Flavones composition and therapeutic potential of Dodonaea viscosa against liver fibrosis

Nagwa Shalaby, Howaida Abd-Alla, manal hamed, Samira Al-Ghamdi, Suhair Jambi


Dodonaea viscosa (L.) Jaeq (Sapindaceae) is used in traditional medicine for the treatment of hemorrhoids, ulcer, and pains of hepatic or stomach origin. The current study was designed to investigate the phytochemical constituents of the plant and evaluate its activity against liver fibrosis induced by carbon tetrachloride (CCl4) in rats.   The phytochemical analysis has afforded one flavanone; 5,7-dihydroxy flavanone (pinocembrin) (1) and eight flavones. The compounds were isolated and elucidated as; 5,7-dihydroxy-3,6,4'-trimethoxyflavone (santin) (2), 5,7,4'-trihydroxy-3-methoxy flavone (kaempferol 3-O-methyl ether) (3), 3,4',5-trihydroxy-7-methoxy flavone (kaempferol 7-O-methyl ether) (4), 3',4',5,7-tetrahydroxy-3-methoxy-flavone (quercetin 3'-O-methyl ether) (5), 3,3',4',5,7-pentahydroxyflavone (quercetin) (6), 5,7,4'-trihydroxy-3,6-dimethoxy flavone (7), 5,7-dihydroxy 3,6,3',4'-tetramethoxy flavone (8), and isorhamnetin-3-O-robinobioside (9).. In vitro screening of ethanol extract, fractions of toluene and ethyl acetate, the flavanone and major flavone compounds as antioxidants was carried out. In addition, D. viscosa ethanol extract and two fractions were examined in vivo against liver fibrosis induced by CCl4 in rats. The evaluation was done through measuring hepatic oxidative stress markers; malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD). The work was extended to measure serum protein content and liver function enzymes; aspartate and alanine aminotransferases (AST and ALT), alkaline phosphatase (ALP­) and gamma glutamyl transferase (GGT). Liver histopathological analysis was done for results confirmation. In conclusion, among the isolated flavones, compounds 3, 4, and 8 were isolated for the first time. The ethanol extract and compound of 6, 5 followed by 7 exhibited the strongest antioxidant activities. Treatment with D. viscosa extract and its fractions attenuates the increments of MDA, AST, ALT, ALP, GGT, total protein and increased GSH and SOD levels. The ethanol extract showed the most potent effect. The data confirmed the rationale for the traditional use of D. viscosa extracts to hepatic disorders. Further studies are needed in order to evaluate the isolated flavones as protective agents against liver injury and for their clinical application.


Dodonaea viscosa, flavones, phytochemical constituents, liver fibrosis, antioxidants, histopathology.

Full Text:



van-Heerden FR, Viljoen AM, van-Wyk BE. The major flavonoid of Dodonaea angustifolia. Fitoterapia 2000; 71: 602–604.

Niu HM, Zeng DQ, Long CL, Peng YH, Wang YH, Luo JF, Wang HS, Shi YN, Tang GH, Zhao FW. Clerodane diterpenoids and prenylated flavonoids from Dodonaea viscosa. J Asian Nat Prod Res 2010; 12: 7–14.

Shanmugavasana A, Ramachandran T. Investigation of the extraction process and phytochemical composition of preparations of Dodonaea viscosa (L.) Jacq. J Ethnopharmacol 2011; 137: 1172-1176.

Pengelly A. Medicinal activity of Dodonaea viscosa—A preliminary study. Regional Industries Research and Development Corporation, Australia, 2008.

Anilreddy B: Preparation, characterization and biological evaluation of some overview of Dodonaea viscosa Linn. J Pharmaceut Sci Tech 2009; 1: 1–9.

Rani MS, Rao, SP, Mohan K. Dodonaea viscosa Linn—an overview. J Pharmaceut Res Health Care 2009; 1: 97–112.

Khalil MN, Sperotto SJ, Manfron PM: Anti-inflammatory activity and acute toxicity of Dodonaea viscosa. Fitoterapia 2006, 77: 478 – 480.

Meenu J, Sunil S, Manoj K. Evaluation of antihyperglycemic activity of Dodonaea viscosa leaves in normal and STZ-diabetic rats. Int J Pharm Pharmaceut Sci 2011, 3: 69-74.

Veerapur VP, Prabhakar KR, Parihar VK, Bansal P, Srinivasan KK, Priyadarsini KI, Unnikrishnan MK: Antidiabetic, hypolipidaemic and antioxidant activity of Dodonaea viscosa aerial parts in streptozotocin-induced diabetic rats. Int J Phytomed 2010; 2: 59–70.

Kanter M, Coskun O, Budancamanak M. Hepatoprotective effects of Nigella sativa L. and Urtica dioica L. on lipid peroxidation, antioxidant enzyme systems and liver enzymes in carbon tetrachloride-treated rats. World J Gastroenterol 2005; 11: 6684–6688.

Nevin KG, Vijayamma L. Effect of Aerva lanata against hepatotoxicity of carbon tetrachloride in rats. Environ Toxicol Pharmacol 2005; 20: 471-477.

Shankar GNL, Manavalan R, Venkappayya D, Raj CD. Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl4-induced oxidative damage in rats. Food Chem Toxicol 2008; 46: 3182–3185.

Mitra SK, Venkataranganna MV, Sundaram R, Gopumadhavan S. Effect of HD-03, an herbal formulation, on the antioxidant defense system in rats. Phytother Res 1998; 12: 114–117.

Abu-Gabal NS, Abd-Alla HI, Ahmed HH, Al-Saigh SM, Shalaby NMM. Efficacy of Aloe vera extracts in attenuating neurological endangerment-induced by dexamethasone in adult male rats. J Arab Soc Med Res 2007; 2: 59-73.

Wyk VEB. A broad review of commercially important southern African medicinal plants. J Ethnopharmacol 2008; 119: 342 – 355.

Agrawal PK, Bansal MC. Flavonoid glycosides. In: studies in organic chemistry 39, 13C-NMR of flavonoids, Agrawal PK (Ed.), Elsevier science, New York, U.S.A., 1989.

Mabry TJ, Markham KR, Thomas MB. The systematic identification of flavonoids. Springer-Verlag, Berlin, 1970, pp. 41–164.

Markham KR. Techniques of flavonoid identification. Academic Press Inc, Ltd, London, 1982, pp. 84.

Harborne JB, Mabry TJ. The Flavonoid: Advances in research, Chapman and Hall Ltd, London, 1982, pp. 1-18.

Chen HY, Lin YC, Hsiech CL. Evaluation of antioxidants activity of aqueous extract of some selected nutraceutical herbs. Food Chem 2007; 104: 1418-1424.

Marsillach J, Camps J, Ferré N, Beltran R, Rul A, Mackness B, Michael MM, Joven J. Paraoxonase-1 is related to inflammation, fibrosis and PPAR delta in experimental liver disease. BMC Gastroenterol 2009; 9: 3.

Yuvaraj P, Subramoniam A. Hepatoprotective property of Thespesia populnea against carbon tetrachloride induced liver damage in rats. J Basic Clin Physiol Pharmacol 2009; 20: 169-177.

Buege JA, Aust SD. Microsomal lipid peroxidation. Meth Enzymol 1978; 52: 302-310.

Moron MS, Depierre JW, Mannervik B. Level of glutathione, glutathione reductase and glutathone-S-transferase activities in rat lung and liver. Biochimica Biophysica Acta 1979; 582: 67-78.

Nishikimi M, Rae NA, Yagi K. The occurrence of superoxide anion in the action of reduced phenazine methosulphate and molecular oxygen. Biochem Biophys Res Commun 1972; 46: 849-853.

Gella FJ, Olivella T, Cruz PM, Arenas J, Moreno R, Durban R, Gomez JA. A simple procedure for routine determination of aspartate aminotransferase and alanine aminotransferase with pyridoxal phosphate. Clin Chem Acta 1985; 153: 241-247.

Rosalki SB, Foo AY, Burlina A. Multicenter evaluation of iso-ALP test kit for measurement of bone alkaline phosphatase activity in serum and plasma. Clin Chem 1993; 39: 648-652.

Szasz G. A kinetic photometric method for serum γ-glutamyl transpeptidase. Clin Chem 1969; 15: 124-136.

Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 1976; 72: 248-254.

Suzuki H, Suzuki K. Rat hypoplastic kidney (hpk/hpk) induces renal anemia, hyperparathyroidism, and osteodystrophy at the end stage of renal failure. J Vet Med Sci 1998; 60: 1051-1058.

Leenhouts PW. Notes on the extra-Australian species of Dodonaea (Sapindaceae). Blumea 1983; 28: 271-289.

Horie T, Ohtsurs Y, Shibata K, Yamashita K, Tsukayama M, Kawamura Y. 13C NMR special assignment of the a-ring of polyoxgenated flavones. Phytochemistry 1998; 47: 865–874.

Rashid MA, Armstrong JA, Gray AI, Waterman PG. Alkaloids, flavonoids and coumarins from Drummondita hassellil and D. calida. Phytochemistry 1992; 31: 1265–1269.

Salah NAM, Mansour RMA, Markham KR. An acylated isorhamnetin glycoside from Aerva javanica. Phytochemistry 1990; 29: 1344-1345.

Halim AF, Saad HEA, Hashish NE. Flavonol glycosides from Nitraria retusa. Phytochemistry 1995; 40: 349-351.

Sachdev K, Kulshreshtha DK. Flavonoids from Dodonaea viscosa. Phytochemistry 1983; 22: 1253–1256.

Getie MG, Gebre-Miriam T, Rietz R, Neubert R. Distribution of quercetin, kaempferol and isorhamnetin in some Ethiopian medicinal plants used for treatment of dermatological disorders. Ethiopian Pharmacol J 2000; 18: 25–34.

Abdel-Mogib M, Basaif SA, Asiri AM, Sobahi TR, Batterjee SM. New clerodane diterpenoid and flavonol-3-methyl ethers from Dodonaea viscosa. Pharmazie 2001; 56: 830-831.

Fukumoto LR, Mazz G. Assessing antioxidant and prooxidant activities of phenolic compounds. J Agric Food Chem 2000; 48: 3597–3604.

Jeong JM, Choi CH, Kang SK, Lee IH, Lee JY, Jung H. Antioxidant and chemosensitizing effects of flavonoids with hydroxy and/or methoxy groups and structure-activity relationship. J Pharm Pharm Sci 2007; 10: 537-546.

Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant relationships of flavonoids and phenolic acids. Free Radic Biol Med 1996; 20: 933–956.

Saskia ABE, Acker V, Van-Den Berg DJ, Bast A: Structural aspects of antioxidant activity of flavonoids. Free Radic Biol Med 1996, 20: 331–342.

Teffo LS, Aderogba MA, Eloff JN. Antibacterial and antioxidant activities of four kaempferol methyl ethers isolated from Dodonaea viscosa Jacq. var. angustifolia leaf extracts. S Afr J Bot 2010; 76: 25-29.

Manna P, Sinha M, Sil PC. Aqueous extract of Terminalia arjuna prevents carbon tetrachloride induced hepatic and renal disorders. BMC Comp Alt Med 2006; 6: 33-42.

April JE, Michael PR, Gwendolyn LK, Edward JN, Evan BS. Experimental diabetes attenuates cerebral cortical –evoked forelimb motor responses. Diabetes 2005; 54: 2764-2771.

Gharib B, Abd-Allah OM, Dessein H, De-Reggi M. Development of eosinophil peroxidase activity and concomitant alteration of antioxidant defenses in the liver of mice infected with Schistosoma mansoni. J Hepatol 1999; 30: 594-602.

Mansour HH, Hafez HF, Fahmy, NM. Silymarin modulates cisplatin-induced oxidative stress and hepatotoxicity in rats. J Biochem Mol Biol 2006; 39: 656-661.

Yadav NP, Pal A, Shanker K, Bawankule DU, Gupta AK, Darokar MP, Khanuja SPS. Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4-induced hepatotoxicityin Rattus norvegicus. Phytomed 2008; 15: 1053–1061.

Opoku AR, Ndlovu IM, Terblanche SE, Hutchings AH. In vivo hepatoprotective effects of Rhoicissus tridentata subsp. cuneifolia, a traditional Zulu medicinal plant, against CCl4-induced acute liver injury in rats. South African J Botany 2007; 73: 372–377.

Romero FJ, Bosch-Morell F, Romero MJ, Jareńo EJ, Romero B, Marίn N, Romá J. Lipid peroxidation products and antioxidants in human disease. Environ Health Perspectives 1998; 106: 1229–1234.

Sharma N, Shukla S. Hepatoprotective potential of aqueous extract of Butea monosperma against CCl4 induced damage in rats. Exp Toxicol Pathol 2011; 63: 671-676.

Reyes-Gordillo K, Segovia J, Shibayama M, Vergara P, Moreno MG, Muriel P. Curcumin protects against acute liver damage in the rat by inhibiting NF-kappa B, proinflammatory cytokines production and oxidative stress. Biochim Biophys Acta 2007; 1770: 989-996.

Hamed MA. Metabolic profile of rats after one hour of intoxication with a single oral dose of ethanol. J Pharmacol Toxicol 2011; 6: 158-165.

Wagner H. Trends and challenge: phytomedicine: research in the new millennium. In: Yaniv Z, Bachrach U (Eds.), Handbook of Medicinal Plants. Haworth press, New York, 2005, pp. 3–25.

Sivanesan D, Selvi VAVT, Bhakyaraj R, Arunachalam T. Protective effect of Dodonaea viscosa (L) against lead acetate induced altered glycoprotein profiles in rats. E J Chem 2009; 6: 725-728.


  • There are currently no refbacks.

Copyright (c)

                AR Journals

Street 1st, Gaytri Vihar, Pinto Park, Gwalior, M.P. India

              Copyright@arjournals.org (Design) 2009-2021


Follow @arjournals on Twitter