Morin exerts cytoprotective effects against oxidative stress in C2C12 myoblasts via the upregulation of Nrf2-dependent HO-1 expression and the activation of the ERK pathway

Lee, Moon Hee,Han, Min Ho,Lee, Dae-Sung,Park, Cheol,Hong, Su-Hyun,Kim, Gi-Young,Hong, Sang Hoon,Song, Kyoung Seob,Choi, Il-Whan,Cha, Hee-Jae,Choi, Yung Hyun UNKNOWN 2017 INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE Vol.39 No.2

<P>In the present study, we investigated the cytoprotective efficacy of morin, a natural flavonoid, against oxidative stress and elucidated the underlying mechanisms in C2C12 myoblasts. Our results indicated that morin treatment prior to hydrogen peroxide (H2O2) exposure significantly increased cell viability and prevented the generation of reactive oxygen species. H2O2-induced comet-like DNA formation and gamma H2AX phosphorylation were also markedly suppressed by morin with a parallel inhibition of apoptosis in C2C12 myoblasts, suggesting that morin prevented H2O2-induced cellular DNA damage. Furthermore, morin markedly enhanced the expression of heme oxygenase-1 (HO-1) associated with the induction and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the inhibition of Kelch-like ECH-associated protein 1 (Keapl) expression. Notably, these events were eliminated by transient transfection with Nrf2-specific small interfering RNA. Additional experiments demonstrated that the activation of the Nrf2/HO-1 pathway by morin was mediated by the extracellular signal-regulated kinase (ERK) signaling cascade. This phenomenon was confirmed with suppressed Nrf2 phosphorylation and consequently diminished HO-1 expression in cells treated with a pharmacological inhibitor of ERK. Collectively, these results demonstrated that morin augments the cellular antioxidant defense capacity through the activation of Nrf2/HO-1 signaling, which involves the activation of the ERK pathway, thereby protecting C2C12 myoblasts from H2O2,-induced oxidative cytotoxicity.</P>

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1

Lee, Yoo-hwan,Kim, Jung-hee,Song, Choon-ho,Jang, Kyung-jeon,kim, Cheol-hong,Kang, Ji-Sook,Choi, Yung-hyun,Yoon, Hyun-Min KOREAN PHARMACOPUNCTURE INSTITUTE 2016 Journal of pharmacopuncture Vol.19 No.1

Objectives: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, $H_2O_2$) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. Methods: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and $H_2O_2$ in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and $H_2O_2$-induced growth inhibition. Results: The results showed that EGL effectively inhibited $H_2O_2$-induced growth and the generation of ROS. EGL markedly suppressed $H_2O_2$-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 ($p-{\gamma}H2AX$), a widely used marker of DNA damage, suggesting that EGL prevented $H_2O_2$-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against $H_2O_2$-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. Conclusion: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from $H_2O_2$-induced oxidative cytotoxicity.

Antioxidant and cytoprotective effects of morin against hydrogen peroxide-induced oxidative stress are associated with the induction of Nrf-2-mediated HO-1 expression in V79-4 Chinese hamster lung fibroblasts

Lee, Moon Hee,Cha, Hee-Jae,Choi, Eun Ok,Han, Min Ho,Kim, Sung Ok,Kim, Gi-Young,Hong, Su Hyun,Park, Cheol,Moon, Sung-Kwon,Jeong, Soon-Jeong,Jeong, Moon-Jin,Kim, Wun-Jae,Choi, Yung Hyun Spandidos Publications 2017 International journal of molecular medicine Vol.39 No.3

<P>Natural phytochemicals of plant origin, including flavonoids, have been found to be potent antioxidants providing beneficial effects against oxidative stress-related diseases. The present study was carried out to investigate the antioxidant properties of morin, a flavonoid originally isolated from the flowering plants of the Moraceae family. Superoxide dismutase (SOD)-like activity and 2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(center dot+)) radical scavenging activity were determined. We also investigated the cytoprotective effects of morin against hydrogen peroxide (H2O2)-induced DNA damage and apoptosis in V79-4 Chinese hamster lung fibroblasts. Our results demonstrated that morin had strong scavenging effects against ABTS' radicals with enhanced SOD activity, which varied in a dose-dependent manner. Morin was found to reduce H2O2-induced intracellular reactive oxygen species generation and nuclear DNA damage, and it recovered cell viability damaged by H2O2 via inhibition of mitochondrial dysfunction-mediated apoptosis. Notably, the treatment of V79-4 cells with morin markedly enhanced the expression of heme oxygenase-1 (HO-1) but not quinone oxidoreductase-1, which was associated with the increased expression and phosphorylation of nuclear factor-erythroid 2-related factor 2 (Nrf2) and the downregulation of Kelch-like ECH-associated protein 1 expression. Based on our findings, we conclude that morin effectively ameliorated oxidative stress-induced DNA damage through intrinsic free radical scavenging activity and activation of the Nrf2/HO-1 pathway.</P>

肺內血管硬化症과 肺胞纖維化를 隨伴한 肺動脈血栓症 : 一例報告 Report of a case

石世一,李寧均,李河,李聖浩,李聖洙,金勇一 醫藥係社 1961 綜合 醫學 Vol.6 No.8

진피 메탄올 추출물의 활성산소종 생성을 통한 인체 백혈병 세포의 apoptosis 유발

김가희(Ga Hee Kim),이문희(Moon Hee Lee),한민호(Min Ho Han),박철(Cheol Park),홍수현(Su Hyun Hong),최영현(Yung Hyun Choi) 한국생명과학회 2013 생명과학회지 Vol.23 No.8

진피(Citri Pericarpium)의 항암작용 기전 해석을 위하여 U937 백혈병 세포의 apoptosis 유발에 미치는 메탄올추출물(EMCP)의 영향을 조사하였으며, apoptosis 조절에 중요한 몇 가지 유전자들의 발현 및 활성 변화, ROS의 생성 변화를 조사하였다. EMCP 처리에 의한 U937 세포의 증식 억제는 apoptosis 유도와 연관성이 있음을 DAPI 염색을 통한 apoptotic body 출현의 증가 및 Flow cytometry 분석에 의한 Sub-G1기 세포 빈도의 증가로 확인하였다. EMCP 처리에 의한 apoptosis 유도에서 Bax 발현 증가, caspases의 활성 및 PARP의 단편화 등이 동반되었으며, ROS 생성의 증가와 연관성이 있었다. 산화적 손상에 대해 세포나 조직을 보호하는 역할을 하는 것으로 알려진 세포 내 항산화 효소인 HO-1의 발현이 EMCP의 처리에 의해 증가되었으나 ROS 생성 억제제인 NAC의 전처리에 의해 감소된 HO-1의 발현은 전사인자인 Nrf2의 핵으로의 이동 억제와 관련되어 있었다. 이상의 결과에서 EMCP 처리에 의한 U937 세포의 apoptosis 유발에는 ROS 생성의 증가와 pNrf2에 의해 조절되는 HO-1의 발현 증가가 중요한 기전으로 작용한다는 것을 알 수 있었다. 이러한 자료는 진피의 항암기전 해석을 이해하는데 중요한 기초자료로서 활용될 수 있을 것으로 생각된다. Citri Pericarpium is one of the most commonly used traditional herbal medicines in Korea, China, and Japan. Its extracts have many properties including the treatment of indigestion and inflammatory respiratory syndromes such as bronchitis and asthma. However, the underlying molecular mechanisms of anti-cancer activity and molecular targets are not fully understood. In this work, we investigated the anti-proliferative activity of Citri Pericapium (EMCP) methanol extract on reactive oxygen species (ROS) production and the association of these effects with apoptotic cell death using U937 human leukemia cells in vitro. EMCP treatment decreased cell proliferation in a dose-dependent manner following an increase of the sub-G1 phase, the down-regulation of Bax proteins, the activation of caspases, the degradation of poly (ADP-ribose) polymerase proteins (PARP), and the induction of ROS generation. However, the quenching of ROS generation by N-acetyl-L-cysteine administration, a scavenger of ROS, reversed the EMCP-induced apoptosis effects. In addition, heme oxygenase-1 expression also recovered by inhibiting the nuclear translocation of phosphorylated NF-E2-related factor 2. Taken together, our data indicate that ROS are involved as key mediators in the early molecular events in the EMCP-induced apoptotic pathway.

심실중격결손증-치험 1예-

조광현,우종수,황윤호,이양행,박철호,김종성,김철호,이경순,조영일,박태인 인제대학교 1985 仁濟醫學 Vol.6 No.4

A successful treatment of infants and children with congenital heart defects depends upon several factors: diagnosis must be accurate, the operative technique, including techniques of perfusion and myocardial preservation, must be suited to the needs of patients and intensive cares, including accurate anesthesia, must be applied through all stages of investigation and treatment, i.e. before, during and after the operation. Recently we performed a open heart surgery successfully for a six-years old girl who had suffered from frequent upper respiratory tract infection and mild to moderate exertional dyspnea with congenital heart defects (ventricular septal defect, Kirklin type II, with patent foramen ovale). The operation and postoperative course were very smooth. And now we report this with review of literatures.

山間村의 所得增大를 위한 適地産業 開發方案

李康寧,高永杜,金正敎,河浩成,姜奉淳,朴道秉,姜淮 慶尙大學校 1978 論文集 Vol.17 No.2

This study attempts to analysis the present situation of farm management and the related industriesin order to present the suitable industries for promoting the farmers' income in mountain area. This study is based on the survey data obtained from 30 sample mountain vellages in 10 Guns located in central, wetern and northen Kyeougnam Province, where lots of mountain vellages are scattered here and there. Major findings obtained from the analysis are summarized as follows: 1) Area of cultivated land in mountian villages was generally smaller than that in plain vellages. BUt major finding of thes tudy indicated that the standard of living in the study area depended upon not only the size of cultivated land but also the skills of management to understand exavtly the regional and togographical situaltion, to utilize the developmental resources effectively, and to diversify income sources. This means that upbringing of competent Saemaul leaders is very important for promoting the income of mountain villages. 2) Various crops were being planted in a samll scale inmountain area. And those crops except rice adn barley were planted for self-sufficiency. Therefore, it is desired to select and cultivate intensively the kinds of crops which are regionally adn topographically suitable for maximizing farm inceomes of subsistant farmers. 3) The survey found out that in mountain area the farming of extensive fruits like chestnuts, persimmons, etc. is more favorable than that of intensive fruits like apples, pears, etc. 4) Because of topographical inappropriateness and lack of fertile cultivates land in mountain area, mowt vegetables, except onions in a few regions, were growing in a small scales for self-sufficiency. And the future of the vegetable cultivationin mountain area is also gloomy. 5) Since various grasses are abundantly growing in the wild in mountain area, the mountain villages are suitable for raising the herbivorous animals. Therefore it is recommeded to encourage raising the herbivorous animals, especially cattle, as one of the major income sources in mountain area. 6) It is true that sericulture has greartly contributed to the economic growth in mountain area with aboundant land suitable for mulberry trees. Recenly sericulture has, however, been shrinking due to the barriers of silk exportation. Without the barriers of silk exportation, sericulture will still play an important role on providing one of the major sources tom mountain villages. 7) The miscellaneous trees in most forest around the mountain villages were growing planlessly. Those parts of the forest are needed to be renewed by planting the useful, endurable, and regionally and topographically suitable kinds of trees.

性惡說에 대한 批判

李英鎬 漢陽大學校 人文科學大學 1987 人文論叢 Vol.14 No.-

Evil is a passive concept that can be evil only by denying good. Evil is not the value, though, which exists by itself in the opposite side of good Evil rather can be in existence with the help of projection and reflexion to good itself of the negative nature or the intrinstic negativity which good has in itself. Therefore, the doctrine of original sin, which says evil is innate in human nature irrespective of good, is not reasonable. Accordingly, this unreasonable theory is consealing the intent of consecreting and beautifying good or the moral law with the theory of innate goodness through deriding good and evil.

Gibberellin의 濃度別 處理가 秋作감자의 塊莖形成에 미치는 影響

李永仁,李喆浩 진주산업대학교 1977 論文集 Vol.15 No.-

GA 處理가 감자의 催芽床 및 圃場에서의 生育 및 收量에 미치는 影響을 調査하기 위하여 1977年 8∼11月까지 晋州農林專門學校에서 實施한 結果를 要約하면 다음과 같다. 1. 催芽床에서는 GA 濃度가 높을수록 徒長하는 傾向이 있었으며 催芽所要日數는 共히 7∼9日만에 完了하였다. 2. 圃場에서 處理區는 無處理區에 比較하여 收量이 많았다. 3. 切片薯 處理區는 CA 濃度가 2ppm 정도에서 全形薯 처리구는 GA 濃度가 높을수록 生育이 좋고 收量이 많아지는 傾向이 있었다. 4. 各 形質別比較에서는 GA 濃度가 높을수록 徙長하며 同時에 收量이 減收하는 傾向이 있었다. This experiment was undertaken to learn the most effective method of GA treatments for the fall crop production of Irish cobbler. In each treatment with sprout inducing bed, about 7-9 days were required to sprout and thin 2-3 sprouts per tuber piece, but the sprouts were slender. When sprouted the tuder pieces were transplanted in field performance trial on the same days, yields were in order of 2ppm GA, 3ppm GA and 5ppm GA treatment for the tuber piece and whole tuber respectively, indicating the correlation between yield and healthiness of sprout status of sdrouted tuber piece. In all the treatments, 2ppm GA treatment of tuber piece were highest yields, 5ppm GA grew more slender.

空思想과 辨證法 : Nagaruzuna의 中觀思想硏究

李英鎬 漢陽大學校 人文科學大學 1994 人文論叢 Vol.24 No.-

Nagaruzuna recognized that in case substances exist at the rear of evanescent objects, there appears something incousistent in movement and the formaton as a result of retribution. He also knew that retribution and movement are possible only in the contradiction of the phenomena which abstrat substances on the basis of self-sameness. His thought was somewhat dialectical, for he saw through the fact that in the changeful objects there still remains the contradiction like existence and nonexistence, sameness and difference, severance and continumance. But Nagaruzuna denied both articles which are struggling and contradictory, there fore as a natural consequence his thought was proved to be anti-dalectical. Dialectics has the positive idea, which means that two contradictary articles move to formation by way of struggle and sublamation. However in Nagaruzuna's thought struggle disappers and only emptiness dominates. Though Nagaruzuna understood the dialectical elements, in other words, the contradiction in objects, he turned his eyesaway from the dialectic thoughts and as a result he returned to anti-dialectics. His anti-dialectical thought was due to the fact that he was a Buddhistic philosopher who strongly stuck to the fundamental tenet containing non-affachment and reconciliation.