Mirodenafil ameliorates skin fibrosis in bleomycin-induced mouse model of systemic sclerosis

노종성,정호임,이범구,송병욱,한승진,손동현,이승근 한국통합생물학회 2021 Animal cells and systems Vol.25 No.6

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis of the skin and internal organs. Despite the recent advances in the pathogenesis and treatment of SSc, effective therapies for fibrosis caused by SSc have not yet been established. In this study, we investigated the potential role of mirodenafil, a potent phosphodiesterase 5 (PDE5) inhibitor, in the treatment of fibrosis in SSc. We used a bleomycin (BLM)-induced SSc mouse model to mimic the typical features of fibrosis in human SSc and examined the dermal thickness to assess the degree of skin fibrosis after staining with hematoxylin and eosin or Masson’s trichrome stains. The effect of mirodenafil on the expression of profibrotic genes was also analyzed by treating fibroblasts with transforming growth factor (TGF)-β and mirodenafil. We showed that mirodenafil ameliorated dermal fibrosis and downregulated the protein levels of fibrosis markers including COL1A1 and α- SMA in the BLM-induced SSc mouse model. Further, using mouse embryonic fibroblasts and human lung fibroblasts, we demonstrated that the expression of collagen and profibrotic genes was reduced by treatment with mirodenafil. Finally, we showed that mirodenafil inhibited TGF-β- induced phosphorylation of Smad2/3 in fibroblasts, which suggested that this drug may ameliorate fibrosis by suppressing the TGF-β/Smad signaling pathway. Our findings suggest that mirodenafil possesses a therapeutic potential for treating fibrosis in SSc.

전신경화증의 한약치료에 대한 국내외 연구 동향

노종성,김상찬,변성희,윤미정,신순식,손동현 대한한의학방제학회 2020 大韓韓醫學方劑學會誌 Vol.28 No.4

Objectives : Systemic sclerosis(SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs and vasculopathy. The purpose of this study was to investigate the trend in the research on SSc using herbal medicine. Methods : We searched for papers which had both systemic sclerosis and herbal medicine from Pubmed, KCI and NDSL. After searching papers, we classified according to the study design and analyzed selected studies. Results : 18 studies were searched. The types and numbers of study were as follows: 11 were in vitro or in vivo studies using herbal medicine or active components, and 7 were clinical research including case reports. 1. Herbal medicines include the therapeutic effects of “tonifying qi(補氣)” or “active blood(活血)” improved systemic sclerosis in vivo and in vitro studies. 2. Active components isolated from Herbal Medicine such as Astragalus membranaceus(黃芪), Zhizi(梔子), Salvia miltiorrhiza(丹蔘) have anti-fibrotic effects. 3. Clinical trials showed that herbal medicine can improve the symptom of systemic sclerosis including skin fibrosis, Raynaud’s phenomenon, pain and gastric dysmotility. Conclusions : This study showed that herbal medicine can be effective for treating SSc. However, further studies are needed to develop novel medicine for SSc.

『東醫寶鑑』의 熟地黃 제조방법

노종성,윤미정,신순식,Roh, Jong Seong,Yoon, Michung,Shin, Soon Shik 대한한의학방제학회 2016 大韓韓醫學方劑學會誌 Vol.24 No.1

Objectives Rehmanniae Radix Preparata was prepared in the traditional Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine(Donguibogam)』 with a view to measuring the contents of 5-Hydroxymethyl-2-furaldehyde(5-HMF) at individual stages of steaming and sundrying and identifying new chemical components.Methods Based on the traditional Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine』, Rehmanniae Radix Preparata steamed and sundried once through nine times was prepared. Thereafter, 5-HMF contents were analyzed and new chemical components were identified in the Rehmanniae Radix Preparata using Waters HPLC e2695, 2640 detectors, a Waters Acquity UPLC system, and a Micromass Q-TOF Premier mass spectrometer.Results The Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine』 is a unique preparation method in Republic of Korea different from that in China. In the first stage of the method, fresh Rehmanniae Radix Crudus was divided into high quality, medium quality, and low quality ones named Rehmanniae Radix Crudus (Caelum)(天黃), Rehmanniae Radix Crudus (Homo)(人黃), and Rehmanniae Radix Crudus (Terra)(地黃) respectively to use Rehmanniae Radix Crudus (Caelum) and Rehmanniae Radix Crudus (Homo) for preparation of juice while using Rehmanniae Radix Crudus (Terra) to make Rehmanniae Radix Preparata. In the second stage, Rehmanniae Radix Crudus (Caelum) and Rehmanniae Radix Crudus (Terra) were made into juice and Rehmanniae Radix Crudus (Terra) was soaked in the juice. In the third stage, among auxiliary materials, rice wine named Purum Vinum Oryzae(淸酒) brewed from sticky rice was sprinkled on Rehmanniae Radix Crudus (Terra) to the extent that Rehmanniae Radix Crudus (Terra) became wet. In the fourth stage, Rehmanniae Radix Preparata steamed in earthenware steamer was dried under natural sunlight. The contents of 5-HMF in Rehmanniae Radix Preparata steamed and sundried once through nine times were shown to be below 0.1% in all cases. Pomolic acid was identified as a new chemical component.Conclusions In conclusion, the Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine』 is thought to be a unique preparation method in South Korea in which Rehmanniae Radix Preparata is completed through the first stage in which fresh Rehmanniae Radix Crudus collected from fields is divided into high, medium, and low quality ones and fresh Rehmanniae Radix Crudus juice is made, the second stage in which the high quality fresh Rehmanniae Radix Crudus is soaked in the fresh Rehmanniae Radix Crudus juice, the third stage in which the fresh Rehmanniae Radix Crudus is steamed, and the fourth stage in which the steamed Rehmanniae Radix Crudus is dried.

『東醫寶鑑』의 熟地黃 제조방법

노종성,윤미정,신순식 대한한의학방제학회 2016 大韓韓醫學方劑學會誌 Vol.24 No.1

Objectives : Rehmanniae Radix Preparata was prepared in the traditional Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine(Donguibogam)』 with a view to measuring the contents of 5-Hydroxymethyl-2-furaldehyde(5-HMF) at individual stages of steaming and sundrying and identifying new chemical components. Methods : Based on the traditional Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine』, Rehmanniae Radix Preparata steamed and sundried once through nine times was prepared. Thereafter, 5-HMF contents were analyzed and new chemical components were identified in the Rehmanniae Radix Preparata using Waters HPLC e2695, 2640 detectors, a Waters Acquity UPLC system, and a Micromass Q-TOF Premier mass spectrometer. Results : The Rehmanniae Radix Preparata preparation method set forth in the『Treasured Mirror of Eastern Medicine』 is a unique preparation method in Republic of Korea different from that in China. In the first stage of the method, fresh Rehmanniae Radix Crudus was divided into high quality, medium quality, and low quality ones named Rehmanniae Radix Crudus (Caelum)(天黃), Rehmanniae Radix Crudus (Homo)(人黃), and Rehmanniae Radix Crudus (Terra)(地黃) respectively to use Rehmanniae Radix Crudus (Caelum) and Rehmanniae Radix Crudus (Homo) for preparation of juice while using Rehmanniae Radix Crudus (Terra) to make Rehmanniae Radix Preparata. In the second stage, Rehmanniae Radix Crudus (Caelum) and Rehmanniae Radix Crudus (Terra) were made into juice and Rehmanniae Radix Crudus (Terra) was soaked in the juice. In the third stage, among auxiliary materials, rice wine named Purum Vinum Oryzae(淸酒) brewed from sticky rice was sprinkled on Rehmanniae Radix Crudus (Terra) to the extent that Rehmanniae Radix Crudus (Terra) became wet. In the fourth stage, Rehmanniae Radix Preparata steamed in earthenware steamer was dried under natural sunlight. The contents of 5-HMF in Rehmanniae Radix Preparata steamed and sundried once through nine times were shown to be below 0.1% in all cases. Pomolic acid was identified as a new chemical component. Conclusions : In conclusion, the Rehmanniae Radix Preparata preparation method set forth in the 『Treasured Mirror of Eastern Medicine』 is thought to be a unique preparation method in South Korea in which Rehmanniae Radix Preparata is completed through the first stage in which fresh Rehmanniae Radix Crudus collected from fields is divided into high, medium, and low quality ones and fresh Rehmanniae Radix Crudus juice is made, the second stage in which the high quality fresh Rehmanniae Radix Crudus is soaked in the fresh Rehmanniae Radix Crudus juice, the third stage in which the fresh Rehmanniae Radix Crudus is steamed, and the fourth stage in which the steamed Rehmanniae Radix Crudus is dried.

Damage-Associated Molecular Patterns in Inflammatory Diseases

노종성,손동현 대한면역학회 2018 Immune Network Vol.18 No.4

Damage-associated molecular patterns (DAMPs) are endogenous danger molecules that are released from damaged or dying cells and activate the innate immune system by interacting with pattern recognition receptors (PRRs). Although DAMPs contribute to the host's defense, they promote pathological inflammatory responses. Recent studies have suggested that various DAMPs, such as high-mobility group box 1 (HMGB1), S100 proteins, and heat shock proteins (HSPs), are increased and considered to have a pathogenic role in inflammatory diseases. Here, we review current research on the role of DAMPs in inflammatory diseases, including rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, atherosclerosis, Alzheimer's disease, Parkinson's disease, and cancer. We also discuss the possibility of DAMPs as biomarkers and therapeutic targets for these diseases.

ECC를 적용한 DRAM의 초기화 시간 최소화 방법

노종성(Roh Jong-sung),김종태(Kim Jong-Tae) 대한전기학회 2006 대한전기학회 학술대회 논문집 Vol.2006 No.10

DRAM with ECC is used widely and the size of DRAM increases. According to this, DRAM initial time, especially the time to make the whole area typical value, 0, increases. This paper introduces the method that without any additional hardware, using characteristic of DRAM and DRAM controller, minimize the memory initial time. Conservative reordering - it eliminates DRAM read time and makes write buffer used - reduces initial time to make the whole DRAM area 0. by 95.36% for DDR DRAM. 93.41% for Rambus DRAM

고지방식이 유도 비알콜성지방간 마우스 모델에서 육신국(六神?)의 지방간(脂肪肝) 개선효과

노종성 ( Jong Seong Roh ),이혜림 ( Hye Rim Lee ),안예지 ( Ye Ji Ahn ),윤미정 ( Mi Chung Yoon ),신순식 ( Soon Shik Shin ) 대한본초학회 2014 大韓本草學會誌 Vol.29 No.2

Objectives : This study was undertaken to verify the effects of Massa Medicata Fermentata (MMF) on nonalcoholic fatty liver disease (NAFLD) using high fat diet-fed male mice. Methods : Fifty four male C57BL/6N mice (age matched) were used for all experiments. Nine standard chow diet-fed mice were used as normal group and forty five high fat diet-fed obese mice were randomly divided into 5 groups: control, atorvastatin-10㎎/㎏, MMF(1)-62.5㎎/㎏, MMF(2)-125㎎/㎏ and MMF(3)-250㎎/㎏. After all groups were treated with several kinds of diets for 8 weeks, we measured body weight gain, adipose tissue weights, plasma lipid and glucose metabolism, visceral organ weights, histological analysis for liver on the mice. Results : MMF-treated mice had lower body weight gain compared with controls. Among MMF-treated mice, the effect was magnified in MMF(2). MMF(3)-treated mice had lower blood plasma total cholesterol (TC) and glucose level compared with controls. MMF decreased hepatic lipid accumulation, liver fibrosis and liver inflammation of mice compared with controls. The effects was maximized in MMF(2) and atorvastatin. Blood plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyltransferase (γ-GT) concentrations tends to be decreased by MMF compared with controls. Blood plasma AST, ALT, γ GT concentrations and organ weights were not changed by MMF, indicating that all three kinds of MMF do not show any hepatotoxicity. Conclusions : These results suggest that MMF improves NAFLD by reducing body weight gain, hepatic lipid accumulation, liver fibrosis, liver inflammation.

生薑의 藥理効能에 대한 最近 國內 硏究 動向

황보샘결,노종성 대한한방내과학회 2023 大韓韓方內科學會誌 Vol.44 No.6

Objectives: This study aims to analyze recent research on the pharmacological effects of Zingiber officinale. Methods: We searched for papers from databases such as ScienceON, RISS, DBPia, and NaNet. The papers were classified according to pharmacological effects, and the selected studies were analyzed. Results: Six studies were finally included in the study. 1. Four studies mainly focused on the effects of anti-inflammation using in vitro or in vivo experiments. 2. Two studies mainly focused on the effects of antioxidants using in vitro experiments. 3. Other pharmacological effects, including improvement of gastrointestinal function, inhibition of body temperature reduction, and anti-aging, were investigated using in vitro or in vivo studies. Conclusion: This study shows that Z. officinale has several pharmacological effects, including anti-inflammation and antioxidant.

Myeloid IPMK promotes the resolution of serum transfer-induced arthritis in mice

안형준,노종성,이슬기,변지윤,이범구,손동현,김세윤 한국통합생물학회 2021 Animal cells and systems Vol.25 No.4

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by widespread joint inflammation, which leads to joint damage, disability, and mortality. Among the several types of immune cells, myeloid cells such as macrophages are critical for controlling the pathogenesis of RA. Inositol phosphates are water-soluble signaling molecules, which are synthesized by a series of enzymes including inositol phosphate kinases. Previous studies revealed actions of inositol phosphates and their metabolic enzymes in the modulation of inflammation such as Toll-like receptor-triggered innate immunity. However, the physiological roles of inositol polyphosphate (IP) metabolism in the regulation of RA remain largely uncharacterized. Therefore, our study sought to determine the role of inositol polyphosphate multikinase (IPMK), a key enzyme for IP metabolism and various cellular signaling control mechanisms, in mediating RA. Using myeloid cell-specific IPMK knockout (KO) mice, arthritis was induced via intraperitoneal K/BxN serum injection, after which disease severity was evaluated. Both wild-type and IPMK KO mice developed similar RA phenotypes; however, conditional deletion of IPMK in myeloid cells led to elevated arthritis scores during the resolution phase, suggesting that IPMK deficiency in myeloid cells impairs the resolution of inflammation. Bone marrow-derived IPMK KO macrophages exhibited no apparent defects in immunoglobulin Fc receptor (FcR) activation, osteoclast differentiation, or resolvin signaling. Taken together, our findings suggest that myeloid IPMK is a key determinant of RA resolution.

交泰丸에 대한 心腎不交의 病機분석과 그 조성약물의 配伍분석

이석희,노종성,신순식 대한한의학원전학회 2022 대한한의학원전학회지 Vol.35 No.3

Objectives : 交泰丸은 전통적으로 心腎不交로 생긴 怔忡과 不眠에 대하여 응용하여 왔고, 그 실험연구와 임상연구가 있으나 그 病機와 配伍에 대한 연구가 미흡하여 이를 조사하였다. Methods : 韓氏醫通과 四科簡效方에 수재된 交泰丸의 病機와 配伍를 분석하였다. 오아시스(OASIS)와 CNKI에서 ‘交泰丸’, ‘교태환’의 검색어로 최근의 연구성과를 반영하였다. Results : 交泰丸은 韓懋의 韓氏醫通에 처음으로 조성약물과 用法이 수재되었으나 用量과 方名은 제시되지 않았으며 心腎相交는 제시되었다. 王士雄의 四科簡效方에서 비로서 조성약물의 구체적인 용량, 用法과 方名이 제시되었으며, 心腎不交로 생긴 怔忡과 不眠을 치료한다는 것을 제시하였다. Conclusions : 交泰丸의 心腎不交의 病機는 心과 肾의 두 臟의 氣, 血, 陰 및 陽이 失调되어 유발된 腎陽虛와 心火旺에 의한 心腎兩不相交이다. 交泰丸은 黃連 5돈과 肉桂 5푼으로 조성되었고, 그 용량비율은 10:1 이다. 黃連은 歸經이 주로 心經이고 性味가 苦寒하여 心火를 瀉하고 君藥으로 쓰였으며, 肉桂는 歸經이 주로 腎經이며 性味가 辛甘熱하여 腎水를 溫하며 또한 引火歸元하고 佐藥으로 쓰였다. 肉桂는 上濟하고 黃連은 下降하여 心과 腎을 交通하고 水와 火를 旣濟하는 효과를 거두게 한다. 결론적으로 交泰丸은 心腎不交 중에서 心腎兩不相交를 君藥인 黃連과 佐藥인 肉桂가 쓰여 心腎相交로 전환시킴으로써 心腎不交로 인한 不眠과 怔忡을 치료하는 방제이다.