Protective Effect of Acteoside on Immunological Liver Injury Induced by Bacillus Calmette-Guerin plus Lipopolysaccharide

Abstract

The hepatoprotective effects of acteoside from O. coerulescens were evaluated in BCG plus LPS-induced immunological liver injury (ILI) in mice. Acteoside (50, 150, or 300 mg/kg) was administered via gavage daily for 12 days. The liver index (liver weight/body weight), liver homogenate levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), hepatic nitric oxide (NO), malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, production of tumor necrosis factor-γ (TNF-γ) and interleukin-2, 4, 10 (IL-2, 4, 10), as well as histopathological changes of the liver were evaluated following the 12-day treatment. Moreover, the modulation influence of acteoside on the expression of B cell lymphoma/leukemia-2 (Bcl-2, hepatocyte apoptosis inhibitor) and Bcl-2 associated X protein (Bax, hepatocyte apoptosis promoter) in the mice liver with immunological hepatic injury was studied also. Acteoside (50, 150, or 300 mg/kg) effectively reduced the BCG/LPS-induced elevated liver index, liver homogenate AST and ALT levels, hepatic NO and MDA contents, restored hepatic SOD activity and reduced the degree of liver injury in ILI mice. The expression of Bax was decreased (vs. BCG + LPS model group), while the expression of Bcl-2 increased (vs. BCG + LPS model group). These results are close to those of DDB (as a reference drug), and suggest that acteoside has a protective and therapeutic effect on ILI mice, which might be associated with its antioxidant properties, immunoregulatory function and regulation of hepatic apoptosis.

Orobanche coerulescens Steph. - Orobanche genus - Orobanchaceae - acteoside - immunological liver injury - hepatoprotective action

References

• 1 Xu Q, Chen X C. CD4 T lymphocytes cause hepatocyte apoptosis by releasing Th1 cytokines in cellular immunological liver injury.  Inflamm Res. 2002;  51 444-450
• 2 Carter L L, Dutton R W. Relative perforin- and Fas-mediated lysis in Tl and T2 CD8+ effector populations.  J Immunol. 1995;  155 1028-1031
• 3 O'Garra A, Murphy K. T-cell subsets in autoimmunity.  Curr Opin Immunol. 1993;  5 880-886
• 4 Hugh B J, Gil-Gomez G. Molecules in focus Bax. The pro-apoptotic Bcl-2 family member, Bax.  Int J Biochem Cell Biol. 1998;  30 647-650
• 5 Ferluga J. Tuberculin hypersensitivity hepatitis in mice infected with Mycobacterium bovis (BCG).  Am J Pathol. 1981;  105 82-90
• 6 Tsuji H, Harada A, Mukaida N, Nakanuma Y, Bluethmann H, Kaneko S, Yamakawa K, Nakamura S I, Kobayashi K I, Matsushima K. Tumor necrosis factor receptor p 55 is essential for intrahepatic granuloma formation and hepatocellular apoptosis in a murine model of bacterium-induced fulminant hepatitis.  Infect Immun. 1997;  65 1892-1898
• 7 Tsuji H, Mukaida N, Harada A, Kaneko S, Matsushita E, Nakanuma Y, Tsutsui H, Okamura H, Nakanishi K, Tagawa Y, Iwakura Y, Kobayashi K, Matsushima K. Alleviation of lipopolysaccharide-induced acute liver injury in Propionibacterium acnes-primed IFN-γ-deficient mice by a concomitant reduction of TNF-α, IL‐12, and IL‐18 production.  J Immunol. 1999;  162 1049-1055
• 8 Zhang G L, Wang Y H, Ni W, Teng H L, Lin Z B. Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice.  World J Gastroenterol. 2002;  8 728-733
• 9 Wang H, Wei W, Shen Y X, Dong C, Zhang L L, Wang N P, Yue L, Xu S Y. Protective effect of melatonin against liver injury in mice induced by Bacillus Calmette-Guerin plus lipopolysaccharide.  World J Gastroenterol. 2004;  10 2690-2696
• 10 Lee K J, Woo E R, Choi C Y, Shin D W, Lee D G, You H J, Jeong H G. Protective effect of acteoside on carbon tetrachloride-induced hepatotoxicity.  Life Sci. 2004;  74 1051-1064
• 11 Xiong Q, Hase K, Tezuka Y, Tani T, Namba T, Kadota S. Hepatoprotective activity of phenylethanoids from Cistanche deserticola.  Planta Med. 1998;  64 120-125
• 12 Wang G S, Liu G T. Role of nitric oxide in immunological liver damage in mice.  Biochem Pharmacol. 1995;  9 1277-1281
• 13 Yajima T, Nishimura H, Saito K, Kuwano H, Yoshikai Y. Overexpression of interleukin-15 increases susceptibility to lipopolysaccharide-induced liver injury in mice primed with Mycobacterium bovis Bacillus Calmette-Guerin.  Infect Immun. 2004;  72 3855-3862
• 14 Shimizu I, Ma Y R, Mizobuchi Y, Liu F, Miura T, Nakai Y, Yasuda M, Shiba M, Horie T, Amagaya S, Kawada N, Hori H, Ito S. Effects of Sho-saiko-to, a Japanese herbal medicine, on hepatic fibrosis in rats.  Hepatology. 1999;  29 149-160
• 15 Polavarapu R, Spitz D R, Sim J E, Follansbee M H, Oberley L W, Rahemtulla A, Nanji A A. Increased lipid peroxidation and impaired antioxidant enzyme function is associated with pathological liver injury in experimental alcoholic liver disease in rats fed diets high in corn oil and fish oil.  Hepatology. 1998;  27 1317-1323
• 16 Kim Y M, Son K. A nitric oxide production bioassay for interferon-gamma.  J Immunol Methods. 1996;  198 203-209
• 17 Laskin D L, Rodriguez del Valle M, Heck D E, Hwang S M, Ohnishi S T, Durham S K, Goller N L, Laskin J D. Hepatic nitric oxide production following acute endotoxemia in rats is mediated by increased inducible nitric oxide synthase gene expression.  Hepatology. 1995;  22 223-234
• 18 Wang P F, Kang J H, Zheng R L, Yang Z H, Lu J F, Gao J J, Jia Z J. Scavenging effects of phenylpropanoid glycosides from Pedicularis on superoxide anion and hydroxyl radical by the spintrapping method.  Biochem Pharmacol. 1996;  51 687-691
• 19 Xiong Q B, Kadota S, Tani T, Namba T. Antioxidative effects of phenylehanoids from Cistanche deserticola.  Biol Pharm Bull. 1996;  19 1580-1585
• 20 Liao F, Zheng R L, Gao J J, Jia Z J. Retardation of skeletal muscle fatigue by the two phenylpropanoid glycosides: verbascoside and martynoside from Pedicularis plicata maxim.  Phytother Res. 1999;  13 621-623
• 21 Kim S N, Kim S Y, Yim S Y, Lee W Y, Ham K S, Kim S K, Yoon M Y, Kim Y C. Effect of dimethyl-4,4′-dimethoxy-5,6,5′,6′-dimethylene dioxybiphenyl-2,2′-dicarboxylate (DDB) on chemical induced liver injury.  Biol Pharm Bull. 1999;  22 93-95
• 22 Abdel-Hameid N A. Protective role of dimethyl diphenyl bicarboxylate (DDB) against erythromycin induced hepatotoxicity in male rats.  Toxicol In Vitro. 2007;  21 618-625
• 23 Xiong Q, Hase K, Tezuka Y, Namba T, Kadota S. Acteoside inhibits apoptosis in D-galactosamine and lipopolysaccharide-induced liver injury.  Life Sci. 1999;  65 421-430
• 24 Ding A H, Nathan C F. Trace levels of bacterial lipopolysaccharide prevent interferon-gamma or tumor necrosis factor-alpha from enhancing mouse peritoneal macrophage respiratory burst capacity.  Immunology. 1987;  139 1971-1976
• 25 Ando K, Hiroishi K, Kaneko T, Moriyama T, Muto Y, Kayagaki N. Perforin, Fas/Fas ligand, and TNF-α pathways as specific and bystander killing mechanisms of hepatitis C virus-specific human CTL.  J Immunol. 1997;  158 5283-5291
• 26 Arai M, Mochida S, Ohno A, Ogata I, Fujiwara K. Sinusoidal endothelial cell damage by activated hepatic macrophages in rat liver necrosis.  Gastroenterology. 1993;  104 1466-1471
• 27 Mochida S, Arai M, Ohno A, Fujiwara K. Deranged blood coagulation equilibrium as a factor of massive liver necrosis following endotoxin administration in partially hepatectomized rats.  Hepatology. 1999;  29 1532-1540
• 28 Mimura S, Mochida S, Inao M, Matsui A, Nagoshi S, Yoshimoto T, Fujiwara K. Massive liver necrosis after provocation of imbalance between Th1 and Th2 immune reactions in osteopontin transgenic mice.  J Gastroenterol. 2004;  39 867-872
• 29 Kang C D, Jang J H, Kim K W, Lee H J, Jeong C S, Kim C M, Kim S H, Chung B S. Activation of c-jun N-terminal kinase/stressactivated protein kinase and the decreased ratio of Bcl-2 to Bax are associated with the auto-oxidized dopamine-induced apoptosis in PC12 cells.  Neurosci Lett. 1998;  256 37-40
• 30 Wei H F, Kang B B, Wei W L, Liang G, Meng Q C, Li Y J, Eckenhoff R G. Isoflurane and sevoflurane affect cell survival and BCL‐2/BAX ratio differently.  Brain Res. 2005;  1037 139-147