SEARCH
検索詳細
柘植 厚志 (ツゲ アツシ)
| 薬学研究院 医療薬学部門 医療薬学分野 | 助教 |
研究者基本情報
■ 学位■ URL
researchmap URLホームページURL■ ID 各種
研究者番号
- 71002870
研究キーワード研究分野■ 担当教育組織
研究活動情報
■ 受賞■ 論文
- Berberine is a key active component underlying the anti-allergic actions of orengedokuto in a murine model of contact hypersensitivity.
Mitsuhiko Nose; Atsushi Tsuge; Meika Mizuno; Yuki Kodama; Atsuki Watanabe; Masato Kishi; Fumiaki Ohashi; Shinsuke Hisaka
Journal of natural medicines, 2026年05月27日, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, Orengedokuto (OGT) is used to treat atopic dermatitis. We previously reported that OGT exerts anti-allergic effects by inhibiting effector T cell activation in a murine model of contact hypersensitivity (CHS). However, the active crude drugs and ingredients responsible for these effects remain unknown. Here, we evaluated the effects of hot water extracts of four crude drugs (Scutellaria radix, Coptidis rhizome, Phellodendri cortex and Gardenia fructus) constituted in OGT. The results showed that Phellodendri cortex is an active crude drug of OGT. As berberine-baicalin and berberine-wogonoside complexes precipitate in OGT decoction, we prepared the supernatant and precipitate fractions of OGT and then compared their anti-allergic effects on a 2,4,6-trinitrichlorobenzene-induced CHS mouse model. Interestingly, the precipitated fraction of OGT exhibited anti-allergic effects. Liquid chromatography-tandem mass spectrometry analysis of the serum concentration of berberine after oral administration of OGT or its fractions suggested that berberine is an active ingredient in OGT. Adoptive transfer experiments and ex vivo and in vitro studies demonstrated that berberine exerts anti-allergic effects via inhibiting effector T cell activation in a murine CHS model. In conclusion, Phellodendri cortex in OGT appears to be an active crude drug with anti-allergic action in a murine 2,4,6-trinitrichlorobenzene-induced CHS model, and berberine may be the active ingredient. The detailed molecular mechanism by which berberine inhibits T cell receptor stimulation and interferon-γ production in effector T cells remains unclear. - A Comparative Study of Serum Glycyrrhetinic Acid Concentrations Following Oral Administration of 24 Types of Kampo Extracts Containing Glycyrrhiza Radix in Mice
Mitsuhiko Nose; Hikari Ota; Sakura Fujii; Asuka Kato; Shunpei Tsuchiya; Momoka Tada; Rika Kojima; Kumiko Nagata; Kazuma Yamanaka; Atsushi Tsuge; Shinsuke Hisaka
Traditional & Kampo Medicine, 13, 1, Wiley, 2026年03月15日, ［査読有り］
研究論文（学術雑誌）, ABSTRACT
Aim
To examine serum glycyrrhetinic acid (GA) concentrations following oral administration of Glycyrrhiza radix (GR) containing Kampo extracts in mice.
Methods
We prepared 24 types of GR‐containing Kampo extracts which were orally administered to mice at 10 times the human dose. Subsequently, serum GA concentrations were measured using high‐performance liquid chromatography. In addition, glycyrrhizin hydrolysis by cecal contents and small intestinal transport were measured to clarify differences in pharmacokinetic parameters among the Kampo extracts.
Results
Concerning blood GA concentrations, the prescriptions showed both bimodal and unimodal profiles, which could be attributed to differences in the constituent crude drugs. We further verified that Scutellaria radix inhibited glycyrrhizin (GL) hydrolysis mediated by intestinal flora. These findings suggest that serum GA concentrations should be established for each prescription. There was a good correlation between Cmax and AUC 0‐48 ; furthermore, a strong correlation was observed between the amounts of GR or GL administered and AUC 0‐48 . In contrast, only a weak correlation was found between the amount of GR and the Cmax of GA. Given that GA enters enterohepatic circulation, AUC 0‐48 is proportional to the administered dose. However, it is influenced by factors such as the rate of intestinal absorption, as well as rates of hydrolysis and reabsorption after biliary excretion; therefore, no simple correlation with Cmax was observed.
Conclusion
Our findings suggest that the total amount of GA absorbed following consumption of a GR‐containing Kampo extract can be estimated from the amount of the crude drug. - 黄連解毒湯の苦味に対する構成生薬の影響
柘植厚志; 後藤佑斗; 伊藤美千穂; 袴塚高志; 児玉有希; 岸正都; 日坂真輔; 能勢充彦; 政田さやか
生薬学雑誌, 78, 2, 139, 146, 2024年08月, ［査読有り］, ［筆頭著者］
日本語, 研究論文（学術雑誌） - Resultant compound from sublimation test for Gentianae Radix in Japanese Pharmacopoeia was 5-(hydroxymethyl)furfural
Atsushi Tsuge; Yuto Goto; Sayaka Masada; Michiho Ito
Journal of Natural Medicines, Springer Science and Business Media LLC, 2024年03月19日, ［査読有り］, ［筆頭著者］
英語, 研究論文（学術雑誌） - Hochuekkito exerts the anti-allergic effects via activating regulatory T cells in a murine model of contact hypersensitivity.
Atsushi Tsuge; Shunsuke Chiba; Yui Yagura; Mari Okamoto; Satoshi Muto; Shinsuke Hisaka; Mitsuhiko Nose
Journal of natural medicines, 2023年02月03日, ［査読有り］, ［筆頭著者］, ［国内誌］
英語, 研究論文（学術雑誌）, Hochuekkito (HET) is a Kampo prescription, used for the clinical treatment of skin diseases such as atopic dermatitis (AD), in Japan. Oral administration of HET exerts anti-allergic effects in an experimental dermatitis mice model and in patients with atopic dermatitis; however, the mechanism underlying the anti-allergic effects of HET is still unclear. Therefore, we investigated the immunopharmacological properties of the anti-allergic actions of HET using a 2,4,6-trinitrochlorobenzene (TNCB)-induced murine contact hypersensitivity (CHS) model and adoptive cell transfer experiments. Oral administration of HET (1.4 g/kg) exhibited anti-allergic effects in a TNCB-induced CHS model via activation of Tregs; this activation was observed even without antigen sensitization in donor mice. Activation was dependent on the duration of HET administration and required at least 4 days of dosing. In addition, the anti-allergic effects of HET through the activation of Tregs were not antigen specific. Flow cytometry results indicated that the proportion of CD4+CD25+Foxp3+ cells in the splenic lymphocytes increased after oral administration of HET. Therefore, oral administration of HET induced both inducible regulatory T cells (iTregs) and thymus-derived naturally occurring regulatory T cells (nTregs). Ginseng radix and Bupleuri radix were involved in the anti-allergic actions of HET through the induction and/or activation of Tregs; Bupleuri radix participated in the activation of nTregs. In conclusion, our findings suggest that HET exerts the anti-allergic effects through the induction and/or activation of Tregs. These findings elucidate the usefulness of HET as an immunomodulator. - Orengedokuto exerts anti-allergic effects via inhibition of effector T cell activation in a murine model of contact hypersensitivity.
Atsushi Tsuge; Atsuki Watanabe; Yuki Kodama; Shinsuke Hisaka; Mitsuhiko Nose
Journal of natural medicines, 76, 1, 144, 151, 2022年01月, ［査読有り］, ［筆頭著者］, ［国内誌］
英語, 研究論文（学術雑誌）, Orengedokuto (OGT) is a Kampo prescription that has been used for the treatment of inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases. It is also used for the treatment of skin diseases such as urticaria and atopic dermatitis. We previously studied its anti-allergic effects of OGT on the murine model of 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying this activity remained unknown. Here, we sought to identify the mechanism involved. Using a murine model of TNCB-induced CHS, together with adoptive cell transfer experiments, we found that the anti-allergic effects of OGT may be due to the inhibition of effector T cell activation and not the induction and/or activation of regulatory T cells. Flow cytometry analysis revealed that oral administration of OGT suppressed the increase in CD8+CD44highCD62L+ cell number in draining lymph nodes (dLNs) of mice sensitized with 5% TNCB. Additionally, ex vivo experiments confirmed the suppressive effect of OGT on the activation of effector T cells, as interferon-γ (IFN-γ) production by cultured lymphocytes obtained from 5% TNCB-sensitized mice and stimulated with anti-CD3ε and anti-CD28 monoclonal antibodies was reduced by OGT administration. In conclusion, our finding suggests that OGT exerts anti-allergic effects by regulating the activation of effector T cells involved in inflammatory skin diseases such as atopic dermatitis. - Juzentaihoto Exerts Anti-Allergic Effects by Inhibiting Effector T-Cell Activation and Inducing and/or Activating Regulatory T Cells in a Murine Model of Contact Hypersensitivity.
Atsushi Tsuge; Sho Yonekura; Satomi Watanabe; Yuta Kurosaki; Shinsuke Hisaka; Mitsuhiko Nose
International archives of allergy and immunology, 183, 1, 1, 13, 2022年, ［査読有り］, ［筆頭著者］, ［国際誌］
英語, 研究論文（学術雑誌）, BACKGROUND: Juzentaihoto (JTT) is a Kampo prescription that has been used clinically for treating skin diseases such as atopic dermatitis in Japan. We have previously studied the anti-allergic effects of JTT on 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) in mice and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying the anti-allergic actions of JTT is obscure. METHODS: We investigated the mechanism underlying the anti-allergic effects of JTT using a TNCB-induced murine CHS model and adoptive cell transfer experiments. RESULTS: We showed that the anti-allergic effects of JTT are due to inhibition of effector T-cell activation and induction and/or activation of regulatory T cells. Furthermore, ex vivo experiments confirmed the effect of JTT on the activation of effector T cells and regulatory T cells, as interferon-γ production decreased, whereas interleukin (IL)-10 production increased, in the cultured lymphocytes obtained from 5% TNCB-sensitized mice treated with anti-CD3ε and anti-CD28 monoclonal antibodies. Flow cytometry showed that the CD4+CD25+Foxp3+, CD4+CD25+Foxp3-, and CD8+CD122+ cell population increased after oral administration of JTT. Finally, the anti-allergic effect of JTT by inducing and/or activating regulatory T cells (Tregs) was confirmed to be mediated by IL-10 through in vivo neutralization experiments with anti-IL-10 monoclonal antibodies. CONCLUSION: We suggested that JTT exerts anti-allergic effects by regulating the activation of effector T cells and Tregs involved in murine CHS model. - Effect of glucoglycyrrhizin on IgE-mediated immediate hypersensitivity in mice.
Mitsuhiko Nose; Shinsuke Hisaka; Atsushi Tsuge; Hiroaki Hayashi
Journal of natural medicines, 75, 4, 994, 997, 2021年09月, ［査読有り］, ［国内誌］
英語, 研究論文（学術雑誌）, To evaluate the pharmacological property of glucoglycyrrhizin (GGL), a unique glycoside of glycyrrhetinic acid (GA), we investigated the anti-allergic effect of GGL on IgE-mediated immediate hypersensitivity in mice. GGL exhibited the antiallergic effect against IgE-mediated immediate hypersensitivity. At a dose of 100 mg/kg, GGL exhibited antiallergic activity equivalent to that of glycyrrhizin (GL). Furthermore, the pretreatment with anti-GA monoclonal antibody eliminated the antiallergic action of GGL. These results indicated that GGL may act in the same way as GL in the human body. Its safety should be verified for its use as a drug similar to GL. - Effect of hot water extract of a glycyrrhizin-deficient strain of Glycyrrhiza uralensis on contact hypersensitivity in mice.
Atsushi Tsuge; Shinsuke Hisaka; Hiroaki Hayashi; Mitsuhiko Nose
Journal of natural medicines, 74, 2, 415, 420, 2020年03月, ［査読有り］, ［筆頭著者］, ［国内誌］
英語, 研究論文（学術雑誌）, To evaluate the medicinal properties of a glycyrrhizin (GL)-deficient strain of Glycyrrhiza uralensis, we investigated the anti-allergic effect of the hot water extract obtained from its roots on contact hypersensitivity in mice, and compared it with that of the hot water extract of a commercial crude drug, Glycyrrhiza Radix. The hot water root extract of the GL-deficient strain contained glucoglycyrrhizin (GGL) and rhaoglucoglycyrrhizin (RGL) instead of GL, and it showed anti-allergic activity against contact hypersensitivity in a fashion similar to that of the crude drug extract. We further confirmed the presence of glycyrrhetinic acid (GA), a major metabolite of GL, in mice serum after oral administration of the hot water root extract of a GL-deficient strain. We demonstrated that GGL underwent hydrolysis by intestinal microflora of mice to form GA. These results suggest that a GL-deficient strain of G. uralensis is a useful medicinal resource since the glycosides of GA work in a fashion similar to that of GL when orally administered.
- メタボロミクスを用いた多成分系医薬品の活性成分の探索および作用機序解析
柘植厚志, ファルマシア, 61, 4, 352, 352, 2025年04月, ［筆頭著者, 責任著者］
記事・総説・解説・論説等（学術雑誌）
- 〔主要な業績〕骨髄由来間葉系間質細胞の増殖能の維持および機能亢進に資する漢方方剤について
小坂 菜々実; 柘植 厚志; 清水 雅也; 陳 佳琪; 坂井 宏旭; 坂井 優夫; 前原 経; 大久保 直登; 大西 俊介
第43回和漢医薬学会学術大会., 2026年08月23日, 日本語, ポスター発表
2026年08月22日 - 2026年08月23日, 53386630 - 〔主要な業績〕骨髄由来間葉系間質細胞の老化抑制および機能強化に資する漢方薬の探索
清水 雅也; 柘植 厚志; 陳 佳琪; 坂井 宏旭; 前原 経; 大久保 直登; 大西 俊介
第25回日本再生医療学会総会, 2026年03月19日, ポスター発表 - 〔主要な業績〕クローン病に伴う痔瘻モデル作製の試み
小松 葉月; 柘植 厚志; 杉浦 弘周; 飯田 千菜; 川村 芳江; 河南 雅成; 前原 経; 大久保 直登; 大西 俊介
第24回日本再生医療学会総会, 2025年03月21日, ポスター発表 - TGF-β-decoy EVを用いた線維化シグナル抑制
山之内 海心; 細野 秀崇; 中嶋 楓; 前原 経; 柘植 厚志; 大久保 直登; 大西 俊介
第24回日本再生医療学会総会, 2025年03月21日, 口頭発表（一般） - 羊膜間葉系幹細胞由来液性因子HSPB6の抗炎症効果についての検討
太田 友里奈; 前原 経; 酒井 真央; 小林 美春; 武井 則雄; 柘植 厚志; 大久保 直登; 林 真広; 中石 智之; 大西 俊介
第24回日本再生医療学会総会, 2025年03月20日, ポスター発表 - TGF-β-decoy EVを用いた線維化シグナル抑制の試み
山之内 海心; 細野 秀崇; 中嶋 楓; 前原 経; 柘植 厚志; 大久保 直登; 大西 俊介
第37回北海道薬物作用談話会, 2024年08月18日, 口頭発表（一般） - 〔主要な業績〕日本薬局方ゲンチアナ確認試験（1）昇華試験で得られる確認成分の同定
柘植 厚志; 政田 さやか; 伊藤 美千穂
日本薬学会第144年会, 2024年03月29日
2024年03月29日 - 2024年03月31日 - 〔主要な業績〕TLCを用いたセネガ確認試験の検討（2）
柘植 厚志; 政田 さやか; 北添 達樹; 白畑 辰弥; 小林 義典; 伊藤 美千穂
日本薬学会第144年会, 2024年03月29日, ポスター発表
2024年03月29日 - 2024年03月31日 - 〔主要な業績〕抑肝散エキスに含まれるgeissoschizine methyl etherの定量法の検討
柘植厚志; 政田さやか; 伊藤美千穂
日本生薬学会第68回年会, 2023年09月10日, ポスター発表 - 漢方処方の科学的解析（第40報）マウス接触性皮膚炎モデルにおける黄連解毒湯の抗アレルギー作用に関わる有効成分について
水野芽衣花; 岸正都; 児玉有希; 渡辺敦貴; 柘植厚志; 日坂真輔; 能勢充彦
日本生薬学会第69回年会, 2023年09月09日, ポスター発表 - 〔主要な業績〕漢方製剤の適用拡大を念頭にした基盤整備研究②～抑肝散を例に～
柘植厚志; 政田さやか; 内山奈穂子; 伊藤美千穂
第40回和漢医薬学会学術大会, 2023年08月27日, ポスター発表 - 〔主要な業績〕TLCを用いたセネガ確認試験法の検討
柘植厚志; 政田さやか; 伊藤美千穂
日本薬学会第143年会, 2023年03月26日, 口頭発表（一般） - 〔Major achievements〕Metabolomic analysis using LC-HRMS to search for characteristic constituent for quality control of Senega
Atsushi TSUGE; Taichi YOSHITOMI; Yuto GOTO; Kazuhiko YAMAMOTO; Takuro MARUYAMA; Noriaki KAWANO; Kayo YOSHIMATSU; Michiho ITO; Sayaka MASADA
The 9th International Symposium of the Western Pacific Regional Forum for the Harmonization of Herbal Medicines, 2023年02月23日, シンポジウム・ワークショップパネル（公募） - Berberine-baicalin複合体が黄連解毒湯の苦味に与える影響について
政田さやか; 後藤佑斗; 伊藤美千穂; 袴塚高志; 柘植厚志; 児玉有希; 岸正都; 日坂真輔; 能勢充彦
日本生薬学会第68回年会, 2022年09月10日, ポスター発表 - 〔主要な業績〕チョウトウコウおよび抑肝散エキス中に含まれるgeissoschizine methyl ether含有量の比較
柘植厚志; 伊藤美千穂; 政田さやか
日本生薬学会第68回年会, 2022年09月10日, ポスター発表 - 〔主要な業績〕日米欧医薬品公定規格に収載される生薬の確認試験法および成分定量法の比較
柘植厚志; 伊藤美千穂; 政田さやか
第8回次世代を担う若手のためのレギュラトリーサイエンスフォーラム, 2022年08月26日, ポスター発表 - 〔主要な業績〕漢方処方の科学的解析（第31報）マウス接触性皮膚炎モデルにおける黄連解毒湯の抗アレルギー作用について
児玉有希; 柘植厚志; 渡辺敦貴; 日坂真輔; 能勢充彦
第38回和漢医薬学会学術大会, 2021年09月04日, 口頭発表（一般） - 〔主要な業績〕漢方処方の科学的解析（第30報）十全大補湯が誘導・活性化する制御性T細胞の同定
柘植厚志; 黒崎雄太; 日坂真輔; 能勢充彦
第37回和漢医薬学会学術大会, 2020年08月29日, ポスター発表 - 〔主要な業績〕Glycyrrhiza uralensis グリチルリチン非産生株の抗アレルギー作用について
柘植厚志; 日坂真輔; 能勢充彦; 林宏明
日本生薬学会第66回年会, 2019年09月22日, ポスター発表 - 〔主要な業績〕漢方処方の科学的解析（第25報）補中益気湯が活性化する内在性制御性T細胞について
柘植厚志; 武藤悟史; 矢倉唯; 日坂真輔; 能勢充彦
日本薬学会第139年会, 2019年03月22日, 口頭発表（一般） - 〔主要な業績〕漢方処方の科学的解析（第21報） マウス接触性皮膚炎モデルにおける補中益気湯の作用機序について
柘植厚志; 武藤悟史; 岡本麻莉; 矢倉唯; 千葉俊輔; 日坂真輔; 能勢充彦
天然物研究方法論アカデミー第20回研究集会, 2017年08月05日, シンポジウム・ワークショップパネル（公募） - 〔主要な業績〕漢方処方の科学的解析（第16報）補剤の制御性T細胞を介した抗アレルギー作用について
柘植厚志; 浅井紀久子; 岡本麻莉; 日坂真輔; 能勢充彦
第33回和漢医薬学会学術大会, 2016年08月27日, ポスター発表
■ 所属学協会
■ 共同研究・競争的資金等の研究課題
- 間葉系間質細胞の線維化抑制性液性因子の同定と機序解明
科学研究費助成事業
2026年04月 - 2029年03月
大西 俊介; 柘植 厚志
日本学術振興会, 基盤研究(C), 北海道大学, 研究分担者, 26K10918 - 十全大補湯による高齢者骨髄由来間葉系間質細胞の老化抑制および機能増強培養法の開発
科学研究費助成事業
2026年04月 - 2029年03月
柘植 厚志
日本学術振興会, 若手研究, 北海道大学, 研究代表者, 26K18837 - 骨髄由来間葉系間質細胞の細胞老化に対する六君子湯の有用性
2026年度 若手研究人材・ネットワーク育成補助金（タレント補助金）
2026年08月 - 2027年03月
柘植 厚志
ノーステック財団, 北海道大学, 研究代表者 - フレイルに応用される漢方薬の血管老化への有効性と作用機序解析
2024年度 若手研究人材・ネットワーク育成補助金（タレント補助金）
2024年08月 - 2025年03月
柘植 厚志
ノーステック財団, 研究代表者
学術貢献活動社会貢献活動
