• Journal of Ginseng Research
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• 제47권6호
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• pp.755-765
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• 2023

Background: Caveolin-1, the scaffolding protein of cholesterol-rich invaginations, plays an important role in store-operated Ca²⁺ influx and its phosphorylation at Tyr14 (p-caveolin-1) is vital to mobilize protection against myocardial ischemia (MI) injury. SOCE, comprising STIM1, ORAI1 and TRPC1, contributes to intracellular Ca²⁺ ([Ca²⁺]_i) accumulation in cardiomyocytes. The purified extract of steamed Panax ginseng (EPG) attenuated [Ca²⁺]_i overload against MI injury. Thus, the aim of this study was to investigate the possibility of EPG affecting p-caveolin-1 to further mediate SOCE/[Ca²⁺]_i against MI injury in neonatal rat cardiomyocytes and a rat model. Methods: PP2, an inhibitor of p-caveolin-1, was used. Cell viability, [Ca²⁺]_i concentration were analyzed in cardiomyocytes. In rats, myocardial infarct size, pathological damages, apoptosis and cardiac fibrosis were evaluated, p-caveolin-1 and STIM1 were detected by immunofluorescence, and the levels of caveolin-1, STIM1, ORAI1 and TRPC1 were determined by RT-PCR and Western blot. And, release of LDH, cTnI and BNP was measured. Results: EPG, ginsenosides accounting for 57.96%, suppressed release of LDH, cTnI and BNP, and protected cardiomyocytes by inhibiting Ca²⁺ influx. And, EPG significantly relieved myocardial infarct size, cardiac apoptosis, fibrosis, and ultrastructure abnormality. Moreover, EPG negatively regulated SOCE via increasing p-caveolin-1 protein, decreasing ORAI1 mRNA and protein levels of ORAI1, TRPC1 and STIM1. More importantly, inhibition of the p-caveolin-1 significantly suppressed all of the above cardioprotection of EPG. Conclusions: Caveolin-1 phosphorylation is involved in the protective effects of EPG against MI injury via increasing p-caveolin-1 to negatively regulate SOCE/[Ca²⁺]_i.

• Journal of Ginseng Research
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• 제47권5호
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• pp.627-637
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• 2023

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment. Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis. Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis. Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

• 동국한의학연구소논문집
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• 제10권
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• pp.1-40
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• 2008

1.The 'Kao Zheng Pai'(考證派) comes from the 'Zhe Zhong Pai(折衷派)' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金峨), Yoshida Koton(古田篁墩 $1745{\sim}1798$) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li'(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 $1739{\sim}1798$) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan(躋壽館) mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken(伊澤蘭軒) taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai(澀江抽齋), Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 $1749{\sim}1787$) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論") and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯). 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken(伊澤蘭軒) and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋詞"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue"("金匱要略"), "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Ritsi(森立之 $1807{\sim}1885$) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken(伊澤蘭軒) and later became a pupil of Shou Gu Yi Zhai(狩谷掖齋), a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"("神農本草經") and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"(枳園隨筆) that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"(說文解字) to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據), Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬, $1804{\sim}1876$) learned scriptures and ancient texts from confucian scholar Asaka Gonsai(安積艮齋), and learned medicine from his father Huai Yaun(槐園), He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju"("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi"("金匱要略疏義") and "Lao Yi Zhi Yan"(老醫巵言) but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 $912{\sim}955$) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 $1755{\sim}1810$) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi"("傷寒論輯義") and "Jin Qui Yao Lue Ji Yi"("金匱要略輯義") are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng"("醫勝") is a collection of essays on research. Also there are the "Su Wen Shi"(素問識), "Ling Shu Shi"("靈樞識"), and the "Guan Ju Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 $1789{\sim}1827$), and his works include works of research such as "Nan Jing Shu Jeng"(難經疏證), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"(疾雅), "Ming Yi Gong An"(名醫公案), and "Yi Ji Kao"(醫籍考). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 $1789{\sim}1827$), Yuan Jian(元堅 $1795{\sim}1857$) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(禦匙). He left about 15 texts, including "Su Wen Shao Shi"("素問紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"("傷寒廣要"), and "Zhen Fu Yao Jue"("診腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(矢數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', the founding of Ji Shou Guan(躋壽館) and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.

• 대한한의학원전학회지
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• 제20권4호
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• pp.211-250
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• 2007

1. The 'Kao Zheng Pai(考證派) comes from the 'Zhe Zhong Pai' and is a school that is influenced by the confucianism of the Qing dynasty. In Japan Inoue Kinga(井上金娥), Yoshida Koton(吉田篁墩) became central members, and the rise of the methodology of historical research(考證學) influenced the members of the 'Zhe Zhong Pai', and the trend of historical research changed from confucianism to medicine, making a school of medicine based on the study of texts and proving that the classics were right. 2. Based on the function of 'Nei Qu Li '(內驅力) the 'Kao Zheng Pai', in the spirit of 'use confucianism as the base', researched letters, meanings and historical origins. Because they were influenced by the methodology of historical research(考證學) of the Qing era, they valued the evidential research of classic texts, and there was even one branch that did only historical research, the 'Rue Xue Kao Zheng Pai'(儒學考證派). Also, the 'Yi Xue Kao Zheng Pai'(醫學考證派) appeared by the influence of Yoshida Kouton and Kariya Ekisai(狩谷掖齋). 3. In the 'Kao Zheng Pai(考證派)'s theories and views the 'Yi Xue Kao Zheng Pai' did not look at medical scriptures like the "Huang Di Nei Jing"("黃帝內經") and did not do research on 'medical' related areas like acupuncture, the meridian and medicinal herbs. Since they were doctors that used medicine, they naturally were based on 'formulas'(方劑) and since their thoughts were based on the historical ideologies, they valued the "Shang Han Ja Bing Lun" which was revered as the 'ancestor of all formulas'(衆方之祖). 4. The lives of the important doctors of the 'Kao Zheng Pai' Meguro Dotaku(目黑道琢) Yamada Seichin(山田正珍), Yamada Kyoko(山田業廣), Mori Ritsi(森立之) Kitamura Naohara(喜多村直寬) are as follows. 1) Meguro Dotaku(目黑道琢 1739${\sim}$1798) was born of lowly descent but, using his intelligence and knowledge, became a professor as a Shi Jing Yi(市井醫) and as a professor for 34 years at Ji Shou Guan mastered the "Huang Di Nei Jing" after giving over 300 lectures. Since his pupil, Isawara Ken taught the Lan Men Wu Zhe(蘭門五哲) and Shibue Chusai, Mori Ritsi(森立之), Okanishi Gentei(岡西玄亭), Kiyokawa Gendoh(淸川玄道) and Yamada Kyoko(山田業廣), Meguro Dotaku is considered the founder of the 'Yi Xue Kao Zheng Pai'. 2) The family of Yamada Seichin(山田正珍 1749${\sim}$1787) had been medical officials in the Makufu(幕府) and the many books that his ancestors had left were the base of his art. Seichin learned from Shan Ben Bei Shan(山本北山), a 'Zhe Zhong Pai' scholar, and put his efforts into learning, teaching and researching the "Shang Han Lun"("傷寒論"). Living in a time between 'Gu Fang Pai'(古方派) member Nakanishi Goretada(中西惟忠) and 'Kao Zheng Pai' member Taki Motohiro(多紀元簡), he wrote 11 books, 2 of which express his thoughts and research clearly, the "Shang Han Lun Ji Cheng"("傷寒論集成") and "Shang Han Kao"("傷寒考"). His comparison of the 'six meridians'(3 yin, 3 yang) between the "Shang Han Lun" and the "Su Wen Re Lun"("素問 熱論) and his acknowledgement of the need and rationality of the concept of Yin-Yang and Deficient-Replete distinguishes him from the other 'Gu Fang Pai'. Also, his dissertation of the need for the concept doesn't use the theories of latter schools but uses the theory of the "Shang Han Lun" itself. He even researched the historical parts, such as terms like 'Shen Nong Chang Bai Cao'(神農嘗百草) and 'Cheng Qi Tang'(承氣湯) 3) The ancestor of Yamada Kyoko(山田業廣) was a court physician, and learned confucianism from Kao Zheng Pai 's Ashikawa Genan(朝川善庵) and medicine from Isawa Ranken and Taki Motokata(多紀元堅), and the secret to smallpox from Ikeda Keisui(池田京水). He later became a lecturer at the Edo Yi Xue Guan(醫學館) and was invited as the director to the Ji Zhong(濟衆) hospital. He also became the first owner of the Wen Zhi She(溫知社), whose main purpose was the revival of kampo, and launched the monthly magazine Wen Zi Yi Tan(溫知醫談). He also diagnosed and prescribed for the prince Ming Gong(明宮). His works include the "Jing Fang Bian"("經方辨"), "Shang Han Lun Si Ci"("傷寒論釋司"), "Huang Zhao Zhu Jia Zhi Yan Ji Yao"("皇朝諸家治驗集要") and "Shang Han Ja Bing Lun Lei Juan"("傷寒雜病論類纂"). of these, the "Jing Fang Bian"("經方辨") states that the Shi Gao(石膏) used in the "Shang Han Lun" had three meanings-Fa Biao(發表), Qing Re(淸熱), Zi Yin(滋陰)-which were from 'symptoms', and first deducted the effects and then told of the reason. Another book, the "Jiu Zhe Tang Du Shu Ji"("九折堂讀書記") researched and translated the difficult parts of the "Shang Han Lun", "Jin Qui Yao Lue", "Qian Jin Fang"("千金方"), and "Wai Tai Mi Yao"("外臺秘要"). He usually analyzed the 'symptoms' of diseases but the composition, measurement, processing and application of medicine were all in the spectrum of 'analystic research' and 'researching analysis'. 4) The ancestors of Mori Rits(森立之 1807${\sim}$ 1885) were warriors but he became a doctor by the will of his mother, and he learned from Shibue Chosai(澁江抽齋) and Isawaran Ken and later became a pupil of Shou Gu Yi Zhai, a historical research scholar. He then became a lecturer of medical herbs at the Yi Xue Guan, and later participated in the proofreading of "Yi Xin Fang"("醫心方") and with Chosai compiled the "Jing Ji Fang Gu Zhi"("神農本草經"). He visited the Chinese scholar Yang Shou Jing(楊守敬) in 1881 and exchanged books and ideas. Of his works, there are the collections(輯複本) of "Shen Nong Ben Cao Jing"(神農本草經) and "You Xiang Yi Hwa"("遊相醫話") and the records, notes, poems, and diaries such as "Zhi Yuan Man Lu"("枳園漫錄") and "Zhi Yuan Sui Bi"("枳園隨筆") that were not published. His thoughts were that in restoring the "Shen Nong Ben Cao Jing", "the herb to the doctor is like the "Shuo Wen Jie Zi"("說文解字") to the scholar", and he tried to restore the ancient herbal text using knowledge of medicine and investigation(考據). Also with Chosai he compiled the "Jing Ji Fang Gu Zhi"("經籍訪古志") using knowledge of ancient text. Ritzi left works on pure investigation, paid much attention to social problems, and through 12 years of poverty treated all people and animals in all branches of medicine, so he is called a 'half confucianist half doctor'(半儒半醫). 5) Kitamurana Ohira(喜多村直寬 1804${\sim}$1876) learned scriptures and ancient texts from confucian scholar Asaka Gonsai, and learned medicine from his father Huai Yaun(槐園). He became a teacher in the Yi Xue Guan in his middle ages, and to repay his country, he printed 266 volumes of "Yi Fang Lei Ju("醫方類聚") and 1000 volumes of "Tai Ping Yu Lan"("太平禦覽") and devoted it to his country to be spread. His works are about 40 volumes including "Jin Qui Yao Lue Shu Yi" and "Lao Yi Zhi Yan" but most of them are researches on the "Shang Han Za Bing Lun". In his "Shang Han Lun Shu Yi"("傷寒論疏義") he shows the concept of the six meridians through the Yin-Yang, Superficial or internal, cold or hot, deficient or replete state of diseases, but did not match the names with the six meridians of the meridian theory, and this has something in common with the research based on the confucianism of Song(宋儒). In clinical treatment he was positive toward old and new methods and also the experience of civilians, but was negative toward western medicine. 6) The ancestor of the Taki family Tanbano Yasuyori(丹波康賴 912-955) became a Yi Bo Shi(醫博士) by his medical skills and compiled the "Yi Xin Fang"("醫心方"). His first son Tanbano Shigeaki(丹波重明) inherited the Shi Yao Yuan(施藥院) and the third son Tanbano Masatada(丹波雅忠) inherited the Dian You Tou(典藥頭). Masatada's descendents succeeded him for 25 generations until the family name was changed to Jin Bao(金保) and five generations later it was changed again to Duo Ji(多紀). The research scholar Taki Motohiro was in the third generation after the last name was changed to Taki, and his family kept an important part in the line of medical officers in Japan. Taki Motohiro(多紀元簡 1755-1810) was a teacher in the Yi Xue Guan where his father was residing, and became the physician for the general Jia Qi(家齊). He had a short temper and was not good at getting on in the world, and went against the will of the king and was banished from Ao Yi Shi(奧醫師). His most famous works, the "Shang Han Lun Ji Yi" and "Jin Qui Yao Lue Ji Yi" are the work of 20 years of collecting the theories of many schools and discussing, and is one of the most famous books on the "Shang Han Lun" in Japan. "Yi Sheng" is a collection of essays on research. Also there are the "Su Wen Shi"("素問識"), "Ling Shu Shi"("靈樞識"), and the "Guan lu Fang Yao Bu"("觀聚方要補"). Taki Motohiro(多紀元簡)'s position was succeeded by his third son Yuan Yin(元胤 1789-1827), and his works include works of research such as "Nan Jing Shu Jeng"("難經疏證"), "Ti Ya"("體雅"), "Yao Ya"("藥雅"), "Ji Ya"("疾雅"), "Ming Yi Gong An"("名醫公案"), and "Yi Ji Kao"("醫籍考"). The "Yi Ji Kao" is 80 volumes in length and lists about 3000 books on medicine in China before the Qing Dao Guang(道光), and under each title are the origin, number of volumes, state of existence, and, if possible, the preface, Ba Yu(跋語) and biography of the author. The younger sibling of Yuan Yin(元胤 1789-1827), Yuan Jian(元堅 1795-1857) expounded ancient writings at the Yi Xue Guan only after he reached middle age, was chosen for the Ao Yi Shi(奧醫師) and later became a Fa Yan(法眼), Fa Yin(法印) and Yu Chi(樂匙). He left about 15 texts, including "Su Wen Shao Shi"("素間紹識"), "Yi Xin Fang"("醫心方"), published in school, "Za Bing Guang Yao"("雜病廣要"), "Shang Han Guang Yao"(傷寒廣要), and "Zhen Fu Yao Jue"("該腹要訣"). On the Taki family's founding and working of the Yi Xue Guan Yasuka Doumei(失數道明) said they were "the people who took the initiative in Edo era kampo medicine" and evaluated their deeds in the fields of 'research of ancient text', 'the founding of Ji Shou Guan and medical education', 'publication business', 'writing of medical text'. 5. The doctors of the 'Kao Zheng Pai ' based their operations on the Edo Yi Xue Guan, and made groups with people with similar ideas to them, making a relationship 'net'. For example the three families of Duo Ji(多紀), Tang Chuan(湯川) and Xi Duo Cun(喜多村) married and adopted with and from each other and made prefaces and epitaphs for each other. Thus, the Taki family, the state science of the Makufu, the tendency of thinking, one's own interests and glory, one's own knowledge, the need of the society all played a role in the development of kampo medicine in the 18th and 19th century.

• 생명과학회지
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• 제25권10호
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• pp.1156-1163
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• 2015

고량강(Alpinia officinarum), 산초(Zanthoxylum schinifolium), 황금(Scutellaria baicalensis Georgi), 왕느릅나무(Ulmus macrocarpa Hance), 네 종류의 식물성 한방 약재의 면역증강효능을 cyclophosphamide를 처리한 동물모델을 이용하여 조사하였다. 실험은 cyclophosphamide로 면역억제를 유도한 후 네 종류의 한방 약재를 식이하여 cyclophosphamide에 의해 억제된 면역인자의 회복 여부를 조사하였다. 네 종류의 한방 약재를 동일한 방법으로 열수 추출한 후 동일한 농도로 마우스에 처리하였다. 이 중 왕느릅나무 열수 추출물(DEU-7)이 cyclophosphamide의 영향으로 면역 억제된 마우스에서 면역인자 혈중 농도를 정상치 준하는 또는 가깝게 유지하는 것으로 나타내었다. DEU-7에 의해 비장의 무게와 비장세포수는 증가하였으나 간과 흉선과 같은 다른 장기에는 통계적으로 유의한 변화가 없었다. Ex vivo 조건에서 DEU-7은 비장세포의 사멸을 지연시키는 것으로 나타났다. 중요한 면역인자인 IL-2와 IL-4 cytokine은 면역억제로 농도가 감소되었으나 DEU-7이 약 2배와 3배 향상시키는 것으로 나타났으며, 이는 정상치의 약 1/2 수준이었다. IgM과 IgG의 농도는 cyclophosphamide 처리로 정상치의 약 1/2로 떨어졌으나, DEU-7에 의해서 정상치와 동일한 농도로 증가하였다. IL-2와 IL-4 결과에서 DEU-7은 T 림프구에 영향을 줄 수 있다고 생각되며, 또한 IgM과 IgG의 결과로서 B 림프구에 영향을 줄 수 있다고 생각된다. 선천성 면역에 중요한 면역인자인 TNF-α, IL-12과 IFN-γ 역시 cyclophosphamide에 의해 농도가 감소되었으나 DEU-7에 의해 정상치에 가깝게 회복되었다. 따라서, DEU-7은 면역 억제 또는 감소된 상태를 정상 상태로 회복 또는 유지하는 기능이 있는 것으로 생각된다.

• Asian Pacific Journal of Cancer Prevention
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• 제16권16호
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• pp.7179-7188
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• 2015

Cancer is a major health obstacle around the world, with hepatocellular carcinoma (HCC) and colorectal cancer (CRC) as major causes of morbidity and mortality. Nowadays, there isgrowing interest in the therapeutic use of natural products for HCC and CRC, owing to the anticancer activity of their bioactive constituents. Boswellia serrata oleo gum resin has long been used in Ayurvedic and traditional Chinese medicine to alleviate a variety of health problems such as inflammatory and arthritic diseases. The current study aimed to identify and explore the in vitro anticancer effect of B. Serrata bioactive constituents on HepG2 and HCT 116 cell lines. Phytochemical analysis of volatile oils of B. Serrata oleo gum resin was carried out using gas chromatography-mass spectrometry (GC/MS). Oleo-gum-resin of B. Serrata was then successively extracted with petroleum ether (extract 1) and methanol (extract 2). Gas-liquid chromatography (GLC) analysis of the lipoidal matter was also performed. In addition, a methanol extract of B. Serrata oleo gum resin was phytochemically studied using column chromatography (CC) and thin layer chromatography (TLC) to obtain four fractions (I, II, III and IV). Sephadex columns were used to isolate ${\beta}$-boswellic acid and identification of the pure compound was done using UV, mass spectra, $^1H$ NMR and $^{13}C$ NMR analysis. Total extracts, fractions and volatile oils of B. Serrata oleo-gum resin were subsequently applied to HCC cells (HepG2 cell line) and CRC cells (HCT 116 cell line) to assess their cytotoxic effects. GLC analysis of the lipoidal matter resulted in identification of tricosane (75.32%) as a major compound with the presence of cholesterol, stigmasterol and ${\beta}$-sitosterol. Twenty two fatty acids were identified of which saturated fatty acids represented 25.6% and unsaturated fatty acids 74.4% of the total saponifiable fraction. GC/MS analysis of three chromatographic fractions (I,II and III) of B. Serrata oleo gum resin revealed the presence of pent-2-ene-1,4-dione, 2-methyl- levulinic acid methyl ester, 3,5- dimethyl- 1-hexane, methyl-1-methylpentadecanoate, 1,1- dimethoxy cyclohexane, 1-methoxy-4-(1-propenyl)benzene and 17a-hydroxy-17a-cyano, preg-4-en-3-one. GC/MS analysis of volatile oils of B. Serrata oleo gum resin revealed the presence of sabinene (19.11%), terpinen-4-ol (14.64%) and terpinyl acetate (13.01%) as major constituents. The anti-cancer effect of two extracts (1 and 2) and four fractions (I, II, III and IV) as well as volatile oils of B. Serrata oleo gum resin on HepG2 and HCT 116 cell lines was investigated using SRB assay. Regarding HepG2 cell line, extracts 1 and 2 elicited the most pronounced cytotoxic activity with $IC_{50}$ values equal 1.58 and $5.82{\mu}g/mL$ at 48 h, respectively which were comparable to doxorubicin with an $IC_{50}$ equal $4.68{\mu}g/mL$ at 48 h. With respect to HCT 116 cells, extracts 1 and 2 exhibited the most obvious cytotoxic effect; with $IC_{50}$ values equal 0.12 and $6.59{\mu}g/mL$ at 48 h, respectively which were comparable to 5-fluorouracil with an $IC_{50}$ equal $3.43{\mu}g/mL$ at 48 h. In conclusion, total extracts, fractions and volatile oils of B. Serrata oleo gum resin proved their usefulness as cytotoxic mediators against HepG2 and HCT 116 cell lines with different potentiality (extracts > fractions > volatile oil). In the two studied cell lines the cytotoxic acivity of each of extract 1 and 2 was comparable to doxorubicin and 5-fluorouracil, respectively. Extensive in vivo research is warranted to explore the precise molecular mechanisms of these bioactive natural products in cytotoxicity against HCC and CRC cells.

• 생명과학회지
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• 제28권3호
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• pp.339-344
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• 2018

오미자는 전통적인 한약재로서 schizandrin과 gomisin A와 같은 다양한 생리활성물질을 함유하고 있는 것으로 알려져 있다. 본 연구에서는 오미자 박의 에탄올 추출물(PSC)과 schizandrin (SZ) 및 gomisin A (GA)에 의한 항염증 활성 및 그들의 작용기전 연구를 수행하였다. 먼저, PSC는 LPS에 의해 염증이 유도된 RAW264.7 세포에서 세포생존율에는 영향을 미치지 않고 농도의존적으로 nitric oxide (NO) 생성을 감소시켰다. PSC는 염증유발유전자인 iNOS와 COX-2의 발현을 감소시켰으나, $TNF-{\alpha}$의 발현에는 영향을 주지 않았다. 또한 오미자 박의 에탄올 추출물은 p38, ERK1/2 및 JNK의 총 단백질의 발현에는 영향을 주지 않으면서, 그들의 인산화를 감소시켰다. 이러한 결과는 PSC가 MAPK 신호를 저해함으로써 염증 반응을 조절할 수 있음을 시사한다. 또한 SZ와 GA도 LPS에 의해 염증이 유도된 RAW264.7 세포에서 세포 생존율에 영향을 미치지 않으면서 NO 생성을 감소시켰다. SZ은 iNOS 유전자의 발현만을 감소시킨 반면, GA는 iNOS와 COX-2 두 유전자의 발현을 모두 감소시켰다. 종합적으로 이러한 연구결과는 오미자 박 추출물, schizandrin 및 gomisin A에 의해 중재되는 항염증 활성 및 작용기전을 이해하는데 도움을 줄 것이다

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4773-4780
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• 2014

Background: To investigate the effects of small interference RNA (siRNA) targeting BCR/ABL mRNA on proliferation and apoptosis in the K562 human chronic myeloid leukemia (CML) cell line and to provide a theoretical rationale and experimental evidence for its potential clinical application for anti-CML treatment. Materials and Methods: The gene sequence for BCR/ABL mRNA was found from the GeneBank. The target gene site on the BCR/ABL mRNA were selected according to Max-Planck-Institute (MPI) and rational siRNA design rules, the secondary structure of the candidate targeted mRNA was predicted, the relevant thermodynamic parameters were analyzed, and the targeted gene sequences were compared with BLAST to eliminate any sequences with significant homology. Inhibition of proliferation was evaluated by MTT assay and colony-formation inhibiting test. Apoptosis was determined by flow cytometry (FCM) and the morphology of apoptotic cells was identified by Giemsa-Wright staining. Western blotting was used to analyze the expression of BCR/ABL fusion protein in K562 cells after siRNA treatment. Results: The mRNA local secondary structure calculated by RNA structure software, and the optimal design of specific siRNA were contributed by bioinformatics rules. Five sequences of BCR/ABL siRNAs were designed and synthesized in vitro. Three sequences, siRNA1384, siRNA1276 and siRNA1786, which showed the most effective inhibition of K562 cell growth, were identified among the five candidate siRNAs, with a cell proliferative inhibitory rate nearly 50% after exposure to 12.5nmol/L~50nmol/L siRNA1384 for 24,48 and 72 hours. The 50% inhibitory concentrations ($IC_{50}$) of siRNA1384, siRNA1276 and siRNA1786 for 24hours were 46.6 nmol/L, 59.3 nmol/L and 62.6 nmol/L, respectively, and 65.668 nmol/L, 76.6 nmol/L, 74.4 nmol/L for 72 hours. The colony-formation inhibiting test also indicated that, compared with control, cell growth of siRNA treated group was inhibited. FCM results showed that the rate of cell apoptosis increased 24 hours after transfecting siRNA. The results of annexinV/PI staining indicated that the rate of apoptosis imcreased (1.53%, 15.3%, 64.5%, 57.5% and 21.5%) following treamtne with siRNAs (siRNA34, siRNA372, siRNA1384, siRNA1276 and siRNA1786). Morphological analysis showed td typical morphologic changes of apoptosis such as shrunken, fragmentation nucleus as well as "apoptotic bodies" after K562 cell exposure to siRNA. Western blot analysis showed that BCR/ABL protein was reduced sharply after a single dose of 50nmol/L siRNA transfection. Conclusions: Proliferation of K562 cells was remarkbly inhibited by siRNAs (siRNA1384, siRNA1276 and siRNA1786) in a concentration-dependent manner in vitro, with effective induction of apoptosis at a concentration of 50 nmol/L. One anti-leukemia mechanism in K562 cells appeared that BCR/ABL targeted protein was highly down-regulated. The siRNAs (siRNA1384, siRNA1276 and siRNA1786) may prove valuable in the treatment of CML.

• Journal of Nutrition and Health
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• 제53권5호
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• pp.452-463
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• 2020

본 연구는 AT의 뿌리를 제외한 전체 AT의 에탄올 및 물 추출물의 면역 조절 효과를 비교하고 THP-1의 cytokine 분비를 조절하는 분자 메커니즘을 조사하였다. AT의 물 추출물 및 에탄올 추출물은 THP-1 세포에 독성이 없으며 세포 증식을 증가키는 것을 확인하였다. 에탄올 추출물은 영향이 없는데 반해, 물 추출물은 THP-1의 IL-1β의 분비를 증가시켰으며 COX-2 및 iNOS 단백질의 발현을 증가시켰다. 또한, MAPK 및 Akt의 인산화와 IkBα의 분해를 유도하는 것을 확인하였다. AT에 의한 IL-1β 분비는 ERK 및 JNK 억제제에 의해 감소되었으며, TNF-α의 분비는 ERK, p38 MAPK 및 JNK 억제제에 의해 감소되었다. 흥미롭게도, p38 MAPK 억제제는 AT에 의한 IL-1β의 생성을 추가로 증가시켰다. 이 결과는 AT 지상부의 물 추출물에 MAPK 신호 전달 경로를 통해 면역 세포를 자극하여 cytokine의 생산을 유도하는 생리활성물질이 존재한다는 것을 의미한다. 따라서, AT 지상부는 면역력 강화제의 천연 소재로써 이용될 수 있을 것으로 사료된다.

• 한국식품과학회지
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• 제37권6호
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• pp.898-904
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• 2005

본 연구는 화살나무의 줄기와 날개를 열수 추출하여 분자량 크기별로 네 분획(F I. F II, F III, F IV)으로 분리하여 각 분획물의 성분조성을 분석하였고, 이들 각 분획물의 생리활성을 알아보기 위해 DPPH를 이용한 유리 라디칼 소거능과 동물 세포에서 활성산소종 제거능에 대하여 조사하였다. 열수 추출물의 정성반응 결과, 네 분획물 모두 대부분 탄수화물이었고, 소량의 단백질을 함유하였으며, 일부 분획물에는 소량의 페놀 화합물 및 유기산이 함유되어 있었다. 주요 구성 성분인 총당과 총단백질 함량은 448mg/g과 21mg/g이었으며, 총 당의 함량은 F III가 가장 높았고, F IV, F II 및 F I의 순서였다. 네 분획물을 가수분해하여 이들의 구성당을 분석한 결과, 중성당은 mannose : fucose : galactose : glucose가 0.01 : 0.02 : 0.14 : 0.83의 비율로, 아미노당은 galactosamine : glucosamine이 0.01 : 0.99의 비율로 구성되어 있었으며, 전체 구성당 함량에서 중성당 : 아미노당의 비율은 0.94 : 0.04로 조성된 다당체였다. 분획물별로 총단백질과 구성 아미노산은 F IV가 가장 높았으며, F III, F II 및 F I의 순서로 함유하였다. 조 추출물에 함유된 아미노산의 종류와 양은 Glu>Asp>Pro>Gly>Leu>Val>Ser>Ala>Thr>Ile>Phe>Cys>His>Arg>Met>Lys>Try>Trp>Cys2의 순서로 19종의 아미노산이 분석되었으며, 특히 산성 아미노산과 중성 아미노산 함량이 높았다. 네 분획물을 각 농도별로 처리하여 DPPH 유리 라디칼 소거능을 조사한 결과는 $50-1,000{\mu}g/mL$ 처리했을 때 농도에 비례하여 네 분획물 모두에서 F IV, F III, F II 및 F I의 순서로 활성을 나타냈다. CHO-k1 동물 세포에서 활성산소종 제거능을 조사한 결과는, 분획물을 $1-100{\mu}g/mL$까지 처리한 농도에 비례하여 활성이 상승되는 것으로 나타났으나 $100{\mu}/mL$ 이상의 처리농도에서는 거의 변화를 보이지 않았다. 각 분획물별로 F IV이 가장 높은 활성을 보였으며, 그 다음 F III, F I이었으며, F II은 가장 낮은 활성을 나타냈다. 화살나무 열수 추출물 중에는 항산화능과 활성산소종 제거능을 나타내는 물질이 여러 가지 있을 것으로 추정되지만 분자량 크기별로 분획한 네 분획물의 정색반응과 성분조성을 조사한 결과, 주요 구성성분은 단백질이 결합되어 있을 가능성이 높으며, DPPH 유리 라디칼 소거능과 CHO-k1의 세포에서 활성산소종 제거능의 생리활성을 나타내는 다당체(bioactive carbohydrate)일 것으로 사료된다.