The Effect of Methanol Extract of Fennel on Bleomycin-Induced Pulmonary Fibrosis in Rats

Authors

1 Assistant Professor, Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 Cardiovascular Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Gasteroenterology & Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

4 Assistant Professor, Department of Pharmacognosy and Herbal and Traditional Medicines Research Center, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

5 School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

6 Herbal and Traditional Medicines Research Center, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

7 Afzalipour School of Medicine, Kerman University of Medical Sciences, Kerman, Iran

8 Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

9 Associate Professor, Endocrinology and Metabolism Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

Abstract

Background & Aims: Idiopathic pulmonary fibrosis (IPF) is a chronic diffuse interstitial lung disease,
which has symptoms such as coughing and shortness of breath. The average survival duration in these
patients is estimated as 3 years after the onset of symptoms. Today, the therapeutic approach used in IPF
cases is the usage of chemical or herbal antioxidants in order to eliminate free radicals and prevent
inflammation and fibrosis. Considering the antioxidant properties of fennel, this research was conducted to
investigate the effect of the methanol extracted of fennel on bleomycin-induced pulmonary fibrosis in rats.
Methods: To induce pulmonary fibrosis in rats, intratracheal administration of 15 mg bleomycin was
conducted in 52 male rates. Subsequently, the rats were injected intraperitoneally with 500 mg/(kg body
weight) of methanol extract of fennel 14-day and 28-day periods. The samples were studied in terms of
inflammation, fibrosis, hydroxyproline concentration, lipid peroxidation, and the catalase activity of lung
tissue. The obtained results were analyzed using SPSS software.
Results: The degree of inflammation, fibrosis, hydroxyproline and lipid peroxidation concentration in lung
tissue in the fennel methanol extract group had significantly decreased compared to other groups. In addition,
a significant increase was observed in tissue catalase concentration in this group in comparison to other
groups on days 14 and 28.
Conclusion: The obtained results illustrated that the methanol extract of fennel may be efficient in the
prevention and treatment of pulmonary fibrosis due to its antioxidant properties. Accordingly, it can be
suggested for the prevention and treatment of pulmonary fibrosis instead of corticosteroids and
immunosuppressant drugs due to their many side effects and most patients’ preference of herbal medicines. 

Keywords


  1. Kubo H, Nakayama K, Yanai M, Suzuki T, Yamaya M, Watanabe M, et al. Anticoagulant therapy for idiopathic pulmonary fibrosis. Chest 2005; 128(3): 1475-82.
  2. Kuwano K, Kunitake R, Maeyama T, Hagimoto N, Kawasaki M, Matsuba T, et al. Attenuation of bleomycin-induced pneumopathy in mice by a caspase inhibitor. Am J Physiol Lung Cell Mol Physiol 2001; 280(2): L316-L325.
  3. Adamson IYR, Bowden DH. The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 1974; 77(2): 185-98.
  4. Krous HF, Hamlin WB. Pulmonary toxicity due to bleomycin. Report of a case. Arch Pathol 1973; 95(6): 407-10.
  5. Bahrami-Karkevandi M, Moshtaghian S, Madani S, Mahzoni P, Adibi S, Kazemi S. The effects of hydroalcoholic extract of Artemisia aucheri on bleomycin induced pulmonary fibrosis in rats. J Shahrekord Univ Med Sci 2011; 12(4): 33-40. [In Persian].
  6. Anwar F, Ali M, Ijaz Hussain A, Shahid M. Antioxidant and antimicrobial activities of essential oil and extracts of fennel (Foeniculum vulgare Mill.) seeds from Pakistan. Flavour and Fragrance Journal 2009; 24(4): 170-6.
  7. Choi EM, Hwang JK. Antiinflammatory, analgesic and antioxidant activities of the fruit of Foeniculum vulgare. Fitoterapia 2004; 75(6): 557-65.
  8. Mohamad RH, El-Bastawesy AM, Abdel-Monem MG, Noor AM, Al-Mehdar HA, Sharawy SM, et al. Antioxidant and anticarcinogenic effects of methanolic extract and volatile oil of fennel seeds (Foeniculum vulgare). J Med Food 2011; 14(9): 986-1001.
  9. Kaileh M, Vanden Berghe W, Boone E, Essawi T, Haegeman G. Screening of indigenous Palestinian medicinal plants for potential anti-inflammatory and cytotoxic activity. J Ethnopharmacol 2007; 113(3): 510-6.
  10. Rather MA, Dar BA, Sofi SN, Bhat BA, Qurishi MA. Foeniculum vulgare: A comprehensive review of its traditional use, phytochemistry, pharmacology, and safety. Arabian Journal of Chemistry 2012: [In Press].
  11. Tanira MOM, Shah AH, Mohsin A, Ageel AM, Qureshi S. Pharmacological and toxicological investigations on Foeniculum vulgare dried fruit extract in experimental animals. Phytotherapy Research 1996; 10(1): 33-6.
  12. Chen M, Cheung FW, Chan MH, Hui PK, Ip SP, Ling YH, et al. Protective roles of Cordyceps on lung fibrosis in cellular and rat models. J Ethnopharmacol 2012; 143(2): 448-54.
  13. Samareh FM, Poursalehi HR, Najafipour H, Dabiri S, Shokoohi M, Siahposht KA, et al. Pulmonary complications of gastric fluid and bile salts aspiration, an experimental study in rat. Iran J Basic Med Sci 2013; 16(6): 790-6.
  14. Liang X, Tian Q, Wei Z, Liu F, Chen J, Zhao Y, et al. Effect of Feining on bleomycin-induced pulmonary injuries in rats. J Ethnopharmacol 2011; 134(3): 971-6.
  15. Izbicki G, Segel MJ, Christensen TG, Conner MW, Breuer R. Time course of bleomycin-induced lung fibrosis. Int J Exp Pathol 2002; 83(3): 111-9.
  16. Zhou XM, Zhang GC, Li JX, Hou J. Inhibitory effects of Hu-qi-yin on the bleomycin-induced pulmonary fibrosis in rats. J Ethnopharmacol 2007; 111(2): 255-64.
  17. Woessner JF. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid. Archives of Biochemistry and Biophysics 1961; 93(2): 440-7.
  18. Sur S, Wild JS, Choudhury BK, Sur N, Alam R, Klinman DM. Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides. J Immunol 1999; 162(10): 6284-93.
  19. Kwak YG, Song CH, Yi HK, Hwang PH, Kim JS, Lee KS, et al. Involvement of PTEN in airway hyperresponsiveness and inflammation in bronchial asthma. J Clin Invest 2003; 111(7): 1083-92.
  20. Ashcroft T, Simpson JM, Timbrell V. Simple method of estimating severity of pulmonary fibrosis on a numerical scale. J Clin Pathol 1988; 41(4): 467-70.
  21. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem 1996; 29(3): 225-9.
  22. Aoki F, Kurabayashi M, Hasegawa Y, Kojima I. Attenuation of bleomycin-induced pulmonary fibrosis by follistatin. Am J Respir Crit Care Med 2005; 172(6): 713-20.
  23. Benzie IF, Strain JJ. Ferric reducing/antioxidant power assay: direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999; 299: 15-27.
  24. Mandegary A, Sezavar M, Saeedi A, Amirheidari B, Naghibi B. Oxidative stress induced in the workers of natural gas refineries, no role for GSTM1 and GSTT1 polymorphisms. Hum Exp Toxicol 2012; 31(12): 1271-9.
  25. Esterbauer H, Cheeseman KH. Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 1990; 186: 407-21.
  26. Beers RF, Sizer IW. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J Biol Chem 1952; 195(1): 133-40.
  27. Ozbek H, Ugras S, Dulger H, Bayram I, Tuncer I, Ozturk G, et al. Hepatoprotective effect of Foeniculum vulgare essential oil. Fitoterapia 2003; 74(3): 317-9.
  28. Alexandrovich I, Rakovitskaya O, Kolmo E, Sidorova T, Shushunov S. The effect of fennel (Foeniculum Vulgare) seed oil emulsion in infantile colic: a randomized, placebo-controlled study. Altern Ther Health Med 2003; 9(4): 58-61.
  29. Birdane FM, Cemek M, Birdane YO, Gulcin I, Buyukokuroglu ME. Beneficial effects of Foeniculum vulgare on ethanol-induced acute gastric mucosal injury in rats. World J Gastroenterol 2007; 13(4): 607-11.
  30. Parejo I, Viladomat F, Bastida J, Schmeda-Hirschmann G, Burillo J, Codina C. Bioguided isolation and identification of the nonvolatile antioxidant compounds from fennel (Foeniculum vulgare Mill.) waste. J Agric Food Chem 2004; 52(7): 1890-7.
  31. Hemmati AA, Rezaie A, Darabpour P. Preventive effects of pomegranate seed extract on bleomycin-induced pulmonary fibrosis in rat. Jundishapur J Nat Pharm Prod 2013; 8(2): 76-80.
  32. Safaian L, Jafarian A, Afshar Moghadam N, Sarhrodi S. Preventive Effects of silimarin on Bleomycin-Induced Pulmonary Fibrosis in Rat. Qom Univ Med Sci J 2009; 3(2): 1-6. [In Persian].
  33. Xiao JH, Zhang JH, Chen HL, Feng XL, Wang JL. Inhibitory effects of isoliensinine on bleomycin-induced pulmonary fibrosis in mice. Planta Med 2005; 71(3): 225-30.
  34. Kim HR, Park BK, Oh YM, Lee YS, Lee DS, Kim HK, et al. Green tea extract inhibits paraquat-induced pulmonary fibrosis by suppression of oxidative stress and endothelin-l expression. Lung 2006; 184(5): 287-95.
  35. Baer-Dubowska W, Szaefer H, Krajka-Kuzniak V. Inhibition of murine hepatic cytochrome P450 activities by natural and synthetic phenolic compounds. Xenobiotica 1998; 28(8): 735-43.