Hepatoprotective Activity of Caspian Saffron (Crocus caspius Fisch and Mey) Flowers against CCl4- Induced Acute Liver Injury in Mice

Document Type : Original paper


1 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

2 Department of Pharmacognosy, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran. Molecular and Cell Biology Research Center, Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

3 Molecular and Cell Biology Research Center, Department of Anatomy, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.

4 Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.

5 Student Research Committee, Faculty of Pharmacy, Mazandaran University of Medical Sciences, Sari, Iran.


Background and objectives: Free radicals and other oxidants have important roles in liver cell toxicity. Some natural products are potent scavengers of oxidative agents. Crocus caspius is an endemic species of Caspian forest. Flowers of Crocus genus contain phenolic compound and carotenoid as antioxidant agent. This study investigated the antioxidant and hepatoprotective activity of Crocus caspius Fisch and Mey flowers (Caspian saffron) hydro-alcoholic extract (CCFE) against acute oxidative hepatotoxicity induced by CCl4 in mice. Methods: The antioxidant activity of the extract was evaluated by 2, 2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging assay. Crocus caspius flowers were investigated for presence of certain phytochemicals and total phenol and flavonoid contents were determined. For evaluation of hepatoprotective activity, the BALB/c mice were pre-treated with 50, 100, 200, and 500 mg/kg, of the extract intraperitoneally for 5 days and then received CCl4 (0.5 mL/kg, in olive oil). Liver injury was determined by serum biochemical markers such as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), glutathione content of liver tissue and histopathological studies. Results: The phytochemical screening in Caspian saffron flowers indicated the presence of carotenoids, saponins, sterols, flavonoids, and tannins. The extract exhibited antioxidant activity in DPPH radical scavenging assay (IC50 171.5 µg/mL). Pre-treatment groups with the extract demonstrated significant decrease in serum levels of ALT, AST, and ALP (p<0.05) and concomitant increase in GSH content (p<0.05). Histopathological observation determined hepatocellular protective effects of the extract. Conclusion: The results represented the protective activity of the extract against oxidative hepatotoxicity.


Main Subjects

[1] Pereira C, Barros L, Ferreira IC. Extraction, identification, fractionation and isolation of phenolic compounds in plants with hepatoprotective effects. J Sci Food Agric. 2016; 96(4): 1068-1084.
[2] Wang Z, Li Z, Ye Y, Xie L, Li W. Oxidative stress and liver cancer: etiology and therapeutic targets. Oxid Med Cell Longev. 2016; 2016(1): 1-10.
[3] Azadbakht M, Talavaki M. Qualitative and quantitative determination of pyrrolizidine alkaloids of wheat and flour contaminated with Senecio in Mazandaran province farms. Iran J Pharm Res. 2010; 2(3): 179-183.
[4] Abboud G, Kaplowitz N. Drug-induced liver injury. Drug Safety. 2007; 30(4): 277-294.
[5] Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health. 2003; 27(4): 277-284.
[6] Laouar A, Klibet F, Benamara A, Boumendjel A, Chefrour A, Messarah F. Potential antioxidant properties and hepatoprotective effects of Juniperus phoenicea berries against CCl4 induced hepatic damage in rats. Asian Pac J Trop Med. 2017; 10(3): 263-269.
[7] Subramoniam A, Pushpangadan P. Development of phytomedicines for liver disease. Indian J Pharmacol. 1999; 31(3): 166-175.
[8] Saxena R. Botany, taxonomy and cytology of Crocus orientales-series. Asian J Sci Tech. 2015; 6(5): 1406-1410.
[9] Asadi M. Antioxidant and antimicrobial activities in the different extracts of Caspian saffron (Crocus caspius Fisch & CA May.). Caspian J Environ Sci. 2016; 4(14): 331-338.
[10] Khalili M, Fathi H, Ebrahimzadeh MA. Antioxidant activity of bulbs and aerial parts of Crocus caspius, impact of extraction methods. Pak J Pharm Sci. 2016; 29(3): 773-777.
[11] Ghorbani A, Sadrzadeh A, Habibi E, Dadgar K, Akbari J, Moosazadeh M, Bakhshi H, Ahangarkani F, Vaeziv A. Efficacy of Camellia sinensis extract against Candida species in patients with denture stomatitis. Curr Med Mycol. 2018; 4(3): 15-18.
[12] Talla E, Nyemb JN, Tchinda Tiabou A, Zambou Djou S, Biyanzi P, Sophie L, Elst LV, Tanyi JM. Antioxidant activity and a new ursane-type triterpene from Vitellaria paradoxa (Sapotaceae) Stem Barks. Eur J Med Plants. 2016; 16(3): 1-20.
[13] Ndhlala AR, Kasiyamhuru A, Mupure C, Benhura MA, Muchuweti M. Phenolic composition of Flacourtia indica, Opuntia megacantha and Sclerocarya birrea. Food Chem. 2000; 103(1): 4-7.
[14] Sembiring EN, Elya B, Sauriasari R. Phytochemical screening, total flavonoid and total phenolic content and antioxidant activity of different parts of Caesalpinia bonduc (L.) Roxb. Phcog J. 2018; 10(1): 123-127.
[15] Balogun FO, Ashafa AOT. Cytotoxic, kinetics of inhibition of carbohydrate-hydrolysing enzymes and oxidative stress mitigation by flavonoids roots extract of Dicoma anomala (Sond.). Asian Pac J Trop Med. 2018; 1(11): 24-31.
[16] Eidi A, Moghadam JZ, Mortazavi P, Rezazadeh S, Olamafar S. Hepatoprotective effects of Juglans regia extract against CCl4-induced oxidative damage in rats. Pharm Biol. 2013; 51(5): 558-565.
[17] El-Newary S, Shaffie N, Omer E. The protection of Thymus vulgaris leaves alcoholic extract against hepatotoxicity of alcohol in rats. Asian Pac J Trop Med. 2017; 10(4): 361-371.
[18] Shokrzadeh M, Chabra A, Ahmadi A, Naghshvar F, Habibi E, Salehi F, Assadpour S. Hepatoprotective effects of Zataria multiflora ethanolic extract on liver toxicity induced by cyclophosphamide in mice. Drug Res. 2015; 65(4): 169-175.
[19] Meharunnisha Begum M, Kiran KR. Evaluation of methanolic extract of Cleome chelidonii for hepatoprotective activity against paracetamol and ethanol induced hepatotoxicity in rats. Int J Pharma Res Rev. 2016; 5(1): 28-36.
[20] Clawson GA. Mechanisms of carbon tetrachloride hepatotoxicity. Pathol Immunopathol Res. 1989; 8(2): 104-112.
[21] Chryssanthi DG, Lamari FN, Iatrou G, Pylara A, Karamanos NK, Cordopatis P. Inhibition of breast cancer cell proliferation by style constituents of different Crocus species. Anticancer Res. 2007; 27(1): 357-362.
[22] Acar G, Dogan NM, Duru ME, Kıvrak I. Phenolic profiles, antimicrobial and antioxidant activity of the various extracts of Crocus species in Anatolia. Afr J Microbiol Res. 2010; 4(11): 1154-1161.
[23] Iranshahi M, Khoshangosht M, Mohammadkhani Z, Karimi G. Protective effects of aqueous and ethanolic extracts of saffron stigma and petal on liver toxicity induced by carbon tetrachloride in mice. Pharmacologyonline. 2011; 1(1): 203-212.
[24] Omidi A, Rahiminia N, Montazer Torbati MB, Behdani MA. Hepatoprotective effect of Crocus sativus (saffron) petals extract against acetaminophen toxicity in male Wistar rats. Avicenna J Phytomed. 2014; 4(5): 330-336.
[25] Gedik S, Erdemli ME, Gul M, Yigitcan B, Gozukara Bag H, Aksungur Z, Altinoz E. Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats. Biomed Pharmacother. 2017; 95(10): 764-770
[26] Hosseinzadeh H, Shamsaie F, Mehri S. Antioxidant activity of aqueous and ethanolic extracts of Crocus sativus L. stigma and its bioactive constituents, crocin and safranal. Pharmacogn Mag. 2009; 5(20): 419-424.
[27] Chen Y, Zhang H, Tian X, Zhao C, Cai L, Liu Y, Jia L, Yin H, Chen C. Antioxidant potential of crocins and ethanol extracts of Gardenia jasminoides ELLIS and Crocus sativus L.: a relationship investigation between antioxidant activity and crocin contents. Food Chem. 2008; 109(3): 484-492.
[28] Rice-Evans CA, Miller NJ, Paganga G. Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med. 1996; 20(7): 933-956.
[29] Norbaek R, Kondo T. Flavonol glycosides from flowers of Crocus speciosus and C. antalyensis. Phytochemistry. 1999; 51(8): 1113-1119.
[30] Ahsan MR, Islam KM, Bulbul IJ, Musaddik MA, Haque E. Hepatoprotective activity of methanol extract of some medicinal plants against carbon tetrachloride-induced hepatotoxicity in rats. Eur J Sci Res. 2009; 37(2): 302-310.
[31] Bahmani M, Shirzad H, Rafieian S, Rafieian-Kopaei M. Silybum marianum: beyond hepatoprotection. J Evid Based Complement Altern Med. 2015; 20(4): 292-301.