• Journal of Ginseng Research
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• 제47권2호
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• pp.311-318
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• 2023

Background: The beneficial effects of compound K (CK) on different chronic diseases have been shown to be at least related to antioxidant action. Nevertheless, since its antioxidant activity in human retinal pigment epithelial (RPE) cells is still unknown, here we investigated whether CK alleviates oxidative stress-stimulated damage in RPE ARPE-19 cells. Methods: The cytoprotective consequence of CK in hydrogen peroxide (H₂O₂)-treated cells was evaluated by cell viability, DNA damage, and apoptosis assays. Fluorescence analysis and immunoblotting were performed to investigate the inhibitory action of CK on reactive oxygen species (ROS) production and mitochondrial dysfunction. Results: H₂O₂-promoted cytotoxicity, oxidative stress, DNA damage, mitochondrial impairment, and apoptosis were significantly attenuated by CK in ARPE-19 cells. Furthermore, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation level and its shuttling to the nucleus were increased, which was correlated with upregulated activation of heme oxygenase-1 (HO-1). However, zinc protoporphyrin, a blocker of HO-1, significantly abrogated the preventive action of CK in H₂O₂-treated ARPE-19 cells. Conclusion: This study indicates that activation of Nrf2/HO-1 signaling by CK plays an important role in rescuing ARPE-19 cells from oxidative cellular damage.

• Parasites, Hosts and Diseases
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• 제51권6호
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• pp.739-742
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• 2013

A 52-year-old woman presented with lower back pain, progressive symmetrical paraparesis with sensory impairment, and sphincter disturbance. Magnetic resonance imaging (MRI) of the whole spine revealed multiple intradural extramedullary serpiginous-mass lesions in the subarachnoid space continuously from the prepontine to the anterior part of the medulla oblongata levels, C7, T2-T8, and T12 vertebral levels distally until the end of the theca sac and filling-in the right S1 neural foramen. Sparganosis was diagnosed by demonstration of the sparganum in histopathological sections of surgically resected tissues and also by the presence of serum IgG antibodies by ELISA. DNA was extracted from unstained tissue sections, and a partial fragment of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene was amplified using a primer set specific for Spirometra spp. cox1. After sequencing of the PCR-amplicon and alignment of the nucleotide sequence data, the causative agent was identified as the larva of Spirometra erinaceieuropaei.

• Toxicological Research
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• 제17권
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• pp.117-125
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• 2001

Envenoming by Russells viper causes a broad spectrum of renal impairment. Renal failure is an important complication in patients bitten by Russells viper. Experimental work in animals and in vitro has elucidated pathophysiological mechanisms that contribute to life threatening complications and have suggested possibilities for therapeutic intervention. The evidence in experimental animals regarding mechanisms of venom action in relation to changes in either extrarenal or intrarenal factors is presented. The cardiovascular system and renal hemodynamics are affected by venom. Reductions of renal function including renal hemodynamics are associated directly with changes in general circulation during envenomation. Possible endogenous mechanisms for releasing the hormone inducing renal vasoconstriction after envenomation are evident. Hormonal factor such as the catecholamine, prostaglandin and renin angiotensin systems induce these changes. Direct nephrotoxicity of venom action is studied in the isolated per-fused kidney. Characteristic polarization of the cell membrane, changes of mitochondrial activity and Na-K ATPase in renal tubular cells are observed. Changes in renal function and the cardiovascular system are observed of ter envenomation and are reversed by the administration of Russells viper antivenom (purified equine immunoglobulin, $Fab_2$ fragment). The neutralizing effects are more efficient when the intravenous injection of antivenom is given within 30 min after the envenomation.

• 대한본초학회지
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• 제30권1호
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• pp.67-75
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• 2015

Objectives : The aim of this study is to examine the neuroprotective effect of wheat bran extract (WBE) against ${\beta}$-amyloid ($A{\beta}$)-induced apoptotic cell death in SH-SY5Y human neuroblastoma cells and memory impairment in triple transgenic animal model's of Alzheimer's disease (3xTg AD mice). Methods : In SH-SY5Y cells, MTT assay and TUNEL staining were conducted to evaluate the protective effect of WBE against $A{\beta}_{25-35}$-induced neurotoxicity and apoptosis. Alterations in mitochondrial transmembrane potential (MMP), expression of proapoptotic Bax and antiapoptotic Bcl-2 proteins, cleavage of PARP, and brain-derived neurotrophic factor (BDNF) levels were analyzed to elucidate the neuroprotective mechanism of WBE. To further investigate the memory enhancing effect of WBE, Morris water maze test was performed in 3xTg AD mice. Results : In SH-SY5Y cells, WBE protected against $A{\beta}_{25-35}$-caused cytotoxicity and apoptosis as shown by the restoration of cell viability in MTT assay and inhibition of DNA fragmentation in TUNEL staining. $A{\beta}_{25-35}$-induced apoptotic signals such as dissipation of MMP, decreased Bcl-2/Bax ratio, and cleavage of PARP were suppressed by WBE. Moreover, WBE up-regulated the protein levels of BDNF, which seemed to be mediated by activation of cAMP response element-binding protein (CREB). In 3xTg AD mice, oral administration of WBE attenuated learning and memory deficit as verified by reduced mean escape latency in water maze test. Conclusions : WBE protects neuronal cells from $A{\beta}_{25-35}$-induced apoptotic cell death and restores learning and memory impairments in 3xTg AD mice. These findings suggest that WBE exhibit neuroprotective potential for the management of AD.

• 대한본초학회지
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• 제30권4호
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• pp.57-64
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• 2015

Objectives : Oxidative stress is one of the most causes of hepatocyte injury. Gleditsia spina, the thorns ofGleditsia sinensisLam., has been known for its anti-cancer and anti-inflammatory effects in Korean medicine. The present study investigated hepatoprotective effect of Gleditsia spina water extract (GSE) against oxidative stress induced by arachidonic acid (AA) + iron in HepG2 cells.Methods : To investigate cytoprotective effect of GSE, cells were pretreated with GSE and then subsequently exposed to 10 μM AA for 12 h, followed by 5 μM iron. Cell viability was monitored by MTT assay, and expression of apoptosis-related proteins was examined by immunoblot analysis. To identify responsible molecular mechanisms, reactive oxygen species (ROS) production, GSH contents, and mitochondrial membrane potential were measured. In addition, effect of GSE on nuclear factor erythroid 2-related factor 2 (Nrf2) activation was determined by immunoblot and antioxidant response element (ARE)-driven reporter gene assays.Results : GSE pretreatment prevented AA + iron-mediated cytotoxicity in concentration dependent manner. In addition, ROS production, glutathione depletion, and mitochondrial impairment by AA + iron were significantly inhibited by GSE. Furthermore, GSE promoted translocation of Nrf2 to nucleus, which acts as essential transcription factor for induction of antioxidant genes. Increased nuclear Nrf2 that caused by GSE treatment promoted transcriptional activity of ARE. Finally, GSE up-regulated sestrin-2 which was widely recognized as target gene of Nrf2.Conclusions : This study demonstrates that GSE protects hepatocytes from oxidative stress via activation of Nrf2 signaling pathway.

• 한국동물학회지
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• 제21권3호
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• pp.87-102
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• 1978

수은이 붕어(Carassius carassius L.)의 간, 신장 아가미에 미치는 영향을 규명하기 위하여 붕어를 1 ppm, 2.5 ppm 농도의 $HgCl_2$에 노출시킨 후 전자현미경을 사용하여 그들의 미세구조 변화에 대한 연구를 수행한 바 다음과 같은 결과를 얻었다. 1. 수은에 처리된 간세포에서는 lysosome이 증가하였으며 결정상의 구조물들을 포함한 원형의 lysosome과 히ㅛ\ulcorner두과립이나 mitochondria를 탐식한 lysosome의 2가지 형태가 관찰되었고 mitochondria는 팽대되어 내부 기질의 전자밀도가 감소되었으며 핵에서는 인의 분리현상이 관찰되었다. 2. 신장의 변화로서는 신사구체 기저막의 비후와 기부선회소관에서는 공포들의 증가와 cytoplasmic body들이 출현하였으며 공포형성은 mitochondria와 연관되어 일어났다. 또한 2.5 ppm에서는 핵의 위축이 관찰되었다. 3. Gill lamella의 상피세포에서는 대, 소형의 lysosome이 증가했으며 lamella의 막에 fuzzy한 구조가 관찰되었다. 4. 본 실험에서 관찰된 결과로써 수은에 의해 초래된 세포의 미세구조의 변화는 세포의 해독과정을 활성화시키며 energy대사과정을 손상시키는 것으로 생각된다.

• Fisheries and Aquatic Sciences
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• 제26권1호
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• pp.35-47
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• 2023

Myelophycus caespitosus, a brown alga belonging to genus Myelophycus, has been traditionally used as a food and medicinal resource in Northeastern Asia. However, few studies have been conducted on its pharmacological activity. In this study, we evaluated whether methanol extract of M. caespitosus (MEMC) could protect against oxidative damage caused by hydrogen peroxide (H₂O₂) in C2C12 murine myoblasts. Our results revealed that MEMC could suppress H₂O₂-induced growth inhibition and DNA damage while blocking the production of reactive oxygen species. In H₂O₂-treated cells, cell cycle progression was halted at the G2/M phase, accompanied by changes in expression of key cell cycle regulators. However, these effects were attenuated by MEMC. In addition, we found that MEMC protected cells from induction of apoptosis associated with mitochondrial impairment caused by H₂O₂ treatment. Furthermore, MEMC enhanced the phosphorylation of nuclear factor-erythroid-2 related factor 2 (Nrf2) and expression and activity of heme oxygenase-1 (HO-1) in H₂O₂-treaetd C2C12 myoblasts. However, such anti-apoptotic and cytoprotective effects of MEMC were greatly abolished by HO-1 inhibitor, suggesting that MEMC could increase Nrf2-mediated activity of HO-1 to protect C2C12 myoblasts from oxidative stress.

• 한국식품과학회지
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• 제51권4호
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• pp.379-392
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• 2019

본 연구에서는 갑주백목 에탄올 추출물(ethanolic extraction from Diospyros kaki (Gabjubaekmok))을 이용하여 in vitro 항산화 활성과 더불어 $A{\beta}$로 유도된 인지기능 저하를 갖는 마우스 모델에서 인지기능 및 뇌 신경세포 보호 효과를 검증하였다. 갑주백목 추출물은 양성대조군과 비교하여 우수한 ABTS 및 DPPH 라디칼 소거활성($IC_{50}=83.30$, $403.88{\mu}g/mL$) 및 MDA 생성 억제 활성($IC_{50}=62.10{\mu}g/mL$)을 보여주었고, in vitro 아세틸콜린 분해효소 억제 활성은 $312.82{\mu}g/mL$의 $IC_{50}$ 값을 나타내었다. 또한, MC-IXC 뇌 신경세포에 과산화수소를 처리하여 산화적 스트레스를 유발시킨 뇌 신경세포 사멸에 대해 보호 효과를 나타냈다. 갑주 백목 추출물의 인지기능 개선 효과를 확인하기 위하여 $A{\beta}$를 사용하여 인지기능 장애 마우스 모델을 수립하였으며, Y-미로, 수동 회피 및 Morris 수중 미로 실험과 같은 행동실험을 통해 인지 및 기억능력에 대한 개선 효과를 나타냈다. 이후 마우스 뇌조직에서의 아세틸콜린 함량의 증가 및 아세틸콜린 분해효소의 활성을 억제함으로써 cholinergic 시스템을 보호하였고, SOD, 환원형 GSH 및 MDA 함량 측정을 통해 항산화 시스템을 개선시켜줌을 확인하였다. 더불어 뇌 조직의 미토콘드리아에서 ROS의 생성 억제, MMP 보호 및 ATP 함량을 회복시켜주었으며, western blot 분석을 통해 $TNF-{\alpha}$와 같은 염증성 사이토카인을 억제시켜 줌으로써 면역반응에 관여하는 JNK의 인산화를 감소시키고 Akt 신호전달을 활성화시켜 세포자동 사멸화를 억제시키는 것으로 확인되었다. 마지막으로 HPLC 분석을 통해서 갑주백목의 주요 생리활성물질이 갈산으로 확인되었다. 이러한 결과를 종합하였을 때, 갑주백목 에탄올 추출물은 뇌 조직에서의 cholinergic 및 항산화 시스템 보호효과를 통해 $A{\beta}$ 처리에 대하여 학습 및 기억 능력을 개선 시킬 수 있는 천연 소재로서의 가능성뿐만 아니라 $A{\beta}$ 및 과산화수소로부터 유발된 산화적 스트레스의 환경에서 뇌신경세포를 보호함으로써 알츠하이머성 질환과 같은 퇴행성 뇌신경질환을 예방할 수 있는 고부가가치 건강기능식품 소재로서의 활용 가능성을 확인하였다.

• Journal of Genetic Medicine
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• 제16권2호
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• pp.85-89
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• 2019

Hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome is a rare autosomal recessive urea cycle disorder. HHH is caused by a deficiency of the mitochondrial ornithine transporter protein, which is encoded by the solute carrier family 25, member 15 (SLC25A15) gene. Recently, government supported Korean newborn screening has been expanded to include a tandem mass spectrometry (MS/MS) measurement of ornithine level. We report a case of a neonate with HHH syndrome showing a normal MS/MS measurement of ornithine level. A female newborn was admitted to neonatal intensive unit due to familial history of HHH syndrome. Her parents were consanguineous Parkistani couple. The subject's older sister was diagnosed with HHH syndrome at age of 30 months based on altered mental status and liver dysfunction. Even though the subject displayed normal ammonia and ornithine levels based on MS/MS analysis, a molecular test confirmed the diagnosis of HHH syndrome. At 1 month of age, amino acid analysis of blood and urine showed high levels of ornithine and homocitrulline. After 11 months of follow up, she showed normal growth and development, whereas affected sister showed progressive cognitive impairment despite no further hyperammonemia after protein restriction and standard therapy. Our report is in agreement with a previous Canadian study, which showed that neonatal samples from HHH syndrome patients demonstrate normal ornithine levels despite having known mutations. Considering the delayed rise of ornithine in affected patients, genetic testing, and repetitive metabolic testing is needed to prevent patient loss in high risk patients.

• 생명과학회지
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• 제30권5호
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• pp.460-467
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• 2020

간암은 전 세계적으로 가장 높게 진단되는 암 중 하나이며, 방사선 및 화학 요법이 일반적으로 사용되는 치료법이지만 다양한 부작용은 치료 효과를 크게 제한한다. 따라서 전통 의학에서 사용되어 온 처방법은 이를 극복할 수 있는 대안이 될 수 있다. 본 연구에서는 동의보감에 기술되어 있는 3가지 한약 처방전(비기환, 대칠기탕 및 목향빈랑환)을 선택하여 인체 간암세포에 대한 항암 효과를 평가하였다. 간암세포에서 3가지 처방전의 에탄올 추출물의 세포 독성을 조사하기 위한 MTT 분석 결과, 비기환 추출물은 대칠기탕 및 목향빈랑환에 비하여 세포 생존력을 현저하게 억제하였다. 그리고, flow cytometry 분석의 결과에서 3가지 처방전 추출물에 의한 간암세포의 증식 억제가 apoptosis 및 autophagy 유도와 관련이 있었다. 특히, 비기환 추출물은 미토콘드리아의 기능을 크게 손상시켰으며 다른 두 처방전과 비교하여 mitophagy 유발 가능성을 보여주었다. 아울러 비기환 추출물은 LC3의 발현을 현저하게 증가시켰으며, 이는 Bcl-2의 발현 감소를 동반하는 반면, Bax의 발현에 영향을 미치지 않았다. PINK1의 발현 또한 비기환 추출물이 처리된 세포에서 매우 증가하였다. 나아가, autophagy 억제제는 3가지 처방전 추출물 처리에 의한 세포 생존율 감소와 apoptosis 유도를 억제하였으며, 이러한 결과는 이들 처방전 추출물 처리에 의한 autophagy가 apoptosis 개시에 관여하고 있음을 보여주는 것이다. 결론적으로, 본 연구 결과는 비기환 추출물이 3가지 처방전 중에서 가장 높은 항암 활성을 보였으며, 비기환 추출물은 autophagy 유도제로서 간암세포의 증식을 억제함을 의미한다.