研究テーマ

創薬をめざした各種生薬成分からの生理活性物質の単離、構造決定

地球上には数多くの生物が生息しています.これら生物が、代謝により作り出す化合物もまた計りしれません.現在、広く使われている医薬品のほとんどは、これら天然有機化合物をリード化合物として開発されたものです.私たちの研究室では、生薬成分の単離、構造解析を行なうともに、その生薬の持つ薬効、用途に基づく多方面からの生理活性の検討を行なっています.
 

キーワード

天然物化学、生薬、サプリメント、タンパク質間相互作用、エピゲノム
 

配属学生

大学院生 0名
学部学生 6年次生:8名、5年次生:11名、4年次生:11名

所属教員

研究内容

(1)各種生薬成分の構造解析と生理活性に関する研究

医薬品開発の元になる天然有機化合物を探索するため,生薬や植物より有効成分を単離し,その構造解析を行うとともに,得られた成分については,その生薬のもつ薬効,用途に基づく多方面からの生理活性の検討を行っている.

(2)サプリメントの有用性に関する研究

サプリメントの有用性を確認するため,主要含有成分を単離し,その生理活性の検討を行っている.現在は,アシタバおよびジャバラについて研究を進めている.

(3)エピゲノム・タンパク質間相互作用を制御する生薬成分の探索

薬用植物から単離した成分を基に,後天的遺伝子修飾(エピジェネティクス)やタンパク質間相互作用を制御する天然成分の探索に励んでいます.

代表的論文

2023年

  1. Kimura Y., Taniguchi M., Okuda T., Acertannin Prevented Dextran Sulfate Sodium-induced Colitis by Inhibiting the Colonic Expression of IL-23 and TNF-α in C57BL/6J Mice, Planta Med. 89(7), 746-753, 2023.
  2. Kimura Y., Sumiyoshi M., Taniguchi M., Geniposide prevents tumor growth by inhibiting colonic interleukin-1β and monocyte chemoattractant protein-1 via down-regulated expression of cyclooxygenase-2 and thymocyte selection-associated high mobility box proteins TOX/TOX2 in azoxymethane/dextran sulfate sodium-treated mice, Int Immunopharmacol., 118, 110077, 2023.
  3. Kimura Y., Taniguchi M., Okuda T., Acertannin prevents azoxymethane/dextran sulfate sodium-induced colon cancer growth by inhibiting the colonic expression of interleukin-1β, monocyte chemoattractant protein-1, cyclooxygenase-2, and thymocyte selection-associated high mobility group box proteins (TOX)/TOX2 in C57BL/6J mice, Eur J Pharmacol., 15;947:175680, 2023.
  4. Tawarayama H., Hirata Y., Uchida K., Himori N., Uesato S., Nakazawa T. Isozyme-specific histone deacetylase 1/2 inhibitor K560 attenuates oxidative stress-induced retinal cell death, Neurosci. Lett. 793, 136978, 2023

2022年

  1. Murakami Y., Azuma S., Baba K., Taniguchi M., Furukawa F., Activation of proteinase-activated receptor-2 (PAR-2) simultaneously induces interleukin 8 (IL-8) and suppresses monocyte chemoattractant protein-1 (MCP-1) in HaCaT cells, Trends in Immunotherapy, 6, 41-49, 2022.
  2. Nishino H., Hirata Y., Nagaoka Y., Uesato S., Isoform Selectivity of HDAC Inhibitors Has a Significant Effect on PD-L1 Expression in the Triple-negative Cancer Cell Line MDA-MB-231, Yakugaku zasshi, 142 (4), 431-437, 2022.
  3. Hirata Y., Nishino H., Sasaki T., Nagaoka Y., Uesato S., Taniguchi M., Sirtuin inhibition and neurite outgrowth effect as new biological activities for Areca catechu nut alkaloids, Phytomedicine Plus, 2 (3), 100294-100294, 2022.
  4. Yan H., Sasaki T., Kanki H., Hirata Y., Nishiyama K., Hisada S., Matsumura S., Nagaoka Y., Sumiyoshi T., Nagano S, Nakata A., Yoshida M., Uesato S., Mochizuki H., MDMX elevation by a novel Mdmx-p53 interaction inhibitor mitigates neuronal damage after ischemic stroke, Sci. Rep., 12 (1), 21110-21110, 2022.
  5. Tawarayama H., Hirata Y., Uchida K., Himori N., Uesato S., Nakazawa T., Isozyme-specific histone deacetylase 1/2 inhibitor K560 attenuates oxidative stress-induced retinal cell death, Neurosci. Lett., 793, 136978-136978, 2022.
  6. Ohkura N., Taniguchi M., Oishi K., Inoue K., Ohta M., Angelica keiskei (Ashitaba) has potential as an antithrombotic health food, Food Research, 6, 18-24, 2022.

2021年

  1. Kimura Y., Taniguchi M.: Effects of Perilla frutescens var. crispa herb extract, the essential oil perillaldehyde, and the caffeetannin rosmarinic acid on gastric emptying and gastrointestinal motility in mice, Traditional & Kampo Medicine, 8(3): 194-203, 2021
  2. Azuma S., Murakami Y., Taniguchi M., Baba K., Mima T., Nakamura K.: Daily intake of Citrus jabara fruit peel powder (Japanese Patent No. 5,323,127) improves allergy-like symptoms: A randomized double-blind parallel-group comparative study, Trends in Immunotherapy, 5(2): 21-31, 2021
  3. See K. L., Ying T. S., Hirata Y., Chan L., Nagaoka Y., Uesato S. and Lim P. B.: Biotic elicitation at different feeding time in cell suspension cultures of Eurycoma longifolia Jack, a valuable medicinal plant, for enhancement of cytotoxic activity of bioactive compounds against human colon cancer cell line, In Vitro Cell. Dev. Biol. Plant, 58: 15-27, 2021.
  4. Matsui M., Hirata Y., Iwakawa A., Toyotake Y., Wakayama M., Asano Y.Combination of Enzymatic Oxidation of Amino Acid and Native Chemical Ligation with Hydroxylamine for Amide Formation toward a One-pot Process Chem. Lett., 50 (9): 1632-1634, 2021

2020年

  1. Ying T. S., See K. L., Hirata Y., Chan L., Nagaoka Y., Uesato S.: Cytotoxic Activity of Cell Suspension Cultured and Plant Derived Crude Extracts of Tongkat Ali (Eurycoma longifolia Jack) against Human Cancer Cell Lines., Int. J. Sci. Res. in Biological Sciences, 7(3): 1, 2020
  2. Azuma S., Murakami Y., Azuma E., Baba K., Taniguchi M.: Anti-inflammatory effects of flavonoids in Citrus jabara fruit peels, Trends in Immunotherapy, 4(1): 5-14, 2020.
  3. Inaba Y., Furukawa F., Azuma S., Baba K., Taniguchi M., Murakami Y.: Evaluation of the safety and usefulness of Citrus jabara fruit peel powder cream for patients with atopic dermatitis, Trends in Immunotherapy, 4(1): 42-46, 2020.

2019年

  1. Ohkura N., Atsumi G., Uehara S., Ohta M., Taniguchi M.: Ashitaba (Angelica keiskei) Exerts Possible Beneficial Effects on Metabolic Syndrome., OBM Integrative and Complementary Medicine, 4(1), 2019
  2. Uchiyama H., Wada Y., Hatanaka Y., Hirata Y., Taniguchi M., Kadota K., Tozuka Y.: Solubility and Permeability Improvement of Quercetin by an Interaction Between α-Glucosyl Stevia Nanoaggregates and Hydrophilic Polymer., J. Pharm. Sci., 108(6): 2033, 2019

2018年

  1. Hirata Y., Sasaki T., Kanki H., Choong C. J., Nishiyama K., Kubo G., Hotei A., Taniguchi M., Mochizuki H., Uesato S.: New 5-Aryl-Substituted 2-Aminobenzamide-Type HDAC Inhibitors with a Diketopiperazine Group and Their Ameliorating Effects on Ischemia-Induced Neuronal Cell Death., Sci. Rep., 8 (1): 1400, 2018
  2. Azuma S., Murakami Y., Azuma E., Baba K., Taniguchi M.: Anti-inflammatory effects of flavonoids in Citrus jabara fruit peels. Trends Immunother. , 2: 844, 2018

2017年

  1. Iwase M., Yamamoto T., Nishimura K., Takahashi H., Mohri S., Li Y., Jheng HF., Nomura W., Takahashi N., Kim CS., Yu R., Taniguchi M., Baba K., Murakami S., Kawada T., Goto T.: Suksdorfin Promotes Adipocyte Differentiation and Improves Abnormalities in Glucose Metabolism via PPARγ Activation., Lipids, 52(7): 657-664, 2017
  2. Oishi K., Yamamoto S., Oike H., Ohkura N., Taniguchi M.: Cinnamic acid shortens the period of the circadian clock in mice., Biochem Biophys Rep., 9: 232-237, 2017
  3. Hirata Y., Tatsu M., Amano C., Kawaratani Y., Hirata M., Ohmomo Y., Nagaoka Y., Shibano M., Sasaki T., Uesato S., Taniguchi M., Synergistic Antitumor Effect of Gefitinib (Iressa® ) with Flavonoids from the Scutellaria baicalensis Root on the Non-Small Cell Lung Cells., The Open Plant Science Journal, 10: 62-69, 2017

2016年

  1. Okkura N., Ohnishi K., Taniguchi M., Nakayama A., Usuba Y., Fujita M., Fujii A., Ishibashi K., Baba K., Atsumi G.: Anti-platelet effects of chalcones from Angelica keiskei Koidzumi (Ashitaba) in vivo., Pharmazie., 71: 651-654, 2016
  2. Li Y., Goto T., Ikutani R., Lin S., Takahashi N., Takahashi H., Jheng H., Yu R., Taniguchi M., Baba M., Murakami S., Kawada T.: Xanthoangelol and 4-​hydroxyderrcin suppress obesity-​induced inflammatory responses., Obesity, 24: 2351-2360, 2016
  3. Li Y., Goto T., Yamakuni K., Takahashi H., Takahashi N., Jheng H., Nomura W., Taniguchi M., Baba K., Murakami S., Kawada T.: 4‑Hydroxyderricin, as a PPARγ Agonist, Promotes Adipogenesis, Adiponectin Secretion, and Glucose Uptake in 3T3‑L1 Cells., Lipids, 51: 787-795, 2016
  4. Uesato S., Hirata Y., Sasaki T.: Potential Application of 5-Aryl-Substituted 2-Amino- benzamide Type of HDAC1/2-Selective Inhibitors to Pharmaceuticals, Curr. Pharm. Des., 2016
  5. Uesato S., Matsuura Y., Matsue S., Sumiyoshi T., Hirata Y., Takemoto S., Kawaratani Y., Yamai Y., Ishida K., Sasaki T., Enari M.. : Discovery of new low-molecular-weight p53-Mdmx disruptors and their anti-cancer activities., Bioorg. Med. Chem., 15: 1919-1926, 2016
  6. Choong C. J., Sasaki T., Hayakawa H., Yasuda T., Baba K., Hirata Y., Uesato S., Mochizuki H.: A novel histone deacetylase 1 and 2 isoform-specific inhibitor alleviates experimental Parkinson's disease. Neurobiol. Aging, 37: 103-116, 2016

2015年

  1. Kawaratani Y., Matsuoka T., Hirata Y., Fukata N., Nagaoka Y., Uesato S.: Influence of the carbamate fungicide benomyl on the gene expression and activity of aromatase in the human breast carcinoma cell line MCF-7., Environ Toxicol Pharmacol., 39: 292-299, 2015
  2. Tabata A., Taniguchi M., Shibano M.: Ecliptamines A-D, four new guanidine alkaloids from Eclipta prostrata L., Phytochemistry Letters, 11: 224-228, 2015
  3. Ohkura N., Oiwa H., Ohnishi K., Taniguchi M., Baba K., Atsumi G.: Inhibition of plasminogen activator inhibitor-​1 release from human endothelial cells by Angelica keiskei Koidzumi (Ashitaba) chalcones is structure-dependent., J. Intercult. Ethnopharmacol., 4: 355-357, 2015
  4. Sumiyoshi M., Taniguchi M., Baba K., Kimura Y.: Antitumor and antimetastatic actions of xanthoangelol and 4-hydroxyderricin isolated from Angelica keiskei roots through the inhibited activation and differentiation of M2 macrophages., Phytomedicine, 22: 759-767, 2015

2014年

  1. Hatashita M., Taniguchi M., Baba K., Koshiba K., Sato T., Jujo Y., Suzuki R., Hayashi S.: Sinodielide A exerts thermosensitizing effects and induces apoptosis and G2/M cell cycle arrest in DU145 human prostate cancer cells via the Ras/Raf/MAPK and PI3K/Akt signaling pathways., Int. J. Mol. Med., 33: 406-414, 2014
  2. Sumiyoshi M., Sakanaka M., Taniguchi M., Baba K., Kimura Y.: Anti-tumor effects of various furocoumarins isolated from the roots, seeds and fruits of Angelica and Cnidium specis under ultraviolet A irradiation., J. Nat. Med., 68: 83-94, 2014
  3. Uesato S., Yamashita H., Maeda R., Hirata Y., Yamamoto M., Matsue S., Nagaoka Y., Shibano M., Taniguchi M., Baba K., Ju-ichi M.: Synergistic Antitumor Effect of a Combination of Paclitaxel and Carboplatin with Nobiletin from Citrus depressa on Non-​Small-​Cell Lung Cancer Cell Lines., Planta Med., 80: 452-457, 1014

2013年

  1. Kimura Y., Sumitomo M., Sakanaka M., Taniguchi M., Baba K.: In vitro and In vivo Antiproliferative Effect of a Combination of Ultraviolet-​A and Alkoxy Furocoumarins Isolated from Umbelliferae Medicinal Plants, in Melanoma Cells., Phytochem. Photobiol., 89: 1216-1225, 2013

2012年

  1. Shibano M., Misaka A., Sugiyama K., Taniguchi M., Baba K.: Two secopregnane-type steroidal glycosides from Cynanchum stauntonii (Decne.) Schltr.ex Levl., Phytochemistry Letters, 5: 304-308, 2012
  2. Kimura Y., Sumiyoshi M., Taniguchi M., Baba K.: Metabolites of 3'-O-acetylhamaudol isolated from Angelica japonica roots, and their antitumor actions., Natural Products Journal, 2: 20-30, 2012
  3. Hirata Y., Hirata M., Kawaratani Y., Shibano M., Taniguchi M., Yasuda M., Ohmomo Y., Nagaoka Y., Baba K., Uesato S.: Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl)benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain., Bioorg. Med. Chem. Lett., 22: 1926-1930, 2012