Metabolic profile and hepatoprotective activity of the anthocyanin-rich extract of Hibiscus sabdariffa calyces
Date
2016
Journal Title
Journal ISSN
Volume Title
Type
Article
Publisher
Taylor & Francis
Series Info
Pharmaceutical biology;54:12, 3172-3181
Scientific Journal Rankings
Abstract
Context: Hibiscus sabdariffa L. (Malvaceae) is a common traditional tea that has many biological activities.
Objectives: To evaluate the hepatoprotective effect and study the metabolic profile of the anthocyaninrich extract of H. sabdariffa calyces (HSARE).
Materials and methods: The hepatoprotective activity of HSARE was assessed (100 mg/kg/d for 4 weeks)
by examining the hepatic, inflammatory, oxidative stress markers and performing a histopathological
examination in rats with thioacetamide (TAA)-induced hepatotoxicity. HSARE was analyzed using ultra-performance liquid chromatography-quadrupole-time-of-flight-photodiode array-mass spectrometry (UPLCqTOF-PDA-MS).
Results: The UPLC-qTOF-PDA-MS analysis of HSARE enabled the identification of 25 compounds represented by delphinidin and its derivatives, cyanidin, kaempferol, quercetin, myricetin aglycones and glycosides, together with hibiscus lactone, hibiscus acid and caffeoylquinic acids. Compared to the TAAintoxicated group, HSARE significantly reduced the serum levels of alanine aminotransferase, aspartate
aminotransferase and hepatic malondialdehyde by 37.96, 42.74 and 45.31%, respectively. It also decreased
hepatic inflammatory markers, including tumour necrosis factor alpha, interleukin-6 and interferon gamma
(INF-c), by 85.39, 14.96 and 70.87%, respectively. Moreover, it decreased the immunopositivity of nuclear
factor kappa-B and CYP2E1 in liver tissue, with an increase in the effector apoptotic marker (caspase-3
positive cells), restoration of the altered hepatic architecture and increases in the activities of superoxide
dismutase (SOD) and glutathione by 150.08 and 89.23%, respectively.
Discussion and conclusion: HSARE revealed pronounced antioxidant and anti-inflammatory potential
where SOD and INF-c were significantly improved. HSARE possesses the added value of being more
water-soluble and of natural origin with fewer side effects expected compared to silymarin.
Description
MSA Google Scholar
Keywords
Ultra-performance liquid, chromatography-quadrupole-time-of-flight-PDAmass spectrometry, delphinidin, Hibiscus sabdariffa L., Malvaceae
Citation
Adetutu A, Owoade AO. 2013. Hepatoprotective and antioxidant effect of Hibiscus polyphenol rich extract (HPE) against carbon tetrachloride (CCl4)-induced damage in rats. Br J Med Med Res. 3:1574–1586. Agarwal SS. 2001. Development of hepatoprotective formulations from plant sources. In: Gupta SK, editor. Pharmacology and therapeutics in the new millennium. New Delhi: Narosa Publishing House; p. 357–358. Alarcon-Aguilar FJ, Zamilpa A, Perez-Garcia MD, Almanza-Perez JC, Romero-Nunez E, Campos-Sepulveda EA, Vazquez-Carrillo LI, Roman- ~ Ramos R. 2007. Effect of Hibiscus sabdariffa on obesity in MSG mice. J Ethnopharmacol. 114:66–71. Borras-Linares I, Fernandez-Arroyoa S, Arraez-Romana D, Palmeros-Suarez PA, Del Val-Dıaz R, Andrade-Gonzales I, Fernandez-Gutierrez A, Gomez-Leyva JF, Segura-Carretero A. 2015. Characterization of phenolic compounds, anthocyanidin, antioxidant and antimicrobial activity of 25 varieties of Mexican Roselle (Hibiscus sabdariffa). Ind Crop Prod. 69:385–394. Bruck RR, Aeed H, Avni Y, Shirin H, Matas Z, Shahmurov M. 2004. Melatonin inhibits nuclear factor kappa B activation and oxidative stress and protects against thioacetamide induced liver damage in rats. J Hepatol. 40:86–93. Castaneda-Ovando A, Pacheco-Hern ~ andez ML, Paez-Hernandez ME, Rodrıguez JA, Galan-Vidal CA. 2009. Chemical studies of anthocyanins: a review. Food Chem. 113:859–871. Chen JJ, Huang SY, Duh CY, Chen IS, Wang TC, Fang HY. 2006a. A new cytotoxic amide from the stem wood of Hibiscus tiliaceus. Planta Med. 72:935–938. Chen LH, Hsu CY, Weng CF. 2006b. Involvement of P53 and Bax/Bad triggering apoptosis in thioacetamide-induced hepatic epithelial cells. World J Gastroenterol. 12:5175–5181. Ellman GL. 1959. Tissue sulfhydryl groups. Arch Biochem Biophys. 82:70–77. Farag MA, Gad HA, Heiss AG, Wessjohann LA. 2014. Metabolomics driven analysis of six Nigella species seeds via UPLC-qTOF-MS and GC-MS coupled to chemometrics. Food Chem. 151:333–342. Gazak R, Walterova D, Kren V. 2007. Silybin and silymarin – new and emerging applications in medicine. Curr Med Chem. 14:315–338. Giusti MM, Rodriguez-Saona LE, Griffin D, Wrolstad RE. 1999. Electrospray and tandem mass spectroscopy as tools for anthocyanin characterization. J Agric Food Chem. 47:4657–4664. Hajovsky H, Hu G, Koen Y, Sarma D, Cui W, Moore DS, Staudinger JL, Hanzlik RP. 2012. Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes. Chem Res Toxicol. 25:1955–1963. Halket JM, Przyborowska A, Stein SE, Mallard WG, Down S, Chalmers RA. 1999. Deconvolution gas chromatography/mass spectrometry of urinary organic acids – potential for pattern recognition and automated identification of metabolic disorders. Rapid Commun Mass Spectrom. 13:279–284. Herranz-Lopez M, Fern andez-Arroyo S, Perez-Sanchez A, Barrajon-Catalan E, Beltran-Debon R, Menendez JA, Alonso-Villaverde C, Segura-Carretero A, Joven J, Micol V. 2012. Synergism of plant-derived polyphenols in adipogenesis: perspectives and implications. Phytomedicine 19:253–261. Hong V, Wrolstad RE. 1990. Use of HPLC separation/photodiode detection for characterization of anthocyanins. J Agric Food Chem. 38:708–715. Jacobs PB, Dennehy C, Ramirez G, Sapp J, Lawrence VA. 2002. Milk thistle for the treatment of liver disease: a systematic review and meta-analysis. Am J Med. 113:506–515. Kiruthiga PV, Shafreen RB, Pandian SK, Devi KP. 2007. Silymarin protection against major reactive oxygen species released by environmental toxins: exogenous H2O2 exposure in erythrocytes. Basic Clin Pharmacol Toxicol. 100:414–419. Liu CL, Wang JM, Chu CY, Cheng MT, Tseng TH. 2002. In vivo protective effect of protocatechuic acid on tert-butyl hydroperoxide induced rat hepatotoxicity. Food Chem Toxicol. 40:635–641. Luster MI, Simeonova PP, Gallucci RM, Matheson JM, Yucesoy B. 2000. Immunotoxicology: role of inflammation in chemical-induced hepatotoxicity. Int J Immunopharmacol. 22:1143–1147. Mahadevan N, Shivali A, Kamboj P. 2009. H. sabdariffa Linn – an overview. Nat Prod Rad. 8:77–83. Mazza G, Miniati E. 1993. Anthocyanins in fruits, vegetables and grains. Boca Raton, FL: CRC Press. Motilva MJ, Serra A, Macia A. 2013. Analysis of food polyphenols by ultra high-performance liquid chromatography coupled to mass spectrometry: an overview. J Chromatogr A. 1292:66–82 Moungjaroen J, Nimmannit U, Callery PS, Wang L, Azad N, Lipipun V, Chanvorachote P, Rojanasakul Y. 2006. Reactive oxygen species mediate caspase activation and apoptosis induced by lipoic acid in human lung epithelial cancer cells through Bcl-2 down-regulation. J Pharmacol Exp Ther. 319:1062–1069. Ohkawa H, Ohishi N, Yagi K. 1979. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 95:351–358. Okoko T, Ere D. 2012. Hibiscus sabdariffa extractivities on cadmium-mediated alterations of human U937 cell viability and activation. Asian Pac J Trop Med. 5:33–36. Ozkol HU, Koyuncu I, Tuluce Y, Dilsiz N, Soral S, Ozkol H. 2015. Anthocyanin-rich extract from Hibiscus sabdariffa calyx counteracts UVCcaused impairments in rats. Pharm Biol. 53:1435–1441. Pradhan SC, Girish C. 2006. Hepatoprotective herbal drug, silymarin from experimental pharmacology to clinical medicine. Indian J Med Res. 124:491–504. Ramirez-Rodrigues MM, Plaza ML, Azeredo A, Balaban MO, Marshall MR. 2011. Physicochemical and phytochemical properties of cold and hot water extraction from Hibiscus sabdariffa. J Food Sci. 76:428–435. Reitman S, Frankel S. 1957. A colorimetric method for the determination of serum glutamic oxalacetic and glutamic pyruvic transaminases. Am J Clin Pathol. 28:56–63. Salama SM, Abdulla MA, AlRashdi AS, Hadi AA. 2013a. Mechanism of hepatoprotective effect of Boesenbergia rotunda in thioacetamide-induced liver damage in rats. Evid Based Complement Alternat Med. 2013:1–13. Salama SM, Abdulla MA, AlRashdi AS, Ismail S, Alkiyumi SS, Golbabapour S. 2013b. Hepatoprotective effect of ethanolic extract of Curcuma longa on thioacetamide induced liver cirrhosis in rats. BMC Complement Altern Med. 13:56–73. Saller R, Brignoli R, Melzer J, Meier R. 2008. An updated systematic review with meta-analysis for the clinical evidence of silymarin. Forsch Komplementmed. 15:9–20. Santos-Buelga C, Garcıa-Viguera C, Tomas-Barberan FA. 2003. On-line identification of flavonoids by HPLC coupled to diode array detection. In: Santos-Buelga C, Williamson G, editors. Methods in polyphenol analysis. The Royal Society of Chemistry: Cambridge; p. 92–127. Sarkar MK, Sil PC. 2007. Hepatocytes are protected by herb Phyllanthus niruri protein isolate against thioacetamide toxicity. Pathophysiology 14:113– 120. Tatsuzawa F, Saito N, Yokoi M. 1994. An acylated cyanidin glycoside in the red-purple flowers of x Laeliocattleya cv mini purple. Phytochemistry 37:1179–1183. Usoh IF, Ekaidem IS, Etim OE, Akpan HD, Akpan EJ, Fakoya A. 2012. Antioxidant and hepatoprotective effects of dried flower extracts of H. sabdariffa L. on rats treated with carbon tetrachloride. J Appl Pharm Sci. 2:156–159. Wang CJ, Wang JM, Lin WL, Chu CY, Chou FP, Tseng TH. 2000. Protective effect of Hibiscus anthocyanins against tert-butyl hydroperoxide-induced hepatic toxicity in rats. Food Chem Toxicol. 38:411–416. Wang ME, Chen YC, Chen IS, Hsieh SC, Chen SS, Chiu CH. 2012. Curcumin protects against thioacetamide induced hepatic fibrosis by attenuating the inflammatory response and inducing apoptosis of damaged hepatocytes. J Nutr Biochem. 23:1352–1366. Wawer I. 2001. Anthocyanidins, structure and antioxidant properties. Farm Pol. 15:728–731. Williamson EM, Driver SB, Baxter K. 2013. Stockley’s herbal medicines interactions: a guide to the interactions of herbal medicines, dietary supplements and nutraceuticals with conventional medicines. London: Pharmaceutical Press. Winterbourn CC, Hawkins RE, Brian M, Carrell RW. 1975. The estimation of red cell superoxide dismutase activity. J Lab Clin Med. 85:337–341. Yang VS, Ahn TH, Lee JC, Moon CJ, Kim SHO, Jun W. 2008. Protective effects of pycnogenol on carbon tetrachloride-induced hepatotoxicity in Sprague-Dawley rats. Food Chem Toxicol. 46:380–387. Zhang LJ, Yu JP, Li D, Huang YH, Chen ZX, Wang XZ. 2004. Effects of cytokines on carbon tetrachloride-induced hepatic fibrogenesis in rats. World J Gastroenterol. 10:77–81