書籍
学術論文
原著論文- 代謝（腸管からの取り込み）
- 代謝（血液脳関門輸送）
- 血圧降下作用
- コレステロール異化作用及び血中脂質低下作用
- オピオイド作用増幅
- 抗炎症作用
- 早流産予防効果
- がんの予防、抗がん作用
- ヘリコバクターの除菌
- 抗真菌(水虫)作用
書籍
ラクトフェリンに関する書籍を記した。
書籍（一般向け）
1. 原田悦守 木元博史 共著 ストレスと痛みを緩和する母乳成分ラクトフェリン 2005. ハート出版
2. 原田悦守 著 安藤邦雄 監修 メタボ、がん、加齢に克つラクトフェリン 2007 ハート出版
3. 安藤邦雄 著 ラクトフェリンとがん 2009 ハート出版
書籍（研究者向け）
1. Geneviève Spik (Editor). Advances in Lactoferrin Research (Advances in Experimental Medicine and Biology). 1998 Springer
2. T. William Hutchens (Editor) and Bo Lönnerdal (Editor). Lactoferrin: Interactions and Biological Functions (Experimental Biology and Medicine) 1997 Humana Press
3. 島崎敬一編Lactoferrin: Structure, Function and Applications 2000 Elsevier Science Pub Co
4. 第2回ラクトフェリンフォーラム実行委員会編 ラクトフェリン2007 日本医学館
5. 第3回ラクトフェリンフォーラム実行委員会編 ラクトフェリン2009 日本医学館
学術論文
ラクトフェリンに関する主要な総説と原著論文を記した。
総説
1. Lönnerdal B and Iyer S. Lactoferrin: molecular structure and biological function. Annu Rev Nutr. 15(1995):93-110
2. Levay PF and Viljoen M. Lactoferrin: a general review Haematologica. 80(1995):252-267
3. 島崎 敬一 ミルクのラクトフェリン 乳業技術 51(2001):1-21
4. OM Conneely. Antiinflammatory activities of lactoferrin. J Am Coll Nutr. 20 (2001, Suppl 5) 389S-397S.
5. Suzuki YA and Lönnerdal B. Characterization of mammalian receptors for lactoferrin. Biochem Cell Biol. 80(2002):75-80
6. 清水洋彦 「ラクトフェリン実用化研究の新たな展開」‐腸溶錠の開発と新規生理作用の発見‐ フードリサーチ 604(2005):54-59
原著論文
代謝（腸管からの取り込み）
1. Harada, E. et al. Characteristic transport of lactoferrin from the intestinal lumen into the bile via the blood in piglets. Comp. Biol. Phsol. 124A (1999): 321-327
2. Talukder. M.J.R. et al. Characteristics of lactoferrin receptors in bovine intestine: higher binding activity to the epithelium overlying Peyer's patch. J. Vet. Med. A50: (2003) 123-131
3. Takeuchi T, Kitagawa H and Harada E. Evidence of lactoferrin transportation into blood circulation from intestine via lymphatic pathway in adult rats. Exp Physiol. 89 (2004):263-70.
代謝（血液脳関門輸送）
1. E. Harada, A. Sugiyama, T. Takeuchi, K. Sitizyo, T. Yajima and T. Kuwata. Characteristic transfer of colostral components into cerebrospinal fluid via serum in neonatal pigs, Biol. Neonate 76: (1999) 33-43
2. C Fillebeen, Descamps L, Dehouck MP, Ferart L, Benaissa M, Spik G and Cecchelli. Receptpr-mediated transcytosis of lactoferrin through the blood-brain barrier. J Biol Chem. 274 (1999) 7011-7017
3. E. Harada, A. Araki, E. Furumura, T. Takeuchi, K. Sitizyo, T. Yajima and T. Kuwata Characteristic transfer of colostrums-derived biologically active substances into cerebrospinal fluid via blood in natural suckling neonate pigs. J. Vet. Med. A 49 (2002) 358-365
4. M.J.R Talukder, T. Takeuchi and E. Harada. Transport of colostral macromolecules into the cerebrospinal fluid via plasma in new born calves. J. Dairy Sci. 85 (2002) 514-524.
5. M.J.R Talukder, T. Takeuchi and E. Harada. Recptor-mediated transport of lactoferrin into cerebrospinal fluid via plasma in young calves. J. Vet. Med. Sci. 65 (2003) 957-964
6. Kitagawa. H. et al. Persorption of bovine lactoferrin from the intestinal lumen into the systemic circulation via the portal vein and mesenteric lymphatics in growing pigs. J. Vet. Med. Sci. 65.(2003) 567-572
7. Ji B, Maeda J, Higuchi M, Inoue K, Akita H, 7. Harashima H and Suhara T. Pharmacokinetics and brain uptake of lactoferrin in rats. Life Sci. 78(2006):851-855
8. Kamemori N, Takeuchi T, Sugiyama A, Miyabayashi M, Kitagawa H, Shimizu H, Ando K and Harada E. Trans-endothelial and trans-epithelial transfer of lactoferrin into the brain through BBB and BCSFB in adult rats. J Vet Med Sci. 70(2008):313-315
9. Huang R, Ke W, Han L, Liu Y, Shao K, Ye L, Lou J, Jiang C and Pei Y. Brain-targeting mechanisms of lactoferrin-modified DNA-loaded nanoparticles. J Cereb Blood Flow Metab. (2009) in press.
血圧降下作用
1. Hayashida K, Takeuchi T, Ozaki T, Shimizu H, Ando K, Miyamoto A and Harada E. Bovine lactoferrin has a nitric oxide-dependent hypotensive effect in rats.
Am J Physiol Regul Integr Comp Physiol. 286 (2004):R359-365
コレステロール異化作用及び血中脂質低下作用
1. 木元博史 ラクトフェリン腸溶錠（アイフェリン）により血清脂質の改善が認められた４例 Ｐｒｏｇ Ｍｅｄ 23(2003):1519-1523
2. 木元博史 クトフェリン腸溶錠により血清脂質の改善が認められた症例 ミルクサイエンス 53(2004):313-314
3. Takeuchi. T. et al. Bovine lactoferrin reduces plasma triacylglycerol and NEFA accompanied by decrease hepatic cholesterol and triglyceride contents in rodents. Br. J. Nutr. 91: (2004) 1-7
4. Moreno-Navarrete JM, Ortega FJ, Bassols J, Castro A, Ricart W, and Fernández-Real JM. Association of circulating lactoferrin concentration and 2 nonsynonymous LTF gene polymorphisms with dyslipidemia in men depends on glucose-tolerance status. Clin Chem. 54(2008):301-309
5. Fernández-Real JM, García-Fuentes E, Moreno-Navarrete JM, Murri-Pierri M, Garrido-Sánchez L, Ricart W, and Tinahones F. Fat Overload Induces Changes in Circulating Lactoferrin That Are Associated With Postprandial Lipemia and Oxidative Stress in Severely Obese Subjects. Obesity (Silver Spring). 2009 in press
オピオイド作用増幅
1. .K. Hayashida, T. Takeuchi, H. Shimizu, K. Ando and E. Harada. Novel function of bovine milk-derived lactoferrin on antinociception mediated by -opioidreceptor in the rat spinal cord. Brain Res. 965 (2003) 239-245
2. K. Hayashida, T. Takeuchi, H. Shimizu, K. Ando and E. Harada. Lactoferrin enhances opioid-mediated analgesia via nitric oxide in the rat spinal cord. Am. J. Physiol. 285: (2003) R306-R312
3. T. Takeuchi, K. Hayashida, H. Inagaki, M. Kuwahara, H. Tsubone, E. Harada. Opioid mediated suppressive effect of milk-derived lactoferrin on distress induced by maternal separation in rat pups. Brain Res. 979 (2003) 216-224
4. T. Takeuchi, M. Iwanaga and E. Harada. Possible regulatory mechanism of DHA-induced anti-stress reaction in rats.
Brain Res. 964 (2003) 136-143
5. N. Kamemori, T. Takeuchi, K. Hayashida and E. Harada. Suppressive effects of milk-derived lactoferrin on psychological stress in adult rats.
Brain Res. 1029 (2004) 34-40
6. Hayashida K, Takeuchi T and Harada E. .Lactoferrin enhances peripheral opioid-mediated antinociception via nitric oxide in rats. Eur J Pharmacol. 484 (2004):175-81.
7. Tsuchiya T, Takeuchi T, Hayashida K, Shimizu H, Ando K and Harada E. Milk-derived lactoferrin may block tolerance to morphine analgesia. Brain Res. 1068(2006):102-108
8. 前田隆子 原田悦守 腸溶性ラクトフェリンによる月経痛緩和とＱＯＬの改善効果 母性衛生 48(2007):239-245
抗炎症作用
1. C Guillen, McInnes IB, Vaughan D, Speekenbrink AB and Brock JH. The effects of local administration of lactoferrin on inflammation in murine autoimmune and infectious arthritis. Arthritis Rheum. 43 (2000) 2073-2080
2. I Kimber, Cumberbatch M, Dearman RJ, Headon DR, Bhushan M and Griffiths CE. Lactoferrin: influences on Langerhans cells, epidermal cytokines, and cutaneous inflammation. Biochem Cell Biol. 80 (2002) 103-107
3. Troost FJ, Saris WH and Brummer RJ. Recombinant human lactoferrin ingestion attenuates indomethacin-induced enteropathy in vivo in healthy volunteers. Eur J Clin Nutr. 57 (2003) 1579-1585
4. Hayashida K, Kaneko T, Takeuchi T, Shimizu H, Ando K and Harada E. Oral administration of lactoferrin inhibits inflammation and nociception in rat adjuvant-induced arthritis. J. Vet. Med. Sci. 66 (2004) 149-154
5. Togawa J, Nagase H, Tanaka K, Inanari M, Nakajima A, Ueno N. and Saito T. Oral administration of lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. J Gastroenterol Hepatoll. 17 (2002) 1291-1298.
6. Togawa J, Nagase H, Tanaka K, Imanari M, Umezawa T, Nakajima A, Naito M, Sato S, Saito T. and Sekihara H. Lactoferrin reduces colitis in rats via modulation of the immune system and correction of cytokine imbalance. Am J Physiol Liver physiol. 283 (2002) G187-G195
7. Ishikado A, Imanaka H, Takeuchi T, Harada E and Makino T.
Liposomalization of lactoferrin enhanced it's anti-inflammatory effects via oral administration. Biol Pharm Bull. 28(2005):1717-1721
早流産予防効果
1. K. Otsuki, A. Yoda, Y. Toma, Y. Shimizu, H. Saito and T. Yanaihara. Lactoferrin and interleukin-6 interaction in amniotic infection. Adv. Exp. Med. Biol. 443 (1998) 267-271
2. K. Otsuki, A. Yoda, H. Saito, Y. Mitsuhashi, Y. Tomita, Y. Shimizu and T. Yanaihara. Amniotic fluid lactoferrin in intrauterine infection. Placenta 20 (1999) 175-179
3. K. Otsuki, A. Yoda, Y. Mitsuhashi, Y. Shimizu, H. Saito and T. Yanaihara and Y. Makino. Isolation and detection of human lactoferrin binding protein in human amniotic membrane. Lactoferrin; Structure, Function and Applications. Excerpta Medica Intern. Congress Series 1195 (2000) 343-346
4. H. Saito, K. Otsuki Y. Mitsuhashi, A. Yoda, T. Yanaihara, Y. Shimizu and T. Yanaihara. Role of lactoferrin in the prevention of preterm delivery. Lactoferrin; Structure, Function and Applications. Excerpta Medica Intern. Congress Series 1195 (2000), 347-352
5. Y. Mitsuhashi, K. Otsuki, A. Yoda, Y. Shimizu, H. Saito and T. Yanaihara. Effect of lactoferrin on lipopolysaccharide (LPS) induced preterm delivery im mice. Acta Obstet. Gynecol. Scand. 79 (2000) 355-358
6. Y. Sasaki, K. Otsuki, A. Hasegawa, M. Sawada, H. Chiba, M. Negishi, M. Nagata and T. Oki. Preventive effect of recombnant human lactoferrin on lipopolysaccharide-induced preterm delivery in mice. Acta Obstet. Gynecol. Scand. 83 (2004) 1035-1038
7. Otsuki K, Yakuwa K, Sawada M, Hasegawa A, Sasaki Y, Mitsukawa K, Chiba H, Nagatsuka M, Saito H and Okai T Recombinant human lactoferrin has preventive effects on lipopolysaccharide-induced preterm delivery and production of inflammatory cytokines in mice. J Perinat Med. 33(2005):320-323
8. Hasegawa A, Otsuki K, Sasaki Y, Sawada M, Mitsukawa K, Chiba H, Nagatsuka M, Okai T and Kato A.
Preventive effect of recombinant human lactoferrin in a rabbit preterm delivery model. Am J Obstet Gynecol. 192(2005):1038-1043
9. Yakuwa K, Otsuki K, Nakayama K, Hasegawa A, Sawada M, Mitsukawa K, Chiba H, Nagatsuka M and Okai T.
Recombinant human lactoferrin has a potential to suppresses uterine cervical ripening in preterm delivery in animal model.
Arch Gynecol Obstet. 275(2007):331-334
10. Nakayama K, Otsuki K, Yakuwa K, Hasegawa A, Sawada M, Mitsukawa K, Chiba H, Nagatsuka M and Okai T.
11. Recombinant human lactoferrin inhibits matrix metalloproteinase (MMP-2, MMP-3, and MMP-9) activity in a rabbit preterm delivery model. J Obstet Gynaecol Res. 34(2008):931-934
がんの予防、抗がん作用
1. K Sekine, Watanabe E, Nakamura J, Takasuka N, Kim DJ, Asamoto M, Krutovskikh V, Baba-Toriyama H, Ota T, Moore MA, Masuda M, Sugimoto H, Nishino H, Kakizoe T. and Tsuda H. Inhibition of azoxymethane-initiated colon tumor by bovine lactoferrin administration in F344 rats. Jpn J Cancer Res. 88 (1997) 523-526
2. K Sekine, Ushida Y, Huhara T, Iigo M, Baba-Toriyama H, Moore MA, Murakoshi M, Satomi Y, Nishino H, Kakizoe T and Tsuda H. Inhibition of initiation and early stage of development of aberrant crypt focci and enhanced natural killer activity in male rats administered lactoferrin concomitantly woth azoxymethane. Cancer Lett. 121 (1997) 211-216
3. Y Ushida, Sekine K, Kuhara T, Takasuka N, Iigo and Tsuda H. Inhibitory effects of bovine lactoferrin on intestinal polyposis in the Apc(min) mouse. Cancer Lett. 134 (1998) 141-145
4. Y Ushida, Sekine K, Kuhara T, Takasuka N, Iigo M and Tsuda H. Possible chemopreventive effects of bovine lactoferrin on esophagus and lung carcinogenesis in the rat. Jpn J Cancer Res. 90 (1999) 262-267
5. M Iigo, Kuhara T, Ushida Y, Sekine K, Moore MA and Tsuda H.; Inhibitory effects of bovine lactoferrin on colon carcinoma 26 lung metastasis in mice. Clin Exp Metasitasis. 17 (1999) 35-40
6. T Tanaka, Kawabata K, Kohno H, Honjo S, Murakami M, Ota T. and Tsuda H.; Chemopreventive effect of bovine lactoferrin on 4-nitroquinoline 1-oxide-induced tongue carcinogenesis in male F344 rats. Jpn J Cnacer Res. 91 (2000) 25-33
7. H Tsuda, Sekine K, Ushida Y, Kuhara T, Takasuka N, Iigo M, Han BS. and Moore MA. Milk and dairy productsi in cancer prevention: focus on bovine lactoferrin. Mutat. Res. 462 (2000) 227-233
8. C Masuda, Wanibuchi H, Sekine K, Yano Y, Otani S, Kishimoto T. and Tsuda H.; Chemopreventive effects of bovine lactoferrin on N-butyl-N-(4-hidroxybutyl) nitrosamine-induced rat bladder carcinogenesis. Jpn J Cancer Res. 91 (2000) 582-588
9. WP Wang, Iigo M, Sato J, Sekine K, Adachi I. and Tsuda H.; Activation of intestinal mucosal immunity in tumor-bearing mice by lactoferrin. Jpn J Cancer Res. 91 (2000) 1022-1027
10. H Tsuda, Sekine K, Takasuka N, Toriyama-Baba H. and Iigo M.; Prevention of colon carcinogenesis and carcinoma metastasis by orally administered bovine lactofriin in animals. Biofactors 12 (2000) 83-88
11. T Kuhara, Iigo M, Itoh T, ushida Y, Sekine K, Terada N, Okamura H. and Tsuda H.; Orally administered lactoferrin exerts an antimetastatic effect and enhances production of IL-18 in the intestinal epithelium. Nutr. Cancer 38 (2000) 192-199
12. H Tsuda, Sekine K, Fujita K. and Iigo M.; Cancer prevention by bovine lactoferrin and underlying mechanisms-a review of experimental and clinical studies. Biochem Cell Biol. 80 (2002) 131-136
13. K Fujita, Ohnishi T, Sekine K, Iigo M. and Tsuda H.; Down-regulation of 2-amino-3,8-dimethylimidazzo{4,5-f}quinoxaline (MeIQx)-induced CYP1A2 expression is associated with bovine lactoferrin inhibition of MeIQx-induced liver and colon carcinogenesis in rats. Jpn J Cancer Res. 93 (2002) 616-625
14. M Iigo, Shimamura M, Matsuda E, Fujita K, Nomoto H, Satoh J, Kojima S, Alexander DB, Moore MA. and Tsuda H.; Orally administered bovine lactoferrin induces caspase-1 and interleukin-18 in the mouse intestinal mucosa: a possible explanation for inhibition of carcinogenesis and metastasis. Cytokine 25 (2004) 36-44
15. K Fujita, Matsuda E, Sekine K, Iigo M. and Tsuda H.; Lactoferrin modifies apoptosis-related gene expression in the colon of the azoxymethane-treated rat. Cancer Lett. 15 (2004) 21-29
16. K Fujita, Matsuda E, Sekine K, Iigo M. and Tsuda h.; Lactoferrin enhances Fas expression and apotosis in the colon mucosa of azoxymethane-treated rats. Carcinogenesis 25 (2004) 1961-1966
17. M Shimamura, Yamamoto Y, Ashino H, Oikawa T, Hazato T, Tsuda H. and Iigo M.; Bovine lactoferrin inhibits tumor-induced angiogenesis. Int. J Cancer 10 (2004) 111-116
18. H. Tsuda et al. Cancer prevention by natural compounds. Drug Metab. Pharmacokin. 19 (2004) 245-263
18. Tsuda H, Ohshima Y, Nomoto H, Fujita K, Matsuda E, Iigo M, Takasuka N and Moore MA.
Cancer prevention by natural compounds. Drug Metab Pharmacokinet. 19(2004):245-263
19. Tsuda H, Ohshima Y, Nomoto H, Fujita K, Matsuda E, Iigo M, Takasuka N and Moore MA.
Cancer prevention by natural compounds. Drug Metab Pharmacokinet. 19(2004):245-263
20. Tamano S, Sekine K, Takase M, Yamauchi K, Iigo M and Tsuda H.
Lack of chronic oral toxicity of chemopreventive bovine lactoferrin in F344/DuCrj rats. Asian Pac J Cancer Prev. 9(2008):313-316
21. Iigo M, Alexander DB, Long N, Xu J, Fukamachi K, Futakuchi M, Takase M and Tsuda H.
Anticarcinogenesis pathways activated by bovine lactoferrin in the murine small intestine. Biochimie. 91(2009):86-101.
22. Kozu T, Iinuma G, Ohashi Y, Saito Y, Akasu T, Saito D, Alexander DB, Iigo M, Kakizoe T and Tsuda H. Effect of orally administered bovine lactoferrin on the growth of adenomatous colorectal polyps in a randomized, placebo-controlled clinical trial. Cancer Prev Res (Phila Pa). 2(2009):975-983
ヘリコバクターの除菌
1. EJ Dial and Lichtenberger LM. Effect of lactoferrin on Helicobacter felis induced gastritis. Biochem Cell Biol. 80(2002):113-117.
2. F. DiMarco et al.; Use of lactoferrin for Helicobacter pylori eradication. Preliminary results. J. Clin. Gastroenterol. 36 (2003) 396-398
3. F. DiMarco et al.: Use of lactoferrin for Helicobacter pylori eradication. Dig. Liver Disease. 35 (2003) 691-693
4. Zou J, Dong J and Yu XF.
Meta-analysis: the effect of supplementation with lactoferrin on eradication rates and adverse events during Helicobacter pylori eradication therapy. Helicobacter. 14(2009):119-127
抗真菌(水虫)作用
1. Yamauchi K, Hiruma M, Yamazaki N, Wakabayashi H, Kuwata H, Teraguchi S, Hayasawa H, Suegara N and Yamaguchi H. Oral administration of bovine lactoferrin for treatment of tinea pedis. A placebo-controlled, double-blind study. Mycoses.43(2000):197-202
2. 安部茂（帝京大（医）真菌研究センター） マウス口腔カンジダ症もデルの開発とその応用： Jpn. J. Med. Mycol. 45 (2004) 227-231