• Journal of Acupuncture Research
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• 제21권3호
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• pp.283-302
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• 2004

Background : Angiogenesis is the proliferation of a network of blood vessels emanating from pre-existing vessels, supplying nutrients and oxygen and removing waste products. Angiogenesis occurs in a variety of normal physiologic and pathologic conditions and is regulated by a balance of stimulatory and inhibitory angiogenic factors. Excessive angiogenesis should be suppressed. However, if blood supply is insufficient, it should be encouraged. Hyul-Mek(血脈) or Hyul-Rark(血絡), known as blood vessels in western medicine, is deeply related to Chung-Ki-Hyul(精 氣 血). The goal of this study is to review the effects of herbal medicines on angiogenesis that is involved in wound healing and enhancement of blood supply. Methods : We conducted a systematic and comprehensive literature search for the identification, retrieval, and bibliographic management of independent studies to locate information on the topic. A computerized search of the published literature of Korea(KISS, RISS), China(CNKI), Japan(Kampo medicine, etc), and western countries(MEDLINE) was performed, and further supplemented with manual searches of print sources(1999 to 2003). Results : The herbal medicines with angiogenic activity were mainly found among herbs that carry replenish Shin-Cheng(補腎益精), foster Eum and improve the circulation of blood(養陰活血), or warm and circulate Kyung-Rark(溫經通絡). In particular, herbs with improve the circulation of blood and clear blood(活血化瘀) activity contain a significant amount of tannin, saponin, and pyrazine. Conclusion : Replenish Ki-Hyul(補氣血) and circulate Kyung-Rark(通經絡) could contribute to the induction of angiogenesis because various growth factors and proliferation, differentiation, and migration of vascular endothelial cells are involved in angiogenic activity.

• Journal of Nutrition and Health
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• 제53권2호
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• pp.111-120
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• 2020

본 연구는 인간 유래 유방 암세포 MDA-MB-231를 대상으로 CA에 의한 세포사멸, 세포 이동 및 침윤 효과를 조사하였다. 암세포의 증식 억제 효과는 CA 농도 의존적으로 증식률이 감소하는 것을 확인하였다. CA에 의한 apoptosis 양성 세포를 확인하기 위해 DAPI stain를 진행한 결과, CA 농도 의존적으로 죽은 세포를 확인하였다. MDA-MB-231 세포에서 CA에 의한apoptosis marker 단백질 발현 증가와 ROS production증가를 확인할 수 있었다. 또한 CA에 의한 MDA-MB-231의 세포 이동률이 유의적으로 감소하는 것을 확인하였다. 마지막으로 세포의 이동과 전이 능력 또한 CA를 처리한 군에서 통계적으로 감소하는 것을 확인하였다. 본 연구 결과를 통해서 CA의 암세포 증식률 억제, 세포사멸 증가, 그리고 세포 이동 및 전이 억제 효과가 나타나는 것을 확인했으며, 이 결과를 통해서 향후 유방암에 대한 항암제로 개발될 수 있는 가능성을 가지고 있는 것으로 사료된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권11호
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• pp.4571-4576
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• 2015

Background: To investigate the inhibitory effect and the underlying mechanism of triptolide on cultured human endometrial carcinoma HEC-1B cells and corresponding xenograft. Materials and Methods: For in vitro studies, the inhibition effect of proliferation on HEC-1B cell by triptolide was determined by MTT assay; cell cycle and apoptosis of the triptolide-treated and untreated cells were detected by flow cytometry. For in vivo studies, a xenograft tumor model of human endometrial carcinoma was established using HEC-1B cells, then the tumor-bearing mice were treated with high, medium, and low-dose ($8{\mu}g$, $4{\mu}g$ and $2{\mu}g/day$) triptolide or cisplatin at $40{\mu}g/day$ or normal saline as control. The mice were treated for 10-15 days, during which body weight of the mice and volume of the xenograft were weighted. Then expression of Bcl-2 and vascular endothelial growth factor (VEGF) was analyzed by SABC immunohistochemistry. Results: Cell growth was significantly inhibited by triptolide as observed by an inverted phase contrast microscope; the results of MTT assay indicated that triptolide inhibits HEC-1B cell proliferation in a dose and time-dependent manner; flow cytometry showed that low concentration (5 ng/ml) of triptolide induces cell cycle arrest of HEC-1B cells mainly at S phase, while higher concentration (40 or 80 ng/ml) induced cell cycle arrest of HEC-1B cells mainly at G2/M phase, and apoptosis of the cells was also induced. High-dose triptolide showed a similar tumor-inhibitory effect as cisplatin (-50%); high-dose triptolide significantly inhibited Bcl-2 and VEGF expression in the xenograft model compared to normal saline control (P<0.05). Conclusions: triptolide inhibits HEC-1B cell growth both in vitro and in mouse xenograft model. Cell cycle of the tumor cells was arrested at S and G2/M phase, and the mechanism may involve induction of tumor cell apoptosis and inhibition of tumor angiogenesis.

• Journal of Periodontal and Implant Science
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• 제27권4호
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• pp.883-908
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• 1997

Bone remodeling is characterized by the coupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation. The process is tightly regualted at the local level by an incompletely known netwotk of peptide and non-peptide fators. Nitric oxide(NO), synthesized by nitric oxide synthetase(NOS) from L-arginine, is becoming recognized as an important bioregualtory molecule in a variety of tissue, but little is known about its possible role in periodontal tissue. The purpose of this study is to investigate the expression of nitric oxide synthetase(NOS) in inflamed gingiva and the effects of cytokine on the expression of NOS protein. The expression of NOS in gingival tissue was evaluated by immunohistochemical staining for $NOS_1$, $NOS_2$, $NOS_3$. The effect of cytokine on the expression of NOS in human periodontal ligament cells and osteoblast-like HOS cells by western blot analysis. Further, we studied that NO functions in periodontal ligament cells as a regulatory molecule. PDL cells incubated with NOS inhibitor and donor. The protein expression, type I collagen & non-collagenous protein, nitrate production and cell proliferation were evaluated The results were as follows. 1. $NOS_1$, $NOS_2$, $NOS_3$ was rarely distributed in healthy gingiva, but stronger stained in gingival epithelium, endothelial cells, and mononuclear cells of inflammed gingiva. 2. The cytokine stimulated $NOS_1$, and $NOS_3$ protein were not inducing or inhibitory effect to compared with control in PDL and HOS cells. 3.Incubation of cells with combination of $TNF-{\alpha}$, $IFN-{\gamma}$, LPS result in a time dependant increase in $NOS_2$ expression, reaching a maximal level after 24 hours of stimulation. 4. The osteonectin protein inhibitory effect of NMA, inhibitor of NOS, was reversed by Larginine in dose dependant manner. 5. NMA decreased cell poliferation and nitrate production, but the inhibitory efffect of NMA was also prevented by the NO donor, sodium nitropruiside. These results suggest that exogenously synthesized NO was playing a stimulating effect on cell proliferation or on non-collagenous protein expression. Therefore NO have an important role in mediation of localized bone destruction associated inflammatory bone disease such as periodontitis.

• 대한한방종양학회지
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• 제7권1호
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• pp.19-37
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• 2001

Object When angiogenesis is excessive, Cancer, RA, Blindness, Psoriasis, Hemangioma, Diabetic retinopathy, Granulation, etc are induced. On the contrary, when it is insufficient, Stroke, Heart disease, Ulcer, Infertility, Scleroderma, artherosclerosis, delay of the wound recovery, etc occur. In recently, the methods which is control of abnormal angiogenesis are researching actively in relathion to anticancer research. This study is search for effective drugs which suppress this angiogenesis, in the ingredients of the herbs that invigorate and dispel blood stasis using to treat intravascular coagulation in the oriental herbal medicine. Methods We maked 80 % methanole extracts of Cnidii Rhizoma, Olibanum, Myrrha, Corydalidis Tuber, Curcumae Radix, Curcumae longe Rhizoma, Zedoariae Rhizoma, Salviae miltiorrhizae Radix, Polygoni cuspidati Rhizoama, Leonuri Herba, Persicae Semen, Carthami Flos, Trogopterorum Faeces, Achyranthis Bidentatae Radix, Manitis Squama, Eupolyphaga, Hirudo, Tabanus, Lycopi Herba, Artemisiae anomalae herba, Vaccariae Semen, Sappan Lignum, Gleditsiae Spina, Draconis Resina, Leonunari Semen, Selaginelliae Folium, Spatholobi Caulis, and these extracts were tested for MTT viabilaty test, BrdU incorporation, Tube foramtion assay on ECV304(immotalized human umbilical vein endothelial cell) at the concentration of $50{\mu}g/ml$, $100{\mu}g/ml$, $200{\mu}g/ml$, $400{\mu}g/ml$ Results All extracts except Draconis Resina have no cytotoxicity at the $100{\mu}g/ml$, and in BrdU incorporation test, proliferation rate were reduced below 60% at the concentaraion of $100{\mu}g/ml$ by Zedoariae Rhizoma, Sappan, Lignum Gleditsiae, Spina Draconis Resina Vaccariae Semen. Zedoariae Rhizoma Sappan Lignum Gleditsiae Spina Draconis Resina Vaccariae Semen Olibanum, Achyranthis Bidentatae Radix showed inhibition effects on tube formation of ECV304 at the concentration of $100{\mu}g/ml$. Conclusion At the concentration of $100{\mu}g/ml$ in which cytotoxicity is not found, Zedoariae Rhizoma, Sappan Lignum, Gleditsiae Spina, Vaccariae Semen showed the inhibition effect on proliferation and tubeformation of ECV304.

• Korean Chemical Engineering Research
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• 제55권1호
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• pp.34-39
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• 2017

본 실험은 방사선을 이용하여 유착방지용 Carboxymethyl cellulose sodium salt (CMC)/Porcine Cartilage Acellular Matrix (PCAM) 수화젤 필름에 대해 연구하였다. 방사선 조사시 CMC/PCAM의 농도 및 혼합비율에 따른 필름의 형태학적 구조, 젤화율, 젤강도, 팽윤도 등을 분석하였다. 방사선에 의해 가교된 CMC/PCAM 필름은 CMC 필름보다 물리적인 특성인 젤화율이 낮게 측정되었다. 또한, 가교된 CMC 필름보다는 CMC/PCAM 필름에서 인간 혈관내피세포의 부착 및 증식율이 감소하였다. 우리는 PCAM에 함유한 세포의 항부착 성분이 도입된 CMC/PCAM 필름과 CMC 필름은 세포의 접착 및 증식율을 낮추는 것을 확인하였다. 결론적으로, 본 연구에서는 방사선 가교된 CMC/PCAM 수화젤 필름은 유착방지 향상을 위한 유착방지제로서 응용이 기대된다.

• 대한임상검사과학회지
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• 제51권3호
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• pp.379-385
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• 2019

골다공증은 호르몬의 변화와 무기질 감소에 의해 골밀도의 감소를 유발하여 골절의 위험을 높이는 질환이다. 최근 보고에 의하면, 간염바이러스 및 에이즈 치료제로 사용되고 있는 Adefovir dipivoxil (ADV)의 장기적 복용에서 골다공증 부작용이 유발할 수 있음이 보고 되고 있다. 이에 대한 연구수행을 위해 골모세포주 hFOB1.19와 혈관내피세포 HUVEC을 이용하여 ADV에 대한 생물학적 연관성을 평가하였다. 우선적으로 ADV를 농도별로 처리한 후 각 세포와 핵의 형태학적 분석을 위해 DAPI와 crystal violet 염색을 시행하였다. 또한 세포 증식에 대한 약물 효과를 평가하기 위하여 CCK-8분석과 골모세포에 대한 분화유도 및 억제 효과를 확인하기 위하여, ALP 염색을 진행하였다. 그 결과, ADV는 hFOB1.19 세포와 HUVEC 세포에서 농도 의존적으로 세포의 비대 현상을 유발하였고, 세포의 증식이 억제되었다. 이러한 원인들을 규명하기 위해 TGF-${\beta}$발현을 조사하였을 뿐만 아니라 이러한 발현 감소에 의한 생물학적 영향이 골모세포로부터 골세포로의 분화 과정에 관여하고 있음을 확인 할 수 있었다. 결론적으로, 본 연구에서는 ADV 약물이 골모세포와 혈관내피세포의 TGF-${\beta}$의 발현을 억제하여 핵의 크기 증가와 세포형태의 비대증을 유발하며, 세포의 증식억제 및 골모세포 분화능에 영향을 줌으로서 골다공증을 유발할 수 있는 가능성을 확인하였다. 이러한 결과는 ADV 복용에 따른 골다공증 발병 원인을 이해하기 위한 기초 연구 및 이를 이용한 임상영역에 활용 될 수 있을 것으로 사료된다.

• 대한물리치료과학회지
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• 제6권3호
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• pp.63-82
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• 1999

Recent studies have revealed that Nitric oxide(NO) was one of the demonstration for the physiological regulator, endothelial derived relaxing factor(EDRF) and that NO was produced by ultraviolet irradiation in human. Thus, the present author have carried out a experimental study on the change of hematological, histological value of ultraviolet irradiation in sprague-dawley rats. The subjects were divided into four groups of ten rats each selected at random. There were 4 groups: 1. no irradiation control; 2. ultraviolet $75mJ/cm^2$ irradiation group; 3. ultraviolet $150mJ/cm^2$ irradiation group; 4. ultraviolet $225mJ/cm^2$ group. After a irradiation, hematological and histological tests were performed to observe erythrocyte, hemoglobin, hematocrit, MCH, MCHC, MCV, $O_2$ saturation, pH, $PO_2,\;PCO_2$ value and to observe histological changes. In hematological tests, erythrocyte, hemoglobin, hematocrit significantly increased in $75mJ/cm^2$ than control group and more $150mJ/cm^2$ ultraviolet irradiation group respectively. Also In blood gas tests, $PO_2$ significantly increased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group. Whereas $PCO_2$ significantly decreased in $75mJ/cm^2$ and more $150mJ/cm^2$ group than control group (Duncan-Tukey test, P<0.05). In histological tests, control and $75mJ/cm^2$ group unchanged, but more $150mJ/cm^2$ group changed that it was cytolysis, cytotoxic effect, acanthosis, proliferation of keratinocyte, appearance of amorphous cell and pyknotic nucleus, production of sunburn cell. In conclusion, the present author results support the importance of the relation between NO effect and hematological, histological value by ultraviolet B irradiation.

• Biomolecules & Therapeutics
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• 제24권3호
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• pp.260-267
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• 2016

Mesenchymal stem cells (MSCs) offer significant therapeutic promise for various regenerative therapies. However, MSC-based therapy for injury exhibits low efficacy due to the pathological environment in target tissues and the differences between in vitro and in vivo conditions. To address this issue, we developed adipose-derived MSC spheroids as a novel delivery method to preserve the stem cell microenvironment. MSC spheroids were generated by suspension culture for 3 days, and their sizes increased in a time-dependent manner. After re-attachment of MSC spheroids to the plastic dish, their adhesion capacity and morphology were not altered. MSC spheroids showed enhanced production of hypoxia-induced angiogenic cytokines such as vascular endothelial growth factor (VEGF), stromal cell derived factor (SDF), and hepatocyte growth factor (HGF). In addition, spheroid culture promoted the preservation of extracellular matrix (ECM) components, such as laminin and fibronectin, in a culture time- and spheroid size-dependent manner. Furthermore, phosphorylation of AKT, a cell survival signal, was significantly higher and the expression of pro-apoptotic molecules, poly (ADP ribose) polymerase-1 (PARP-1) and cleaved caspase-3, was markedly lower in the spheroids than in MSCs in monolayers. In the murine hindlimb ischemia model, transplanted MSC spheroids showed better proliferation than MSCs in monolayer. These findings suggest that MSC spheroids promote MSC bioactivities via secretion of angiogenic cytokines, preservation of ECM components, and regulation of apoptotic signals. Therefore, MSC spheroid-based cell therapy may serve as a simple and effective strategy for regenerative medicine.

• 대한수의학회지
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• 제36권2호
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• pp.417-428
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• 1996

In order to know the toxic effect and carcinogenic activity in rats and mice fed with juice of Korean native Petasites japonicus Maxim of its pellet(4% or 8%) which were dried, milled and mixed with basal diet, the investigations were carried out by macroscopy and histopathology. Macroscopically, although remarkable changes were not observed in the liver of mice, there were slight to moderate swelling of rat livers in the whole groups at 12 to 14 weeks after feeding and milky spots in rats fed with its juice and 8% pelleted Petasites japonicus Maxim diet and a normal diet for 1 week alternatively for 14 weeks. Moreover, moderate to severe swelling and milk spots were recognized in livers of all rats fed with its juice and 8% pellet or 8% pelleted Petasites japonicus Maxim for 16 weeks. But, in cases of rats fed with its juice and 4% pellet or 4% pelleted Petasites japonicus Maxim, only swelling of livers was recognized moderately or severely. Histopathologically, major lesions were found in livers of both rats and mice. There were congestion, hemorrhage, fatty change, focal necrosis, megalocytosis and hyperplasia of endothelial cell in livers of mice and rats, the additional lesions such as proliferation of bile duct and nodular regeneration with diffuse regenerating cells were seen in livers of rats. In addition, preneoplastic lesions, the areas of milky spots macroscopically, were observed in livers of rats fed with Petasites japonicus Maxim for 14 to 16 weeks. In a few cases, haemangioendothelial sarcoma in livers was detected in rats fed with Petasites japonicus Maxim for 16 weeks. Petasites japonicus maxim growing naturally in Korea seem to exhibit toxic effect especially in liver and it contained a causative agent of primary liver tumors.