臺灣博碩士論文加值系統

第一部份
實際應用
深層海水已廣泛被應用於很多方面，包括水產養殖、農業、食品製程、化妝品與醫學等等，近來我們更已經證實飲用深層海洋電解透析水可以有效降低血清脂質、血壓以及改善血液中各種膽固醇的比例，本研究更進一步發現深層海洋電解透析水可以保護餵食高膽固醇食物之小白鼠的心肌結構、左心室的細胞程序凋亡、增加心肌細胞存活信息如胰島素樣-1受體、PI3激酶與p-AKT/AKT比例 總體而言，綜合以上發現深層海洋電解透析水對心肌有保護作用，在潛在的多種市場中，可以運用於開發做為保護心臟之健康飲食的食品添加物。

第二部份
中藥在東方醫學仍然廣泛地被應用為重要的醫療用途。在最近幾年中，各種中藥的生物活性成份已被分離純化，並在研究實驗中被確認具有多種生理調節功能。「和厚朴酚」是一種由木蘭屬植物分離出的小分子植物多酚。它伴隨著其他相關多酚類包括「厚朴酚」等一同被發現，並具有相似的一些生理活性功能。近年來，和厚朴酚與厚朴酚在臨床前模式被發現具有抗氧化，抗發炎，抗腫瘤，抗微生物等作用，同時不具明顯的毒性。這些發現使得和厚朴酚與厚朴酚具有新的治療藥物開發潛力。在本論文中，我們對和厚朴酚與厚朴酚的近期實驗成果加以調查研究，並對於其可能的分子機制進行了描述。對於和厚朴酚與厚朴酚知識的多加了解，可以協助發展抗氧化中藥厚朴衍生物與臨床試驗的設計，未來有機會將和厚朴酚與厚朴酚應用在臨床皮膚疾患的治療上。

Part 1
PRACTICAL APPLICATIONS
Deep-sea water (DSW) has been applied on several fields including aquaculture, agriculture, food processing, cosmetics, and medicine. Recently, we have indicated that high-cholesterol dietary mice drinking ED-DSW showed decreased serum lipids, blood pressure and improving blood cholesterol profile. In this study, we further demonstrated the beneficial effects of ED-DSW on high-cholesterol-dietary mice by reducing abnormal cardiac architecture, apoptosis in left ventricle and increasing cardiac survival signaling, such as insulin-like growth factor-1 receptor (IGF-1R), phosphoinositide-3-kinases (PI3K) and p-AKT/AKT ratio. Altogether, these findings indicated that ED-DSW revealed the cardiac protective effects and might be suggested as an ingredient of cardiovascular health food in a variety of niche markets.

Part 2
Chinese herbs have been and still are widely used as important remedies in Oriental medicine. Over the recent years, a variety of biologically active constituents have been isolated from these sources and confirmed to have multifunctional activity in experimental studies. Honokiol is a small-molecule polyphenol isolated from the genus Magnolia. It is accompanied by other related polyphenols, including magnolol, with which it shares certain biological properties. Recently, honokiol and magnolol have been found to have anti-oxidative, anti-inflammatory, anti-tumor, and anti-microbial properties in preclinical models, without appreciable toxicity. These findings have increased interest in bringing honokiol and magnolol to the clinic as novel therapeutic agents in dermatology. In this review, the findings concerning the major mechanisms of action of honokiol and magnolol are described. Knowledge of the multiple activities of honokiol and magnolol can assist with the development of honokiol and magnolol derivatives and the design of clinical trials that will maximize the potential benefit of honokiol and magnolol in the patient setting for dermatologic disorders.

封面內頁
授權書
口試委員簽名單
指導教授簽名單
重要名詞中英文對照及縮寫表 Ⅰ.
第一部份中文摘要 Ⅱ.
第二部份中文摘要 Ⅲ.
第一部份英文摘要 Ⅳ.
第二部份英文摘要 Ⅴ.
誌謝 Ⅵ.
第一部份:
第一章前言 1.
第二章材料與方法 3.
第三章結果 7.
第四章討論 9.
第五章結論 11.
第六章參考文獻 12.
第七章圖表與圖表說明 18.
第二部份:
第一章前言 25.
第二章研究動機 27.
第三章材料與方法 28.
第四章結果 29.
第五章討論 36.
第六章參考文獻 37.
第七章圖表與圖表說明 51.

1.Buchness, M. R. Alternative medicine and dermatology. Semin. Cutan. Med. Surg. 1998, 17 (4), 284-290.
2.Neldner, K. H. Complementary and alternative medicine. Dermatol. Clin. 2000, 18 (1), 189-193, xi.
3.Koo, J.; Desai, R. Traditional Chinese medicine in dermatology. Dermatol. Ther. 2003, 16 (2), 98-105.
4.Dattner, A. M. Herbal and complementary medicine in dermatology. Dermatol. Clin. 2004, 22 (3), 325-332, vii.
5.Baumann, L. Botanical ingredients in cosmeceuticals. J. Drugs Dermatol. 2007, 6 (11), 1084-1088.
6.Bedi, M. K.; Shenefelt, P. D. Herbal therapy in dermatology. Arch. Dermatol. 2002, 138 (2), 232-242.
7.Fujita, M.; Itokawa, H.; Sashida, Y. Studies on the components of Magnolia obovata Thunb. 3. Occurrence of magnolol and honokiol in M. obovata and other allied plants. Yakugaku Zasshi 1973, 93 (4), 429-434.
8.Watanabe, H.; Watanabe, K.; Hagino, K. Chemostructural requirement for centrally acting muscle relaxant effect of magnolol and honokiol, neolignane derivatives. J. Pharmacobiodyn. 1983, 6 (3), 184-190.
9.Taira, J.; Ikemoto, T.; Mimura, K.; Hagi, A.; Murakami, A.; Makino, K. Effective inhibition of hydroxyl radicals by hydroxylated biphenyl compounds. Free Radic. Res. Commun. 1993, 19 (Suppl. 1), S71-S77.
10.Fujita, S.; Taira, J. Biphenyl compounds are hydroxyl radical scavengers: their effective inhibition for UV-induced mutation in Salmonella typhimurium TA102. Free Radic. Biol. Med. 1994, 17 (3), 273-277.
11.Lo, Y. C.; Teng, C. M.; Chen, C. F.; Chen, C. C.; Hong, C. Y. Magnolol and honokiol isolated from Magnolia officinalis protect rat heart mitochondria against lipid peroxidation. Biochem. Pharmacol. 1994, 47 (3), 549-553.
12.Hon, K. L.; Leung, T. F.; Ng, P. C.; Lam, M. C.; Kam, W. Y.; Wong, K. Y.; Lee, K. C.; Sung, Y. T.; Cheng, K. F.; Fok, T. F.; Fung, K. P.; Leung, P. C. Efficacy and tolerability of a Chinese herbal medicine concoction for treatment of atopic dermatitis: a randomized, double-blind, placebo-controlled study. Br. J. Dermatol. 2007, 157 (2), 357-363.
13.Fried, L. E.; Arbiser, J. L. A multifunctional antiangiogenic and antitumor agent. Antioxid Redox Signal 2009, 11 (5), 1139-1148.
14.Chiu, J. H.; Wang, J. C.; Lui, W. Y.; Wu, C. W.; Hong, C. Y. Effect of magnolol on in vitro mitochondrial lipid peroxidation and isolated cold-preserved warm-reperfused rat livers. J. Surg. Res. 1999, 82 (1), 11-16.
15.Hong, C. Y.; Huang, S. S.; Tsai, S. K. Magnolol reduces infarct size and suppresses ventricular arrhythmia in rats subjected to coronary ligation. Clin. Exp. Pharmacol. Physiol. 1996, 23 (8), 660-664.
16.Chang, C. P.; Hsu, Y. C.; Lin, M. T. Magnolol protects against cerebral ischaemic injury of rat heatstroke. Clin. Exp. Pharmacol. Physiol. 2003, 30 (5-6), 387-392.
17.Li, H. B.; Gao, J. M.; Ying, X. X.; Wang, S. P.; Li, J. C. Protective effect of magnolol on TBHP-induced injury in H460 cells partially via a p53 dependent mechanism. Arch. Pharm. Res. 2007, 30 (7), 850-857.
18.Loong, C. C.; Chiu, J. H.; Tiao, R. C.; Chiu, Y. Y.; Wu, C. W.; Lui, W. Y. Pretreatment with magnolol attenuates ischemia-reperfusion injury in rat small intestine. Transplant. Proc. 2001, 33 (7-8), 3737-3738.
19.Loong, C. C.; Chiu, J. H.; Tiao, R. C.; Chiu, Y. Y.; Wu, C. W.; Lui, W. Y. Protective effect of magnolol on the small intestinal ischemia-reperfusion injury. Transplant. Proc. 2002, 34 (7), 2679-2680.
20.Chang, W. S.; Chang, Y. H.; Lu, F. J.; Chiang, H. C. Inhibitory effects of phenolics on xanthine oxidase. Anticancer Res. 1994, 14 (2A), 501-506.
21.Wang, J. P.; Hsu, M. F.; Raung, S. L.; Chang, L. C.; Tsao, L. T.; Lin, P. L.; Chen, C. C. Inhibition by magnolol of formylmethionyl-leucyl-phenyl alanine-induced respiratory burst in rat neutrophils. J. Pharm. Pharmacol. 1999, 51 (3), 285-294.
22.Haraguchi, H.; Ishikawa, H.; Shirataki, N.; Fukuda, A. Antiperoxidative activity of neolignans from Magnolia obovata. J. Pharm. Pharmacol. 1997, 49 (2), 209-212.
23.Dikalov, S.; Losik, T.; Arbiser, J. L. Honokiol is a potent scavenger of superoxide and peroxyl radicals. Biochem. Pharmacol. 2008, 76 (5), 589-596.
24.Graf, J. Herbal anti-inflammatory agents for skin disease. Skin Therapy Lett. 2000, 5 (4), 3-5.
25.Katiyar, S. K. Skin photoprotection by green tea: antioxidant and immunomodulatory effects. Curr. Drug Targets Immune Endocr Metabol Disord 2003, 3 (3), 234-242.
26.Halliday, G. M. Inflammation, gene mutation and photoimmunosuppression in response to UVR-induced oxidative damage contributes to photocarcinogenesis. Mutat. Res. 2005, 571 (1-2), 107-120.
27.Nichols, J. A.; Katiyar, S. K. Skin photoprotection by natural polyphenols: anti-inflammatory, antioxidant and DNA repair mechanisms. Arch. Dermatol. Res. 2010, 302 (2), 71-83.
28.Konoshima, T.; Kozuka, M.; Tokuda, H.; Nishino, H.; Iwashima, A.; Haruna, M.; Ito, K.; Tanabe, M. Studies on inhibitors of skin tumor promotion, IX. Neolignans from Magnolia officinalis.
J. Nat. Prod. 1991, 54 (3), 816-822.
29.Liou, K. T.; Shen, Y. C.; Chen, C. F.; Tsao, C. M.; Tsai, S. K. The anti-inflammatory effect of honokiol on neutrophils: mechanisms in the inhibition of reactive oxygen species production.
Eur J Pharmacol 2003, 475 (1-3), 19-27.
30.Wang, J. P.; Hsu, M. F.; Raung, S. L.; Chen, C. C.; Kuo, J. S.; Teng, C. M. Anti-inflammatory and analgesic effects of magnolol. Naunyn Schmiedebergs Arch. Pharmacol. 1992, 346 (6), 707-712.
31.Hsu, M. F.; Lu, M. C.; Tsao, L. T.; Kuan, Y. H.; Chen, C. C.; Wang, J. P. Mechanisms of the influence of magnolol on eicosanoid metabolism in neutrophils. Biochem. Pharmacol. 2004, 67 (5), 831-840.
32.Wang, J. P.; Ho, T. F.; Chang, L. C.; Chen, C. C. Anti-inflammatory effect of magnolol, isolated from Magnolia officinalis, on A23187-induced pleurisy in mice. J. Pharm. Pharmacol. 1995, 47 (10), 857-860.
33.Yamazaki, R.; Sugatani, J.; Fujii, I.; Kuroyanagi, M.; Umehara, K.; Ueno, A.; Suzuki, Y.; Miwa, M. Development of a novel method for determination of acetyl-CoA:1-alkyl-sn-glycero-3-phosphocholine acetyltransferase activity and its application to screening for acetyltransferase inhibitors. Inhibition by magnolol and honokiol from Magnoliae cortex. Biochem. Pharmacol. 1994, 47 (6), 995-1006.
34.Homma, M.; Minami, M.; Taniguchi, C.; Oka, K.; Morita, S.; Niitsuma, T.; Hayashi, T. Inhibitory effects of lignans and flavonoids in saiboku-to, a herbal medicine for bronchial asthma, on the release of leukotrienes from human polymorphonuclear leukocytes. Planta Med. 2000, 66 (1), 88-91.
35.Homma, M.; Oka, K.; Niitsuma, T.; Itoh, H. A novel 11 beta-hydroxysteroid dehydrogenase inhibitor contained in saiboku-to, a herbal remedy for steroid-dependent bronchial asthma.
J. Pharm. Pharmacol. 1994, 46 (4), 305-309.
36.Homma, M.; Oka, K.; Yamada, T.; Niitsuma, T.; Ihto, H.; Takahashi, N. A strategy for discovering biologically active compounds with high probability in traditional Chinese herb remedies: an application of saiboku-to in bronchial asthma. Anal. Biochem. 1992, 202 (1), 179-187.
37.Ikarashi, Y.; Yuzurihara, M.; Sakakibara, I.; Nakai, Y.; Hattori, N.; Maruyama, Y. Effects of the extract of the bark of Magnolia obovata and its biphenolic constituents magnolol and honokiol on histamine release from peritoneal mast cells in rats. Planta Med. 2001, 67 (8), 709-713.
38.Niitsuma, T.; Morita, S.; Hayashi, T.; Homma, M.; Oka, K. Effects of absorbed components of saiboku-to on the release of leukotrienes from polymorphonuclear leukocytes of patients with bronchial asthma. Methods Find Exp. Clin. Pharmacol. 2001, 23 (2), 99-104.
39.Taniguchi, C.; Homma, M.; Takano, O.; Hirano, T.; Oka, K.; Aoyagi, Y.; Niitsuma, T.; Hayashi, T. Pharmacological effects of urinary products obtained after treatment with saiboku-to, a herbal medicine for bronchial asthma, on type IV allergic reaction. Planta Med. 2000, 66 (7), 607-611.
40.Hamasaki, Y.; Kobayashi, I.; Zaitu, M.; Tsuji, K.; Kita, M.; Hayasaki, R.; Muro, E.; Yamamoto, S.; Matsuo, M.; Ichimaru, T.; Miyazaki, S. Magnolol inhibits leukotriene synthesis in rat basophilic leukemia-2H3 cells. Planta Med. 1999, 65 (3), 222-226.
41.Han, S. J.; Bae, E. A.; Trinh, H. T.; Yang, J. H.; Youn, U. J.; Bae, K. H.; Kim, D. H. Magnolol and honokiol: inhibitors against mouse passive cutaneous anaphylaxis reaction and scratching behaviors. Biol. Pharm. Bull 2007, 30 (11), 2201-2203.
42.Son, H. J.; Lee, H. J.; Yun-Choi, H. S.; Ryu, J. H. Inhibitors of nitric oxide synthesis and TNF-alpha expression from Magnolia obovata in activated macrophages. Planta Med. 2000, 66 (5), 469-471.
43.Tanaka, K.; Hasegawa, J.; Asamitsu, K.; Okamoto, T. Magnolia ovovata extract and its active component magnolol prevent skin photoaging via inhibition of nuclear factor kappaB. Eur. J. Pharmacol. 2007, 565 (1-3), 212-219.
44.Wang, J. P.; Raung, S. L.; Chen, C. C.; Kuo, J. S.; Teng, C. M. The inhibitory effect of magnolol on cutaneous permeability in mice is probably mediated by a nonselective vascular hyporeactivity to mediators. Naunyn Schmiedebergs Arch. Pharmacol. 1993, 348 (6), 663-669.
45.Kim, B. H.; Cho, J. Y. Anti-inflammatory effect of honokiol is mediated by PI3K/Akt pathway suppression. Acta Pharmacol. Sin. 2008, 29 (1), 113-122.
46.Wang, J. P.; Chen, C. C. Magnolol induces cytosolic-free Ca2+ elevation in rat neutrophils primarily via inositol trisphosphate signalling pathway. Eur. J. Pharmacol. 1998, 352 (2-3), 329-334.
47.Wang, J. P.; Lin, P. L.; Hsu, M. F.; Chen, C. C. Possible involvement of protein kinase c inhibition in the reduction of phorbol ester-induced neutrophil aggregation by magnolol in the rat. J. Pharm. Pharmacol. 1998, 50 (10), 1167-72.
48.Matsuda, H.; Kageura, T.; Oda, M.; Morikawa, T.; Sakamoto, Y.; Yoshikawa, M. Effects of constituents from the bark of Magnolia obovata on nitric oxide production in lipopolysaccharide-activated macrophages. Chem. Pharm. Bull 2001, 49 (6), 716-720.
49.Tse, A. K.; Wan, C. K.; Zhu, G. Y.; Shen, X. L.; Cheung, H. Y.; Yang, M.; Fong, W. F. Magnolol suppresses NF-kappaB activation and NF-kappaB regulated gene expression through inhibition of IkappaB kinase activation. Mol. Immunol. 2007, 44 (10), 2647-2658.
50.Chilampalli, S.; Zhang, X.; Fahmy, H.; Kaushik, R. S.; Zeman, D.;
Hildreth, M. B.; Dwivedi, C. Chemopreventive effects of honokiol on UVB-induced skin cancer development. Anticancer Res. 2010, 30 (3), 777-783.
51.Ikeda, K.; Sakai, Y.; Nagase, H. Inhibitory effect of magnolol on tumour metastasis in mice. Phytother. Res. 2003, 17 (8), 933-937.
52.You, Q.; Li, M.; Jiao, G. Magnolol induces apoptosis via activation of both mitochondrial and death receptor pathways in A375-S2 cells. Arch. Pharm. Res. 2009, 32 (12), 1789-1794.
53.Kong, C. W.; Tsai, K.; Chin, J. H.; Chan, W. L.; Hong, C. Y. Magnolol attenuates peroxidative damage and improves survival of rats with sepsis. Shock 2000, 13 (1), 24-28.
54.Shih, H. C.; Wei, Y. H.; Lee, C. H. Magnolol alters cytokine response after hemorrhagic shock and increases survival in subsequent intraabdominal sepsis in rats. Shock 2003, 20 (3), 264-268.
55.Shih, H. C.; Wei, Y. H.; Lee, C. H. Magnolol alters the course of endotoxin tolerance and provides early protection against endotoxin challenge following sublethal hemorrhage in rats. Shock 2004, 22 (4), 358-363.
56.Bang, K. H.; Kim, Y. K.; Min, B. S.; Na, M. K.; Rhee, Y. H.; Lee, J. P.; Bae, K. H. Antifungal activity of magnolol and honokiol. Arch. Pharm. Res. 2000, 23 (1), 46-49.
57.Clark, A. M.; El-Feraly, F. S.; Li, W. S. Antimicrobial activity of phenolic constituents of Magnolia grandiflora L. J. Pharm. Sci. 1981, 70 (8), 951-952.
58.Bae, E. A.; Han, M. J.; Kim, N. J.; Kim, D. H. Anti-Helicobacter pylori activity of herbal medicines. Biol. Pharm. Bull 1998, 21 (9), 990-992.
59.Park, J.; Lee, J.; Jung, E.; Park, Y.; Kim, K.; Park, B.; Jung, K.; Park, E.; Kim, J.; Park, D. In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. Eur. J. Pharmacol. 2004, 496 (1-3), 189-195.
60.Lee, J.; Jung, E.; Park, J.; Jung, K.; Lee, S.; Hong, S.; Park, E.; Kim, J.; Park, S.; Park, D.Anti-inflammatory effects of magnolol and honokiol are mediated through inhibition of the downstream pathway of MEKK-1 in NF-kappaB activation signaling. Planta Med. 2005, 71 (4), 338-343.
61.Kim, Y. S.; Lee, J. Y.; Park, J.; Hwang, W.; Lee, J.; Park, D. Synthesis and microbiological evaluation of honokiol derivatives as new antimicrobial agents. Arch. Pharm. Res. 2010, 33 (1), 61-65.
62.Nicolaou, N.; Johnston, G. A. The use of complementary medicine by patients referred to a contact dermatitis clinic. Contact Dermatitis 2004, 51 (1), 30-33.
63.Zhong, S.; Wu, Y.; Soo-Mi, A.; Zhao, J.; Wang, K.; Yang, S.; Jae-Ho, Y.; Zhu, X. Depigmentation of melanocytes by the treatment of extracts from traditional Chinese herbs: a cell culture assay. Biol. Pharm. Bull 2006, 29 (9), 1947-1951.
64.Walker, P. S.; Donovan, J. A. Herbal remedies: natural caveats. Int. J. Dermatol. 1999, 38 (10), 746-748.
65.Boneberger, S.; Rupec, R. A.; Ruzicka, T. Complementary therapy for atopic dermatitis and other allergic skin diseases: facts and controversies. Clin. Dermatol. 2010, 28 (1), 57-61.
66.Ernst, E. Adverse effects of herbal drugs in dermatology. Br. J. Dermatol. 2000, 143 (5), 923-929.
67.Dattner, A. M. From medical herbalism to phytotherapy in dermatology: back to the future. Dermatol. Ther. 2003, 16 (2), 106-113.
68.Keane, F. M.; Munn, S. E.; Vivier, A. W.; Higgins, E. M.; Taylor, N. F. Analysis of Chinese herbal creams prescribed for dermatological conditions. West J. Med. 1999, 170 (5), 257-259.
69.Keane, F. M.; Munn, S. E.; du Vivier, A. W.; Taylor, N. F.; Higgins, E. M. Analysis of Chinese herbal creams prescribed for dermatological conditions. BMJ 1999, 318 (7183), 563-564.
70.Wang, K. H.; Lin, R. D.; Hsu, F. L.; Huang, Y. H.; Chang, H. C.; Huang, C. Y.; Lee, M. H. Cosmetic applications of selected traditional Chinese herbal medicines. J. Ethnopharmacol. 2006, 106 (3), 353-359.
71.Hughes, R.; Ward, D.; Tobin, A. M.; Keegan, K.; Kirby, B. The use of alternative medicine in pediatric patients with atopic dermatitis. Pediatr. Dermatol. 2007, 24 (2), 118-120.
72.Salameh, F.; Perla, D.; Solomon, M.; Gamus, D.; Barzilai, A.; Greenberger, S.; Trau, H. The effectiveness of combined Chinese herbal medicine and acupuncture in the treatment of atopic dermatitis. J. Altern. Complement. Med. 2008, 14 (8), 1043-1048.
73.Lin, M. H.; Chao, H. T.; Hong, C. Y. Magnolol protects human sperm motility against lipid peroxidation: a sperm head fixation method. Arch. Androl. 1995, 34 (3), 151-156.
74.Chen, H. Y.; Hung, Y. C.; Lee, E. J.; Chen, T. Y.; Chuang, I. C.; Wu, T. S. The protective efficacy of magnolol in hind limb ischemia-reperfusion injury. Phytomedicine 2009, 16 (10), 976-981.
75.Wu, S. N.; Chen, C. C.; Li, H. F.; Lo, Y. K.; Chen, S. A.; Chiang, H. T. Stimulation of the BK(Ca) channel in cultured smooth muscle cells of human trachea by magnolol. Thorax 2002, 57 (1), 67-74.
76.Ko, C. H.; Chen, H. H.; Lin, Y. R.; Chan, M. H. Inhibition of smooth muscle contraction by magnolol and honokiol in porcine trachea. Planta Med. 2003, 69 (6), 532-536.
77.Syu, W. J.; Shen, C. C.; Lu, J. J.; Lee, G. H.; Sun, C. M. Antimicrobial and cytotoxic activities of neolignans from Magnolia officinalis. Chem. Biodivers. 2004, 1 (3), 530-537.
78.Ho, K. Y.; Tsai, C. C.; Chen, C. P.; Huang, J. S.; Lin, C. C. Antimicrobial activity of honokiol and magnolol isolated from Magnolia officinalis. Phytother. Res. 2001, 15 (2), 139-141.