簡易檢索 / 詳目顯示

研究生: 連聰蓉
Tsung-Jung Lien
論文名稱: 探討香料萃取物抑制痤瘡桿菌生長與抗發炎之作用與機轉
The antimicrobial and anti-inflammatory effects of spice extracts against Propionibacterium acnes
指導教授: 蔡帛蓉
Tsai, Po-Jung
學位類別: 碩士
Master
系所名稱: 人類發展與家庭學系
Department of Human Development and Family Studies
論文出版年: 2010
畢業學年度: 98
語文別: 中文
論文頁數: 119
中文關鍵詞: 香料痤瘡桿菌抗菌抗發炎
英文關鍵詞: culinary spice, Propionibacterium acnes, antimicrobial, anti-inflammatory, NF-κB, Toll-like receptor 2
論文種類: 學術論文
相關次數: 點閱:350下載:30
分享至:
查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報
  • 尋常性痤瘡(acne vulgaris)俗稱青春痘是一個非常常見的皮膚疾病,好發年紀除了青春期的青少年外,在成年人也常見。痤瘡的致病機轉牽涉到非常多的因素,包括不正常的過度角質化、皮脂分泌增加、荷爾蒙、免疫反應、皮膚內微生物特別是痤瘡桿菌。常見的治療方式是使用抗生素,但是現行資料顯示人體皮膚內的痤瘡桿菌對於常用抗生素有越來越多抗藥性的情形出現,因此開發非抗生素類的治療藥物是一個漸受重視的議題。本研究的目的為篩選出具有抗菌作用能夠抑制痤瘡桿菌(Propionibacterium acnes)的生長,或具有抗發炎作用的天然食材能夠抑制由P. acnes 所誘發的發炎反應以緩解尋常性痤瘡。
    首先進行預實驗,以抗菌能力作為篩選標的,得知4種香料(culinary spices)的乙醇萃取物具有抑制痤瘡桿菌生長的作用。這4種香料為迷迭香、百里香、丁香和奧勒岡,其最低抑菌濃度(MIC)分別為4 , 8, 8, 16 mg/mL。接著進行本研究,
    將這4種香料以不同溶劑(乙醇、乙酸乙酯、水)萃取,分析項目有(1)抑制P. acnes與表皮葡萄球菌(S. epidermidis)生長的能力,(2)抗發炎活性:抑制P. acnes刺激單核球細胞THP-1細胞產生促發炎細胞激素的能力,(3)探討其抗發炎作用的可能機制。
    本研究結果發現,在乙醇萃取物中,抑制P. acnes 和S. epidermidis生長效果最好的是迷迭香,百里香與奧勒岡次之,丁香最差;乙酸乙酯萃取物抑制P. acnes生長的效果以奧勒岡最好,抑制S. epidermidis生長的效果以迷迭香效果最好,而丁香乙酸乙酯萃取物於本實驗條件下,對於兩株菌皆無抗菌的效果;在水萃取物的部份,抑制P. acnes和S. epidermidis生長的效果以丁香效果最好,迷迭香和百里香於本實驗的條件下,不具有抑菌的效果。在抗發炎活性方面,以不影響細胞存活率的萃取物濃度與THP-1細胞共培養,發現迷迭香、丁香與奧勒岡的乙醇萃取物均能夠抑制P. acnes刺激THP-1細胞產生促發炎細胞激素 (TNF-α, IL-8 and IL-1β)的分泌與mRNA基因表現量。然而這些香料的乙酸乙酯與水萃取物卻有促發炎的現象。由於已知P. acnes活化toll-like receptor 2(TLR2)以及下游的訊息傳遞路徑,活化轉錄因子NFκB,進而調控促發炎細胞激素的表現。所以我們進一步探討其抗發炎機制是否經由TLR2和NFκB路徑。結果發現P. acnes顯著的誘導THP-1細胞的NFκB活化情形以及TLR2的mRNA表現,而這些活化路徑均能被迷迭香、丁香與奧勒岡乙醇萃取物所抑制。所以綜合上述實驗結果,我們推測這3種香料乙醇萃取物的抗發炎機制是能透過減弱單核球細胞膜上的TLR2的表現以及轉錄因子NFκB的活化,進而降低促發炎細胞激素的分泌與基因表現。
    綜合而論,迷迭香、丁香與奧勒岡的乙醇萃取物具有抑制痤瘡致病菌的生長以及所引起的發炎反應,推測迷迭香、丁香與奧勒岡的乙醇萃取物含有活性成分,因而具有緩解痤瘡發炎之功效。

    Acne vulgaris is a skin disorder of the pilosebaceous follicles that commonly occurs in adolescence and in young adulthood. The pathogenesis of acne is complex, but this process occurs in the pilosebaceous unit and there is strong evidence to suggest that it involves sebaceous hyperplasia, follicular hyperkeratinization, bacterial hypercolonization, together with the immune reaction and inflammation. Several lines of evidence suggest that the anaerobic bacterium Propionibacterium acnes is the etiological agent of inflammatory acne. For many years, antibiotics have been used to treat acne vulgaris, however, antibiotic resistance has been increasing in prevalence within the dermatologic setting. Bacterial resistance is an ongoing problem in the treatment of acne vulgaris, therefore, an agent which can inhibit P. acnes growth and suppress the inflammatory response will provide promising benefits to patients with acne vulgaris. The objective of this study was to screen and evaluate the antimicrobial and anti-inflammatory effects of culinary spice extracts against P. acnes.
    In the preliminary study, the inhibitory effects of various ethanolic spice extracts on P. acnes growth were determined by broth dilution method. We found that 4 ethanolic spice extracts possessed antibacterial activity against P. acnes. The minimum inhibition concentrations (MICs) of rosemary, clove, thyme, and oregano were 4, 8, 8, and 16 mg/mL, respectively. We examined the antimicrobial and anti-inflammatory effects of the above spice extracts and addressed possible mechanism of anti-inflammation in the subsequent study.
    In this study, ethanol, ethyl acetate and aqueous extracts of rosemary, clove, thyme, and oregano were prepared. Results showed that, rosemary showed the greatest antimicrobial activity against P. acnes and S. epidermidis than thyme, oregano and clove in ethanolic extracts. For ethyl acetate extracts, oregano showed the greatest antimicrobial activity against P. acnes, and rosemary showed the greatest antimicrobial activity against S. epidermidis, however, clove has no inhibitory effect on growth of both P. acnes and S. epidermidis. For aqueous extracts, clove showed the greatest antimicrobial activity against P. acnes and S. epidermidis, rosemary and thyme has no bactericidal effect. It is widely accepted that inflammatory acne may be induced by host immune reactions to P. acnes and production of pro-inflammatory cytokines such as IL-1β, IL-8, and TNF-α. We also found that P. acnes lead to increased production and gene expression of TNF-α, IL-8, and IL-1β in THP-1 cells. Ethanolic extracts of rosemary, clove and oregano strongly suppressed the secretion of P. acnes-induced pro-inflammatory cytokines by THP-1 cells, including TNF-α, IL-8, and IL-1β, without inhibition of cell viability. Whereas, ethyl acetate and aqueous extracts of rosemary, clove and oregano raised production of P. acnes-induced pro-inflammatory cytokines. P. acnes, by acting on TLR2, may stimulate the secretion of cytokines by macrophages. TLR2 was also proved to be sufficient for NF-B activation in response to P acnes. We found that ethanolic extracts of rosemary, clove and oregano suppressed P. acnes-induced TLR2 mRNA expression and NF-κB activation. Taken together, these spice extracts possess the anti-inflammatory activity against P. acnes, which may be through down-regulating TLR2 expression and NF-κB activation.
    In conclusion, these results suggest that ethanolic extracts of rosemary, clove and oregano, or their components, exhibit antimicrobiral and anti-inflammatory activities and may be useful in the treatment of acne vulgaris.

    第一章 緒論 1 壹、研究動機 1 貳、研究目的 2 第二章 文獻探討 3 第一節 皮膚的構造 3 一、表皮(epidermis) 3 二、真皮(dermis) 4 第二節 痤瘡的致病機制 5 一、與痤瘡相關的微生物 6 二、Toll-like receptors與免疫反應 7 三、細胞激素的分泌 10 四、營養 11 第三節 痤瘡的治療方法 12 第四節 實驗材料 15 一、迷迭香 16 二、丁香 17 三、百里香 18 四、奧勒岡 19 五、肉桂 20 六、荳蔻 20 七、小茴香籽 21 八、紫蘇 22 第三章 材料與方法 23 第一節 樣品製備 23 第二節 研究材料 23 一、細菌培養 23 二、細胞培養 25 第三節 實驗設計 27 第四節 實驗方法 28 一、細胞存活率分析 28 (1)MTT assay 28 (2)Alamar Blue assay 28 二、抑菌能力評估 29 (1)培養液稀釋法(Broth Dilution Method) 28 三、抗發炎活性評估 31 (1)P.acnes處理 31 (2)P.acnes誘導THP-1 細胞產生促發炎細胞激素時間與劑量的關係 31 (3)香料萃取物抑制P.acnes誘導THP-1細胞促發炎細胞激素的生成 31 (4)促發炎細胞激素蛋白質測定(酵素免疫分析法 32 (5)促發炎細胞激素mRNA表現量 32 (6)轉錄因子nuclear factor-kappa B(NFκB)活化分析 35 四、抗發炎能力評估 - in vivo 36 (1)實驗動物 36 (2)實驗方法 36 第五節 統計分析 40 第四章 結果 41 第一節 香料樣品於各種溶劑之萃取率 41 第二節 香料萃取物之抑菌能力評估 41 一、香料乙醇萃取物的抑菌能力 42 二、香料乙酸乙酯萃取物的抑制菌效果 44 三、香料水萃取物的抑制菌效果 46 第三節 樣品對細胞存活的影響 49 第四節 評估香料萃取物的抗發炎活性 56 一、建立P.acnes刺激單核球細胞THP-1的實驗模式 56 二、香料萃取物對於P.acnes刺激THP-1細胞促發炎細胞激素分泌的影響 61 (1)香料乙醇萃取物 61 (2)香料乙酸乙酯萃取物 65 (3)香料水萃取物 68 三、香料萃取物抑制P. acnes刺激THP-1細胞促發炎細胞激素mRNA的表 71 (1)Quantitative real-time PCR實驗條件建立 71 (2)香料萃取物抑制P.acnes誘導之促發炎細胞激素mRNA表現 73 四、香料乙醇萃取物對於P. acnes刺激 THP-1細胞NFκB活化之影響 77 五、香料乙醇萃取物抑制P. acnes 誘導之Toll-like receptor 2 mRNA的表現 82 六、香料乙醇萃取物對於P. acnes引起小鼠耳朵發炎反應之影響 88 第五章 結論與討論 93 第一節 評估香料萃取物的抑菌能力 93 第二節 評估香料乙醇萃取物之抗發炎活性 96 一、香料乙醇萃取物對於促發炎細胞激素之分泌與基因表現之影響 96 二、探討香料乙醇萃取物的抗發炎作用機制 100 第三節 評估香料乙醇萃取物in vivo抗發炎活性 107 一、香料乙醇萃取物對於P. acnes引起小鼠耳朵發炎反應之影響 107 第四節 結論 109 第六章 參考文獻 110

    Acharya, M. R., Venitz, J., Figg, W. D., & Sparreboom, A. (2004). Chemically modified tetracyclines as inhibitors of matrix metalloproteinases. Drug Resistance Updates, 7(3), 195-208.
    Adebamowo, C. A., Spiegelman, D., Danby, F. W., Frazier, A. L., Willett, W. C., & Holmes, M. D. (2005). High school dietary dairy intake and teenage acne. Journal of the American Academy of Dermatology, 52(2), 207-214.
    Aggarwal, B. B., & Shishodia, S. (2004). Suppression of the nuclear factor-kappaB activation pathway by spice-derived phytochemicals: reasoning for seasoning. Annals of the New York Academy of Sciences, 1030, 434-441.
    al-Sereiti, M. R., Abu-Amer, K. M., & Sen, P. (1999). Pharmacology of rosemary (Rosmarinus officinalis L.) and its therapeutic potentials. Indian Journal of Experimental Biology, 37(2), 124-130.
    Allahghadri, T., Rasooli, I., Owlia, P., Nadooshan, M. J., Ghazanfari, T., Taghizadeh, M. & Astaneh, S. D. (2010). Antimicrobial property, antioxidant capacity, and cytotoxicity of essential oil from cumin produced in Iran. Journal of Food Science, 75(2), 54-61.
    Angel, P., Szabowski, A., & Schorpp-Kistner, M. (2001). Function and regulation of AP-1 subunits in skin physiology and pathology. Oncogene, 20(19), 2413-2423.
    Aureli, P., Costantini, A., & Zolea, S. (1992). Antimicrobial activity of some plant essential oils against Listeria monocytogenes. Journal of Food Protection, 55, 344-348.
    Baranauskiene, R., Venskutonis, P. R., Viskelis, P., & Dambrauskiene, E. (2003). Influence of nitrogen fertilizers on the yield and composition of thyme (Thymus vulgaris). Journal of Agricultural and Food Chemistry, 51(26), 7751-7758.
    Banerjee, S., & Das, S. (2005). Anticarcinogenic effects of an aqueous infusion of cloves on skin carcinogenesis. Asian Pacific Journal of Cancer Prevention, 6(3), 304-308.
    Barnes, P. J., & Karin, M. (1997). Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. New England Journal of Medicine, 336(15), 1066-1071.
    Betoni, J. E., Mantovani, R. P., Barbosa, L. N., Di Stasi, L. C., & Fernandes Junior, A. (2006). Synergism between plant extract and antimicrobial drugs used on Staphylococcus aureus diseases. Memórias do Instituto Oswaldo Cruz, 101(4), 387-390.
    Bialecka, A., Mak, M., Biedron, R., Bobek, M., Kasprowicz, A., & Marcinkiewicz, J. (2005). Different pro-inflammatory and immunogenic potentials of Propionibacterium acnes and Staphylococcus epidermidis: implications for chronic inflammatory acne. Archivum Immunologiae et Therapiae Experimentalis, 53(1), 79-85.
    Bozin, B., Mimica-Dukic, N., Samojlik, I., & Jovin, E. (2007). Antimicrobial and antioxidant properties of rosemary and sage (Rosmarinus officinalis L. and Salvia officinalis L., Lamiaceae) essential oils. Journal of Agricultural and Food Chemistry, 55(19), 7879-7885.
    Bruggemann, H., Henne, A., Hoster, F., Liesegang, H., Wiezer, A., Strittmatter, A., Hujer, S., Durre, P., & Gottschalk, G. (2004). The complete genome sequence of Propionibacterium acnes, a commensal of human skin. Science, 305(5684), 671-673.
    Bruunsgaard, H., Andersen-Ranberg, K., Jeune, B., Pedersen, A. N., Skinhoj, P., & Pedersen, B. K. (1999). A high plasma concentration of TNF-alpha is associated with dementia in centenarians. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 54(7), 357-364.
    Chen, Q., Koga. T., Uchi, H., Hara, H., Terao, H., Moroi, Y., Urabe, K., & Furue, M. (2002). Propionibacterium acnes-induced IL-8 production may be mediated by NF-κB activation in human monocytes. Journal of Dermatological Science, 29(2), 97-103.
    Cheung, S., & Tai, J. (2007). Anti-proliferative and antioxidant properties of rosemary Rosmarinus officinalis. Oncology Reports, 17(6), 1525-1531.
    Chomnawang, M. T., Surassmo, S., Nukoolkarn, V. S., & Gritsanapan, W. (2005). Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria. Journal of Ethnopharmacology, 101(3), 330-333.
    Cowan, M. M. (1999). Plant products as antimicrobial agents. Clinical Microbiology Reviews, 12(4), 564-582.
    Crocoll, C., Asbach, J., Novak, J., Gershenzon, J., & Degenhardt, J. (2010). Terpene synthases of oregano (Origanum vulgare L.) and their roles in the pathway and regulation of terpene biosynthesis. Plant Molecular Biology, 73,587–603.
    Cuvelier, M. E., Berset, C., & Richard, H. (1994). Antioxidant Constituents in Sage (Salvia officinalis). Journal Agriculture Food Chemistry, 42, 665-669.
    Danby, F. W. (2007). Acne and iodine: reply. Journal of the American Academy of Dermatology, 56(1), 164-165.
    Darling, J. A., Laing, A. H., & Harkness, R. A. (1974). A survey of the steroids in cows' milk. The Journal of Endocrinology, 62(2), 291-297.
    Elgayyar, M., Draughon, F. A., Golden, D. A., & Mount, J. R. (2001). Antimicrobial activity of essential oils from plants against selected pathogenic and saprophytic microorganisms. Journal of Food Protection, 64(7), 1019-1024.
    Fan, M., & Chen, J. (2001). Studies on antimicrobial activity of extracts from thyme. Wei Sheng Wu Xue Tong Bao, 41(4), 499-504.
    Foster, N., Lea, S. R., Preshaw, P. M., & Taylor, J. J. (2007). Pivotal advance: vasoactive intestinal peptide inhibits up-regulation of human monocyte TLR2 and TLR4 by LPS and differentiation of monocytes to macrophages. Journal of Leukocyte Biology, 81(4), 893-903.
    Fu, Y., Zu, Y., Chen, L., Efferth, T., Liang, H., Liu, Z., & Liu, W. (2007). Investigation of antibacterial activity of rosemary essential oil against Propionibacterium acnes with atomic force microscopy. Planta Medica, 73(12), 1275-1280.
    Fu, Y., Zu, Y., Chen, L., Shi, X., Wang, Z., Sun, S., & Efferth, T. (2007). Antimicrobial activity of clove and rosemary essential oils alone and in combination. Phytotherapy Research, 21(10), 989-994.
    Fujioka, S., Niu, J., Schmidt, C., Sclabas, G. M., Peng, B., Uwagawa, T., Li, Z., Evans, D. B., Abbruzzese, J. L., & Chiao, P. J. (2004). NF-kappaB and AP-1 connection: mechanism of NF-kappaB-dependent regulation of AP-1 activity. Molecular and Cellular Biology, 24(17), 7806-7819.
    Galli, C., & Calder, P. C. (2009). Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review. Annals of Nutrition & Metabolism, 55(1-3), 123-139.
    Ganceviciene, R., Graziene, V., Fimmel, S., & Zouboulis, C. C. (2009). Involvement of the corticotropin-releasing hormone system in the pathogenesis of acne vulgaris. The British Journal of Dermatology, 160(2), 345-352.
    Gilani, A. H., Jabeen, Q., Khan, A. U., & Shah, A. J. (2008). Gut modulatory, blood pressure lowering, diuretic and sedative activities of cardamom. Journal of Ethnopharmacology, 115(3), 463-472.
    Gloor, M., Wasik, B., Becker, A., & Hoffler, U. (2002). Inhibition of lipase activity in antibiotic-resistant Propionibacterium acnes strains. Dermatology, 205(3), 260-264.
    Gomariz, R. P., Arranz, A., Juarranz, Y., Gutierrez-Canas, I., Garcia-Gomez, M., Leceta, J., & Martinez, C. (2007). Regulation of TLR expression, a new perspective for the role of VIP in immunity. Peptides, 28(9), 1825-1832.
    Goodhart, G. L. (1979). Further evidence for the role of bivalent cations in human polymorphonuclear leukocyte locomotion: recovery from tetracycline-induced inhibition in the presence of cation ionophores. Journal of the Reticuloendothelial Society, 25(5), 545-554.
    Graham, G. M., Farrar, M. D., Cruse-Sawyer, J. E., Holland, K. T., & Ingham, E. (2004). Proinflammatory cytokine production by human keratinocytes stimulated with Propionibacterium acnes and P. acnes GroEL. The British Journal of Dermatology, 150(3), 421-428.
    Grange, P. A., Raingeaud, J., Calvez, V., & Dupin, N. (2009). Nicotinamide inhibits Propionibacterium acnes-induced IL-8 production in keratinocytes through the NF-kappaB and MAPK pathways. Journal of Dermatological Science, 56(2), 106-112.
    Gutierrez, J., Barry-Ryan, C., & Bourke, P. (2008). The antimicrobial efficacy of plant essential oil combinations and interactions with food ingredients. International Journal of Food Microbiology, 124(1), 91-97.
    Heuking, S., Adam-Malpel, S., Sublet, E., Iannitelli, A., Stefano, A., & Borchard, G. (2009). Stimulation of human macrophages (THP-1) using Toll-like receptor-2 (TLR-2) agonist decorated nanocarriers. Journal of Drug Targeting, 17(8), 662-670.
    Hoyt, G., Hickey, M. S., & Cordain, L. (2005). Dissociation of the glycaemic and insulinaemic responses to whole and skimmed milk. The British Journal of Nutrition, 93(2), 175-177.
    Huang, S. S., & Zheng, R. L. (2006). Rosmarinic acid inhibits angiogenesis and its mechanism of action in vitro. Cancer Letters, 239(2), 271-280.
    Hur, Y. G., Suh, C. H., Kim, S., & Won, J. (2007). Rosmarinic acid induces apoptosis of activated T cells from rheumatoid arthritis patients via mitochondrial pathway. Journal of Clinical Immunology, 27(1), 36-45.
    Jarrousse, V., Castex-Rizzi, N., Khammari, A., Charveron, M., & Dreno, B. (2007). Zinc salts inhibit in vitro Toll-like receptor 2 surface expression by keratinocytes. European Journal of Dermatology, 17(6), 492-496.
    Johnson, B. A., & Nunley, J. R. (2000). Topical therapy for acne vulgaris. How do you choose the best drug for each patient? Postgraduate Medicine, 107(3), 69-70, 73-66, 79-80.
    Joo, S. S., Jang, S. K., Kim, S. G., Choi, J. S., Hwang, K. W., & Lee do, I. (2008). Anti-acne activity of Selaginella involvens extract and its non-antibiotic antimicrobial potential on Propionibacterium acnes. Phytotherapy Research, 22(3), 335-339.
    Jugeau, S., Tenaud, I., Knol, A. C., Jarrousse, V., Quereux, G., Khammari, A., & Dreno, B. (2005). Induction of toll-like receptors by Propionibacterium acnes. The British journal of Dermatology, 153(6), 1105-1113.
    Kalemba, D., & Kunicka, A. (2003). Antibacterial and antifungal properties of essential oils. Current Medicinal Chemistry, 10(10), 813-829.
    Kang, S., Cho, S., Chung, J. H., Hammerberg, C., Fisher, G. J., & Voorhees, J. J. (2005). Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo. The American Journal of Pathology, 166(6), 1691-1699.
    Kawahata, T., Otake, T., Mori, H., Kojima, Y., Oishi, I., Oka, S., Fukumori Y., & Sano K. (2002). A novel substance purified from Perilla frutescens Britton inhibits an early stage of HIV-1 replication without blocking viral adsorption. Antiviral Chemistry & Chemotherapy, 13(5), 283-288.
    Kim, J. (2005). Review of the innate immune response in acne vulgaris: activation of Toll-like receptor 2 in acne triggers inflammatory cytokine responses. Dermatology, 211(3), 193-198.
    Kim, J., Ochoa, M. T., Krutzik, S. R., Takeuchi, O., Uematsu, S., Legaspi, A. J., Fukumori, Y., & Sano, K. (2002). Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. Journal of Immunology, 169(3), 1535-1541.
    Kim, S. S., Kim, J. Y., Lee, N. H., & Hyun, C. G. (2008). Antibacterial and anti-inflammatory effects of Jeju medicinal plants against acne-inducing bacteria. The Journal of General and Applied Microbiology, 54(2), 101-106.
    Kim, S. S., Oh, O. J., Min, H. Y., Park, E. J., Kim, Y., Park, H. J., Nam Han, Y., & Lee, S. K. (2003). Eugenol suppresses cyclooxygenase-2 expression in lipopolysaccharide-stimulated mouse macrophage RAW264.7 cells. Life Sciences, 73(3), 337-348.
    Kurokawa, I., Danby, F. W., Ju, Q., Wang, X., Xiang, L. F., Xia, L., Chen, W., Nagy, I., Picardo, M., Suh, D. H., Ganceviciene, R., Schagen, S., Tsatsou, F., & Zouboulis, C. C. (2009). New developments in our understanding of acne pathogenesis and treatment. Experimental Dermatology, 18(10), 821-832.
    Lai, C. S., Lee, J. H., Ho, C. T., Liu, C. B., Wang, J. M., Wang, Y. J., & Pan, M. H. (2009). Rosmanol potently inhibits lipopolysaccharide-induced iNOS and COX-2 expression through downregulating MAPK, NF-kappaB, STAT3 and C/EBP signaling pathways. Journal of Agricultural and Food Chemistry, 57(22), 10990-10998.
    Lakshminarayanan, V., Drab-Weiss, E. A., & Roebuck, K. A. (1998). H2O2 and tumor necrosis factor-alpha induce differential binding of the redox-responsive transcription factors AP-1 and NF-kappaB to the interleukin-8 promoter in endothelial and epithelial cells. The Journal of Biological Chemistry, 273(49), 32670-32678.
    Lambert, R. J., Skandamis, P. N., Coote, P. J., & Nychas, G. J. (2001). A study of the minimum inhibitory concentration and mode of action of oregano essential oil, thymol and carvacrol. Journal of Applied Microbiology, 91(3), 453-462.
    Lee, H. J., Hyun, E. A., Yoon, W. J., Kim, B. H., Rhee, M. H., Kang, H. K., Cho, J. Y., & Yoo, E. S. (2006). In vitro anti-inflammatory and anti-oxidative effects of Cinnamomum camphora extracts. Journal of Ethnopharmacology, 103(2), 208-216.
    Lee, K. G., & Shibamoto, T. (2001). Inhibition of malonaldehyde formation from blood plasma oxidation by aroma extracts and aroma components isolated from clove and eucalyptus. Food and Chemical Toxicology, 39(12), 1199-1204.
    Lee, S. W., Han, S. I., Kim, H. H., & Lee, Z. H. (2002). TAK1-dependent activation of AP-1 and c-Jun N-terminal kinase by receptor activator of NF-kappaB. Journal of Biochemistry and Molecular Biology, 35(4), 371-376.
    Lee, W. L., Shalita, A. R., Suntharaligam, K., & Fikrig, S. (1982). Neutorphil chemotaxis by Propionibacterium acnes lipase and its inhibition. Infection and Immunity, 35, 71-78.
    Leyden, J. J. (1997). Therapy for acne vulgaris. The New England Journal of Medicine, 336(16), 1156-1162.
    Leyden, J. J. (2001). Current issues in antimicrobial therapy for the treatment of acne. Journal of the American Academy of Dermatology, 15(3 Suppl), 51-55.
    Leyden, J. J. (2003). A review of the use of combination therapies for the treatment of acne vulgaris. Journal of the American Academy of Dermatology, 49(3 Suppl), 200-210.
    Lian, K. C., Chuang, J. J., Hsieh, C. W., Wung, B. S., Huang, G. D., Jian, T. Y., & Sun, Y. W. (2010). Dual mechanisms of NF-kappaB inhibition in carnosol-treated endothelial cells. Toxicology and Applied Pharmacology, 245(1), 21-35.
    Liang, C. H., Chou, T. H., & Ding, H. Y. (2010). Inhibition of melanogensis by a novel origanoside from Origanum vulgare. Journal of Dermatological Science, 57(3), 170-177.
    Liu, P. T., Krutzik, S. R., Kim, J., & Modlin, R. L. (2005). Cutting edge: all-trans retinoic acid down-regulates TLR2 expression and function. Journal of Immunology, 174(5), 2467-2470.
    Lo, A. H., Liang, Y. C., Lin-Shiau, S. Y., Ho, C. T., & Lin, J. K. (2002). Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis, 23(6), 983-991.
    Mahato, S. B., & Garai, S. (1998). Triterpenoid saponins. Fortschritte der Chemie Organischer Naturstoffe, 74, 1-196.
    Marples, R. R., & McGinley, K. J. (1974). Corynebacterium acnes and other anaerobic diphtheroids from human skin. Journal of Medical Microbiology, 7(3), 349-357.
    McInturff, J. E., Modlin, R. L., & Kim, J. (2005). The role of toll-like receptors in the pathogenesis and treatment of dermatological disease. The Journal of Investigative Dermatology, 125(1), 1-8.
    Means, T. K., Jones, B. W., Schromm, A. B., Shurtleff, B. A., Smith, J. A., Keane, J., Golenbock, D. T., Vogel, S. N., & Fenton, M. J. (2001). Differential effects of a Toll-like receptor antagonist on Mycobacterium tuberculosis-induced macrophage responses. Journal of Immunology, 166(6), 4074-4082.
    Muthamma Milana, K. S., Hemang D., Purnima K. T., & Prakash V. (2008). Enhancement of digestive enzymatic activity by cumin (Cuminum cyminum L.) and role of spent cumin as a bionutrient. Food Chemistry, 110(3), 678-683.
    Nagy, I., Pivarcsi, A., Kis, K., Koreck, A., Bodai, L., McDowell, A., Seltmann, H., Patrick, S., Zouboulis, C. C., & Kemeny, L. (2006). Propionibacterium acnes and lipopolysaccharide induce the expression of antimicrobial peptides and proinflammatory cytokines/chemokines in human sebocytes. Microbes and Infection, 8(8), 2195-2205.
    Nakatsuji, T., Kao, M. C., Fang, J. Y., Zouboulis, C. C., Zhang, L., Gallo, R. L., & Huang, C. M. (2009). Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. The Journal of Investigative Dermatology, 129(10), 2480-2488.
    Nakatsuji, T., Liu, Y. T., Huang, C. P., Zoubouis, C. C., Gallo, R. L., & Huang, C. M. (2008). Antibodies elicited by inactivated Propionibacterium acnes-based vaccines exert protective immunity and attenuate the IL-8 production in human sebocytes: relevance to therapy for acne vulgaris. The Journal of Investigative Dermatology, 128(10), 2451-2457.
    Norris, J. F., & Cunliffe, W. J. (1988). A histological and immunocytochemical study of early acne lesions. The British Journal of Dermatology, 118(5), 651-659.
    Pal, D., Banerjee, S., Mukherjee, S., Roy, A., Panda, C. K., & Das, S. (2010). Eugenol restricts DMBA croton oil induced skin carcinogenesis in mice: Downregulation of c-Myc and H-ras, and activation of p53 dependent apoptotic pathway. Journal of Dermatological Science.
    Park, J., Lee, J., Jung, E., Park, Y., Kim, K., Park, B., Jung, K., Park, E., Kim, J., & Park, D. (2004). In vitro antibacterial and anti-inflammatory effects of honokiol and magnolol against Propionibacterium sp. European Journal of Pharmacology, 496(1-3), 189-195.
    Pawar, V. C., & Thaker, V. S. (2006). In vitro efficacy of 75 essential oils against Aspergillus niger. Mycoses, 49(4), 316-323.
    Petersen, M., & Simmonds, M. S. (2003). Rosmarinic acid. Phytochemistry, 62(2), 121-125.
    Pochi, P. E. (1990). The pathogenesis and treatment of acne. Annual Review of Medicine, 41, 187-198.
    Qaralleh, H. N., Abboud, M. M., Khleifat, K. M., Tarawneh, K. A., & Althunibat, O. Y. (2009). Antibacterial activity in vitro of Thymus capitatus from Jordan. Pakistan journal of Pharmaceutical Sciences, 22(3), 247-251.
    Reichling, J., Nolkemper, S., Stintzing, F. C., & Schnitzler, P. (2008). Impact of ethanolic lamiaceae extracts on herpesvirus infectivity in cell culture. Forschende Komplementärmedizin, 15(6), 313-320.
    Richard, I. T., Akashi, S., Miyake, K., Godowski, P. J., & Tobias, P. S. (2000). Toll-like receptor 4, but not toll-like receptor 2, is a siganling receptor for Escherichia and Salmonella lipopolysaccharides. Journal of Immunology, 165, 5780-5787.
    Rodrigues, T. G., Fernandes, A., Jr., Sousa, J. P., Bastos, J. K., & Sforcin, J. M. (2009). In vitro and in vivo effects of clove on pro-inflammatory cytokines production by macrophages. Natural Product Research, 23(4), 319-326.
    Romano, C. S., Abadi, K., Repetto, V., Vojnov, A. A., & Moreno, S. (2009). Synergistic antioxidant and antibacterial activity of rosemary plus butylated derivatives. Food Chemistry, 115(2), 456-461.
    Scheckel, K. A., Degner, S. C., & Romagnolo, D. F. (2008). Rosmarinic acid antagonizes activator protein-1-dependent activation of cyclooxygenase-2 expression in human cancer and nonmalignant cell lines. Journal of Nutrition, 138(11), 2098-2105.
    Schreck, R., Rieber, P., & Baeuerle, P. A. (1991). Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. The EMBO Journal, 10(8), 2247-2258.
    Shen, D., Pan, M. H., Wu, Q. L., Park, C. H., Juliani, H. R., Ho, C. T., & Simon, J. E. (2010). LC-MS method for the simultaneous quantitation of the anti-inflammatory constituents in oregano (Origanum species). Journal of Agricultural and Food Chemistry, 58(12), 7119-7125.
    Shirwaikar, A., Srinivasan, K.K., Kumar, A.V., & Krishnanand, B.R. (1992). Anti-hepatotoxic activity of 'Kamilari' a marketed Ayurvedic preparation. Indian Drugs, 29, 219-224.
    Sreenivasamurthy, V., & Krishnamurthy, K. (1995). Place of spices and aromatics in Indian Dietary. Journal of Food Science, 8, 284-288.
    Tada, M., Ohkanda, T., & Kurabe, J. (2010). Syntheses of carnosic acid and carnosol, anti-oxidants in Rosemary, from pisiferic acid, the major constituent of Sawara. Chemical & Pharmaceutical Bulletin, 58(1), 27-29.
    Taherian, A. A., Babaei, M., Vafaei, A. A., Jarrahi, M., Jadidi, M., & Sadeghi, H. (2009). Antinociceptive effects of hydroalcoholic extract of Thymus vulgaris. Pakistan Journal of Pharmaceutical Sciences, 22(1), 83-89.
    Tak, P. P., & Firestein, G. S. (2001). NF-kappaB: a key role in inflammatory diseases. The Journal of Clinical Investigation, 107(1), 7-11.
    Takano, H., Osakabe, N., Sanbongi, C., Yanagisawa, R., Inoue, K., Yasuda, A., Natsume, M., Baba, S., Ichiishi, E., & Yoshikawa, T. (2004). Extract of Perilla frutescens enriched for rosmarinic acid, a polyphenolic phytochemical, inhibits seasonal allergic rhinoconjunctivitis in humans. Experimental Biology and Medicine, 229(3), 247-254.
    Takeda, K., Kaisho, T., & Akira, S. (2003). Toll-like receptors. Annual Review of Immunology, 21, 335-376.
    Takemura, H., Yamamoto, H., Kunishima, H., Ikejima, H., Hara, T., Kanemitsu, K., Terakubo, S., Shoji, Y., Kaku, M., & Shimada, J. (2000). Evaluation of a human monocytic cell line THP-1 model for assay of the intracellular activities of antimicrobial agents against Legionella pneumophila. The Journal of Antimicrobial Chemotherapy, 46(4), 589-594.
    Tayel, A. A., & El-Tras, W. F. (2009). Possibility of fighting food borne bacteria by Egyptian folk medicinal herbs and spices extracts. The Journal of the Egyptian Public Health Association, 84(2), 21-32.
    Tortora, G. J. (2005). Principles of Human Anatomy (10 ed.): John Wiley & Sons, Inc.
    Treloar, V., Logan, A. C., Danby, F. W., Cordain, L., & Mann, N. J. (2008). Comment on acne and glycemic index. Journal of the American Academy of Dermatology, 58(1), 175-177.
    Tsai, T. H., Tsai, T.H., Wu, W.H., Tseng, T.P., Tsai, P.J. (2010). In vitro antimicrobial and anti-inflammatory effects of herbs against Propionibacterium acnes. Food Chemistry, 119(3), 964-968.
    Ueda, H., Yamazaki, C., Yamazaki, M. (2002). Luteolin as an anti-inflammatory and anti-allergic constituent of Perilla frutescens. Biological & Pharmaceutical Bulletin, 25, 1197-1202.
    Velicer, C. M., Heckbert, S. R., Lampe, J. W., Potter, J. D., Robertson, C. A., & Taplin, S. H. (2004). Antibiotic use in relation to the risk of breast cancer. The Journal of the American Medical Association, 291(7), 827-835.
    Verma, S. K., Jain, V., & Katewa, S. S. (2009). Blood pressure lowering, fibrinolysis enhancing and antioxidant activities of cardamom (Elettaria cardamomum). Indian Journal of Biochemistry & Biophysics, 46(6), 503-506.
    Vowels, B. R., Yang, S., & Leyden, J. J. (1995). Induction of proinflammatory cytokines by a soluble factor of Propionibacterium acnes: implications for chronic inflammatory acne. Infection and Immunity, 63(8), 3158-3165.
    Wang, S. Y., Chen, P. F., & Chang, S. T. (2005). Antifungal activities of essential oils and their constituents from indigenous cinnamon (Cinnamomum osmophloeum) leaves against wood decay fungi. Bioresource Technology, 96(7), 813-818.
    Wang, Q., Dziarski, R., Kirschning, C. J., Muzio, M., & Gupta, D. (2001). Micrococci and peptidoglycan activate TLR2-->MyD88-->IRAK-->TRAF-->NIK-->IKK -->NF-kappaB signal transduction pathway that induces transcription of interleukin-8. Infection and Immunity, 69(4), 2270-2276.
    Wang, Z. M., Liu, C., & Dziarski, R. (2000). Chemokines are the main proinflammatory mediators in human monocytes activated by Staphylococcus aureus, peptidoglycan, and endotoxin. The Journal of Biological Chemistry, 275(27), 20260-20267.
    Webster, G. F., & Leyden, J. J. (1980). Characterization of serum-independent polymorphonuclear leukocyte chemotactic factors produced by Propionibacterium acnes. Inflammation, 4(3), 261-269.
    Webster, G. F. (1998). Inflammatory acne represents hypersensitivity to Propionibacterium acnes. Dermatology, 196(1), 80-81.
    Webster, G. F. (2002). Acne vulgaris. British medical journal, 325(7362), 475-479.
    Webster, G. F., & Graber, E. M. (2008). Antibiotic treatment for acne vulgaris. Seminars in Cutaneous Medicine and Surgery, 27(3), 183-187.
    Yoshimura, A., Lien, E., Ingalls, R. R., Tuomanen, E., Dziarski, R., & Golenbock, D. (1999). Cutting edge: recognition of Gram-positive bacterial cell wall components by the innate immune system occurs via Toll-like receptor 2. Journal of Immunology, 163(1), 1-5.
    Zarember, K. A., & Godowski, P. J. (2002). Tissue expression of human Toll-like receptors and differential regulation of Toll-like receptor mRNAs in leukocytes in response to microbes, their products, and cytokines. Journal of Immunology, 168(2), 554-561.

    下載圖示
    QR CODE