• The Journal of Dong Guk Oriental Medicine
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• v.10
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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.

• Journal of Korean Medical classics
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• v.20 no.4
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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.

• Journal of Life Science
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• v.25 no.10
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• pp.1156-1163
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• 2015

The present study investigated the immunomodulatory properties of four different medicinal plants in a cyclophosphamide-treated Balb/c mouse model. One of the four plants, Ulmus macrocarpa, showed partial resistance against immune suppression induced by cyclophosphamide. The bark of U. macrocarpa, commonly known as the Chinese elm, has been used as a pharmaceutical material in Korean traditional medicine to treat bacterial inflammation and induce wound healing. In this study, water extract of U. macrocarpa, named DEU-7, was used for its immunomodulating functional activity. DEU-7 increased the weight of the spleen and the number of splenocytes but did not significantly affect the liver, kidney, and thymus in vivo. A splenocyte viability assay confirmed that DEU-7 influenced ex vivo splenocyte survival. DEU-7 also increased the levels of cytokines, such as IL-2 and IL-4, and immunoglobulins, such as IgM, IgG, and IgA. These results indicated that DEU-7 is involved in the activation of T and B lymphocytes. In addition, DEU-7 was able to maintain the production of cytokines, such as TNF-α, IL-12, and IFN-γ, in the condition of cyclophosphamide-induced immune suppression, suggesting that DEU-7 activated innate immune cells, even under immune suppression. We concluded that DEU-7 aids immunological homeostasis, thereby preventing immune suppression, and aids both innate and adaptive immune response by maintaining the levels of various cytokines and immunoglobulins. Consequently, it is worth investigating the potential of DEU-7 as a supplemental source for immune-enhancing agents.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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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.

• Journal of Life Science
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• v.28 no.3
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• pp.339-344
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• 2018

Schizandra chinensis has been used as a traditional Chinese medicine and is known to have various bioactive components, including schizandrin and gomisin A. In the current study, we investigated the anti-inflammatory activities and their working mechanisms of ethanol extracts of pomace of Schizandra chinensis (PSC), schizandrin (SZ), and gomisin A (GA). First, we analyzed the effects of PSC on nitric oxide (NO) production and cell viabilities in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. The results indicated that PSC dramatically reduced NO production in LPS-activated RAW264.7 cells in a dose-dependent manner without affecting cell viabilities. PSC also decreased the expression of pro-inflammatory genes iNOS and COX-2, whereas the expression of TNF-${\alpha}$ was not affected by PSC. In addition, PSC inhibited phosphorylation of p38, ERK1/2, and JNK but did not change the expression of their total protein. The results indicate that PSC can regulate LPS-induced inflammatory responses by suppressing MAPK (mitogen-activated protein kinase) signaling. We also analyzed the effects of SZ and GA on NO production and cell viabilities in RAW264.7 cells. The results showed that SZ and GA also decreased NO production in a dose-dependent manner in LPS-activated RAW 264.7 cells without affecting cell viabilities. SZ reduced the expression of iNOS, whereas GA downregulated iNOS and COX-2. Overall, these findings clarify the molecular mechanisms of the anti-inflammatory effects mediated by PSC, SZ, and GA.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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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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• v.53 no.5
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• pp.452-463
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• 2020

Purpose: Aster tataricus (AT) is one of the Asteraceae perennial herbs used in traditional Chinese medicine. The herb contains various bioactive substances, such as flavonoids, isoflavonoids, and phenolic compounds in the roots, and exhibits a range of effects including anti-bacterial, anti-oxidant, and anti-inflammatory activities. This study compared the immunomodulatory effects of ethanol and water extracts of whole AT, except the roots, and analyzed the molecular mechanisms for the regulatory effects on cytokine secretion from THP-1 cells. Methods: The effects of AT extract on the cell viability and proliferation of THP-1 cells were analyzed using the Cell Counting Kit-8 method. The concentrations of interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) in the cell culture supernatant of the AT-treated THP-1 cells were measured using an enzyme-linked immunosorbent assay. The protein levels of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), inhibitor of nuclear factor kappa B (IκBα), and mitogen-activated protein kinase (MAPK) phosphorylation in the cell lysates were determined by western blotting. Results: The water extract and the ethanol extract of AT did not affect the cell viability, and increased the proliferation of THP-1 cells significantly compared to the vehicle. The water extract increased the secretion of IL-1β from THP-1 cells in a dose-dependent manner, but the ethanol extract had no effect. The expression of COX-2 and iNOS protein and the phosphorylation of MAPK and Akt were induced in AT-treated cells. In addition, IκBα was degraded by AT in a concentration-dependent manner. IL-1β secretion by AT was reduced by extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) inhibitors, while TNF-α secretion was decreased by inhibitors of ERK, p38 MAPK, and JNK. Interestingly, the p38 MAPK inhibitor increased the production of IL-1β by AT further. Conclusion: The water extract of the above-ground parts of AT contains immunomodulatory bioactive substances that stimulate immune cells through the MAPK signaling pathway.

• Korean Journal of Food Science and Technology
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• v.37 no.6
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• pp.898-904
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• 2005

Although Euonymus alatus (EA) has been used as traditional medicine for cancer treatment, exact substances involved in curing of the disease are not yet known. Free radical scavenging and reactive oxygen species (ROS) removal activities of aqueous extract components isolated from winged stem of EA in animal cell line were investigated. Aqueous extract of EA (AEEA) was fractionated by ultrafiltration. All fractions mainly consisted of polysaccharide (44.8%), protein (2.1%), small amounts of phenol compounds and organic acids. Antioxidant activity of AEEA increased depending on concentration fractions, as determined by 1,1-diphenyl-2-picrylhydrazyl method. ROS removal activity was visualized in Chinese hamster ovary cell line using laser scanning confocal microscope, and AEEA activity increased in order of F IV>F III>F I>F II. These results suggest AETA has bioactive carbohydrates with potentials as functional foods and antioxidants.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.4
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• pp.417-425
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• 2017

Cnidium monnieri (L.) Cusson is distributed in China and Korea, and the fruit of C. monnieri is used as traditional Chinese medicine to treat carbuncle and pain in female genitalia. In this study, we examined the anti-proliferation and cell cycle arrest effects of ethanol extracts from C. monnieri (CME) in AGS gastric cancer cells. Our results show that CME suppressed cell proliferation and induced release of lactate dehydrogenase (LDH) in AGS cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and LDH assay. Cell morphology was altered by CME in a dose-dependent manner. In order to identify the cell cycle arrest effects of CME, we investigated cell cycle analysis after CME treatment. In our results, CME induced cell cycle arrest at G1 phase. Protein kinase B (Akt) plays a major role in cell survival mechanisms such as growth, division, and metastasis. Akt protein regulates various downstream proteins such as glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) and tumor protein p53 (p53). Expression levels of p-Akt, p-GSK-$3{\beta}$, p53, p21, cyclin E, and cyclin-dependent kinase 2 (CDK2) were determined by Western blot analysis. Protein levels of p-Akt, p-GSK-$3{\beta}$, and cyclin E were reduced while those of p53, p21, and p-CDK2 (T14/Y15) were elevated by CME. Moreover, treatment with CME, LY294002 (phosphoinositide 3-kinase/Akt inhibitor), BIO (GSK-$3{\beta}$ inhibitor), and Pifithrin-${\alpha}$ (p53 inhibitor) showed that cell cycle arrest effects were mediated through regulation of the Akt/GSK-$3{\beta}$/p53 signaling pathway. These results suggest that CME induces cell cycle arrest at G1 phase via the Akt/GSK-$3{\beta}$/p53 signaling pathway in AGS gastric cancer cells.

• Microbiology and Biotechnology Letters
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• v.42 no.1
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• pp.73-81
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• 2014

Salsola collina, also known as Russian thistle, is widely distributed in and around waste facilities, roadsides, and drought and semi-drought areas, and is used as a traditional folk remedy in Chinese medicine for the treatment of hypertension. In this study, we have evaluated the anti-oxidative and anti-cancer activities of the ethanol extract of S. collina Pall. (EESC), and the molecular mechanisms of its anti-cancer effects on human colon carcinoma HT29 cells. EESC exhibited anti-oxidative activity through DPPH radical scavenging capacity and showed cytotoxic activity in a dose-dependent manner in HT29 cells. After EESC treatment, HT29 cells altered their morphology, becoming smaller and irregular in shape. EESC also induced cell accumulation in the G2/M phase in a dose-dependent manner, accompanied by a decrease of cell population in the G1 phase. The G2/M arrest by EESC was associated with the increased expression of cyclin-dependent kinase (CDK) inhibitor p21 and Wee1 kinase, which phosphorylates, or inactivates, Cdc2. EESC treatment induced the phosphorylation of Cdc2 and Cdc25C, and inhibited cyclin A and Cdc25C protein expression. In addition, S arrest was induced by the highest concentration of EESC treatment, associated with a decrease of cyclin A and Cdk2 expression. These findings suggest that EESC may possess remarkable anti-oxidative activity and exert an anti-cancer effect in HT29 cells by cell cycle regulation.