原著論文


2018

  1. Kawahata I, and Yamakuni T.
    Imidacloprid, a neonicotinoid insecticide, facilitates tyrosine hydroxylase transcription and phenylethanolamine N-methyltransferase mRNA expression to enhance catecholamine synthesis and its nicotine-evoked elevation in PC12D cells. Toxicology. 394:84-92 (2018). doi:10.1016/j.tox.2017.12.004.
  2. Xia CY, Wang ZZ, Yamakuni T, and Chen NH.
    A novel mechanism of depression: role for connexins.Eur Neuropsychopharmacol. pii: S0924-977X(18)30029-4 (2018). doi: 10.1016/j.euroneuro.2018.01.009.
  3. Kawahata I, Xu H, Takahashi M, Murata K, Han W, Yamaguchi Y, Fujii A, Yamaguchi K, and Yamakuni T.
    Royal jelly coordinately enhances hippocampal neuronal expression of somatostatin and neprilysin genes conferring neuronal protection against toxic soluble amyloid-β oligomers implicated in Alzheimer’s disease pathogenesis. J Funct Foods. 51, 28-38 (2018).

2017

  1. Sun W, Kawahata I, Xu H, Yoshida M, Ando H, Yokosuka A, Mimaki Y, and Yamakuni T.
    Oral sinensetin, but not nobiletin alone, prevents MK801-induced impairment of memory formation in mice, like nobiletin-rich chinpi, a kampo medicine. Tradt. Kampo Med. 4(2): 116-120.
    https://onlinelibrary.wiley.com/doi/abs/10.1002/tkm2.1076
  2. Xia CY, Chu SF, Zhang S, Gao Y, Ren Q, Lou YX, Luo P, Tian MT, Wang ZQ, Du GH, Tomioka Y, Yamakuni T, Zhang Y, Wang ZZ, and Chen NH. Ginsenoside Rg1 alleviates corticosterone-induced dysfunction of gap junctions in astrocytes. J Ethnopharmacol. 208:207-213 (2017). doi: 10.1016/j.jep.2017.06.031.
  3. Kawahata I, Suzuki T, Rico EG, Kusano S, Tamura H, Mimaki Y, and Yamakuni T. Fermented Citrus reticulata (ponkan) fruit squeezed draff that contains a large amount of 4′-demethylnobiletin prevents MK801-induced memory impairment. J Nat Med. 71(4):617-631 (2017). doi: 10.1007/s11418-017-1091-8.
  4. Tyrosine hydroxylase gene expression is facilitated by alcohol followed by the degradation of the protein by ubiquitin proteasome system. Kawahata I, Evelyn GR, Huinan X, Ohtaku S, Tomioka Y, and Yamakuni T. Neuro Endocrinol Lett. 38(1):43-49 (2017).

2016

  1. Jin C, Wang ZZ, Zhou H, Lou YX, Chen J, Zuo W, Tian MT, Wang ZQ, Du GH, Kawahata I, Yamakuni T, Zhang Y, Chen NH, and Zhang DS.
    Ginsenoside Rg1-induced antidepressant effects involve the protection of astrocyte gap junctions within the prefrontal cortex.
    Prog Neuropsychopharmacol Biol Psychiatry. 75:183-191 (2016). doi: 10.1016/j.pnpbp.2016.09.006.
  2. Yamakuni T
    Anti-dementia action of nobiletin-rich chinpi. Journal of Japanese Society of Medical Use of Functional Foods. 10:349-353 (2016).

2015

  1. Kawahata I, Ohtaku S, Tomioka Y, Ichinose H, and Yamakuni T.      Dopamine or biopterin deficiency potentiates phosphorylation at (40)Ser and ubiquitination of tyrosine hydroxylase to be degraded by the ubiquitin proteasome system. Biochem Biophys Res Commun. 465(1):53-58 (2015). doi: 10.1016/j.bbrc.2015.07.125.
  2. Yamakuni T, and Kawahata I. Pharmacological superiority of nobiletin-rich Citrus reticulata peel, a multicomponent drug, over nobiletin alone regarding anti-dementia action. Nihon Yakurigaku Zasshi. 145(5):229-233 (2015). doi: 10.1254/fpj.145.229.

2013

  1. Ichiro Kawahata, Masaaki Yoshida, Wen Sun, Akira Nakajima, Yanxin Lai, Naoya Osaka, Kentaro Matsuzaki, Akihito Yokosuka, Yoshihiro Mimaki, Akira Naganuma, Yoshihisa Tomioka, and Tohru Yamakuni. Potent activity of nobiletin-rich Citrus reticulata peel extract to facilitate cAMP/PKA/ERK/CREB signaling associated with learning and memory in cultured hippocampal neurons - Identification of the substances responsible for the pharmacological action J. Neural Trans. 120, 1397-1409 (2013).
  2. Koichi Aoki, Akihito Yokosuka, Yoshihiro Mimaki, Kohji Fukunaga, and Tohru Yamakuni. Nobiletin induces inhibitions of Ras activity and mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling to suppress cell proliferation in C6 rat glioma cells. Biol. Pharm. Bull. 36, 540-547 (2013).
  3. Takuya Abe, Yoshitomi Kanemitu, Masateru Nakasone, Ichiro Kawahata, Tohru Yamakuni, Akira Nakajima, Naoto Suzuki, Masazumi Nishikawa, Takanori Hishinuma and Yoshihisa Tomioka. SLC10A4 is a protease-activated transporter that transports bile acids. J. Biochem. 154, 93-101 (2013).
  4. Takashi Seki, Tetsuharu Kamiya, Katsutoshi Furukawa, Masako Azumi, Satoshi Ishizuka, Shin Takayama, Satoru Nagase, Hiroyuki Arai, Tohru Yamakuni and Nobuo Yaegashi. Nobiletin-rich Citrus reticulata peels, a kampo medicine for Alzheimer’s disease: A case series, Geriatr. Gerontol. Int. 13, 236-238 (2013).

2012

  1. kira Nakajima, Yukari Kinugasa, Jun Torii, Takanori Hishinuma, Yoshihisa Tomioka, Kiyofumi Yamada and Tohru Yamakuni. Repeated treatment with nicotine induces phosphorylation of NMDA receptor NR2B subunit in the brain regions involved in behavioral sensitization. Neurosci. Lett. 524, 133-138 (2012). 

2011

  1. Saigusa D., Shibuya M., Jinno D., Yamakoshi H., Iwabuchi Y., Yokosuka A., Mimaki Y., Naganuma A., Ohizumi Y., Tomioka Y. & Yamakuni T.  High-performance liquid chromatography with photodiode array detection for determination of nobiletin content in the brain and serum of mice administered the natural compound, Anal. Bioanal. Chem. 400, 3635-3641 (2011).
  2. Saigusa D., Takahashi M., Kanemitsu Y., Shiba K., Ishida A., Jinno D., Abe T., Yamakuni T., Suzuki N. & Tomioka Y. Determination of asymmetric dimethylarginine and symmetric dimethylarginine in biological samples of mice using LC/MS/MS. Am. J. Anal. Chem. 2, 303-313 (2011).
  3. Nakanishi, K., Kawahata, I.,Sun, W., Wang, Y., Masaaki Yoshida, M., Ohizumi, Y. & Yamakuni, T. Shishihakuhito, a traditional Chinese medicine for atopic dermatitis, suppresses NGF-induced neurite extension by inhibition of MEK/ERK signaling in PC12D cells, J. Trad. Med. 28, 16-21 (2011).

2010

  1. Zhang H, Toyohira Y, Ueno S, Shinohara Y, Itoh H, Furuno Y, Yamakuni T, Tsutsumi M, Takahashi K and Yanagihara N. Dual effects of nobiletin, a citrus polymethoxy flavone, on catecholamine secretion in cultured bovine adrenal medullary cells. J. Neurochem. 114, 1030-1038 (2010).
  2. Takeda, S., Minakata, S., Koike, R., Kawahata, I., Narita, A., Kitazawa, M., Ota, M., Yamakuni, T., Maéda, Y. & Nitanai, Y. Two distinct mechanisms for actin capping protein regulation – steric and allosteric inhibition. PLoS Biology, e1000416, 2010.

2009

  1. Kakizaki, A., Oka, N., Tachikawa, E., Miyate, Y., Takahashi, K., Yamamoto, T., Taira, E., Ohizumi, Y. & Yamakuni, T. V-1, a Positive Regulator of Tyrosine Hydroxylase Gene Expression, Promotes Maitotoxin- and Palytoxin-induced Norepinephrine Secretion in PC12D Cells. Pharmacometrics in press.
  2. Tagaya, S., Suetake, Y., Yoshida, K., Shimura, S., Ohizumi Y. & Yamakuni., T. Search for Herbal Extracts with the Activity to Stimulate Tyrosine Hydroxylase Gene Transcription in PC12D Cells. Pharmacometrics, 77, 131-135 (2009).
  3. Nakajima, A., Saigusa, D., Tetsu, N., Yamakuni, T., Tomioka, Y. & Hishinuma, T. Neurobehavioral effects of tetrabromobisphenol A, a brominated flame retardant, in mice. Toxicol. Lett. 189, 78-83 (2009).
  4. Rahim, Md. Al,, Nakajima, A., Saigusa, D., Tetsu, N., Maruyama, Y., Shibuya, M., Yamakoshi, H., Tomioka, Y., Iwabuchi, Y., Ohizumi, Y. & Yamakuni, T. 4′-Demethlynobiletin, a bioactive metabolite of nobiletin enhancing PKA/ERK/CREB signaling, rescues learning impairment associated with NMDA receptor antagonism via stimulation of the ERK cascade. Biochemistry 48, 7713-7721 (2009).
  5. Yamamoto, Y., Shioda, N., Han, F., Moriguchi, S., Nakajima, A., Yokosuka, A., Mimaki, Y., Sashida, Y., Yamakuni, T., Ohizumi, Y. & Fukunaga, K. Nobiletin improves brain ischemia-induced learning and memory deficits through stimulation of CaMKII and CREB phosphorylation. Brain Res. 1292, 218-229 (2009).
  6. Wakabayashi, M., Sakurai, E., Yanai, K., Umemura, K., Yoshida, M., Ohizumi, Y. & Yamakuni, T. Shishihakuhito, a traditional Chinese medicine for atopic dermatitis, inhibits IgE-mediated histamine release from rat RBL-2H3 basophilic leukocyte cells. J. Trad. Med. 26, 44-49, (2009).
  7. Yamaguchi, K., Kogure, A., Murata, K., Hitomi, N., Nakajima, A., Yamakuni, T. & Ohizumi, Y. Honeybee Royal Jelly Stimulates CRE-mediated Transcription in a PKA- but Not MEK/ERK-dependent Manner in PC12D Cells. Pharmacometrics 76, 33-38 (2009).

2008

  1. Rahim, Md. Al., Nakajima, A., Misawa, N., Shindo, K., Adachi, K., Shizuri, Y., Ohizumi, Y. & Yamakuni, T. A novel diol-derivative of chalcone produced by bioconversion, 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one, activates PKA/MEK/ERK signaling and antagonizes A -inhibition of the cascade in cultured rat CNS neurons. Eur. J. Pharmacol. 600, 10-17 (2008).
  2. Rahim, Md. Al, Nakajima, A., Misawa, N., Shindo, K., Adachi, K., Shizuri, Y., Ohizumi, Y. & Yamakuni, T. A Novel Diol-Derivative of Chalcone Produced by Bioconversion, 3-(2,3-dihydroxyphenyl)-1-phenylpropan-1-one, Activates Phosphorylation of ERK and CREB in Cultured Rat Cortical Neurons. Pharmacometrics 74, 131-135 (2008).
  3. Onozuka, H., Nakajima, A., Matsuzaki, K., Shin, R.W., Ogino, K., Saigusa, D., Tetsu, N., Yokosuka, A., Sashida, Y., Mimaki, Y., Yamakuni, T. & Ohizumi, Y. (2008) Nobiletin, a citrus flavonoid, improves memory impairment and A pathology in a transgenic mouse model of Alzheimer’s disease. J. Pharmacol. Exp. Ther. 326, 739-744 (2008).
  4. Aoki, K., Yoshida, M., Ohizumi Y. & Yamakuni, T. Shishihakuhito, a Kampo Medicine for Atopic Dermatitis, Prevents Lipopolysaccharide-Induced Activation of NF- B-Dependent Transcription in C6 Rat Glioma Cells. Pharmacometrics 74, 107-110 (2008).
  5. Ono, Y., Fukaya, Y., Imai, S. & Yamakuni, T. Beneficial effects of Ajuga decumbens on osteoporosis and arthritis. Biol. Pharm. Bull. 31, 1199-1204 (2008).
  6. Matsuzaki, K., Miyazaki, K., Sakai, S., Yawo, H., Nakata, N., Moriguchi, S., Fukunaga, K., Yokosuka, A., Sashida, Y., Mimaki, Y., Yamakuni T. & Yasushi Ohizumi, Y. Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinase A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus. Eur. J. Pharmacol. 578, 194-200 (2008).

2007

  1. 深谷幸隆、小野裕香、今井昇治、山國 徹 自然発症糖尿病マウスに対する「雲南田七」の効果. 応用薬理73, 221-225 (2007).
  2. Guo, Y., Li, Y., Xu, J., Li, N., Yamakuni, T. & Ohizumi, Y. Clerodane diterpenoids and flavonoids with NGF-potentiating activity from the aerial parts of Baccharis gaudichaudiana. Chem. Pharm. Bull. 55, 1532-1534 (2007).
  3. Nakajima, A., Yamakuni, T., Haraguchi, M., Omae, N., Song, S.-Y., Kato, C., Tadano, T, Yokosuka, A, Sashida, Y., Mimaki, Y. & Ohizumi, Y. Nobiletin, A citrus flavonoid, rescues bulbectomy-induced cholinergic neurodegeneration in mice. J. Pharmacol. Sci. 105, 122-126 (2007).
  4. Nakajima, A., Yamakuni, T., Matsuzaki K., Nakata, N., Onozuka, H., Yokosuka, A., Sashida, Y., Yoshihiro Mimaki, Y. & Ohizumi, Y. Nobiletin, a citrus flavonoid, reverses learning impairment associated with NMDA receptor antagonism by activation of ERK signaling. J. Pharmacol. Exp.Ther. 321, 784-790 (2007).

2006

  1. Koizumi, T., Abe, M., Yamakuni, T., Ohizumi, Y., Hitotsuyanagi, Y., Takeya, K. & Sato, Y. Metronomic scheduling of a cyclic hexapeptide RA-VII for anti-angiogenesis, tumor vessel maturation, and anti-tumor activity. Cancer Sci. 97, 665-674 (2006).
  2. Kitazawa, M., Shibata, Y., Hashimoto, S., Ohizumi, Y. & Yamakuni, T. Proinsulin C-peptide stimulates a PKC/I B/NF- B signaling pathway to activate COX-2 gene transcription in Swiss 3T3 fibroblast. J. Biochem. 139, 1083-1088 (2006).
  3. Matsuzaki, K., Yamakuni, T., Hashimoto, M., Haque, A. M., Shido, O., Mimaki, Y., Sashida, Y. & Ohizumi, Y. Nobiletin restoring β-amyloid-impaired CREB phosphorylation rescues memory deterioration in Alzheimer’s disease model rats. Neurosci. Lett. 400, 230-234 (2006).
  4. Kakizaki, A., Takahashi, M., Akagi, H., Tachikawa, E., Yamamoto, T., Taira, E., Yamakuni, T. & Ohizumi, Y. Ca2+ channel activating action of maitotoxin in cultured brainstem neurons. Eur. J. Pharmacol. 536, 223-231 (2006).
  5. Hiwatashi, Y., Yamakuni, T. & Ohizumi, Y. V-1 enhances PMA-induced activation of NF-κB-dependent transcription in PC12D cells. Pharmacometrics 70, 17-20 (2006).
  6. Guo, Y., Li, Y., Xu, J., Watanabe, R., Yamakuni, T., Oshima, Y. & Ohizumi, Y. Clerodane diterpenes from the aerial parts of Baccharis gaudichaudiana. J. Nat. Prod. 69, 274-276 (2006).
  7. Guo, Y., Xu, J., Li, Y., Yamakuni, T. & Ohizumi, Y. Three-membered ring sesquiterpenoids with NGF-potentiating activity from the roots of Valeriana fauriei. Planta Medica 72, 373-375 (2006).
  8. Yamakuni, T., Aoki, K., Nakatani, K., Kondo, N., Oku, H., Ishiguro, K. & Ohizumi, Y. Garcinone B reduces prostaglandin E2 release and NF-κB-mediated transcription in C6 cells. Neurosci. Lett. 394, 206-210 (2006).
  9. Guo, Y., Xu, J., Li, Y., Watanabe, R., Oshima, Y., Yamakuni, T. & Ohizumi, Y. Iridoids and sesquiterpenoids with NGF-potentiating activity from rhizomes and roots of Valeriana fauriei. Chem. Pharm. Bull. 54, 123-125 (2006).

2005

  1. Kakizaki, A., Tachikawa, E., Yamamoto, T., Taira, E., Yamakuni, T., & Ohizumi, Y. Grayanotoxin III nduces catecholamine secretion in bovine adrenal chromaffin cells but not PC 12D cells. Pharmacometrics 69, 65-69 (2005).
  2. Nagase, H., Omae, N., Omori, A., Nakagawasai, O., Tadano, T., Yokosuka, A., Sashida, Y., Mimaki, Y., Yamakuni, T. & Ohizumi, Y. Nobiletin and its related flavonoids with CRE-dependent transcription-stimulating and neuritegenic activities. Biochem. Biophys. Res. Commun. 377, 1330-1336 (2005).
  3. Nagase, H., Yamakuni, T., Matsuzaki, K., Maruyama, Y., Kasahara, J., Fukunaga, K., Hinohara, Y., Kondo, S., Mimaki, Y., Sashida, Y., Tank, A. W. & Ohizumi, Y. Mechanism of neurotropic action of nobiletin in PC12D cells. Biochemistry 44, 13683-13691 (2005).
  4. Kakizaki, A., Tachikawa, E., Yamamoto, T., Taira, E., Yamakuni, T. & Ohizumi, Y. Maitotoxin, palytoxin and grayanotoxin differentially elicit catecholamine secretion in cultured bovine adrenal chromaffin cells. Pharmacometrics 68, 145-152 (2005).
  5. Aoki, K., Yamakuni, T., Yoshida, M. & Ohizumi, Y. Ephedorae herba decreases lipopolysaccharide-induced cyclooxgenase-2 protein expression and NF- B-dependent transcription in C6 rat glioma cells. J. Pharmacol. Sci. 98, 327-330 (2005).
  6. Kitazawa, M., Yamakuni, T., Song, S.-Y., Kato, C., Tsuchiya, R., Ishida, M., Suzuki, N., Adachi, E., Iwashita, S., Ueno, S., Yanagihara, N., Taoka, M., Isobe, T. & Ohizumi, Y. Intracellular cAMP controls a physical association of V-1 with Cap Z in cultured mammalian endocrine cells. Biochem. Biophys. Res. Commun. 331, 181-186 (2005).

 

総説・書籍


  1. 山國 徹  認知症研究に用いられる動物・細胞実験モデル 嗅覚・嗅神経破壊モデル動物, 認知症学上(日本臨牀)69, 247- 25 1(2011).
  2. 山國 徹,中島 晶,大泉 康 日本薬理学会 実験薬理学シリーズ第1巻「創薬、育薬、病態解明のための実践行動薬理学」(金芳堂)「陳皮成分nobiletinの抗認知症作用の行動薬理学的証明と機能性食品開発への応用」
  3. 山國 徹、中島 晶、大泉 康
    陳皮の抗認知症成分ノビレチンによるアミロイドβペプチド(A )の神経毒性発現抑制とA 誘発性記憶障害改善 薬学雑誌 130, 517-520 (2010).
  4. 山國 徹
    アミロイドβペプチドの凝集・毒性発現の分子メカニズムの解明と低分子化合物による阻害:アルツハイマー病の克服に向けて 薬学雑誌 130, 493-494 (2010).
  5. 山國 徹、中島 晶、大泉 康
    陳皮の抗認知症成分nobiletinの薬理作用とその機能性食品開発への応用 応用薬理 76, 1- 5 (2009).
  6. 山國 徹 
    漢方生薬陳皮成分nobiletinの抗認知症作用 日本統合医療学雑誌 1, 60-63 (2008).
  7. 山國 徹、中島 晶、大泉 康
    陳皮成分nobiletinの抗アルツハイマー病作用Clinical Neuroscience 26, 1178-1179 (2008).
  8. 山國 徹、中島 晶、大泉 康
    陳皮の抗認知症成分nobiletinの薬理作用とその機能性食品開発への応用
    日薬理誌 132, 155-159 (2008).
  9. 山國 徹、大泉 康 陳皮の抗アルツハイマー病活性成分ノビレチン ―アルツハイマー病の新しい予防法と根本治療法の確立を目指して― 漢方と最新治療 16, 247-250 (2007).
  10. 山國 徹、大泉 康 ミニ総説:タイ産マンゴスティーン果実抽出物の有効利用の研究―機能性食品、多機能性化粧品への応用 応用薬理 70, 46- 51 (2006).
  11. 山國 徹、大泉 康 最近の研究の話題:「PKA/ERK/CREB依存的シグナル伝達経路を活性化する柑橘類フラボノイドnobiletinはアルツハイマー病モデル動物におけるA 誘発性記憶障害を改善する」応用薬理 70, 35-39 (2006).
  12. 山國 徹 最近の研究の話題:新たな創薬のターゲット-新規カテコラミン合成制御因子V-1 応用薬理 69, 89-94 (2005)