논문(論文) : 「천원기대론(天元紀大論)」 중 상하주기(上下周紀)에 대한 석곡(石谷) 이규준(李圭晙)의 교정(校訂)에 관한 고찰(考察)

황원덕 ( Won Deok Hwang ) 대한한의학원전학회 ( 구 대한원전의사학회 ) 2009 대한한의학원전학회지 Vol.22 No.4

In the chapter 「Cheonwon-gidaeron(天元紀大論)」 of 『Hwangjenaegyeong(黃帝內經)』, Lee-Gyujun(李圭晙) corrected "heaven has the rule of six and earth has the rule of five[天六地五]" to "heaven has the rule of five and earth has the rule of six[天五地六]" and "sovereign fire is bright[君火以明] to "sovereign fire is summoning[君火以召]", which changes the meaning of the rule of circulation of the heaven and earth. Considering the context and many scholars` opinions, it was suggested that "sovereign fire naming[君火以名]" which was noted from Tang dynasty to Jin & Wen dynasty was corrected to "sovereign fire is bright[君火以明]" over Ming dynasty. In the corrections of Wangbing(王氷)`s Plain Questions, the sentence is written as "sovereign fire naming[君火以名]". The two characters, `明` and `名` are hardly similar in both shape and meaning, that it is only plausible to assume that it was mistaken for `召`. Consequently, we corrected "sovereign fire is bright[君火以明]" to "sovereign fire is summoning[君火以名]". And "sovereign fire is summoning, ministerial fire is locating[君火以召, 相火以位]", it raise "the rule of five and six is combined together[五六相合]". "The rule of five and six is combined together` means `heaven`s number of five" coincide "earth`s number of six", and it says former times before dividing up and down.

Calpain protease에 의한 cyclin D3의 post-translation조절

황원덕(Won Deok Hwang),최영현(Yung Hyun Choi) 한국생명과학회 2015 생명과학회지 Vol.25 No.1

칼슘 의존적으로 활성화되는 neutral protease calpain에 의한 단백질 분해는 세포의 성장을 조절하는데 중요한 단백질들의 역할에 매우 중요한 역할을 한다. Cyclin의 분해는 세포주기의 진행을 위한 필연적인 과정이다. D-type cyclins는 외부자극이나 신호에 의하여 세포주기의 G1 초기에 합성이 된 후 cyclin-dependent kinases (cdk4 및 cdk6)와의 결합하여 세포주기 S기 진입을 촉진하는 역할을 한다. 본 연구에서는 cyclin D3 단백질이 calpain protease에 의하여 번역 후 수준에서 조절 받고 있음을 제시하였다. 본 실험의 조건에서 lovastatin과 actinomycin D가 처리된 PC-3-M 전립선 암세포에서 cyclin D3 단백질의 발현이 완전히 사라졌지만, calpain inhibitor인 LLnL의 처리에 의하여 정상 수준으로 회복되었음을 알 수 있었다. 그러나 26S proteasome의 선택적 억제제인 lactacystin, lysosome 억제제인 ammonium chloride 및 chloroquine, serine protease 억제제인 PMSF는 동일 조건에서 lovastatin과 actinomycin D 처리에 의한 cyclin D3 단백질의 발현저하를 억제하지는 못하였다. In vitro 조건에서 순수 분리된 calpain은 cyclin D3 단백질을 칼슘 농도 의존적으로 분해하였으며, cyclin D3 단백질의 반감기는 LLnL 처리에 의하여 매우 유의적으로 증가되었다. 또한 calpain 저해인자인 calpastatin의 과발현은 PC-3-M 세포에서 뿐만 아니라 NIH 3T3 섬유아세포에서도 cyclin D3 단백질의 반감기 및 안전성을 증대시켰다. 이러한 결과는 cyclin D3 단백질이 칼슘에 의해 활성화 되는 protease calpain에 의해 조절됨을 보여주는 것이다. Cyclin D is a member of the cyclin protein family, which plays a critical role as a core member of the mammalian cell cycle machinery. D-type cyclins (D1, D2, and D3) bind to and activate the cyclin-dependent kinases 4 and 6, which can then phosphorylate the retinoblastoma tumor suppressor gene products. This phosphorylation in turn leads to release or derepression of E2F transcription factors that promote progression from the G1 to S phase of the cell cycle. Among the D-type cyclins, cyclin D3 encoded by the CCND3 gene is one of the least well studied. In the present study, we have investigated the biochemistry of the proteolytic mechanism that leads to loss of cyclin D3 protein. Treatment of human prostate carcinoma PC-3-M cells with lovastatin and actinomycin D resulted in a loss of cyclin D3 protein that was completely reversible by the peptide aldehyde calpain inhibitor, LLnL. Additionally, using inhibitors for various proteolytic systems, we show that degradation of cyclin D3 protein involves the Ca2+-activated neutral protease calpain. Moreover, the half-life of cyclin D3 protein half-life increased by at least 10-fold in PC-3M cells in response to the calpain inhibitor. We have also demonstrated that the transient expression of the calpain inhibitor calpastatin increased cyclin D3 protein in serum-starved NIH 3T3 cells. These data suggested that the function of cyclin D3 is regulated by Ca2+-dependent protease calpain.

황금(黃芩) 에탄올 추출물에 의한 인체 신세포암 Caki-1 세포의 자가세포사멸 유도

황원덕(Won Deok Hwang),임용균(Yong-Gyun Im),손병일(Byoung Yil Son),박철(Cheol Park),박동일(Dong Il Park),최영현(Yung Hyun Choi) 한국생명과학회 2013 생명과학회지 Vol.23 No.4

꿀풀과(Labiatae)에 속하는 황금(黃芩, S. baicalensis)은 한국, 중국, 몽골 및 시베리아 동부 등지에 분포하는 여러해살이 초본식물로서 예로부터 민간처방 약재로 사용되었으며, 한방에서는 뿌리 말린 것을 이질, 발열 및 황달의 치료제로 사용되고 있다. 또한 최근 연구에 따르면 황금 추출물은 항염증, 항당뇨, 항균, 항알레르기, 항바이러스, 항고혈압, 항산화 및 항암 효능을 가지는 것으로 알려져 있으나 신세포암에서의 항암효능 및 분자생물학적 기전에 대해서는 명확히 밝혀져 있지 않다. 본 연구에서는 인체 신세포암 Caki-1 세포에서 황금 에탄올 추출물(ethanol extract of S. baicalensis, EESB)이 유발하는 항암효과 및 항암기전을 조사하였다. 본 연구의 결과에 의하면 EESB 처리에 의한 Caki-1 세포의 증식억제는 apoptosis 유발과 밀접한 연관이 있었으며, 이는 DR4 Fas ligand 및 Bax 단백질의 발현 증가와 Bid, XIAP 및 cIAP-1의 발현 억제와 관련이 있었다. EESB는 또한 미토콘드리아의 기능 손상과 caspase-3의 기질단백질인 PARP, β-catenin 및 PLCγ-1 단백질의 단편화를 유발하였다. 그러나 EESB처리에 의하여 유발되었던 apoptosis가 pan-caspases inhibitor인 z-VED-fmk를 이용하여 caspases의 활성을 억제하였을 경우 현저하게 감소되어, EESB에 의한 apoptosis 과정에 caspase의 활성 증대가 중요한 역할을 한다는 것을 알 수 있었다. 이러한 결과들은 황금의 항암작용을 이해하는데 중요한 자료가 될 것이고 나아가 향후 수행될 추가 실험을 위한 기초 자료로서 그 가치가 매우 높을 것으로 생각된다. Scutellaria baicalensis, belonging to the family Labiatae, is widely distributed in Korea, China, Mongolia, and eastern Siberia. It has been used in traditional medicine for various diseases, such as dysentery, pyrexia, jaundice, and carbuncles. In addition, S. baicalensis is reported to possess various beneficial pharmacological activities, including anti-inflammatory, antidiabetic, antiviral, antihypertension, antioxidant, and anticancer effects. However, the molecular mechanisms of its anticancer activity have not been clearly elucidated. In the present study, we investigated the proapoptotic effects of ethanol extract of S. baicalensis (EESB) on human renal cell carcinoma Caki-1 cells. The anti-proliferative activity of EESB was associated with apoptosis induction, which was associated with the up-regulation of death receptor 4, the Fas ligand, and Bax and the down-regulation of Bid, XIAP, and cIAP-1 proteins. EESB treatment also induced mitochondrial dysfunction, proteolytic activation of caspase-3, -8, and -9 and degradation of caspase-3 substrate proteins, such as poly (ADP-ribose) polymerase, β-catenin, and phospholipase C-γ1. However, pretreatment of a pan-caspase inhibitor, z-VAD-fmk, significantly attenuated the EESB-induced apoptosis. Taken together, these findings suggest that EESB may be a potential chemotherapeutic agent. Further studies will be needed to identify the active compounds that confer the anticancer activity of S. baicalensis.

부자(附子) 및 천오(川烏)를 포함한 처방이 심전도 변화에 미치는 영향

안수연,황원덕,김원일,Ahn, Su-yeun,Hwang, Won-deok,Kim, Won-ill 대한한방내과학회 2015 大韓韓方內科學會誌 Vol.36 No.4

Objectives: Buja and Cheono, containing aconitine known for its cardiotoxicity, are not commonly prescribed, but they are necessary for some clinical conditions. Hence, consequences for electrocardiography (EKG) after short- and long-term dosage of herbal medicine including Buja and Cheono are here reported.Methods: From September 2014 to April 2015, 36 patients belonging to the sixth internal medicine department of the Dong Eui Oriental Medicine Hospital took herbal medicine including Buja and Cheono, and after these doses, they underwent an EKG. Thirty-one patients who took the medicine for 7-8 days comprised the short-term group, and 18 patients taking the medicine for 17-106 days comprised the long-term group. The results of the EKGs for each group, before and after dosage with herbal medicine, are compared.Results: No significant changes in EKG appeared in either the short- or the long-term group after taking herbal medicine including Buja and Cheono.Conclusions: If Buja or Cheono are prescribed along with other suitable herbs by a doctor of Korean medicine, no cardiac trouble will occur on an EKG regardless of the term of the dosage.

만성 경막하 혈종(Chronic Subdural Hematoma)의 한의 치료에 대한 최신 임상연구 동향 - CNKI 검색을 중심으로 -

제유란,김경림,황원덕,Je, Yu-ran,Kim, Kyong-lim,Hwang, Won-deok 대한한방내과학회 2021 大韓韓方內科學會誌 Vol.42 No.3

Objectives: This study investigates the latest clinical studies on Korean medicine treatment of chronic subdural hematoma (CSDH) in China. Methods: A CNKI search investigated the last 10 years of clinical studies of Korean medicine treatments in Chinese medical journals for CSDH. The search focused on authors, publication years, types of studies, purposes of studies, methods and duration of treatment, evaluation criteria, and results of treatment. Results: In 19 studies, there were 14 randomized controlled trials (RCTs), 4 case series, and 1 case-control study. In all 19 studies, Korean medical treatment and Western treatment were combined. Herbal medicine was used in 19 studies and acupuncture treatment in 2 studies. The most frequently used prescription was Hyeolbuchukeo-tang-gagambang, and the most frequently used acupoint was PC6. In all 19 studies, the effectiveness of Korean medicine treatment performed in parallel with Western treatment was confirmed. Conclusions: In this study, Korean medicine combined with Western treatment for CSDH was effective. More clinical studies and case reports are required to develop a guided treatment for CSDH.

다발성 신경병증에 대한 한방 치험 1례

손변우,정해룡,황원덕,Son, Byun-woo,Jeong, Hae-ryong,Hwang, Won-deok 대한한방내과학회 2016 大韓韓方內科學會誌 Vol.37 No.5

Objective: To describe the effects of Korean medical treatment on a 51-year-old male patient with polyneuropathy and chief complaints of lower limb paralysis and dysarthria. Methods: The Toronto Clinical Neuropathy Scoring System (TCNSS) was used to evaluate the function of the lower limb and the symptoms of the patient were observed daily. We applied herbal medication and acupuncture daily, depending on the patient’s symptoms. Results: After the treatment, the TCNSS score was improved. Conclusions: In this case, Korean medical therapy was effective in improving lower limb function.

RAW 264.7 대식세포에서 청뇌명신환(淸腦明神丸)에 의한 염증성 및 산화적 스트레스 반응 억제 효능

손변우,이명화,황원덕,Son, Byun Woo,Lee, Myeong Hwa,Hwang, Won Deok 대한한의학방제학회 2018 大韓韓醫學方劑學會誌 Vol.26 No.1

Objectives : Cheongnoimyungshin-hwan (CNMSH) is a Herbal compound prescription that is composed mainly of herbal medicines such as Ginseng Radix Alba, Angelicae Gigantis Radix, Dioscoreae Rhizoma, Longan Arillus and cornus cervi parvum, and for the purpose of improving memory and preventing dementia. Methods : In this study, it was investigated whether CNMSH could suppress inflammatory response and oxidative stress in the lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells. As a result, CNMSH decreased expression of inducible nitric oxide (NO) synthase and cyclooxygenase-2, and also inhibited production of NO, prostaglandin E2. Results : This effect was associated with the suppression of the expression of p65, one of the nuclear factor-kappaB ($NF-{\kappa}B$) subunits, and increased expression of $I{\kappa}B-{\alpha}$, inhibit the $NF-{\kappa}B$ transcription factor. In addition, CNMSH significantly blocked intracellular reactive oxygen species accumulation in response to LPS stimulation. Furthermore, CNMSH increased expression of nuclear factor erythroid 2-related factor (Nrf)-2 activation and heme oxygenase (HO)-1. Conclusions : Therefore, it has been shown anti-inflammatory and antioxidant effects by inhibiting the expression and production of inflammatory mediators in LPS-stimulated macrophages, and is associated with ROS generation and is activated by Nrf2/HO-1 signaling pathway.

산삼 약침이 정상 중년여성의 맥파요인에 미치는 영향

박상욱,김이순,황원덕,김경철,Park, Sang-Wook,Kim, Yi-Soon,Hwang, Won-Deok,Kim, Gyeong-Cheol 대한약침학회 2011 Journal of pharmacopuncture Vol.14 No.1

Objectives: The aim of this experiment is to know about Effect of pulse-wave factors in Middle Aged Women by Mountain Cultivated Ginseng Pharmacopuncture. Methods: First 20 Middle Aged women are diagnosed by pulse diagnosis, and then Mountain Cultivated Ginseng Pharmacopuncture(1 injection 20cc) were injected. 30 minutes later, pulse diagnosis again performed. As a result, method of one-group pretest-posttes design were used for evaluation. Results: T(Total pulse cycle) time statistically significant increased on both left and right chon, kwan, cheok. T4 time statistically significant increased on both left and right chon, kwan, cheok. T4-T1/T indexs except left cheokmaek, Right cheokmaek observation area decreased significantly in four sites. Wm(indicating high pressure retention time) indexs increased significantly in the five sites were observed except right chon maek. Conclusions: Effect of pulse-wave factors in Middle Aged Women by Mountain Cultivated Ginseng Pharmacopuncture increased T, T4, Wm and decreased T4-T1/T indexs. The results of this experiment, Mountain Cultivated Ginseng Pharmacopuncture induced to increase the Pulse-wave's stability and strength.

Cordycepin에 의한 LNCap 인체 전립선 암세포의 apoptosis 및 G2/M arrest 유발

이혜현(Hye Hyeon Lee),황원덕(Won Deok Hwang),정진우(Jin-Woo Jeong),박철(Cheol Park),한민호(Min Ho Han),홍수현(Su Hyun Hong),정영기(Yong Kee Jeong),최영현(Yung Hyun Choi) 한국생명과학회 2014 생명과학회지 Vol.24 No.1

Cordycepin은 Cordyceps militaris에서 처음 유래된 nucleoside adenosine 유도체의 일종으로 면역증강 및 항암활성을 포함한 다양한 약리 기능이 있는 것으로 알려져 있다. 본 연구에서는 LNCap 인체 전립선 암세포 모델을 이용하여 cordycepin에 의한 항암활성 기전을 연구하였다. Cordycepin 처리에 따라 LNCap 세포는 처리 농도 의존적으로 증식이 억제되었으며, 이는 apoptosis 유발과 연관성이 있음을 poly ADP-ribose polymerase의 단편화 현상과 Annexin V 염색에 의한 정량적 분석으로 확인하였다. Cordycepin 처리에 따른 flow cytometric analysis 결과로서 cordycepin이 세포주기 G2/M기 정체 현상을 유발하였음을 알 수 있었으며, 이는 cyclin B1 및 cyclin A의 발현 감소와 연관성이 있었다. 또한 cordycepin이 처리된 LNCap 세포에서 cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1의 발현이 증가되었지만, CDK2, CDC2 및 Cdc25C의 발현에는 큰 영향을 미치지 않았으며, cordycepin에 의하여 증가된 p21 단백질은 CDK2 및 CDC2와의 복합체를 형성하고 있었다. 본 연구의 결과는 LNCap 전립선 암세포에서 cordycepin에 의한 G2/M 및 apoptosis 유발은 p53 비존적인 CDK inhibitor p21의 발현 증가가 중요한 역할을 하고 있음을 보여주는 것이다. Cordycepin, an active component originally isolated from the traditional medicine Cordyceps militaris, is a derivative of the nucleoside adenosine, which has been shown to possess a number of pharmacological properties, including antioxidant and anti-inflammatory activities, immunological stimulation, and antitumor effects. This study was conducted on cultured human prostate carcinoma LNCap cells to elucidate the possible mechanisms by which cordycepin exerts its anticancer activity, which, until now, has remained poorly understood. Cordycepin treatment of LNCap cells resulted in dose-dependent inhibition of cell growth and the induction of apoptotic cell death as detected by an MTT assay, cleavage of poly ADP-ribose polymerase, and annexin V-FITC staining. Flow cytometric analysis revealed that cordycepin resulted in G2/M arrest in cell cycle progression and downregulation of cyclin B1 and cyclin A expression in a concentration-dependent manner. Moreover, the incubation of cells with cordycepin caused a striking induction in the expression of the cyclin-dependent kinase (CDK) inhibitor p21Waf1/Cip1 without affecting the expression of the tumor suppressor p53. It also resulted in a significant increase in the binding of CDK2 and CDC2 to p21. These findings suggest that cordycepin-induced G2/M arrest and apoptosis in human prostate carcinoma cells is mediated through p53-independent upregulation of the CDK inhibitor p21.

미세아교세포의 염증반응에 미치는 청뇌명신환의 영향

임용균 ( Yong Gyun Im ),최영현 ( Yung Hyun Choi ),황원덕 ( Won Deok Hwang ) 대한한방신경정신과학회 2014 동의신경정신과학회지 Vol.25 No.4

Objectives: Activated microglia cells play an important role in inflammatory responses in the central nervous system (CNS) which are involved in neurodegenerative diseases. We attempted to determine the anti-inflammatory effects of Cheongnoimyungshin-hwan (CNMSH) in microglia cells. Methods: We examined the effect of CNMSH on the inflammatory responses in BV2 microglia cells induced by lipopolysaccharide (LPS) and explored the mechanism underlying the action of CNMSH. Results: BV2 cells treated with LPS showed an up-regulation of nitric oxide (NO), prostaglandin PGE2 (PGE2) and interleukin 1b (IL-1b) release, whereas CNMSH suppressed this up-regulation. CNMSH inhibited the induction of COX-2, iNOS and IL-1b proteins in LPS-treated BV2 cells and blocked the LPS-induced phosphorylation and nuclear translocation of nuclear factor kB (NF-kB). Furthermore, CNMSH attenuated the LPS-induced phosphorylation of extracellular signal-regulated kinase and p38 mitogen activated protein kinase (MAPK), as well as the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway, but did not inhibit the LPS-induced phosphorylation of c-Jun amino terminal kinase. Conclusions: These results suggest that the inhibitory effect of CNMSH on the LPS-induced production of inflammatory mediators and cytokines in BV2 cells is associated with the suppression of the NF-kB and PI3KAkt signaling pathways.