Amelioration of lipopolysaccharide-induced liver injury by aqueous rooibos (Aspalathus linearis) extract via inhibition of pro-inflammatory cytokines and oxidative stress

BMC Complementary and Alternative Medicine

Jeanine Lucasta Marnewick¹  Oluwafemi Omoniyi Oguntibeju¹  Olawale Razaq Ajuwon² 

[1] Oxidative Stress Research Centre, Institute of Biomedical and Microbial Biotechnology, Faculty of Health and Wellness Sciences, Cape Peninsula University of Technology, PO Box 1906 Bellville 7535, South Africa;Present Address: Redox Laboratory, Department of Human Biology, Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory 7925, Cape Town, South Africa

关键词: Oxidative stress;    Lipopolysaccharide;    Hepatotoxicity;    Cytokine;    Anti-inflammatory;    Aspalathus linearis;   

Others  :  1086086
DOI  :  10.1186/1472-6882-14-392

 received in 2014-07-01, accepted in 2014-10-07,  发布年份 2014

【 摘 要 】

Background

Acute liver injury occur after intraperitoneal administration of lipopolysaccharide (LPS). Oxidative stress and release of pro-inflammatory cytokines are both implicated in the pathogenesis of LPS-induced acute liver injury. This study investigated the ameliorative effect of fermented rooibos (Aspalathus linearis) extract on LPS-induced acute liver injury.

Method

Major phenolic compounds in the fermented rooibos extract by HPLC-DAD, as well as the in vitro antioxidant capacity were quantified before the start of the experiment. Male Wistar rats were randomized into 4 groups (n = 10 per group) and given either water or fermented rooibos extract for 4 weeks before LPS injection. Hepatic function markers, including aminotransferases and lactate dehydrogenase, lipid peroxidation markers, antioxidant enzymes, glutathione redox status, as well as cytokine levels were monitored in the rats.

Results

Injection of LPS significantly increased serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and lactate dehydrogenase (LDH). Oxidative stress, evidenced by increased thiobarbituric acid reactive substances (TBARS) measured as malondialdehyde (MDA) in plasma and liver, and decreased glutathione redox status (GSH: GSSG ratio) in whole blood and liver was induced in LPS-challenged rats. Furthermore, hepatic levels of pro-inflammatory response markers TNF-α, IL-1β and IL-6 were increased significantly. Pre-feeding the fermented rooibos extract for 4 weeks decreased LPS-induced elevated levels of serum AST and LDH (significantly, p < 0.05) as well as ALT marginally. Consuming rooibos caused an attenuation of the observed increase in plasma and hepatic MDA, decrease in whole blood and liver GSH:GSSG ratio, as well as the changes noted in various antioxidant enzymes. The elevation in TNF-α and IL-6 was significantly suppressed, indicating an inhibition of the induced inflammatory response by rooibos.

Conclusion

Overall, our data showed that aqueous rooibos extract attenuated LPS-induced liver injury possibly by modulating oxidative stress and suppressing pro-inflammatory cytokines formation.

【 授权许可】

   
2014 Ajuwon et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Larrosa M, Azorín-Ortuño M, Yanez-Gascon M, Garcia-Conesa M, Tomás-Barberán F, Espin J: Lack of effect of oral administration of resveratrol in LPS-induced systemic inflammation. Eur J Nutr 2011, 50(8):673-680.
• [2]Sebai H, Ben-Attia M, Sani M, Aouani E, Ghanem-Boughanmi N: Protective effect of resveratrol in endotoxemia-induced acute phase response in rats. Arch Toxicol 2009, 83(4):335-340.
• [3]Sun S, Zhang H, Xue B, Wu Y, Wang J, Yin Z, Luo L: Protective effect of glutathione against lipopolysaccharide-induced inflammation and mortality in rats. Inflamm Res 2006, 55(11):504-510.
• [4]Sebai H, Ben-Attia M, Sani M, Aouani E, Ghanem-Boughanmi N: Protective effect of resveratrol on acute endotoxemia-induced nephrotoxicity in rat through nitric oxide independent mechanism. Free Radic Res 2008, 42:913-920.
• [5]Krzyzanowska J, Czubacka A, Oleszek W: Dietary Phytochemicals and Human Health. In Bio-Farms for Nutraceuticals: Functional Food and Safety Control by Biosensors. Edited by Giardi MT, Rea G, Berra B. New York: Springer; 2010:74-98.
• [6]Joubert E, Gelderblom W, Louw A, De Beer D: South African herbal teas: Aspalathus linearis, Cyclopia spp. and Athrixia phylicoides - A review. J Ethnopharmacol 2008, 119(3):376-412.
• [7]Yoo KM, Lee CH, Lee H, Moon BK, Lee CY: Relative antioxidant and cytoprotective activities of common herbs. Food Chem 2008, 106(3):929-936.
• [8]Awoniyi DO, Aboua YG, Marnewick J, Brooks N: The Effects of rooibos (Aspalathus linearis), green tea (Camellia sinensis) and commercial rooibos and green tea supplements on epididymal sperm in oxidative Stress-induced rats. Phytother Res 2012, 26(8):1231-1239.
• [9]Ajuwon OR, Thamahane-Katengua E, Van Rooyen J, Oguntibeju OO, Marnewick JL: Protective effects of rooibos (Aspalathus linearis) and/or red palm oil (Elaeis guineensis) supplementation of tert-butyl hydroperoxide-induced oxidative hepatotoxicity in Wistar rats. Evid Based Compliment Alternat Med 2013, 2013(984273):19.
• [10]Nikolova V, Petrova S, Petkova V, Pavlova S, Michailova A, Georgieva T: Antioxidative effects of rooibos tea on workers occupationally exposed to lead. Toxicol Lett 2007, 172:S120-S121.
• [11]Marnewick JL, Rautenbach F, Venter I, Neethling H, Blackhurst DM, Wolmarans P, Macharia M: Effects of rooibos (Aspalathus linearis) on oxidative stress and biochemical parameters in adults at risk for cardiovascular disease. J Ethnopharmacol 2011, 133(1):46-52.
• [12]Kunishiro K, Tai A, Yamamoto I: Effects of rooibos tea extract on antigen-specific antibody production and cytokine generation in vitro and in vivo. Biosci Biotechnol Biochem 2001, 65(10):2137-2145.
• [13]Hendricks R, Pool EJ: The in vitro effects of rooibos and black tea on immune pathways. J Immunoassay Immunochem 2010, 31(2):169-180.
• [14]Mueller M, Hobiger S, Jungbauer A: Anti-inflammatory activity of extracts from fruits, herbs and spices. Food Chem 2010, 122(4):987-996.
• [15]Marnewick JL, Joubert E, Swart P, van der Westhuizen F, Gelderblom WC: Modulation of hepatic drug metabolizing enzymes and oxidative status by rooibos (Aspalathus linearis) and honeybush (Cyclopia intermedia), green and black (Camellia sinensis) teas in rats. J Agric Food Chem 2003, 51(27):8113-8119.
• [16]Singleton VL, Orthofer R, Lamuela-Raventós RM: Analysis of total phenols and other oxidation substrates and antioxidants by means of folin-ciocalteu reagent. Methods Enzymol 1999, 299:152-178.
• [17]Treutter D: Chemical reaction detection of catechins and proanthocyanidins with 4-dimethylaminocinnamaldehyde. J Chromatogr A 1989, 467:185-193.
• [18]Mazza G, Fukumoto L, Delaquis P, Girard B, Ewert B: Anthocyanins, phenolics, and color of Cabernet franc, Merlot, and Pinot noir wines from British Columbia. J Agric Food Chem 1999, 47:4009-4017.
• [19]Ou B, Hampsch-Woodill M, Prior RL: Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J Agric Food Chem 2001, 49:4619-4626.
• [20]Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C: Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 1999, 26:1231-1237.
• [21]Benzie IFF, Strain J: The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem 1996, 239:70-76.
• [22]Bramati L, Minoggio M, Gardana C, Simonetti P, Mauri P, Pietta P: Quantitative characterization of flavonoid compounds in Rooibos tea (Aspalathus linearis) by LC-UV/DAD. J Agric Food Chem 2002, 50:5513-5519.
• [23]Ohsaki Y, Shirakawa H, Hiwatashi K, Furukawa Y, Mizutani T, Komai M: Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem 2006, 70:926-932.
• [24]Robles-Sanchez M, Astiazaran-Garcia H, Martin-Belloso O, Gorinstein S, Alvarez-Parrilla E, De la Rosa LA, Yepiz-Plascencia G, Gonzalez-Aguilar G: Influence of whole and fresh-cut mango intake on plasma lipids and antioxidant capacity of healthy adults. Food Res Int 2011, 44:1386-1391.
• [25]Khoschsorur G, Winklhofer-Roob B, Rabl H, Auer T, Peng Z, Schaur R: Evaluation of a sensitive HPLC method for the determination of malondialdehyde, and application of the method to different biological materials. Chromatographia 2000, 52:181-184.
• [26]Recknagel RO, Glende E Jr: Spectrophotometric detection of lipid conjugated dienes. Methods Enzymol 1984, 105:331-337.
• [27]Aebi H: Catalase in vitro. Methods Enzymol 1984, 105:121-126.
• [28]Crosti N, Servidei T, Bajer J, Serra A: Modification of the 6-hydroxydopamine technique for the correct determination of superoxide dismutase. J Clin Chem Clin Biochem 1987, 25:265-266.
• [29]Ellerby LM, Bredesen DE: Measurement of cellular oxidation reactive oxygen species and antioxidant enzymes during apoptosis. Methods Enzymol 2000, 322:413-421.
• [30]Staal GEJ, Visser J, Veeger C: Purification and properties of glutathione reductase of human erythrocytes. Biochim Biophys Acta 1969, 185:39-48.
• [31]Tietze F: Enzymic method for quantitative determination of nanogram amounts of total and oxidized glutathione: Applications to mammalian blood and other tissues. Anal Biochem 1969, 27:502-522.
• [32]Cheng YJ, Yang BC, Liu MY: Lead increases lipopolysaccharide-induced liver injury through tumor necrosis factor-α overexpression by monocytes/macrophages: role of protein kinase C and p42/44 mitogen-activated protein kinase. Environ Health Perspect 2006, 114:507-513.
• [33]Kaur G, Tirkey N, Bharrhan S, Chanana V, Rishi P, Chopra K: Inhibition of oxidative stress and cytokine activity by curcumin in amelioration of endotoxin‒induced experimental hepatotoxicity in rodents. Clin Exp Immunol 2006, 145:313-321.
• [34]Kaur G, Tirkey N, Chopra K: Beneficial effect of hesperidin on lipopolysaccharide-induced hepatotoxicity. Toxicology 2006, 226:152-160.
• [35]Sebai H, Sani M, Yacoubi MT, Aouani E, Ghanem-Boughanmi N, Ben-Attia M: Resveratrol, a red wine polyphenol, attenuates lipopolysaccharide-induced oxidative stress in rat liver. Ecotoxicol Environ Saf 2010, 73:1078-1083.
• [36]Amat N, Upur H, Blazekovic B: In vivo hepatoprotective activity of the aqueous extract of Artemisia absinthium L. against chemically and immunologically induced liver injuries in mice. J Ethnopharmacol 2010, 131:478-484.
• [37]Qu XJ, Xia X, Wang YS, Song MJ, Liu LL, Xie YY, Cheng YN, Liu XJ, Qiu LL, Xiang L: Protective effects of Salvia plebeia compound homoplantaginin on hepatocyte injury. Food Chem Toxicol 2009, 47:1710-1715.
• [38]Sugimoto K, Sakamoto S, Nakagawa K, Hayashi S, Harada N, Yamaji R, Nakano Y, Inui H: Suppression of inducible nitric oxide synthase expression and amelioration of lipopolysaccharide-induced liver injury by polyphenolic compounds in Eucalyptus globulus leaf extract. Food Chem 2011, 125:442-446.
• [39]Kao ES, Hsu JD, Wang CJ, Yang SH, Cheng SY, Lee HJ: Polyphenols extracted from Hibiscus sabdariffa L. inhibited lipopolysaccharide-induced inflammation by improving antioxidative conditions and regulating cyclooxygenase-2 expression. Biosci Biotechnol Biochem 2009, 73(2):385-390.
• [40]Bharrhan S, Chopra K, Rishi P: Vitamin E supplementation modulates endotoxin-induced liver damage in a rat model. Am J Biomed Sci 2010, 2(1):51-62.
• [41]Hsieh CH, Frink M, Hsieh YC, Kan WH, Hsu JT, Schwacha MG, Choudhry MA, Chaudry IH: The role of MIP-1α in the development of systemic inflammatory response and organ injury following trauma hemorrhage. J Immunol 2008, 181(4):2806-2812.
• [42]Jaeschke H: Reactive oxygen and mechanisms of inflammatory liver injury. J Gastroenterol Hepatol 2000, 15(7):718-724.
• [43]Takahashi K, Morikawa A, Kato Y, Sugiyama T, Koide N, Mu MM, Yoshida T, Yokochi T: Flavonoids protect mice from two types of lethal shock induced by endotoxin. FEMS Immunol Med Microbiol 2001, 31(1):29-33.
• [44]Kotanidou A, Xagorari A, Bagli E, Kitsanta P, Fotsis T, Papapetropoulos A, Roussos C: Luteolin reduces lipopolysaccharide-induced lethal toxicity and expression of pro-inflammatory molecules in mice. Am J Respir Crit Care Med 2002, 165(6):818-823.
• [45]Jaffer U, Wade R, Gourlay T: Cytokines in the systemic inflammatory response syndrome. HSR Proc Intensive Care Cardiovasc Anesth 2010, 2(3):161-175.
• [46]Oberholzer A, Oberholzer C, Moldawer LL: Interleukin-10: a complex role in the pathogenesis of sepsis syndromes and its potential as an anti-inflammatory drug. Crit Care Med 2002, 30(1):S58-S63.
• [47]Halliwell B, Gutteridge JMC: Free Radicals in Biology and Medicine. Oxford, UK: Oxford University Press; 2007.
• [48]Depboylu B, Giriş M, Olgaç V, Doğru-Abbasoğlu S, Uysal M: Response of liver to lipopolysaccharide treatment in male and female rats. Exp Toxicol Pathol 2013, 65(5):645-650.
• [49]Pari L, Shagirtha K: Hesperetin protects against oxidative stress related hepatic dysfunction by cadmium in rats. Exp Toxicol Pathol 2010, 64(5):513-520.
• [50]Inanami O, Asanuma T, Inukai N, Jin T, Shimokawa S, Kasai N, Nakano M, Sato F, Kuwabara M: The suppression of age-related accumulation of lipid peroxides in rat brain by administration of rooibos tea (Aspalathus linearis). Neurosci Lett 1995, 196(1–2):85-88.
• [51]Ulicna O, Greksák M, Vancova O, Zlatos L, Galbavy S, Bosek P, Nakano M: Hepatoprotective effect of rooibos tea (Aspalathus linearis) on CCl4-induced liver damage in rats. Physiol Res 2003, 52(4):461-466.
• [52]Ulicna O, Vancova O, Bozek P, Carsky J, Sebekova K, Boor P, Nakano M, Greksák M: Rooibos tea (Aspalathus linearis) partially prevents oxidative stress in streptozotocin-induced diabetic rats. Physiol Res 2006, 55(2):157-164.
• [53]Kono Y, Fridovich I: Superoxide radical inhibits catalase. J Biol Chem 1982, 257:5751-5754.
• [54]Naik SR, Thakare VN, Patil SR: Protective effect of curcumin on experimentally induced inflammation, hepatotoxicity and cardiotoxicity in rats: Evidence of its antioxidant property. Exp Toxicol Pathol 2011, 63:419-431.
• [55]Suntres ZE: Liposomal antioxidants for protection against oxidant-induced damage. J Toxicol 2011, 2011(152474):16.
• [56]Dickinson DA, Forman HJ: Glutathione in defense and signaling. Ann NY Acad Sci 2002, 973(1):488-504.
• [57]Marnewick JL, Van Der Westhuizen FH, Joubert E, Swanevelder S, Swart P, Gelderblom WCA: Chemoprotective properties of rooibos (Aspalathus linearis), honeybush (Cyclopia intermedia) herbal and green and black (Camellia sinensis) teas against cancer promotion induced by fumonisin B1 in rat liver. Food Chem Toxicol 2009, 47(1):220-229.
• [58]Pantsi W, Marnewick J, Esterhuyse A, Rautenbach F, van Rooyen J: Rooibos (Aspalathus linearis) offers cardiac protection against ischaemia/reperfusion in the isolated perfused rat heart. Phytomedicine 2011, 18:1220-1228.
• [59]Moskaug JU, Carlsen H, Myhrstad MCW, Blomhoff R: Polyphenols and glutathione synthesis regulation. Am J Clin Nutr 2005, 81(1):277S-283S.
• [60]Harada H, Bharwani S, Pavlick KP, Korach KS, Grisham MB: Estrogen receptor-alpha, sexual dimorphism and reduced-size liver ischemia and reperfusion injury in mice. Pediatr Res 2004, 55:450-456.
• [61]Yokoyama Y, Nimura Y, Nagino M, Bland KI, Chaudry IH: Current understanding of gender dimorphism in hepatic pathophysiology. J Surg Res 2005, 128:147-156.
• [62]Chen Y, Ji LL, Liu TY, Wang ZT: Evaluation of gender-related differences in various oxidative stress enzymes in mice. Chinese J Physiol 2011, 54:385-390.
• [63]Chang KA, Lin IC, Sheen JM, Chen YC, Chen CC, Tain YL, Hsieh CS, Huang LT: Gender differences of oxidative stress to cholestatic liver and kidney injury in young rats. Pediatr Neonatol 2013, 54:95-101.
• [64]Pattar J, Shridhar NB, Sanganal J, Satyanarayana ML, Suhasini K, Kadagi M: Gender difference of oxidative stress to CCl4 induced hepatoxicity and protective role of Ficus virens in rats: A biochemical study. J Cell Tissue Res 2013, 13:3971-3975.