• 생명과학회지
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• 제31권9호
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• pp.796-805
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• 2021

간 소포체(ER) 스트레스는 비알콜성지방간과 인슐린 저항성의 발달에 기여하고, unfolded protein response(UPR)의 구성요소는 지질 대사를 조절한다. 최근 연구에 따르면 ER 스트레스와 비정상적인 세포 지질 대사 사이의 연관성이 보고되었으며, 이 과정에서 지질 대사의 중심 조절자인 sterol regulatory element binding proteins(SREBPs)의 관련성이 확인되었다. 그러나 ER 스트레스 동안 지질 대사를 조절하는 SREBP의 정확한 역할과 비알콜성지방간에 대한 기여는 아직 밝혀지지 않았다. 본 연구에서 SREBP-1c 결핍은 UPR, 염증 및 지방산 산화 조절을 통해 ER 스트레스에 의해 유도된 비알콜성지방간으로부터 생쥐를 보호한다는 것을 보여준다. SREBP-1c는 inositol requiring kinase 1α (IRE1α) 발현을 직접적으로 조절하고 ER 스트레스에 의해 유도된 tumor necrosis factor-α의 활성화를 매개하여 peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α)의 감소와 그에 따른 지방산 산화의 장애를 유발한다. 그러나, SREBP-1c의 유전적 결핍은 이러한 현상을 보호하여 간 염증과 지방 축적을 완화시킨다. SREBP-1c 결핍이 ER 스트레스에 의해 유도된 염증 신호를 방지하는 메커니즘은 아직 밝혀지지 않았지만, SREBP-1c가 결핍된 Kupffer 세포에서 IRE1α 신호의 변화가 염증 신호에 관여할 수 있을 것으로 생각된다. 본 연구결과는 SREBP-1c가 ER 스트레스에 의해 유도된 비알콜성지방간에서 UPR 및 염증의 조절에 중요한 역할을 함을 시사한다.

• 생명과학회지
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• 제29권4호
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• pp.470-477
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• 2019

흰목이 버섯(Tremella fuciformis Berk)은 고혈압, 당뇨병, 비만, 폐질환, 미용에 효과가 있으며, 고대 중국에서는 불로장생약이라고 알려져 있다. 본 연구에서는 생물전환공정을 통해 발효된 흰목이 버섯 추출물의 항비만 및 당뇨병 효과를 조사하였다. 우리는 비만 유도 시킨 C57BL / 6N 마우스에 High Fats Diet (HFD), 5% non-fermented Tremella fuciformis (TF), 2.5% fermented Tremilla fuciformis (FTF), 5% FTF를 8주간 투여하였다. 경구당 부하검사는 7주간 식이섭취 후 실시하였으며, 8주간 식이섭취 후 섭취량, 식이섭취효율, 체중, 간, 부고환 지방량 및 혈청 인슐린 수치 및 HOMA-IR을 분석하였다. 또한, 혈청 총콜레스테롤 함량 및 중성지방 함량을 분석하였다. FTF (실험)군과 TF (실험)군 및 HFD (실험)군과 비교한 결과 5% FTF (실험)군이 체중, 조직 중량, 중성지방 함량 및 HOMA-IR을 감소시키는 것을 확인하였다. 이 결과를 통해 발효 흰목이 버섯은 항비만 효과를 확인하였다. 마지막으로, 본 연구는 발효 흰목이 버섯을 이용한 비만 치료의 기초자료로 사용하고자 한다.

• 생명과학회지
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• 제29권9호
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• pp.964-971
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• 2019

간의 지질 축적과 인슐린 저항성은 비알콜성 지방간 환자에게서 증가한다. Piperine은 후추(Piper nigrum)와 필발(인도산 후추, P. longum)의 주요 성분으로 항암, 항비만, 항 당뇨병, 항염증 및 항산화 등의 생리활성이 보고되었다. 그러나 piperine의 인간 간세포 HepG2 세포에서 지질 축적과 인슐린 저항성의 억제제로서의 연구는 보고된 바가 없다. 본 연구의 목적은 지질 축적 및 인슐린 저항성에 대한 piperine의 효과를 palmitate처리된 HepG2 세포에서 잠재적인 분자 기전을 밝히는 것이다. 그 결과 piperine처리군은 지질 함량을 감소시켰고, 지방 형성 표적 유전자인 SREBP-1c와 FAS의 발현을 억제함으로써 palmitate처리된 세포내 지질 축적을 감소시켰다. 게다가 piperine처리군은 지방산 산화에 관련된 CPT-1과 인산화된 ACC 및 인산화된 IRS-1 (Tyr632)와 Akt의 레벨을 증가시켰다. 또한, piperine처리군은 인산화된 IRS-1 (Ser307)의 레벨을 감소시켰다. 결론적으로 palmitate처리된 HepG2 세포에서 piperine은 SREBP-1와 FAS발현의 감소 및 CPT-1과 ACC 인산화의 증가 및 인산화된 IRS-1(Try632)와 Akt 신호전달 경로를 조절함으로써 지질 축적 및 인슐린 저항성을 개선함을 확인하였다. 따라서 piperine의 지질 축적 및 인슐린 저항성을 예방하는 약물로써 가능성이 제시되었다.

• Journal of Nutrition and Health
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• 제52권1호
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• pp.17-25
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• 2019

본 연구에서는 댕댕이나무 열매 추출물이 3T3-L1과 마우스 지방유래줄기세포의 지방 분화유도 및 지방생성에 미치는 영향을 살펴보았다. 3T3-L1에 댕댕이나무 열매 추출물을 처리하였을 때, 농도의존적으로 지방구의 생성을 줄였고 지방세포 분화에 있어서 중요한 전사인자인 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 발현을 억제시켜 지방 합성이 감소됨을 확인하였다. 또한, 마우스 지방에서 분리한 줄기세포의 지방 분화과정에서도 댕댕이나무 열매 추출물이 $PPAR{\gamma}$, $C/EBP{\alpha}$, SREBP1의 단백질 발현을 감소시켜 지방 축적을 농도 의존적으로 억제하였다. 이상의 결과로 댕댕이나무 열매 추출물은 세포독성이 없는 농도에서 지방 세포의 분화를 억제 하는 것으로 확인되어 항비만 기능성 소재로서의 활용 가능성이 있을 것으로 사료된다.

• 대한본초학회지
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• 제36권5호
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• pp.81-91
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• 2021

Objectives : Osteoporosis is a systemic skeletal disease that decreases bone density and increases the risk of fractures. Bisphosphonates and SERMs are mainly used to treat osteoporosis, but, long-term use increases the risk of side effects such as jaw bone necrosis and breast cancer. Therefore, it is necessary to develop a therapeutic agent for a natural product with few side effects. Water extract of Lonicerae Japonicae Flos (wLF) was mainly found to have anti-cancer and anti-inflammatory effects. However, the effect of wLF on osteoporosis has not been elucidated. Therefore, this experiment investigated the effect of wLF on osteoclasts, osteoblasts and osteoporosis models. Methods : In order to study the effect of wLF on osteoporosis, the OVX-induced rat model was used for in vivo study. After 8 weeks, we measured body weight, uterine weight, liver weight, femur weight, bone density, trabecular area and tibia ash weight. To determine the effect of wLF on osteoclast differentiation, we measured the number of TRAP-positive cells and TRAP activity. To examine the effect of wLF on the expression of osteoblast-related genes, we measured the mRNA expression of alkaline phosphatase (ALP, Alpl) and osteocalcin (OCN, Bglap2). Results : In vivo experiment, wLF inhibited the reduction of femur weight, trabecular area, bone density and tibia ash weight. In vitro experiment, wLF had no significant effect on osteoclast differentiation. However, wLF increased the mRNA expression of Alpl and Bglap2 in MC3T3-E1 cell. Conclusions : This result suggested that wLF may be used for the treatment and prevention of postmenopausal osteoporosis.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• 제24권2호
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• pp.173-186
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• 2021

Purpose: Biliary atresia (BA) is a disease that manifests as jaundice after birth and leads to progressive destruction of the ductal system in the liver. The aim of this study was to investigate histopathological changes and immunohistochemically examine the expression of glial cell line-derived neurotrophic factor (GDNF), synaptophysin, and S-100 protein in the gallbladder of BA patients. Methods: The study included a BA group of 29 patients and a control group of 41 children with cholecystectomy. Gallbladder tissue removed during surgery was obtained and examined immunohistochemically and histopathologically. Tissue samples of both groups were immunohistochemically assessed in terms of GDNF, S-100 protein, and synaptophysin expression. Expression was classified as present or absent. Inflammatory activity assessment with hematoxylin and eosin staining and fibrosis assessment with Masson's trichrome staining were performed for tissue sample sections of both groups. Results: Ganglion cells were not present in gallbladder tissue samples of the BA group. Immunohistochemically, GDNF, synaptophysin, and S-100 expression was not detected in the BA group. Histopathological examination revealed more frequent fibrosis and slightly higher inflammatory activity in the BA than in the control group. Conclusion: We speculate that GDNF expression will no longer continue in this region, when the damage caused by inflammation of the extrahepatic bile ducts reaches a critical threshold. The study's findings may represent a missing link in the chain of events forming the etiology of BA and may be helpful in its diagnosis.

• Journal of Korean Neurosurgical Society
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• 제64권4호
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• pp.562-574
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• 2021

Objective : This study is to evaluate the efficacy and safety of demineralized bone matrix (DBM) gel versus DBM gel with recombinant human bone morphogenetic protein-2 (rhBMP-2) used in transforaminal lumbar interbody fusion (TLIF). Methods : This study was designed as a prospective, multi-center, double-blind method, randomized study. All randomized subjects underwent TLIF with DBM gel with rhBMP-2 group (40 patients) as an experimental group or DBM gel group (36 patients) as a control group. Post-operative observations were performed at 12, 24, and 48 weeks. The spinal fusion rate on computed tomography scans and X-rays films, Visual analog scale pain scores, Oswestry disability index and SF-36 quality of life (QOL) scores were used for the efficacy evaluation. The incidence rate of adverse device effects (ADEs) and serious adverse device effects (SADEs) were used for safety evaluation. Results : The spinal fusion rate at 12 weeks for the DBM gel with rhBMP-2 group was higher with 73.68% compared to 58.82% for the DBM gel group. The 24 and 48 weeks were 72.22% and 82.86% for the DBM gel with rhBMP-2 group and 78.79% and 78.13%, respectively, for the DBM gel group. However, there were no significant differences between two groups in the spinal fusion rate at 12, 24, and 48 weeks post-treatment (p=0.1817, p=0.5272, p=0.6247). There was no significant difference between the two groups in the incidence rate of ADEs (p=0.3836). For ADEs in the experimental group, 'Pyrexia' (5.00%) was the most common ADE, followed by 'Hypesthesia', 'Paresthesia', 'Transient peripheral paralysis', 'Spondylitis' and 'Insomnia' (2.50%, respectively). ADEs reported in control group included 'Pyrexia', 'Chest discomfort', 'Pain', 'Osteoarthritis', 'Nephropathy toxic', 'Neurogenic bladder', 'Liver function analyses' and 'Urticaria' (2.86%, respectively). There was no significant difference between the two groups in the incidence rate of SADEs (p=0.6594). For SADE in the experimental group, ''Pyrexia' and 'Spondylitis' were 2.50%. SADE reported in the control group included 'Chest discomfort', 'Osteoarthritis' and 'Neurogenic bladder'. All SADEs described above were resolved after medical treatment. Conclusion : This study demonstrated that the spinal fusion rates of DBM gel group and DBM gel with rhBMP-2 group were not significantly different. But, this study provides knowledge regarding the earlier postoperative effect of rhBMP-2 containing DBM gel and also supports the idea that the longer term follow-up results are essential to confirm the safety and effectiveness.

• 한국미생물·생명공학회지
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• 제50권1호
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• pp.135-146
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• 2022

비만은 지질대사 불균형으로 인한 이상지질혈증과 밀접한 관련이 있으며, 장내 미생물의 군집 및 기능의 변화를 유도하여 장내 미생물 불균형을 초래할 수 있다. 본 연구에서는 민들레 김치에서 분리한 김치 유래 유산균 W. confuse WIKIM51의 항비만 효능을 in vitro와 in vivo에서 평가하였다. 먼저, WIKIM51은 지방세포 분화를 유도한 3T3-L1 세포에서 지방대사 관련 유전자의 발현 조절을 통해 지방구 생성을 억제하였다. 후천적 비만 동물 모델을 이용한 in vivo 실험에서 10주간 W. confusa WIKIM51의 경구 투여는 고지방식이에 의해 유도된 체중 증가를 현저히 감소시켰다. 특히, 부고환 주위 지방량, 조직학적 분석을 통한 지방구의 크기 및 혈중 지표인 TG, TC, adiponectin, 그리고 leptin의 수준이 HFD군에 비해 W. confusa WIKIM51 섭취군에서 유의적으로 개선되었다. 또한 W. confusa WIKIM51 섭취군은 Ppar𝛾, C/EBP𝛼, Srebp-1c, Fas와 같은 지방 생성 및 지방산 합성 관련 유전자의 발현을 억제하였고, 반면 에너지 소비 관련 유전자 Ppar𝛼와 Cpt1의 발현은 증가시켰다. 더 나아가, W. confusa WIKIM51은 고지방식이로 인해 유도된 Firmicutes/Bacteroidetes 비율을 정상식이군의 수준으로 감소시켜 장내미생물의 불균형을 개선시켰다. 이러한 결과들을 종합해 볼 때, W. confusa WIKIM51의 섭취는 고지방식이로 인한 지방 축적을 억제하여 효과적으로 비만을 개선할 수 있으며, 이는 항비만 기능성 소재 및 식품 개발로의 활용이 가능함을 제시한다.

• 대한본초학회지
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• 제33권2호
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• pp.53-58
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• 2018

Objectives : Plantaginis asiaticae Folium (PA) has been widely used in Korean medicine for treatment of liver disease, stomach troubles and inflammation. We investigated the effect of PA on lipid accumulation in 3T3-L1 according to extraction conditions. Methods : The MTT assay was employed to evaluate the cytotoxicity of PA extracted by different solvents (water, 50% ethanol, and 95% ethanol) on 3T3-L1 preadipocytes. Oil red O staining was used to identify intracellular lipid accumulation in 3T3-L1. 3T3-L1 adipocytes were treated with PA at concentration ranging in 0.1, 0.2 and $0.4mg/m{\ell}$. PA was extracted by different extraction conditions such as extraction solvents, extraction time, and extraction temperature. In addition, UPLC analysis was used for determination of candidates of active ingredients in PA. Results : 3T3-L1 preadipocytes were treated with PA extracted by different solvents (water, 50% ethanol, and 95% ethanol) and there was no cytotoxicity. Oil red O staining was employed to identify the effect of PA on lipid accumulation in 3T3-L1. In the present study, PA water extraction at $70^{\circ}C$ for 6 hours decreased greatly in lipid accumulation. The range of concentrations was 0.1, 0.2 and $0.4mg/m{\ell}$. Concentration at $0.2mg/m{\ell}$ was the most effective one among them. Candidates of active ingredients in PA were shown plantamajoside and acteoside through UPLC. Conclusions : These results suggest that the effect of PA water extraction at $70^{\circ}C$ on lipid accumulation in 3T3-L1 is superior to other extraction conditions. We suppose that plantamajoside and acteoside may be candidates of active ingredients in PA.

• Biomolecules & Therapeutics
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• 제31권1호
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.