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研究生: 李宥苡
You-Yi Li
論文名稱: 山苦瓜萃取物暨其區分物對於痤瘡桿菌誘導發炎反應的影響
Effects of wild bitter melon extracts on Propionibacterium acnes-induced inflammation
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: 2012
畢業學年度: 100
語文別: 中文
論文頁數: 138
中文關鍵詞: 痤瘡痤瘡桿菌山苦瓜發炎
英文關鍵詞: acne, Propionibacterium acne, Momordica Charantia, inflammation
論文種類: 學術論文
相關次數: 點閱:237下載:11
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  • 痤瘡(acne)俗稱青春痘,其致病因子複雜。過度皮脂生成(sebaceous hyperproduction)、毛囊過度角質化(follicular hyperkeratinization)、痤瘡桿菌增生(Propionibacterium acnes colonization)和發炎反應(periglandular dermal inflammation)是重要的致病因子。其中痤瘡桿菌(P. acnes)被認為在痤瘡發展過程中扮演重要的角色,P. acnes藉由活化單核球細胞(monocytes)與角質細胞(keratinocytes)的toll-like receptor,啟動下游的訊息傳遞路徑產生發炎介質誘導痤瘡發炎情形;另外P. acnes誘發產生活性氧分子(reactive oxygen species, ROS) 與基質金屬蛋白酶(matrix metalloproteinases, MMP)亦參與發炎反應。苦瓜(Momordica charantia)萃取物具有抗發炎、抗氧化能力。因此,本研究欲探討台灣山苦瓜(Momordica charantia Linn. var. abbreviata Ser.; wild bitter melon)萃取物是否具有抑制P. acnes生長與其誘發之發炎反應的效用。
    製備數種山苦瓜萃取物,收集山苦瓜樣品(育種之花蓮1~4號,67-11品系與野生品種)之不同部位(果實、葉、藤),果實以溶劑(乙醇、正己烷、乙酸乙酯和水)進行萃取,而葉以甲醇進行萃取。以broth dilution method實驗的結果發現67-11與野生品種葉、藤甲醇萃物能抑制痤瘡桿菌生長。以P. acnes刺激THP-1 monocytes的模式發現山苦瓜果實乙酸乙酯和乙醇萃取物與葉子甲醇萃物具in vitro抗發炎作用。為進一步探討山苦瓜果實萃取物之區分物(fractions)的抗發炎作用,取得皂化物、非皂化物、oleic acid, linoleic acid, α-linolenic acid, conjugated-linolenic acid, phytol和lutein,結果顯示不皂化物和lutein抑制cytokine和MMP-9表現量,皆具有in vitro抗發炎作用,而長鏈脂肪酸(oleic acid, linoleic acid, α-linolenic acid, CLN)僅降低IL-1β濃度。另發現中鏈脂肪酸(capric acid和lauric acid)能夠減少P. acnes刺激THP-1 monocytes的cytokines產生。在in vivo抗發炎實驗,將P. acnes注射至ICR小鼠耳朵測試樣品的抗發炎能力,結果顯示山苦瓜果實EA萃物、capric acid、山苦瓜葉子甲醇萃物與總多酚萃取物能夠抑制P. acnes誘發的發炎反應與耳朵腫脹情形。
    綜合論述,山苦瓜果實EA萃物與葉子甲醇萃物在in vitro and in vivo實驗中顯示具有抑制P. acnes誘發的促發炎介質與小鼠耳朵腫脹情形,而果實EA萃物中含的lutein與葉子中含的總多酚可能是抗發炎的有效成份。

    Acne vulgaris is a common skin disease involving pilosebaceous follicle. The pathogenesis of acne vulgaris is multifactorial, including increased sebum production, comedogenesis and Propionibacterium acnes proliferation. P. acnes plays an important role not only in the process of inflammation but in the formation of comedones. Previous studies have shown P. acnes would activate monocytes to secrete pro-inflammatory cytokines, some studies have found that matrix metalloproteinases (MMPs) will participate in the progression of acne. Wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) possesses numerous pharmacological actions such as antibacterial, antioxidant, anti-diabetic, and anti-inflammatory activities. The aim of this study was to evaluate the anti-microbial activity as well as in vitro and in vivo inhibitory effect of wild bitter melons extracts and carpic acid on P. acnes-induced inflammation.
    Our results showed that leaves and vine extracts from #67-11 and wild varirties of wild bitter melons effectively inhibited the growth of P. acnes. The ethyl acetate and ethanol extract from WBM fruit significantly reduced IL-8, TNF-α, IL-1β and MMP-9 levels by P. acnes-stimulated THP-1 cells. We further evaluated the fractions and composition of WBM fruit EA extract, the results showed that saponification and unsaponification fractions of WBM fruit, phytol, lutein, capric acid, and lauric acid can reduce cytokine levels. Unsaponification fraction of WBM fruit, lutein, and lauric acid can reduce MMP-9 protein levels. Fatty acids including oleic acid, linoleic acid, α-linolenic acid and conjugated linolenic acid reduced IL-1β production. In addition, ethyl acetate extract of WBM fruit, capric acid, methanolic extract and total phenol extract of WBM leaves reduced P. acnes-induced inflammation of mice ear and then showed in vivo anti-inflammatory activity.
    Our results suggested that wild bitter melon extracts have anti-inflammatory effects against P. acnes and may be useful in the adjuvant treatment of acne.

    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 皮膚結構 3 第二節 痤瘡的致病機轉 5 壹、痤瘡的成因 5 貳、痤瘡桿菌與發炎反應 7 (一) 細胞外基質(Extracellular matrix, ECM) 10 (二) 基質金屬蛋白酶(Matrix metalloproteinases, MMPs) 10 參、 誘發發炎的訊息傳遞路徑 12 肆、 痤瘡與基質重塑(Matrix remodeling) 16 第三節 痤瘡的治療 18 第四節 實驗材料 19 一、山苦瓜 19 二、脂肪酸 23 第三章 材料與方法 30 第一節 實驗架構 30 (一) 抗菌與抗發炎評估 30 (二) 萃物暨其區分物抗發炎評估 30 第二節 樣品製備 31 第三節 研究材料 32 一、藥品與試劑 32 二、儀器設備與耗材 34 三、細胞培養 35 四、細菌培養 36 第四節 實驗方法 38 一、抑菌實驗 38 二、細胞存活率測定 (MTT) 38 三、抗發炎活性評估 39 四、轉錄因子nuclear factor-kappa B (NFκB)活化分析 40 五、MMP-9蛋白質表現量評估 42 六、動物實驗 (in vivo抗發炎能力評估) 46 七、脂肪酸成分分析 50 八、總多酚含量測定 51 九、Maximum inhibition(%)計算 52 十、統計分析 52 第四章 結果與討論 53 第一節 山苦瓜萃取物之抑菌與抗發炎作用 54 壹、山苦瓜萃取物之萃取率 54 貳、抑菌實驗 54 參、細胞存活率測定 54 肆、In vitro抗發炎活性評估 55 伍、討論 63 第二節 評估山苦瓜果實萃物暨其區分物之抗發炎作用 66 壹、In vivo anti-inflammatory effect of WBM EA extract 66 貳、皂化物與不皂化物之成分 67 參、細胞存活率測定 67 肆、In vitro抗發炎活性評估 68 伍、討論 87 第三節 評估山苦瓜葉甲醇萃物與其多酚萃物之抗發炎作用 94 壹、總多酚含量測定 94 貳、細胞存活率測定 94 參、In vitro抗發炎活性評估 95 肆、轉錄因子nuclear factor-kappa B (NFκB)活化分析 95 伍、In vivo anti-inflammatory effect 96 陸、討論 105 第四節 評估capric acid之抗菌、抗發炎作用 107 壹、抑菌實驗 107 貳、細胞存活率測定 107 參、In vitro抗發炎活性評估 107 肆、In vivo anti-inflammatory effect 108 伍、討論 115 第五章 綜合討論 118 第六章 參考文獻 127 第七章 附錄(動物實驗同意書) 137

    連聰蓉。(2010)。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。國立臺灣師範大學人類發展與家庭學系營養科學與教育組碩士論文,未出版,台北市。
    呂孟凡。(2011)。山苦瓜萃物對人類角質細胞及皮脂細胞之增生與分化的影響。國立臺灣大學生命科學院生化科技研究所碩士論文,未出版,台北市。
    黃懿寧。(2007)。癸酸降低脂多醣活化巨噬細胞株前列腺素E2生成之機制探討。國立臺灣大學生命科學院微生物與生化學研究所碩士論文,未出版,台北市。
    黃育亭。(2011)。山苦瓜萃取物抑制黑色素生成及抗光老化效應的評估。國立臺灣師範大學人類發展與家庭學系營養科學與教育組碩士論文,未出版,台北市。
    邱思魁、陳翠卿。(2009)。數種藥用植物甲醇及熱水萃取物的抗氧化性。臺灣農業化學與食品科學, 47(5), 260-267.
    莊佳穎。(2004)。山苦瓜活化過氧化體增殖劑活化受器PPARs之成分分離與鑑定。 國立臺灣大學微生物與生化學研究所碩士論文,未出版,台北市。
    鄭瑋宜、黃青真、金鴻榮。(2011)。癸酸降低脂多醣活化巨噬細胞株前列腺素E2生成之機制探討。行政院國家科學委員會專題研究成果報告(編號: NSC98-2320-B214-002-MY3),未出版。
    周友民、趙哲毅。(2008)。山苦瓜萃取物活化轉錄因子PPARγ及抑制巨噬細胞發炎介質之分泌。臺灣營養學會雜誌, 33(3), 108-115。
    陳奇慕、徐錫樑。(2010)。蕎麥不同溶劑萃取物之抗氧化能力及抗氧化成分分析。 臺灣農業化學與食品科學, 48(2), 84-91。
    吳雪月。(2006)。台灣新野菜主義(頁47-49)。臺北市:天下遠見。
    Abdel Fattah, N. S., Shaheen, M. A., Ebrahim, A. A., & El Okda, E. S. (2008). Tissue and blood superoxide dismutase activities and malondialdehyde levels in different clinical severities of acne vulgaris. Br J Dermatol, 159(5), 1086-1091.
    Akamatsu, H., Komura, J., Miyachi, Y., Asada, Y., & Niwa, Y. (1990). Suppressive effects of linoleic acid on neutrophil oxygen metabolism and phagocytosis. J Invest Dermatol, 95(3), 271-274.
    Babayan, V. K. (1987). Medium chain triglycerides and structured lipids. Lipids, 22, 417–420.
    Bansal, V., Syres, KM., Makarenkova, V., et al. (2005). Interactions between fatty acids and argininemetabolism: implications for the design of immune-enhancing diets. JPENJParenterEnteralNutr, 29(suppl), S75–80.
    Bastianetto, S., & Quirion, R. (2010). Heme oxygenase 1: another possible target to explain the neuroprotective action of resveratrol, a multifaceted nutrient-based molecule. Exp Neurol, 225(2), 237-239.
    Cakici, I., Hurmoglu, C., Tunctan, B., Abacioglu, N., Kanzik, I., & Sener, B. (1994). Hypoglycaemic effect of Momordica charantia extracts in nor moglycaemic or cyproheptadine-induced hyperglycaemic mice. Journal of Ethnopharmacology, 44, 117–121.
    Calder, P. C. (2006). n-3 polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr, 83(6 Suppl), 1505S-1519S.
    Carluccio, M. A., Massaro, M., Bonfrate, C., Siculella, L., Maffia, M., Nicolardi, G., et al. (1999). Oleic acid inhibits endothelial activation : A direct vascular antiatherogenic mechanism of a nutritional component in the mediterranean diet. Arterioscler Thromb Vasc Biol, 19(2), 220-228.
    Chakraborti, S., Mandal, M., Das, S., Mandal, A., & Chakraborti, T. (2003). Regulation of matrix metalloproteinases: an overview. Mol Cell Biochem, 253(1-2), 269-285.
    Chao, C. Y., & Huang, C. J. (2003). Bitter gourd (Momordica charantia) extract activates peroxisome proliferator-activated receptors and upregulates the expression of the acyl CoA oxidase gene in H4IIEC3 hepatoma cells. J Biomed Sci, 10(6 Pt 2), 782-791.
    Chaturvedi, P. (2009). Bitter melon protects against lipid peroxidation caused by immobilization stress in albino rats. Int J Vitam Nutr Res, 79(1), 48-56.
    Choi, J. Y., Piao, M. S., Lee, J. B., Oh, J. S., Kim, I. G., & Lee, S. C. (2008). Propionibacterium acnes stimulates pro-matrix metalloproteinase-2 expression through tumor necrosis factor-alpha in human dermal fibroblasts. J Invest Dermatol, 128(4), 846-854.
    Chomnawang, M. T., Surassmo, S., Nukoolkarn, V. S., Dessinioti., & Gritsanapan, W. (2005). Antimicrobial effects of Thai medicinal plants against acne-inducing bacteria. Journal of Ethnopharmacology, 101, 330-333.
    Coates, P., Vyakrnam, S., Eady, E. A., Jones, C. E., Cove, J. H., & Cunliffe, W. J. (2002). Prevalence of antibiotic-resistant propionibacteria on the skin of acne patients: 10-year surveillance data and snapshot distribution study. Br J Dermatol, 146(5), 840-848.
    Costa, A., Lage, D., & Moises, T. A. (2010). Acne and diet: truth or myth? An Bras Dermatol, 85(3), 346-353.
    Deckelbaum RJ, Worgall TS, & Seo T. n-3 Fatty acids and gene expression. Am J Clin Nutr, 83(suppl), S1520–1525.
    Dessinioti, C., & Katsambas, A. D. (2010). The role of Propionibacterium acnes in acne pathogenesis: facts and controversies. Clin Dermatol, 28(1), 2-7.
    Espersen, F. (1998). Resistance to antibiotics used in dermatological practice. Br J Dermatol, 139 Suppl 53, 4-8.
    Feige, J. N., Gelman, L., Michalik, L., Desvergne, B., & Wahli, W. (2006). From molecular action to physiological outputs: peroxisome proliferator-activated receptors are nuclear receptors at the crossroads of key cellular functions. Progress in Lipid Research, 45, 120-159.
    Frank, S., G. Hubner, G. Breier, M.T. Longaker, D.G. Greenhalgh, & S. Werner. (1995). Regulation of vascular endothelial growth factor expression in cultured keratinocytes. Implications for normal and impaired wound healing. J Biol Chem, 270, 12607-12613.
    Goto, T., Takahashi, N., Kato, S., Egawa, K., Ebisu, S., Moriyama, T., et al. (2005). Phytol directly activates peroxisome proliferator-activated receptor α (PPARα) and regulates gene expression involved in lipid metabolism in PPARα-expressing HepG2 hepatocytes. Biochemical and Biophysical Research Communications, 337(2), 440-445.
    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. Br J Dermatol, 150(3), 421-428.
    Grange, P. A., Weill, B., Dupin, N., Batteux, F. (2010). Does inflammatory acne result from imbalance in the keratinocyte innate immune response? . Microbes and Infection, 12(14-15), 1085-1090.
    Grimaldi, P. A. (2005). Regulatory role of peroxisome proliferator-activated receptor delta (PPAR delta) in muscle metabolism. A new target for metabolic syndrome treatment? Biochimie, 87, 5-8.
    Grange, P. A., Chereau, C., Raingeaud, J., Nicco, C., Weill, B., Dupin, N., et al. (2009). Production of superoxide anions by keratinocytes initiates P. acnes-induced inflammation of the skin. PLoS Pathog, 5(7), e1000527.
    Greene, R. S., Downing, D. T., Pochi, P. E., & Strauss, J. S. (1970). Anatomical variation in the amount and composition of human skin surface lipid. J Invest Dermatol, 54(3), 240-247.
    Grover, J.K., Rathi, S.S., & Vats, V. (2002). Amelioration of experimental diabetic neuropathy and gastropathy in rats following oral administration of plant (Eugenia jambolana, Mucuna pruriens and Tinospora cordifolia) extracts. Indian Journal of Experimental Biology, 40, 273–276.
    Grover, J. K., & Yadav, S. P. (2004). Pharmacological actions and potential uses of Momordica charantia: a review. J Ethnopharmacol, 93(1), 123-132.
    Han JR, Farmer SR, Kirkland JL, et al. (2002). Octanoate attenuates adipogenesis in 3T3–L1 preadipocytes. J Nutr, 132, 904–910.
    Hansen, K. K., Oikonomopoulou, K., Baruch, A., Ramachandran, R., Beck, P., Diamandis, E. P., et al. (2008). Proteinases as hormones: targets and mechanisms for proteolytic signaling. Biol Chem, 389(8), 971-982.
    Hoeffler, U. (1977). Enzymatic and hemolytic properties of Propionibacterium acnes and related bacteria. J Clin Microbiol, 6(6), 555-558.
    Holland, K. T., Cunliffe, W. J., & Roberts, C. D. (1978). The role of bacteria in acne vulgaris: a new approach. Clin Exp Dermatol, 3(3), 253-257.
    Holvoet, S., Vincent, C., Schmitt, D., & Serres, M. (2003). The inhibition of MAPK pathway is correlated with down-regulation of MMP-9 secretion induced by TNF-alpha in human keratinocytes. Exp Cell Res, 290(1), 108-119.
    Hsu, C., Hsieh, C. L., Kuo, Y. H., & Huang, C. J. (2011). Isolation and identification of cucurbitane-type triterpenoids with partial agonist/antagonist potential for estrogen receptors from Momordica charantia. J Agric Food Chem, 59(9), 4553-4561.
    Huang, C. J., & Wu, M. C. (2002). Differential effects of foods traditionally regarded as 'heating' and 'cooling' on prostaglandin E(2) production by a macrophage cell line. J Biomed Sci, 9(6 Pt 2), 596-606.
    Isard, O., Knol, A. C., Castex-Rizzi, N., Khammari, A., Charveron, M., & Dreno, B. (2009). Cutaneous induction of corticotropin releasing hormone by Propionibacterium acnes extracts. Dermatoendocrinol, 1(2), 96-99.
    Ibrahim, T. A., El-Hefnawy, H. M., & El-Hela, A. A. (2010). Antioxidant potential and phenolic acid content of certain cucurbitaceous plants cultivated in Egypt. Nat Prod Res, 24(16), 1537-1545.
    Ingham, E., Walters, C. E., Eady, E. A., Cove, J. H., Kearney, J. N., & Cunliffe, W. J. (1998). Inflammation in acne vulgaris: failure of skin micro-organisms to modulate keratinocyte interleukin 1 alpha production in vitro. Dermatology, 196(1), 86-88.
    Iwasaki, A., & Medzhitov, R. (2004). Toll-like receptor control of the adaptive immune responses. Nat Immunol, 5(10), 987-995.
    Jalian, H. R., Liu, P. T., Kanchanapoomi, M., Phan, J. N., Legaspi, A. J., & Kim, J. (2008). All-trans retinoic acid shifts Propionibacterium acnes-induced matrix degradation expression profile toward matrix preservation in human monocytes. J Invest Dermatol, 128(12), 2777-2782.
    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. Eur J Dermatol, 17(6), 492-496.
    Jayasooriya, A.P., Sakono, M., Yukizaki, C., Kawano, M., Yamamoto, K., & Fukuda, N. (2000). Effects of Momordica charantia powder on serum glucose levels and various lipid parameters in rats fed with cholesterolfree and cholesterol-enriched diets. Journal of Ethnopharmacology, 72, 331–336.
    Jittawan, K., Siriamornpun, S. (2008). Phenolic contents and antioxidant activities of bitter gourd (Momordica charantia L.) leaf stemand fruit fraction extracts in vitro. Food Chem, 110, 881-890.
    Jugeau, S., Tenaud, I., Knol, A. C., Jarrousse, V., Quereux, G., Khammari, A., et al. (2005). Induction of toll-like receptors by Propionibacterium acnes. Br J Dermatol, 153(6), 1105-1113.
    Kahari, V. M., & Saarialho-Kere, U. (1997). Matrix metalloproteinases in skin. Exp Dermatol, 6(5), 199-213.
    Kaisho, T., & Akira, S. (2006). Toll-like receptor function and signaling. J Allergy Clin Immunol, 117(5), 979-987; quiz 988.
    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. Am J Pathol, 166(6), 1691-1699.
    Kar, A., Choudhary, B.K., & Bandyopadhyay, N.G. (2003). Comparative evaluation of hypoglycaemic activity of some Indian medicinal plants in alloxan diabetic rats. Journal of Ethnopharmacology, 84, 105–108.
    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., et al. (2002). Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses. J Immunol, 169(3), 1535-1541.
    Kim, J.-H., Na, H.-J., Kim, C.-K., Kim, J.-Y., Ha, K.-S., Lee, H., et al. (2008). The non-provitamin A carotenoid, lutein, inhibits NF-κB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-κB-inducing kinase pathways: Role of H2O2 in NF-κB activation. Free Radical Biology and Medicine, 45(6), 885-896.
    Kobori, M., Nakayama, H., Fukushima, K., Ohnishi-Kameyama, M., Ono, H., Fukushima, T., et al. (2008). Bitter gourd suppresses lipopolysaccharide-induced inflammatory responses. J Agric Food Chem, 56(11), 4004-4011.
    Kohno, H., Yasui, Y., Suzuki, R., Hosokawa, M., Miyashita, K., & Tanaka, T. (2004). Dietary seed oil rich in conjugated linolenic acid from bitter melon inhibits azoxymethane-induced rat colon carcinogenesis through elevation of colonic PPARgamma expression and alteration of lipid composition. Int. J. Cancer, 110, 896–901
    Kubola, J., & Siriamornpun, S. (2008). Phenolic contents and antioxidant activities of bitter gourd (Momordica charantia L.) leaf, stem and fruit fraction extracts in vitro. Food Chemistry, 110(4), 881-890.
    Kumar, R., Balaji, S., Sripriya, R., Nithya, N., Uma, T. S., & Sehgal, P. K. (2010). In vitro evaluation of antioxidants of fruit extract of Momordica charantia L. on fibroblasts and keratinocytes. J Agric Food Chem, 58(3), 1518-1522.
    Kupper, T. S., & Fuhlbrigge, R. C. (2004). Immune surveillance in the skin: mechanisms and clinical consequences. Nat Rev Immunol, 4(3), 211-222.
    Lagente, V., Manoury, B., Nenan, S., Le Quement, C., Martin-Chouly, C., & Boichot, E. (2005). Role of matrix metalloproteinases in the development of airway inflammation and remodeling. Braz J Med Biol Res, 38(10), 1521-1530.
    Landrum, J. T., & Bone, R. A. (2001). Lutein, Zeaxanthin, and the Macular Pigment. Archives of Biochemistry and Biophysics, 385(1), 28-40.
    Lee JY, Sohn KH, Rhee SH, & Hwang D. (2001) Saturated fatty acids, but not unsaturated fatty acids induce the expression of cyclooxygenase-2mediated through Toll-like receptor 4. J Biol Chem, 276, 16683–16689.
    Lee JY, PlakidasA, Lee WH, et al. (2003). Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n 3 polyunsaturated fatty acids. J Lipid Res, 44, 479–86.
    Lee, S. E., Kim, J. M., Jeong, S. K., Jeon, J. E., Yoon, H. J., Jeong, M. K., et al. (2010). Protease-activated receptor-2 mediates the expression of inflammatory cytokines, antimicrobial peptides, and matrix metalloproteinases in keratinocytes in response to Propionibacterium acnes. Arch Dermatol Res, 302(10), 745-756.
    Lii, C. K., Chen, H. W., Yun, W. T., & Liu, K. L. (2009). Suppressive effects of wild bitter gourd (Momordica charantia Linn. var. abbreviata ser.) fruit extracts on inflammatory responses in RAW264.7 macrophages. J Ethnopharmacol, 122(2), 227-233.
    Manabe, M., Takenaka, R., Nakasa, T., & Okinaka, O. (2003). Induction of anti-inflammatory responses by dietary Momordica charantia L. (bitter gourd). Biosci Biotechnol Biochem, 67(12), 2512-2517.
    Medzhitov, R. (2001). Toll-like receptors and innate immunity. Nat Rev Immunol, 1(2), 135-145.
    Medzhitov, R., & Janeway, C., Jr. (2000). Innate immunity. N Engl J Med, 343(5), 338-344.
    Miller, L. S., & Modlin, R. L. (2007). Toll-like receptors in the skin. Semin Immunopathol, 29(1), 15-26.
    Miura, T., Itoh, C., Iwamoto, N., Kato, M., Kawai, M., Park, S.R., & Suzuki, I. (2001). Hypoglycemic activity of the fruit of the Momordica charantia in type 2 diabetic mice. Journal of Nutrition Sciences Vitaminology (Tokyo), 47, 340–344.
    Mouser, P. E., Baker, B. S., Seaton, E. D., & Chu, A. C. (2003). Propionibacterium acnes-reactive T helper-1 cells in the skin of patients with acne vulgaris. J Invest Dermatol, 121(5), 1226-1228.
    Mukaida N., Okamoto S., Ishikawa Y., & Matsushima K. (1994). Molecular mechanism of interleukin-8 gene expression. J Leukoc Biol, 56, 554-558.
    Nagy, I., Pivarcsi, A., Koreck, A., Szell, M., Urban, E., & Kemeny, L. (2005). Distinct strains of Propionibacterium acnes induce selective human beta-defensin-2 and interleukin-8 expression in human keratinocytes through toll-like receptors. J Invest Dermatol, 124(5), 931-938.
    Nakatsuji, T., Kao, M. C., Fang, J. Y., Zouboulis, C. C., Zhang, L., Gallo, R. L., et al. (2009). Antimicrobial property of lauric acid against Propionibacterium acnes: its therapeutic potential for inflammatory acne vulgaris. J Invest Dermatol, 129(10), 2480-2488.
    Nikawa, T., Schulz, W.A., van den Brink, C.E., Hanusch, M., van der Saag, P., Stahl, W., Sies, H., 1995. Efficacy of all-trans-beta-carotene, canthaxanthin, and all-trans-, 9-cis-, and 4-oxoretinoic acids in inducing differentiation of an F9 embryonal carcinoma RAR beta-lacZ reporter cell line. Arch. Biochem. Biophys. 316, 665–672.
    Olutunmbi, Y., Paley, K., & English, J. C., 3rd. (2008). Adolescent female acne: etiology and management. J Pediatr Adolesc Gynecol, 21(4), 171-176.
    Papakonstantinou, E., Aletras, A. J., Glass, E., Tsogas, P., Dionyssopoulos, A., Adjaye, J., et al. (2005). Matrix metalloproteinases of epithelial origin in facial sebum of patients with acne and their regulation by isotretinoin. J Invest Dermatol, 125(4), 673-684.
    Pitchakarn, P., Ogawa, K., Suzuki, S., Takahashi, S., Asamoto, M., Chewonarin, T., et al. (2010). Momordica charantia leaf extract suppresses rat prostate cancer progression in vitro and in vivo. Cancer Sci, 101(10), 2234-2240.
    Rattenholl, A., Steinhoff, M. (2003). Role of proteinase-activated receptors in cutaneous biology and disease. Drug Dev Res, 59, 408-416.
    Rattenholl, A., Steinhoff, M. (2008). Proteinase-activated receptor-2 in the skin: receptor expression, activation and function during health and disease. Drug News Perspect, 21, 369-381.
    Ryan, K. A., Smith, M. F., Jr., Sanders, M. K., & Ernst, P. B. (2004). Reactive oxygen and nitrogen species differentially regulate Toll-like receptor 4-mediated activation of NF-kappa B and interleukin-8 expression. Infect Immun, 72(4), 2123-2130.
    Sarici, G., Cinar, S., Armutcu, F., Altinyazar, C., Koca, R., & Tekin, N. S. (2010). Oxidative stress in acne vulgaris. J Eur Acad Dermatol Venereol, 24(7), 763-767.
    Sarkar, S., Pranava, M., & Marita, R. (1996). Demonstration of the hypoglycemic action of Momordica charantia in a validated animal model of diabetes. Pharmacology Research, 33, 1–4.
    Selvaraj, R.K., Klasing, K.C., 2006. Lutein and eicosapentaenoic acid interact to modify iNOS mRNA levels through the PPARγ/RXR pathway in chickens and HD11 cell lines. J. Nutr, 136, 1610–1616.
    Selvaraj, R.K., Koutsos, E.A., Calvert, C.C., Klasing, K.C., 2006. Dietary lutein and fat interact to modify macrophage properties in chicks hatched from carotenoid deplete or replete eggs. J. Anim. Physiol. Anim. Nutr, (Berl) 90, 70–80.
    Sertznig, P., Seifert, M., Tilgen, W. Reichrath, J. (2008). Peroxisome Proliferator-Activated Receptors(PPARs) and the Human Skin. Am J Clin Dermatol, 9(1), 15-31.
    Singh, J. (2006). Antioxidant phytochemicals in cabbage (Brassica oleracea L. var. capitata). Scientia horticulturae, 108(3), 233.
    Sitasawad, S.L., Shewade, Y., & Bhonde, R. (2000). Role of bittergourd fruit juice in stz-induced diabetic state in vivo and in vitro. Journal of Ethnopharmacology, 73, 71–79.
    Strauss, J. S., & Kligman, A. M. (1960). The pathologic dynamics of acne vulgaris. Arch Dermatol, 82(5), 779-790.
    Tan, N. S., Michalik, L., Desvergne, B. Wahli, W. (2003). Peroxisome proliferator-activated receptor (PPAR)-beta as a target for wound healing drugs: what is possible? . American Journal of Clinical Dermatology, 4, 523-530.
    Thiboutot, D. (2002). Acne: 1991-2001. J Am Acad Dermatol, 47(1), 109-117.
    Tortora, G. J. (2005). Principles of Human Anatomy (10 ed): John Wiley & Sons, Inc.
    Trivedi, N. R., Gilliland, K. L., Zhao, W., Liu, W., & Thiboutot, D. M. (2006). Gene array expression profiling in acne lesions reveals marked upregulation of genes involved in inflammation and matrix remodeling. J Invest Dermatol, 126(5), 1071-1079.
    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. Infect Immun, 63(8), 3158-3165.
    Wadsworth, T. L., & Koop, D. R. (2001). Effects of Ginkgo biloba extract (EGb 761) and quercetin on lipopolysaccharide-induced release of nitric oxide. Chem Biol Interact, 137(1), 43-58.
    Wajant, H., Pfizenmaier, K., & Scheurich. P. (2003). Tumor necrosis factor signalling. Cell Death Differ, 10, 45-65.
    Walters, C. E., Ingham, E., Eady, E. A., Cove, J. H., Kearney, J. N., & Cunliffe, W. J. (1995). In vitro modulation of keratinocyte-derived interleukin-1 alpha (IL-1 alpha) and peripheral blood mononuclear cell-derived IL-1 beta release in response to cutaneous commensal microorganisms. Infect Immun, 63(4), 1223-1228.
    Wanten G, Rops A, van Emst-de Vries S, Naber T, & Willems P. (2002). Prompt inhibition of fMLP-induced Ca2+ mobilization by parenteral lipid emulsions in human neutrophils. J Lipid Res, 43, 550–5566.
    Wanten G, van Emst-de Vries S, Naber T, & Willems P. (2001). Nutritional lipid emulsionsmodulate cellular signaling and activation of human neutrophils. J Lipid Res, 42, 428–436.
    Wanten GJ, Curfs JH, Meis JF, & Naber AH. (2001). Phagocytosis and killing of Candida albicans by human neutrophils after exposure to structurally different lipid emulsions. JPEN J Parenter Enteral Nutr, 25, 9–13
    Wanten GJ, Geijtenbeek TB, Raymakers RA, et al. (2000). Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation. JPEN J Parenter Enteral Nutr, 24, 228–233.
    Webster, G. F. (2002). Acne vulgaris. BMJ, 325(7362), 475-479.
    Wertz, P. W., Miethke, M. C., Long, S. A., Strauss, J. S., & Downing, D. T. (1985). The composition of the ceramides from human stratum corneum and from comedones. J Invest Dermatol, 84(5), 410-412.
    Whitmarsh, A. J., & Davis, R. J. (1996). Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J Mol Med 74, 589-607.
    Wu, S. J., & Ng, L. T. (2008). Antioxidant and free radical scavenging activities of wild bitter melon (Momordica charantia Linn. var. abbreviata Ser.) in Taiwan. . Swiss Society of Food Science and Technology, 323-330.
    Wu, W. H., Lin, B. Y., Kuo, Y. H., & Huang, C. J. (2009). Triglycerides constituted of short and medium chain fatty acids and dicarboxylic acids in Momordica charantia, as well as capric acid, inhibit PGE2 production in RAW264.7 macrophages. Food Chemistry, 117(2), 306-311.
    Yasui, Y., Hosokawa, M., Sahara, T., Suzuki, R., Ohgiya, S., Kohno, H., Tanaka, T., & Miyashita, K. (2005). Bitter gourd seed fatty acid rich in 9c,11t,13t-conjugated linolenic acid induces apoptosis and up-regulates the GADD45, p53 and PPARγ in human colon cancer Caco-2 cells. Prostaglandins, Leukotrienes Essent. Fatty Acids, 73, 113–119.
    Ziboh, V. A. (1989). Implications of dietary oils and polyunsaturated fatty acids in the management of cutaneous disorders. Arch Dermatol, 125(2), 241-245.
    Ziboh, V. A., & Chapkin, R. S. (1987). Biologic significance of polyunsaturated fatty acids in the skin. Arch Dermatol, 123(12), 1686a-1690.

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