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我々の研究室は、薬用資源として有効なリード化合物および新規化合物の探索と漢方補腎剤の作用機序の解明について研究を行っています。漢方薬を含め天然物には、薬用資源として有効な様々な化合物が含まれています。研究テーマとして、蘚苔類植物に含まれる化学成分に注目し研究を行っています。苔類には様々な炭素骨格を持つテルペノイドや芳香族化合物が含まれ、新奇な炭素骨格を持つ化合物も含まれています。薬用資源として有効なリード化合物探索の一環として、苔類の新規化学成分および生物活性物質について研究を行っています。漢方補腎剤は、薬局等で簡単に購入でき多くの人々が服用しています。しかし作用メカニズムについては、解明されていない部分があります。このことから漢方補腎剤の作用メカニズムの解明を目的として研究を行っています。

[原著論文]

＜長島＞

1. Potential anti-allergic effects of bibenzyl derivatives from liverworts, Radula perrottetii. H. Asai, K. Kato, M. Suzuki, M. Takahashi, E. Miyata, M. Aoi, R. Kumazawa, F. Nagashima, H. Kurosaki, Y. Aoyagi, N. Fukuishi*, Planta Medica, 88(12), 1069-1077 (2022)
2. Distribution of Bibenzyls, Prenyl Bibenzyls, Bis-bibenzyls, and Terpenoids in the Liverwort Genus Radula. Y. Asakawa, F. Nagashima, A. Ludwiczuk, Journal of Natural Products, 83(3), 756-769 (2020)
3. Diterpenoids from the Argentine and Malaysian Liverworts Anastrophyllum and Jungermannia species. F. Nagashima, Y.Asakawa, Natural Product Communications, 14(12), 1-8 (2019).
4. Sesqui- and Diterpenoids from Tahitian and Japanese liverworts Jungermannia species. F. Nagashima, Y. Asakawa, Natural Product Communications, 12(8), 1171-1175 (2017).
5. Terpenoids, Flavonoids and Acetogenins from some Malagasy plants. F. Nagashima, T. Tabuchi, T. Ito, L. Harinantenaina, Y. Asakawa, Natural Product Communications, 11(2), 153-157 (2016).
6. Terpenoids and Steroid components from selected Liverworts. A. Tosun, F. Nagashima, Y. Asakawa, Chemistry of Natural Compounds (Khimiya Prirodnykh Soedinenii), 51(2), 387-391 (2015).
7. Pungent and Bitter, Cytotoxic and Antiviral Terpenoids from Some Bryophytes and Inedible Fungi. Y. Asakawa, F. Nagashima, T. Hashimoto, M. Toyota, A. Ludwiczuk, I. Komala, T. Ito, Y. Yagi, Natural Product Communications, 9 (3), 409-417 (2014).

[著書＆総説]

1. Heterocyclic Stilbene and Bibenzyl Derivatives in Liverworts: Distribution, Structures, Total Synthesis and Biological Activity. Y. Asakawa, F. Nagashima, Heterocycles, 105 (1), 179-201 (2022).
2. Chemical Constituents of Bryophytes: Bio- and Chemical Diversity, Biological Activity, and Chemosystematics. in Progress in the Chemistry of Organic Natural Products; Y. Asakawa, A. Ludwiczuk, F. Nagashima, Springer-Verlag: Wien, New York, Austria, 2013; Vol. 95, pp. 1-796.
3. Y. Asakawa, A. Ludwiczuk, F. Nagashima, Phytochemical and biological studies of bryophytes. Phytochemistry, 91 (1-7), 52-80 (2013).

＜香川＞

1. Hachimijiogan, a traditional herbal medicine, modulates adipose cell function and ameliorates diet-induced obesity and insulin resistance in mice. S. Kagawa*, K. Tanabe*, M. Hiromura, K. Ogawa, T. Koga, T. Maeda, K. Amo-Shiinoki, H. Ochi, Y. Ichiki, S. Fukuyama, S. Suzuki, N. Suizu, T. Ohmine, S. Hamachi, H. Tsuneki, S. Okuya, T. Sasaoka, Y. Tanizawa, F, Nagashima, Frontiers in Pharmacology, 14:1167934 (2023). doi: 10.3389/fphar.2023.1167934
2. Multitasking bamboo leaf-derived compounds in prevention of infectious, inflammatory, atherosclerotic, metabolic, and neuropsychiatric diseases. Kimura I, Kagawa S, Tsuneki H, Tanaka K, Nagashima F, Pharmacology and Therapeutics, 235 (2022). doi.org/10.1016/j.pharmthera.2022.108159
3. Self-administered rhubarb-free kyoseihatekigan has novel anti-asthma effects: Two case reports. Kimura I, Kagawa S*, Nishimura K. Traditional & Kampo Medicine, 4(1), 58-61 (2017).
4. Indoleamine 2,3-dioxygenase promotes peritoneal dissemination of ovarian cancer through inhibition of natural killercell function and angiogenesis promotion. Nonaka H, Saga Y, Fujiwara H, Akimoto H, Yamada A, Kagawa S, Takei Y, Machida S, Takikawa O, Suzuki M. Int J Oncol. 38(1), 113-20 (2011).
5. The inositol phosphatase SHIP2 negatively regulates insulin/IGF-I actions implicated in neuroprotection and memory function in mouse brain. Soeda Y, Tsuneki H, Muranaka H, Mori N, Hosoh S, Ichihara Y, Kagawa S, Wang X, Toyooka N, Takamura Y, Uwano T, Nishijo H, Wada T, Sasaoka T. Mol Endocrinol. 24(10), 1965-77 (2010).
6. Proinflammatory cytokine interferon-gamma increases induction of indoleamine 2,3-dioxygenase in monocytic cells primed with amyloid beta peptide 1-42: implications for the pathogenesis of Alzheimer’s disease. Yamada A, Akimoto H, Kagawa S, Guillemin GJ, Takikawa O. J Neurochem. 110(3), 791-800 (2009).
7. Impact of transgenic overexpression of SH2-containing inositol 5′-phosphatase 2 on glucose metabolism and insulin signaling in mice. Kagawa S, Soeda Y, Ishihara H, Oya T, Sasahara M, Yaguchi S, Oshita R, Wada T, Tsuneki H, Sasaoka T. Endocrinology.149(2), 642-50 (2008).
8. Impact of SRC homology 2-containing inositol 5′-phosphatase 2 gene polymorphisms detected in a Japanese population on insulin signaling. Kagawa S, Sasaoka T, Yaguchi S, Ishihara H, Tsuneki H, Murakami S, Fukui K, Wada T, Kobayashi S, Kimura I, Kobayashi M. J Clin Endocrinol Metab. 90(5), 2911-2919 (2005).