散血草在民間用於治療發炎、解毒等功效，並有文獻報導同屬植 物具有抗腫瘤、抗發炎、保肝等作用。本研究目的主要探討散血草對
四氯化碳誘導小鼠肝纖維的保護功效，並解明其氯仿萃取物抑制 LPS
誘發RAW264.7 放出發炎細胞激素的機轉。
結果顯示散血草減輕四氯化碳引起的肝損傷與其抑制庫氏細胞 的活化有密切的關係。庫氏細胞是存在於肝臟中的巨噬細胞。先在大
鼠初代庫氏細胞證實散血草能抑制 LPS 誘發的發炎反應後，進一步
以巨噬細胞RAW264.7 來解明散血草的作用機轉。散血草氯仿分層的 作用最明顯，實驗結果也顯示散血草氯仿分層能經由抑制NFκB 途徑 及MAPK 途徑抑 LPS 誘發的發炎反應。
五、參考文獻
Baroni, G. S., D'Ambrosio, L., Curto, P., Casini, A., Mancini, R., Jezequel, A. M. & Benedetti, A. 1996: Interferon gamma decreases hepatic stellate cell activation and extracellular matrix deposition in rat liver fibrosis. Hepatology, 23, 1189-1199.
Bruccoleri, A., Gallucci, R., Germolec, D. R., Blackshear, P., Simeonova, P., Thurman, R. G. & Luster, M. I. 1997: Induction of
early-immediate genes by tumor necrosis factor alpha contribute to liver repair following chemical-induced hepatotoxicity. Hepatology, 25, 133-141.
Cameron GR, K. W. 1936: Carbon tetrachloride cirrhosis in relation to liver regeneration. J.Pathol.Bacterol., 42, 1-21.
Cantrell, C. L., Rajab, M. S., Franzblau, S. G., Fronczek, F. R. & Fischer, N. H. 1999: Antimycobacterial ergosterol-5,8-endoperoxide from Ajuga remota. Planta Med, 65, 732-734.
Dang, S. S., Wang, B. F., Cheng, Y. A., Song, P., Liu, Z. G. & Li, Z. F.
2007: Inhibitory effects of saikosaponin-d on CCl4-induced hepatic fibrogenesis in rats. World J Gastroenterol, 13, 557-563.
DeCicco, L. A., Rikans, L. E., Tutor, C. G. & Hornbrook, K. R. 1998:
Serum and liver concentrations of tumor necrosis factor alpha and interleukin-1beta following administration of carbon tetrachloride to male rats. Toxicol Lett, 98, 115-121.
Elsharkawy, A. M. & Mann, D. A. 2007: Nuclear factor-kappaB and the hepatic inflammation-fibrosis-cancer axis. Hepatology, 46,
590-597.
Fang, H. L., Lai, J. T. & Lin, W. C. 2008: Inhibitory effect of olive oil on fibrosis induced by carbon tetrachloride in rat liver. Clin Nutr, 27, 900-907.
Friedman, S. L. 2000: Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem, 275, 2247-2250.
Froh, M., Konno, A. & Thurman, R. G. 2002: Isolation of Liver Kupffer Cells. Current Protocols in Toxicology. John Wiley & Sons.
Geerts, A. 2001: History, heterogeneity, developmental biology, and functions of quiescent hepatic stellate cells. Semin Liver Dis, 21, 311-335.
Geerts, A., Lazou, J. M., De Bleser, P. & Wisse, E. 1991: Tissue
distribution, quantitation and proliferation kinetics of fat-storing cells in carbon tetrachloride-injured rat liver. Hepatology, 13, 1193-1202.
Geesin, J. C., Hendricks, L. J., Falkenstein, P. A., Gordon, J. S. & Berg, R.
A. 1991: Regulation of collagen synthesis by ascorbic acid:
characterization of the role of ascorbate-stimulated lipid peroxidation. Arch Biochem Biophys, 290, 127-132.
Gines, P., Cardenas, A., Arroyo, V. & Rodes, J. 2004: Management of cirrhosis and ascites. N Engl J Med, 350, 1646-1654.
Gregory, S. H., Cousens, L. P., van Rooijen, N., Dopp, E. A., Carlos, T. M.
& Wing, E. J. 2002: Complementary adhesion molecules promote neutrophil-Kupffer cell interaction and the elimination of bacteria taken up by the liver. J Immunol, 168, 308-315.
Gregory, S. H. & Wing, E. J. 2002: Neutrophil-Kupffer cell interaction: a critical component of host defenses to systemic bacterial infections.
J Leukoc Biol, 72, 239-248.
Gregory, S. H., Wing, E. J., Danowski, K. L., van Rooijen, N., Dyer, K. F.
& Tweardy, D. J. 1998: IL-6 produced by Kupffer cells induces STAT protein activation in hepatocytes early during the course of systemic listerial infections. J Immunol, 160, 6056-6061.
Harris, G. K., Qian, Y., Leonard, S. S., Sbarra, D. C. & Shi, X. 2006:
Luteolin and chrysin differentially inhibit cyclooxygenase-2 expression and scavenge reactive oxygen species but similarly inhibit prostaglandin-E2 formation in RAW 264.7 cells. J Nutr, 136, 1517-1521.
Haubrich, W. S. 2004: Kupffer of Kupffer cells. Gastroenterology, 127, 16.
Heinrich, P. C., Castell, J. V. & Andus, T. 1990: Interleukin-6 and the acute phase response. Biochem J, 265, 621-636.
Herlaar, E. & Brown, Z. 1999: p38 MAPK signalling cascades in inflammatory disease. Mol Med Today, 5, 439-447.
Hilaly, J. E. & Lyoussi, B. 2002: Hypoglycaemic effect of the lyophilised aqueous extract of Ajuga iva in normal and streptozotocin diabetic rats. J Ethnopharmacol, 80, 109-113.
Hommes, D. W., Peppelenbosch, M. P. & van Deventer, S. J. 2003:
Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets. Gut, 52, 144-151.
Horn, T. L., O'Brien, T. D., Schook, L. B. & Rutherford, M. S. 2000:
Acute hepatotoxicant exposure induces TNFR-mediated hepatic injury and cytokine/apoptotic gene expression. Toxicol Sci, 54, 262-273.
Jeffrey, K. L., Camps, M., Rommel, C. & Mackay, C. R. 2007: Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov, 6, 391-403.
Johnson, G. L. & Lapadat, R. 2002: Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science, 298, 1911-1912.
Kariba, R. M. 2001: Antifungal activity of Ajuga remota. Fitoterapia, 72, 177-178.
Kim, H. G., Yoon, D. H., Kim, C. H., Shrestha, B., Chang, W. C., Lim, S.
Y., Lee, W. H., Han, S. G., Lee, J. O., Lim, M. H., Kim, G. Y., Choi, S., Song, W. O., Sung, J. M., Hwang, K. C. & Kim, T. W. 2007a:
Ethanol extract of Inonotus obliquus inhibits
lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells. J Med Food, 10, 80-89.
Kim, H. G., Yoon, D. H., Lee, W. H., Han, S. K., Shrestha, B., Kim, C. H., Lim, M. H., Chang, W., Lim, S., Choi, S., Song, W. O., Sung, J. M., Hwang, K. C. & Kim, T. W. 2007b: Phellinus linteus inhibits
inflammatory mediators by suppressing redox-based NF-κB and MAPKs activation in lipopolysaccharide-induced RAW 264.7 macrophage. J Ethnopharmacol, 114, 307-315.
Kolios, G., Valatas, V. & Kouroumalis, E. 2006: Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol, 12, 7413-7420.
Konoshima, T., Takasaki, M., Tokuda, H. & Nishino, H. 2000: Cancer chemopreventive activity of an iridoid glycoside, 8-acetylharpagide, from Ajuga decumbens. Cancer Lett, 157, 87-92.
Koo, D. J., Chaudry, I. H. & Wang, P. 1999: Kupffer cells are responsible for producing inflammatory cytokines and hepatocellular
dysfunction during early sepsis. J Surg Res, 83, 151-157.
Kovalovich, K., DeAngelis, R. A., Li, W., Furth, E. E., Ciliberto, G. &
Taub, R. 2000: Increased toxin-induced liver injury and fibrosis in interleukin-6-deficient mice. Hepatology, 31, 149-159.
Lorenzo-Zuniga, V., Rodriguez-Ortigosa, C. M., Bartoli, R., Martinez-Chantar, M. L., Martinez-Peralta, L., Pardo, A.,
Ojanguren, I., Quiroga, J., Planas, R. & Prieto, J. 2006: Insulin-like
growth factor I improves intestinal barrier function in cirrhotic rats.
Gut, 55, 1306-1312.
Louis, H., Van Laethem, J. L., Wu, W., Quertinmont, E., Degraef, C., Van den Berg, K., Demols, A., Goldman, M., Le Moine, O., Geerts, A.
& Deviere, J. 1998: Interleukin-10 controls neutrophilic infiltration, hepatocyte proliferation, and liver fibrosis induced by carbon
tetrachloride in mice. Hepatology, 28, 1607-1615.
Luckey, S. W. & Petersen, D. R. 2001: Activation of Kupffer cells during the course of carbon tetrachloride-induced liver injury and fibrosis in rats. Exp Mol Pathol, 71, 226-240.
Luoma, J. S. & Yla-Herttuala, S. 1999: Expression of inducible nitric oxide synthase in macrophages and smooth muscle cells in various types of human atherosclerotic lesions. Virchows Arch, 434,
561-568.
Makarov, S. S. 2000: NF-κB as a therapeutic target in chronic
inflammation: recent advances Molecular Medicine Today, 6, 441-448.
McGregor, D. & Lang, M. 1996: Carbon tetrachloride: genetic effects and other modes of action. Mutat Res, 366, 181-195.
Mi Jeong, S., Davaatseren, M., Kim, W., Sung Kwang, P., Kim, S. H., Haeng Jeon, H., Myung Sunny, K., Kim, Y. S. & Dae Young, K.
2009: Vitisin A suppresses LPS-induced NO production by
inhibiting ERK, p38, and NF-κB activation in RAW 264.7 cells. Int Immunopharmacol, 9, 319-323.
Moore, K. W., Vieira, P., Fiorentino, D. F., Trounstine, M. L., Khan, T. A.
& Mosmann, T. R. 1990: Homology of cytokine synthesis inhibitory factor (IL-10) to the Epstein-Barr virus gene BCRFI.
Science, 248, 1230-1234.
Morio, L. A., Chiu, H., Sprowles, K. A., Zhou, P., Heck, D. E., Gordon, M. K. & Laskin, D. L. 2001: Distinct roles of tumor necrosis
factor-alpha and nitric oxide in acute liver injury induced by carbon tetrachloride in mice. Toxicol Appl Pharmacol, 172, 44-51.
Moynagh, P. N. 2005: The NF-κB pathway. J Cell Sci, 118, 4589-4592.
Muriel, P., Alba, N., Perez-Alvarez, V. M., Shibayama, M. & Tsutsumi, V.
K. 2001: Kupffer cells inhibition prevents hepatic lipid
peroxidation and damage induced by carbon tetrachloride. Comp Biochem Physiol C Toxicol Pharmacol, 130, 219-226.
Muriel, P. & Escobar, Y. 2003: Kupffer cells are responsible for liver
cirrhosis induced by carbon tetrachloride. J Appl Toxicol, 23, 103-108.
Neubauer, K., Lindhorst, A., Tron, K., Ramadori, G. & Saile, B. 2008:
Decrease of PECAM-1-gene-expression induced by
proinflammatory cytokines IFN-γ and IFN-α is reversed by TGF-β in sinusoidal endothelial cells and hepatic mononuclear phagocytes.
BMC Physiol, 8, 1-14.
Neuman, R. E. & Logan, M. A. 1950: The determination of hydroxyproline. J Biol Chem, 184, 299-306.
Odek-Ogunde, M., Rajab, M. S., Migwi, G. J. & Ndegwa, J. M. 1993:
Blood pressure responses to an extract of Ajuga remota in experimentally hypertensive rats. Planta Med, 59, 573-574.
Ohkawa, H., Ohishi, N. & Yagi, K. 1979: Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem, 95, 351-358.
Ono, Y., Fukaya, Y., Imai, S. & Yamakuni, T. 2008: Beneficial effects of Ajuga decumbens on osteoporosis and arthritis. Biol Pharm Bull, 31, 1199-1204.
Poli, G. 2000: Pathogenesis of liver fibrosis: role of oxidative stress. Mol Aspects Med, 21, 49-98.
Qiu, D. K., Hua, J., Li, J. Q. & Li, E. L. 2005: CD14 expression on Kupffer cells during the course of carbon tetrachloride-mediated liver injury. Chin J Dig Dis, 6, 137-141.
Ramadori., G. & Saile., B. 2005: Signaling Pathways in Liver Diseases.
In J.F.Dufour & P.-A.Clavien (eds.) hepatocyte. Springer Berlin Heidelberg, 1-13.
Riaz, N., Malik, A., Nawaz, S. A., Muhammad, P. & Choudhary, M. I.
2004: Cholinesterase-inhibiting withanolides from Ajuga bracteosa.
Chem Biodivers, 1, 1289-1295.
Riaz, N., Nawaz, S. A., Mukhtar, N., Malik, A., Afza, N., Ali, S., Ullah, S., Muhammad, P. & Choudhary, M. I. 2007: Isolation and
enzyme-inhibition studies of the chemical constituents from Ajuga bracteosa. Chem Biodivers, 4, 72-83.
Rivera, C. A., Bradford, B. U., Hunt, K. J., Adachi, Y., Schrum, L. W., Koop, D. R., Burchardt, E. R., Rippe, R. A. & Thurman, R. G. 2001:
Attenuation of CCl4-induced hepatic fibrosis by GdCl(3) treatment or dietary glycine. Am J Physiol Gastrointest Liver Physiol, 281, G200-207.
Roberts, R. A., Ganey, P. E., Ju, C., Kamendulis, L. M., Rusyn, I. &
Klaunig, J. E. 2007: Role of the Kupffer cell in mediating hepatic toxicity and carcinogenesis. Toxicol Sci, 96, 2-15.
Rockey, D. C. & Chung, J. J. 1994: Interferon gamma inhibits lipocyte activation and extracellular matrix mRNA expression during experimental liver injury: implications for treatment of hepatic fibrosis. J Investig Med, 42, 660-670.
Rockey, D. C., Maher, J. J., Jarnagin, W. R., Gabbiani, G. & Friedman, S.
L. 1992: Inhibition of rat hepatic lipocyte activation in culture by interferon-gamma. Hepatology, 16, 776-784.
Schwacha, M. G. 2003: Macrophages and post-burn immune dysfunction.
Burns, 29, 1-14.
Sturgill, M. G. & Lambert, G. H. 1997: Xenobiotic-induced hepatotoxicity:
mechanisms of liver injury and methods of monitoring hepatic function. Clin Chem, 43, 1512-1526.
Su, G. L. 2002: Lipopolysaccharides in liver injury: molecular
mechanisms of Kupffer cell activation. Am J Physiol Gastrointest Liver Physiol, 283, G256-265.
Szabo, G., Mandrekar, P. & Dolganiuc, A. 2007: Innate immune response and hepatic inflammation. Semin Liver Dis, 27, 339-350.
Teng, F. Y., Wu, S. K., Hsia, Y. Y., Kao, W. B. & Hsieh, Y. D. 2006:
Modulation of Inflammation, Apoptosis, and Oncogenesis by the Nuclear Transcription Factor, NF-κB. Chin Dent J., 25, 12-24.
Wake, K. 1980: Perisinusoidal stellate cells (fat-storing cells, interstitial cells, lipocytes), their related structure in and around the liver sinusoids, and vitamin A-storing cells in extrahepatic organs. Int Rev Cytol, 66, 303-353.
Wang, S. C., Ohata, M., Schrum, L., Rippe, R. A. & Tsukamoto, H. 1998:
Expression of interleukin-10 by in vitro and in vivo activated hepatic stellate cells. J Biol Chem, 273, 302-308.
Weber, L. W., Boll, M. & Stampfl, A. 2003: Hepatotoxicity and mechanism of action of haloalkanes: carbon tetrachloride as a toxicological model. Crit Rev Toxicol, 33, 105-136.
Wheeler, M. D. 2003: Endotoxin and Kupffer cell activation in alcoholic liver disease. Alcohol Res Health, 27, 300-306.
Willcox, R. R. 1952: The Ito skin test for chancroid in the adult and juvenile African. Am J Syph Gonorrhea Vener Dis, 36, 284-288.
Williams, L. M., Ricchetti, G., Sarma, U., Smallie, T. & Foxwell, B. M.
2004: Interleukin-10 suppression of myeloid cell activation--a continuing puzzle. Immunology, 113, 281-292.
Yu, X. H., Zhu, J. S., Yu, H. F. & Zhu, L. 2004: Immunomodulatory effect of oxymatrine on induced CCl4-hepatic fibrosis in rats. Chin Med J (Engl), 117, 1856-1858.
王實強、王曉洪、許敏（1996）。筋骨草總二萜的降壓實驗研究。湖 南中醫藥導報，2（3），28。
行政院衛生署統計室（2007）。台灣地區死因統計結果摘要(民國九十 六年) 。
江蘇新醫學院（1992）。中藥大辭典(上)。白毛夏枯草（頁 751）。上 海：上海科學技術出版社。
李衛文、吳文玲、劉守金、方成武、梁益敏（2009）。筋骨草屬植物 的化學成分。安徽醫藥，13（3），325-339。
邱年永、張光雄（1992）。原色台灣藥用植物圖鑑(3)。有苞筋骨草（頁 187）。台北：南天書局。
馬志平、黃榕（2002）。筋骨草有效部位黃酮類粗品的保肝試驗。海 峽藥學，14（5），40-41。
陳嬿如（2003）。仙草對tert-butyl hydroperoxide 誘發大鼠急性肝損傷 與人類肝癌細胞(hepg2)氧化傷害之保護效果。國立中興大學食 品科學系研究所碩士論文。
曾茂貴、賈銣、吳符火（2003）。筋骨草對小鼠 s_(180)肉瘤的抑瘤試
楊丁林（1989）。筋骨草治膽汁瘺驗案。新中醫，21（5），22。
詹明哲（2003）。牛磺酸對四氯化碳誘發大鼠肝臟纖維化的改善效果。 中國醫藥學院醫學研究所碩士學位論文。
劉斌、石任兵、葛小俠、周瑩、周靜（2001）。筋骨草屬植物化學成 分與藥理活性。國外醫藥.植物藥分冊，16（3），96-101。