• Title/Summary/Keyword: 약물 농도

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A Study on Bone Formation & Osteoporosis by Taeyoungion-Jahage Extracts

  • Kim, Yi-Geun;Seong, Jun-Ho;Kim, Dong-Il;Lee, Tae-Kyun;Kim, Jun-Ki;Park, Young-Duck
    • The Journal of Korean Obstetrics and Gynecology
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    • v.15 no.4
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    • pp.45-60
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    • 2002
  • Mouse calvarial osteoblast cells were isolated and cultured. To examine whether the cells produce active gelatinases in culture medium or not,the cells were analyzed using by zymograsphic analysis on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). We show that mouse calvarial osteoblasts in culture constitutively synthesize progelatinase- A. Then, mouse osteoblasts, which were stimulated by PTH, $1,25(OH)_2D_3$, mononuclear cell conditioned medium (MCM) and IL-1 as bone resorption agent's, showed increased collagenolysis by producing the active gelatinase. However, treatment of indomethacin and dexamethasone significantly decreased those effects of collagenolysis in mouse osteoblastic cells. On the other hand, IL-1 in stimulating bone resorption was examined using fetal mouse long bone organ culture. IL-1 stimulated bone resorption and produced marked resorption when present simultaneously. Furthermore, when it was examined the effects of indomethacin and dexamethasone on the dose dependent responses of $IL-1{\alpha}$, indomethacin and dexametasone produced a rightward shift in the IL-1 dose response curve. The results of in vitro cytotoxicities showed that Taeyoungjon-Jahage water extracts(T.Y.J-J.H.G extracts) have no any cytotoxicities in concentrations of $1-200\;{\mu}g/ml$ and furthermore there is no any cytotoxicity even in concentration of $300\;{\mu}g/ml$ on mouse calvarial bone cells. T.Y.J.-J.H.G. extracts had protective activity against PTH (2 units/mI), or MCM (5%, v/v), or $rhIL-1{\alpha}$ (1 ng/mI) or $1,25(OH)_2D3$ (10 ng/ml) , $IL-1{\alpha}$ and $IL-1{\beta}-induced$ collagenolysis in the mouse calvarial cells. Pretreatment of the T.Y.J.-J.H.G.extracts for 1 h, which by itself had little effect on cell survival, did not enhance the collagenolysis, nor significantly reduced the collagenolysis by pretreatment. Furthermore. the medicinal extracts were shown to have the protective effects against collagenolysis induced by $IL-1{\alpha}$ and $IL-1{\beta}$. Pretreatment of the extracts for 1 h significantly reduced the collagenolysis. Interestingly, the T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against gelatinase enzyme and processing activity induced by the bone resortion agents of PTH, $1,25(OH)_2D_3$, $IL-1{\beta}$ and $IL-1{\alpha}$, with strong protective effect in pretreatment with the extracts. T.Y.J.-J.H.G. extracts were shown to have the inhibiting effects against $IL-1{\alpha}-$ and $IL-1{\beta}-stimulated$ bone resorption and the effect of the pretreatment with a various concentrations of the medicinal extracts were significant. The inhibition extent and phenomena of IL-1 stimulated bone resorption by nonsteroidal anti-inflammatory agents of indomethacin and dexamethasone were similar to those obtained by T.Y.J.-J.H.G. extracts treatment in the mouse calvarial tissue culture system. These results indicated that the T.Y.J.-J.H.G.-water extracts are highly stable and applicable to clinical uses in osteoporosis.

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Protective Effects of Enzymatic Oyster Hydrolysate on Acetaminophen-induced HepG-2 Cell Damage (아세트아미노펜 유도 HepG-2 세포주 손상에 대한 굴 효소 가수분해물의 보호 효과)

  • Park, Si-Hyang;Moon, Sung-Sil;Xie, Cheng-Liang;Choung, Se-Young;Choi, Yeung-Joon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.43 no.8
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    • pp.1166-1173
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    • 2014
  • This study investigated the detoxification effects of enzymatic hydrolysate from oyster on acetaminophen-induced toxicity using HepG-2 cells. Oyster hydrolysate was made with 1% Protamex and 1% Neutrase after treatment with transglutaminase (TGPN) or without (PN). Two types of oyster hydrolysate were added to human-derived HepG-2 hepatocytes damaged by acetaminophen, after which the survival rate of HepG-2 cell was measured. In addition, glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) activities in the culture media were evaluated. The survival rates of HepG-2 cells were $136.2{\pm}1.4%$ at $100{\mu}g/mL$ of TGPN and $179.6{\pm}3.8%$ at $200{\mu}g/mL$ of TGPN. These cell survival rates were higher compared to that of the negative control group ($60.7{\pm}3.2%$) treated only with acetaminophen. GOT activity was $38.3{\pm}0.2$ Karmen/mL in the negative control group, whereas it was $19.9{\pm}0.5$ for TGPN ($200{\mu}g/mL$) and $22.0{\pm}2.4$ Karmen/mL for PN ($200{\mu}g/mL$). GOT and GTP activities were shown to be dependent on TGPN concentration, and significant reduction in activities could be conformed. The detoxification efficacy of TGPN was higher compared to that of PN. These results suggest that oyster hydrolysate has potential as a healthy food or pro-drug for liver protection.

Acute Renal Failure after On-pump Coronary Artery Bypass Surgery (체외순환하 시행한 관상동맥우회술 후 발생한 급성신부전증)

  • Jin, Ung;Jo, Min-Seop;Park, Chan-Beom;Sa, Young-Jo;Kim, Chi-Kyung
    • Journal of Chest Surgery
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    • v.37 no.5
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    • pp.416-422
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    • 2004
  • Acute renal failure (ARF) is a common postoperative complication after the cardiac surgery. Postoperative ARF have various causes, and are combined with other complications rather than being the only a complication. It deteriorates the general condition of the patient, and makes it difficult to manage the combined complications by disturbing the adequate medication and fluid therapy. We have planned this study to evaluate the effects of postoperative ARF after the on-pump coronary artery bypass surgery (CABG) on the recovery of patients and identify the risk factors. Method and Material: We reviewed the medical records of patients who underwent CABG with cardiopulmonary bypass by a single surgeon from Jan. 2000 to Dec. 2002, We checked the preoperative factors; sex, age, history of previous serum creationism over 2.0 mg/㎗, preoperatively last checked serum creatinine, diabetes, hypertension, left ventricular ejection fraction, intraoperative factors; whether the operation is an emergent case or not, cardiopulmonary bypass time, aortic cross clamp time, the number of distal anastomosis, postoperative factors: IABP. Then we have studied the relations of these factors and the cases of postoperative peak serum creatinine over 2.0 mg/㎗. Result: There were 19 cases with postoperative peak serum creatinine over 2.0 mg/㎗ in a total 97 cases. Dialysis were done in 3 cases for ARF with pulmonary edema and severely reduced urine output. There were 8 cases (42.1%) with combined complications among the 19 patients. This finding showed a significant difference from the 5 cases (6,4%) in the patients whose creatinine level have not increased over 2.0 mg/㎗. The mortalities are different as 1.3% to 10.5%. The risk factors that are related with postoperative serum creatinine increment over 2.0 mg/㎗ are diabetes, the history of previous serum creatinine over 2.0 mg/㎗ and left ventricular ejection fraction. Conclusion: Postoperative ARF after the on-pump CABG is related with preoperative diabetes, the history of previous serum creatinine over 2,0 mg/㎗ and left ventricular ejection fraction. Postoperative ARF could De the reason for increased rate of complications and mortality after on-pump CABG. Therefore, in the patients with these risk factors, the efforts to prevent postoperative ARF like off-pump CABG should be considered.

A Case of Pharmacokinetics of Cisplatin in Concurrent Chemoradiation for Hemodialysis Patient with Advanced Head and Neck Cancer (혈액 투석을 받는 두경부암 환자의 동시화학방사선요법에서 Cisplatin의 약력학 조사 1예)

  • Jeon, Youn-Joo;Shim, Byoung-Yong;Kim, Hyung-Wook;Lee, Sang-Hun;Lee, Ho-Sang;Park, Cheol-Whee;Kim, Su-Zy;Kuh, Hyo-Jeong;Kim, Hoon-Kyo
    • Korean Journal of Head & Neck Oncology
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    • v.23 no.2
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    • pp.153-156
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    • 2007
  • Objectives : We study the feasibility and pharmacokinetics of cisplatin concurrent chemoradiation for advanced head and neck cancer patient undergoing hemodialysis. Materials and Methods : A 57-year old male with end stage renal disease developed stage III external auditory canal cancer. Complete resection surgery was done. Postoperative 6 months, local recurrence was occurred. Despite excision and adjuvant radiotherapy, local tumor was recurred. We decided to treat a cisplatin concurrent chemoradiotherapy. Cisplatin was administered at a dose of $20mg/m^2$ for 30 min. Hemodialysis was started 30 min after completion of the cisplatin infusion and performed for 4 hours. Hemodialysis was performed on day 3 and 5 of chemotherapy. Plasma samples were collected at specified times after administration of cisplatin. Result : At the end of the third cycle of cisplatin concurrent chemoradiotherapy, the tumor size was markedly decreased. The maximum plasma concentrations of plasma platinum and free platinum were 0.74 and $0.37{\mu}g/ml$ respectively. The area under the curve of plasma platinum and free platinum were 94.7 and $11.3{\mu}g{\cdot}h/ml$ respectively. Conclusion : We report a case of Cisplatin concurrent chemoradiation for hemodialysis patient with advanced head and neck cancer and suggest full dose cisplatin concurrent chemoradiotherpay is tolerable for these patients.

Optimum Population in Korea : An Economic Perspective (한국의 적정인구: 경제학적 관점)

  • Koo, Sung-Yeal
    • Korea journal of population studies
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    • v.28 no.2
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    • pp.1-32
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    • 2005
  • The optimum population of a society or country can be defined as 'the population growth path that maximizes the welfare level of the society over the whole generations of both the present and the future, under the paths allowed by its endowments of production factors such as technology, capital and labor'. Thus, the optimum size or growth rate of population depends on: (i) the social welfare function, (ii) the production function, and (iii)demographic economic interrelationship which defines how the national income is disposed into consumption(birth and education of children included) and savings on the one hand and how the demographic and economic change induced thereby, in turn, affect production capacities on the other. The optimum population growth path can, then, be derived in the process of dynamic optimization of (i) under the constraints of (ii) and (iii), which will give us the optimum population growth rate defined as a function of parameters thereof. This paper estimates the optimum population growth rate of Korea by: specifying (i), (ii), and (iii) based on the recent development of economic theories, solving the dynamic optimization problem and inserting empirical estimates in Korea as the parametric values. The result shows that the optimum path of population growth in Korea is around TFR=1.81, which is affected most sensitively, in terms of the size of the partial elasticity around the optimum path, by the cost of children, share of capital income, consumption rate, time preference, population elasticity of utility function, etc. According to a survey implemented as a follow up study, there are quite a significant variations in the perceived cost of children, time preference rate, population elasticity of utility across different socio-economic classes in Korea, which implied that, compared to their counterparts, older generation and more highly educated classes prefer higher growth path for the population of Korea.

Tenebrio molitor (Mealworm) Extract Improves Insulin Sensitivity and Alleviates Hyperglycemia in C57BL/Ksj-db/db Mice (C57BL/Ksj-db/db 제 2형 당뇨모델을 이용한 갈색거저리 유충(밀웜) 추출물의 인슐린 감수성 및 혈당개선효과)

  • Kim, Seon Young;Park, Jae Eun;Han, Ji Sook
    • Journal of Life Science
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    • v.29 no.5
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    • pp.570-579
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    • 2019
  • Diabetes is one of the serious chronic metabolic diseases caused by Westernized eating habits, and the goal of diabetes treatment is to keep blood glucose at a normal level and prevent diabetic complications. This study was designed to investigate the anti-diabetic effects of a mealworm (Tenebrio molitor larva) extract (MWE) on hyperglycemia in an animal model with type 2 diabetes. Diabetic C57BL/Ksj-db/db mice were divided into three groups: diabetic control, rosiglitazone, and MWE. The mice supplemented with MWE showed significantly lower blood levels of glucose and glycosylated hemoglobin when compared with the diabetic control mice. The homeostatic index of insulin resistance was significantly lower in mice supplemented with MWE than in diabetic control mice. MWE supplementation significantly stimulated the phosphorylation of insulin receptor substrate-1 and Akt, and activation of phosphatidylinositol 3-kinase in insulin signaling pathway of skeletal muscles. Eventually, MWE increased the expression of the plasma membrane glucose transporter 4 (GLUT4) via PI3K/Akt activation. These findings demonstrate that the increase in plasma membrane GLUT4 expression by MWE promoted the uptake of blood glucose into cells and relieved hyperglycemia in skeletal muscles of diabetic C57BL/Ksj-db/db mice. Therefore, mealworms are expected to prove useful for the prevention and treatment of diabetes, and further studies are needed to improve type 2 diabetes in the future.

An Appreciation of Functional Role of Macrophage in the Acute Lung Injury in the Neutropenic Rat. (호중구 감소증을 보이는 백서의 급성폐손상에서 대식세포의 기능적 역할)

  • Kim, Yong-Hoon;Ki, Sin-Young;Im, Keon-Il;Moon, Seung-Hyug;Cheong, Seung-Whan;Kim, Hyeon-Tae;Uh, Soo-Taek;Park, Choon-Sik;Jin, Byung-Won
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.2
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    • pp.379-390
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    • 1997
  • Background : It has long been suggested that neutrophils and their products are implicated as the central mediators of the acute lung injuries. Contrary to the dominant role of neutrophils in ARDS, many cases of ARDS has occurred in the setting of severe neutropenia without pulmonary neutrophil infiltration. Therefore it is certain that effector cell(s) other than neutrophil play an important role in the pathogenesis of ARDS. This experiment was performed to define the mechanism of ARDS in the setting of neutropenia, 1) by comparing the severity of endotoxin-induced lung injury, 2) by measurement of hydrogen peroxide production and cytokine concentration in the bronchoalveolar lavage cells and fluids obtained from different rats with and without cyclophosphamide-pretreatment. Method : The male Sprague-Dawleys were divided into the normal control (NC)-, endotoxin (ETX)-, and cyclophosphamide (CPA)-group in which neutropenia was induced by injecting cyclophosphamide intraperitoneally. Acute lung injury was evoked by injecting lipopolysaccharide (LPS) into a tail vein. The bronchoalveolar lavage (BAL) was performed at 3 and 6 hour after administration of LPS to measure the change of cell counts and concentrations of protein and cytokines, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6). Hydrogen peroxide (HPO) production from BAL cells was measured at 6 hour after LPS administration by phenol red microassay with and without zymosan stimulation. Results : The results were as follows. A change of leukocyte counts in the peripheral blood after treatment with CPA : More than 95% of total leukocytes and neutrophils were reduced after CPA administration, resulting in severe neutropenia. A change of BAL cells : In the ETX-group, the number of total cells (p < 0.01) and of macrophage and neutrophil (p < 0.05) were increased at 3 and 6 hour after LPS administration compared to those of NC-group. In the CPA-group, the number of total leukocyte and macrophage were not changed after LPS administration, but neutrophil counts were significantly reduced and it took part in less than 0.1% of total BAL cells (p < 0.01 vs NC-group). BAL cells in this group were almost all macrophages (99.7%). A change of protein concentration in the BALF : In the ETX-group, protein concentration was increased at 3 hour and was more increased at 6 hour after LPS administration (p < 0.05 and < 0.01 vs NC-group, respectively). In the CPA-group, it was also significantly elevated at 3 hour after LPS administration (p < 0.05 vs NC-group), but the value was statistically not different from that of ETX-group. The value measured at 6 hour after LPS administration in the CPA-group became lower than that of ETX-group (p < 0.05), but showed still a higher value compared to that of NC-group (p < 0.05). A change of cytokine concentration in the BALF : TNF -alpha and IL-6 were elevated in the ETX - and CPA-group compared to those of NC-group at both time intervals. There was no statistical difference in the values of both cytokines between the ETX- and CPA-groups. Measurement of hydrogen peroxide production from BAL cells : There was no intergroup difference of HPO production from resting cells. HPO production after incubation with opsonized zymosan was significantly elevated in all groups. The percent increment of HPO production was highest in the ETX-group (89.0%, p < 0.0008 vs NC-group), and was 42.85 in the CPA-group (p = 0.003 vs NC-group ). Conclusion : Acute lung injury in the setting of neutropenia might be caused by functional activation of resident alveolar macrophages.

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Fabrication of PLGA/Dextran Double-Layered Microspheres by Oil-in-Water Solvent Evaporation Method (O/W 용매 증발법을 이용한 PLGA와 덱스트란의 이중층 미립구 제조)

  • Ko Jong Tae;Lee Jae-Ho;Lee Chang-Rae;Shin Hyung Sik;Yuk Soon Hong;Kim Moon Suk;Khang Gilson;Rhee John M.;Lee Hai Bang
    • Polymer(Korea)
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    • v.29 no.6
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    • pp.543-548
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    • 2005
  • Double-layered spheres play an important role in controlling drug delivery for pharmaceutical application, because of the low initial burst compared with single-layered spheres and targetable delivery to specific organ. But it has drawback in loading drug and controlling size. In this study, we developed double-layered spheres using relatively simple oil-in-water (O/W) solvent evaporation method witw/without ultrasonication and investigated the size variation of the double-layered microspheres on the contents of poly(lactide- co-glycolide) (PLGA). Double - layered spheres were char-acterized by scanning elecron microscope (SEM), camscope, and confocal fluorescence laser microscope (CFLM). Double-layered spheres showed smooth surfaces and obvious difference between core and corona by SEM observation and camscope. We observed the fluorescent core in the double-walled spheres composed of FlTC-dextran and PLGA using CFLM. It was found that the core of the microsphere was dextran and the corona of the fabricate microsphere was PLGA. Also, the more PLGA concentration, the more the size of the fabricating double-layered sphere observed.

The Effect of Aralia Cordata Thunb and Cimicifuga Heracleifolia on Cartilage Protection by the Regulation of Metabolism in Human Osteoarthric Chondrocytes (퇴행성 관절염에 대한 독활.승마 복합처방의 대사조절을 통한 연골보호 효과)

  • Shin, Ye-Ji;Beak, Yong-Hyeon;Park, Dong-Suk;Kim, Jae-Kyu;Koh, Hyung-Kyun
    • Journal of Acupuncture Research
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    • v.27 no.4
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    • pp.39-53
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    • 2010
  • 목적 : 퇴행성 관절염은 염증성 사이토카인인 IL-$1\beta$에 의해 연골관절이 파괴되고 이로 인해 염증성 사이토카인이 더욱 증가하는 질환이다. 퇴행성 관절염을 치료하기 위해서는 연골 파괴를 가속화시키는 catabolic cytokines의 활성을 줄이고, 성장인자인 anabolic factor의 활성을 증가시는 연골 보호 작용이 있어야 한다. 본 연구에서는 독활 승마 처방(OAH19T)이 catabolic/anabolic 대사 조절에 어떤 영향을 미치는지와 그 신호 전달 기전에 대해 연구하였다. 또한 OAH19T를 구성하는 단미재 및 임상에서 사용되는 COX-2 inhibitor인 Celebrex(CEL)와 효능을 비교 실험하였다. 방법 : 배양된 세포에 IL-$1\beta$로 자극한 후 (1) glycosaminoglycan(GAG)의 분해 억제 정도, (2) OAH19T와 CEL에 대하여 MMP-1과 MMP-3의 유전자 발현 및 활성 억제, (3) Aggrecan 및 Aggrecanases의 유전자 발현 및 활성 억제, (4) OAH19T의 growth factor의 조절 능력, (5) MAPK pathway 등을 RT-PCR(reverse transcriptase-polymerase chain reaction), ELISA(Enzyme-linked immunosorbent assay), western blot, viability 측정을 통해 검증했다. 결과 : 사람 관절 세포에서 (1) 독활 승마 각각의 단미재, 임상에서 사용중인 셀레콕시브(CEL), 조인스보다 실험 약물(OAH19T)이 저농도에서 GAG 분해 억제 효과가 우수하였고, 부탄올로 분획한 OAH19B와는 동등한 효과를 보였다. (2) OAH19T는 IL-$1\beta$에 의하여 활성화된 MMP-1과 MMP-3의 발현을 모두 억제하였으나, CEL은 MMP-1의 발현은 억제하였으나 MMP-3의 발현은 억제하지 못하였다. (3) OAH19T는 IL-$1\beta$에 의하여 손상된 Aggrecan을 회복시켰으며 이는 활성화된 Aggrecanase-1과 Aggrecanase-2를 억제시킴으로써 나타난 결과이다. 그러나 CEL의 경우, 손상된 Aggrecan을 회복시키지 못하였다. (4) 배양된 세포는 IL-$1\beta$에 의하여 TGF-$\beta$II및 TGF-$\beta$ receptor II의 발현이 억제되었으나, OAH19T는 TGF-$\beta$II및 TGF-$\beta$ receptor II의 발현을 회복시켜 OAH19T가 anabolic한 조절능력이 있음을 시사한다. 그러나 CEL의 경우 growth factor에 대한 조절 능력이 없었다. (5) 대사 조절 작용에 대한 기전으로서 MAPK pathway에 대해서 연구한 결과 IL-$1\beta$에 의하여 유도된 pERK, pp38 kinase의 활성은 억제하였고, pJNK의 활성은 변하지 않았다. 또한 OAH19T는 연골 세포에 독성이 없었으며 IL-$1\beta$에 의해 유도된 세포 증식만을 억제시켰다. 이 결과로, OAH19T가 OA chondrocyte의 탈분화 및 세포 고사를 억제하여 연골보호 및 회복 효과가 있음을 알 수 있었다. 결론 : OAH19T는 이를 구성하는 단미재 및 CEL보다 연골보호 효과가 월등하였고, 이러한 연골보호 효과는 catabolic cytokines/growth factors의 균형으로 대사조절을 통해 연골세포의 탈분화 및 세포 고사를 억제하여 연골보호 및 회복 효과가 있음을 알 수 있었다.

The Inhibitory Effects of Cordycepin on Phosphoproteins including PI3K, Akt, and p38 (PI3K, Akt, p38을 포함한 인산화단백질에 대한 Cordycepin의 억제효과)

  • Kwon, Hyuk-Woo;Lee, Dong-Ha
    • Korean Journal of Clinical Laboratory Science
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    • v.49 no.2
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    • pp.99-107
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    • 2017
  • A species of Cordyceps, an ingredient in Chinese traditional medicine well-known for its major component, cordycepin (3'-deoxyadenosine), has been known to have antiplatelet effects; however, its effects on regulation of phosphoprotein have not been fully elucidated. In this study, we investigated how cordycepin regulates the phosphoprotein, including phosphatidylinositol 3-kinase (PI3K)/Akt and p38, to inhibit platelet aggregation, which are concerned with fibrinogen binding to glycoprotein IIb/IIIa (${\alpha}IIb/{\beta}_3$) and granule secretion in platelets. Our finding suggests that cordycepin inhibits collagen-induced platelet aggregation with $261.1{\mu}M$ of $IC_{50}$ and also inhibits fibrinogen binding to ${\alpha}IIb/{\beta}_3$ by a suppression of PI3K/Akt phosphorylation in a dose dependent manner. In addition, cordycepin further showed to inhibit collagen-induced p38 phosphorylation, reducing granule secretion (i.e. ATP- and serotonin-release) and thromboxane $A_2$ ($TXA_2$) production without regulating cyclooxygenase-1 (COX-1) and thromboxane A synthase (TXAS) activities, as well as phospholipase $C-{\gamma}_2$ ($PLC-{\gamma}_2$) phosphorylation. In conclusion, these results demonstrate that cordycepin-mediated antiplatelet effects were due to the inhibition of fibrinogen binding to ${\alpha}IIb/{\beta}_3$ via the suppression of PI3K/Akt phosphorylation and inhibition of granule secretion & $TXA_2$ production by suppressing p38 phosphorylation. These results strongly indicate that cordycepin might have therapeutic or preventive potential for platelet aggregation-mediated disorders, regulating the phosphoprotein, including PI3K/Akt and p38.