• Clinical and Experimental Reproductive Medicine
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• 제37권4호
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• pp.293-305
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• 2010

난소과자극증후군은 발생 시 생명을 위협하는 심각한 의인성 합병증으로, 불임 치료를 목적으로 성선자극호르몬을 사용하여 과배란을 유도할 때 발생한다. 따라서, 과배란 유도를 하기에 앞서 위험요인을 가진 환자를 파악하여 저용량의 성선자극호르몬을 사용하거나, GnRH antagonist protocol을 이용함으로써 발생을 예방하는 것이 중요하고, 과배란 유도 중 ovarian hyperstimulation syndrome (OHSS)의 발생이 예측될 때는 성선자극호르몬 투여 시 coasting을 하고 난포 성숙을 유도할 때 저용량의 hCG 혹은 GnRH agonist를 이용하고, 중증의 OHSS가 예측될 때에는 주기취소로 OHSS의 유병기간을 줄이거나 배아동결 등을 통해 후발성 난소과자극증후군을 예방할 수 있다. 그리고, metformin과 dopamine agonist를 난소과자극증후군을 예방을 위해 고려해 볼 수 있겠다.

• 약학회지
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• 제55권4호
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• pp.301-308
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• 2011

Diabetes has been one of major health risks in industrialized countries. AMP-activated protein kinase (AMPK) has been focused as a novel therapeutic target for the treatment of metabolic syndromes, because AMPK increases glucose uptake through independent insulin signal pathway. In this study, we investigated the anti-diabetic effect of Angelica gigas Nakai extract (AGNEX), a mixture of decursin and decursinol angelate (53 : 47), decursin and decursinol angelate on blood glucose, glucose transport (GLUT) and AMPK expression levels in streptozotocin (STZ)-induced diabetic rats. To induce diabetes, 50 mg/kg of STZ was injected via i.v. route and AGNEX 2 mg/kg (STZ+AG), decursin 2 mg/kg (STZ+D), decursinol angelate 2 mg/kg (STZ+DA), and metformin 100 mg/kg (STZ+M) were administered orally for 21 days. STZ+DA group showed a significant decrease in fasting blood glucose levels compared to the other groups. Decursinol angelate significantly upregulated expression of glucose transporter 4 (GLUT4) and phosphorylation of AMPK (p-AMPK) in skeletal muscle of rats. In pancreas of rats, decursinol angelate significantly increased expression of GLUT2 through down-regulation of p-AMPK. In addition to the result of pancreatic islets morphology, AGNEX, decursin, decursinol angelate, and metformin treated group recovered ${\beta}$-cell damage by hyperglycemia. These results indicate that decursinol angelate might be a potential anti-diabetic agent and AGNEX could be useful in the treatment of diabetes mellitus.

• 대한한방내과학회지
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• 제43권4호
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• pp.606-624
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• 2022

Objective: The aim of this study was to compare the effects of different doses of Geumnyeonyijin-tang (GNYJT) water extracts with those of metformin (250 mg/kg) in mild diabetic-obese mice. Methods and Results: The 48 mice were divided into 1 normal pellet diet (NFD) group and 5 high-fat diet (HFD) groups. At the end of 12 weeks of oral administration of metformin (250 mg/kg) or GNYJT water extracts (400, 200, or100 mg/kg), the effects were evaluated. The HFD control mice showed noticeable increases in body weight, adipose tissue density, fat pad weight of the periovarian and abdominal wall, and insulin, blood glucose, and HbA1c levels, with decreases in serum HDL levels. Increases in the periovarian and dorsal abdominal fat pad, regions of steatohepatitis, adipocyte hypertrophy, and hepatocyte hypertrophy were also discovered. The HFD group showed a decline in glucose levels and elevation of hepatic gluconeogenesis, suggesting an HFD-induced AMPK downregulation related to glucose dysregulation, as well as lipid metabolism related to obese insulin-resistant type II diabetes, dyslipidemia, and oxidative stress related diabetic hepatopathy (non-alcoholic fatty liver disease, NAFLD). Conclusion: Assessment of the key parameters for inhibition of diabetes and related complications in HFD-fed diabetic-obese mice demonstrated that GNYJT water extracts have favorable ameliorating effects. The effect of GNYJT was manifested through the stimulation of AMPK upregulation of related hepatic glucose enzyme activities and expression of lipid metabolism-related genes. Therefore, appropriate oral dosages of GNYJT could be promising as a new preventive candidate for controlling diabetes and related complications. Further screening of biologically active compounds, elucidation of detailed mechanisms, and more animal studies are warranted.

• The Korean Journal of Physiology and Pharmacology
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• 제26권2호
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• pp.95-111
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• 2022

Chronic obstructive pulmonary disease (COPD) is an important healthcare problem worldwide. Often, glucocorticoid (GC) resistance develops during COPD treatment. As a classic hypoglycemic drug, metformin (MET) can be used as a treatment strategy for COPD due to its anti-inflammatory and antioxidant effects, but its specific mechanism of action is not known. We aimed to clarify the role of MET on COPD and cigarette smoke extract (CSE)-induced GC resistance. Through establishment of a COPD model in rats, we found that MET could improve lung function, reduce pathological injury, as well as reduce the level of inflammation and oxidative stress in COPD, and upregulate expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), multidrug resistance protein 1 (MRP1), and histone deacetylase 2 (HDAC2). By establishing a model of GC resistance in human bronchial epithelial cells stimulated by CSE, we found that MET reduced secretion of interleukin-8, and could upregulate expression of Nrf2, HO-1, MRP1, and HDAC2. MET could also increase the inhibition of MRP1 efflux by MK571 significantly, and increase expression of HDAC2 mRNA and protein. In conclusion, MET may upregulate MRP1 expression by activating the Nrf2/HO-1 signaling pathway, and then regulate expression of HDAC2 protein to reduce GC resistance.

• Journal of Periodontal and Implant Science
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• 제53권1호
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• pp.54-68
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• 2023

Purpose: The purpose of this study was to determine whether metformin (MF) could alleviate the expresssion of reactive oxygen species (ROS) and improve the osteogenic ability of bone marrow mesenchymal stem cells derived from diabetic rats (drBMSCs) in vitro, and to evaluate the effect of MF on the ectopic osteogenesis of drBMSCs in a nude mouse model in vivo. Methods: BMSCs were extracted from normal and diabetic rats. In vitro, a cell viability assay (Cell Counting Kit-8), tests of alkaline phosphatase (ALP) activity, and western blot analysis were first used to determine the cell proliferation and osteogenic differentiation of drBMSCs that were subjected to treatment with different concentrations of MF (0, 50, 100, 200, 500 µM). The cells were then divided into 5 groups: (1) normal rat BMSCs (the BMSCs derived from normal rats group), (2) the drBMSCs group, (3) the drBMSCs + Mito-TEMPO (10 µM, ROS scavenger) group, (4) the drBMSCs + MF (200 µM) group, and (5) the drBMSCs + MF (200 µM) + H₂O₂ (50 µM, ROS activator) group. Intracellular ROS detection, a senescence-associated β-galactosidase assay, ALP staining, alizarin red staining, western blotting, and immunofluorescence assays were performed to determine the effects of MF on oxidative stress and osteogenic differentiation in drBMSCs. In vivo, the effect of MF on the ectopic osteogenesis of drBMSCs was evaluated in a nude mouse model. Results: MF effectively reduced ROS levels in drBMSCs. The cell proliferation, ALP activity, mineral deposition, and osteogenic-related protein expression of drBMSCs were demonstrably higher in the MF-treated group than in the non-MF-treated group. H₂O₂ inhibited the effects of MF. In addition, ectopic osteogenesis was significantly increased in drBMSCs treated with MF. Conclusions: MF promoted the proliferation and osteogenic differentiation of drBMSCs by inhibiting the oxidative stress induced by diabetes and enhenced the ectopic bone formation of drBMSCs in nude mice.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2005년도 생물공학의 동향(XVII)
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• pp.1020-1021
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• 2005

• 대한임상약리학회:학술대회논문집
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• 대한임상약리학회 2007년도 추계학술대회
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• pp.98-98
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• 2007

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• 정신신체의학
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• 제22권2호
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• pp.63-70
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• 2014

기분장애에서 과체중과 비만의 문제가 일반인구보다 더 심각하고, 심혈관 치명률의 증가와 무관하지 않기 때문에 비만에 대한 치료가 필수적이다. 일반적인 상황에서 비만에 대한 치료와 동일하게 생활습관교정과 같은 비약물치료가 선행되어야 한다. 이 같은 시도가 실패하는 경우에는 약물치료가 필요하다. 기분장애의 비만치료로 공식 승인된 약은 없다. 따라서 일반인구의 비만에 승인된 약을 처방하거나 여러 연구를 통해서 효과가 입증된 약을 처방하게 된다. 여러 치료 지침과 연구 등은 orlistat, metformin, topiramate와 bupropion 등이 효과적임을 지지한다.

• Journal of Yeungnam Medical Science
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• 제29권2호
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• pp.77-82
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• 2012

AMP-activated protein kinase (AMPK) is an important cellular fuel sensor. Its activation requires phosphorylation at Thr-172, which resides in the activation loop of the ${\alpha}1$ and ${\alpha}2$ subunits. Several AMPK upstream kinases are capable of phosphorylating AMPK at Thr-172, including LKB1 and CaMKK${\beta}$ ($Ca^{2+}$/calmodulin-dependent protein kinase kinase${\beta}$). AMPK has been implicated in the regulation of physiological signals, such as in the inhibition of cholesterol fatty acid, and protein synthesis, and enhancement of glucose uptake and blood flow. AMPK activation also exhibits several salutary effects on the vascular function and improves vascular abnormalities. AMPK is modulated by numerous hormones and cytokines that regulate the energy balance in the whole body. These hormone and cytokines include leptin, adiponectin, ghrelin, and even thyroid hormones. Moreover, AMPK is activated by several drugs and xenobiotics. Some of these are in being clinically used to treat type 2 diabetes (e.g., metformin and thiazolidinediones), hypertension (e.g., nifedipine and losartan), and impaired blood flow (e.g., aspirin, statins, and cilostazol). I reviewed the precise mechanisms of the AMPK activation pathway and AMPK-modulating drugs.

• 대한의생명과학회지
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• 제25권2호
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• pp.159-169
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• 2019

Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.