 약물 내성이 연장된 1례

고명현 ( Myung-hyun Ko ),반경태 ( Gyung-tae Ban ),박소정 ( So-jung Park ),박지혜 ( Ji-hye Park ),이연월 ( Yeon-weol Lee ),조정효 ( Jung-hyo Cho ),유화승 ( Hwa-seung Yoo ) 대전대학교 한의학연구소 2021 혜화의학회지 Vol.30 No.2

Objective : The purpose of this study was to report the case of prolonged drug resistance non-small cell lung cancer (NSCLC) with Samchilchoongcho-Jung (HAD-B1) in combining with Gefitinib. Methods : The patient was diagnosed with Epidermal Growth Factor Receptor mutation (EGFR) NSCLC adenocarcinoma. The patient being treated with Gefitinib was treated with HAD-B1 for prolonged drug resistance. The clinical outcomes were measured by Response Evaluation Criteria in Solid Tumors (RECIST), National Cancer Institute Common Terminology Criteria for Adverse Event (NCI -CTCAE), laboratory findings, etc. Results : After combining treatment, the drug resistance of Gefitinib was prolonged about 20 months. The tumor marker levels were also maintained. NCI-CTCAE 6.0 showed no adverse events. Conclusion: This case study suggested that HAD-B1 may prolong the drug resistance of Gefitinib.

Analysis of anti-angiogenic mechanism of HangAmDan-B (HAD-B), a Korean traditional medicine, using antibody microarray chip

방지영,김응윤,심태경,유화승,이연월,김용수,조종관,최용진,정현자,강인철 한국바이오칩학회 2010 BioChip Journal Vol.4 No.4

The inhibitory effects of the water extract of HangAmDan-B(WEHAD-B), which is a crude extract of eight Korean medicinal animals and plants on bFGF-induced neovascularization were investigated. WEHAD-B significantly prevented bFGF-induced HUVE cell proliferation, adhesion, migration, and capillary-like tubular network formation. Half-maximal inhibition of proliferation on the endothelial cells by WEHAD-B was observed at a concentration of approximately 250 μg/mL. Our antibody microarray-based ProteoChip data showed that WEHAD-B increased the expression of STAT1 and Rb2, which are involved in cell growth, apoptosis, and controlling the cell cycle in bFGF-induced HUVECs. These results indicate that the inhibition of bFGF-induced angiogenesis by WEHAD-B may be due to upregulation of cell signaling proteins, STAT1 and Rb2. The blood vessel formation in a chick chorioallantoic membrane (CAM) treated with WEHAD-B was markedly reduced in length compared with a PBS-treated control group. Taken together, these data suggest that antibody-arrayed ProteoChip technology may be an useful tool for determining molecular mechanism of natural products in biological samples.

시와 시인에 대한 이슬람의 견해 - 코란과 순나를 중심으로

임병필 한국아랍어아랍문학회 2015 아랍어와 아랍문학 Vol.19 No.1

This paper aims to study why the Prophet Muhammad had negative perceptions against poetry and poet. So I tried to search the ground of his negative perceptions of poetry and poets from the Qur’ān and the Sunnah. Because the two sources of the Islamic law were the decisive evidentiary material to look into the perceptions of everything that Muhammad and Muslims have. According to research data, overall in the Qur’ān, poetry is considered to be negative, except that its contents contain good deeds and defending Islam. In the Sunnah, one may find both positive and negative perceptions of poetry and poet.

이즈티하드에 대한 연구 : 출현과정과 무즈타히드의 자격조건을 중심으로

김종도 국제언어인문학회 2015 인문언어 Vol.17 No.2

This paper focusses on the concept of Ijtihād in Islam, its appearance and the qualifications for a mujtahid. Ijtihād means a judgement through reasoned deduction by scholars (ʿUlamāʾ) and lawyers (Fuqahāʾ) with adequate knowledge of Islam in order to obtain the answers to certain matters. According to some of Muslim traditionalists and western scholars, the door of Ijtihād in Islam has been closed since the ninth or tenth century due to their misconception of Ijtihād despite its intermittent activities. With the introduction of western laws to Islamic countries in the nineteenth century, Islamic law had to be in harmony with Ijtihād to resolve various secular issues. In order to be a Mujtahid, a scholar was required to have the power of discernment, because it was a foundation of the Islamic legal sources like Ijtihād or Ijmāʿ.