Skip to main content
SpringerLink
Log in

Protective effect of Pelargonium graveolens against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive constituents by HPLC–PDA–ESI–MS/MS analysis

  • Original Research
  • Published:
Medicinal Chemistry Research Aims and scope Submit manuscript

Abstract

The hepatoprotective and antioxidant activity of Pelargonium graveolens ethanol extract (PGE) against CCl4-induced liver injury was investigated in mice. The treatment of intoxicated mice with PGE (500 and 1000 mg/kg/day p.o for 6 weeks) significantly inhibited the CCl4-induced increase in alanine aminotransferase (by 37 and 43 %, at the tested doses, respectively), aspartate aminotransferase (by 33 and 35 %), alkaline phosphatase (by 26 and 33 %), and malondialdehyde levels (by 34 and 51 %). Moreover, PGE treatment markedly increased the activity of antioxidant enzymes (superoxide dismutase, glutathione peroxidase, glutathione reductase, and glutathione-S-transferase), as well as the level of reduced glutathione. A marked amelioration of the inflammatory cell infiltration and hydropic degeneration was evident in the groups treated with PGE. Notably, treatment with PGE reduced the central vein congestion more than in the silymarin-treated group. PGE was as effective as silymarin in reducing the fatty changes, Kupffer cell hyperplasia, and necrosis induced by CCl4 intoxication. These results suggest that a dietary supplement of PGE could exert a beneficial effect against oxidative stress and various liver diseases by enhancing the antioxidant defense status, reducing lipid peroxidation and protecting against the pathological changes of the liver. The hepatoprotective activity of PGE is mediated, at least in part, by the antioxidant effect of its constituents. The active constituents of PGE were identified by HPLC–PDA–ESI/MS/MS.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Abad-García B, Berrueta LA, López-Márquez DM, Crespo-Ferrer I, Gallo B, Vicente F (2007) Optimization and validation of a methodology based on solvent extraction and liquid chromatography for the simultaneous determination of several polyphenolic families in fruit juices. J Chromatogr A 1154:87–96

    Article  PubMed  Google Scholar 

  • Abdallah H, Mohamed M, Abdou A, Hamed M, Abdel-Naim A, Ashour O (2013) Protective effect of Centaurea pallescens Del. against CCl4-induced injury on a human hepatoma cell line (Huh7). Med Chem Res 22:5700–5706

    Article  CAS  Google Scholar 

  • Adewusi EA, Afolayan AJ (2010) A review of natural products with hepatoprotective activity. J Med Plants Res 4:1318–1334

    Google Scholar 

  • Ben Hsouna A, Hamdi N (2012) Phytochemical composition and antimicrobial activities of the essential oils and organic extracts from Pelargonium graveolens growing in Tunisia. Lipids Health Dis 11:167–174

    Article  CAS  PubMed  Google Scholar 

  • Boukhris M, Simmonds MS, Sayadi S, Bouaziz M (2013) Chemical composition and biological activities of polar extracts and essential oil of rose-scented geranium, Pelargonium graveolens. Phytother Res 27:1206–1213

    Article  CAS  PubMed  Google Scholar 

  • Bruce RD (1985) An up-and-down procedure for acute toxicity testing. Fundam Appl Toxicol 5:151–157

    Article  CAS  PubMed  Google Scholar 

  • Bystrom LM, Lewis BA, Brown DL, Rodriguez E, Obendorf RL (2008) Characterisation of phenolics by LC–UV/Vis, LC–MS/MS and sugars by GC in Melicoccus bijugatus Jacq. ‘Montgomery’ fruits. Food Chem 111:1017–1024

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Ćavar S, Maksimović M (2012) Antioxidant activity of essential oil and aqueous extract of Pelargonium graveolens L’Her. Food Control 23:263–267

    Article  Google Scholar 

  • Del Rio D, Stewart AJ, Mullen W, Burns J, Lean MEJ, Brighenti F, Crozier A (2004) HPLC-MSn analysis of phenolic compounds and purine alkaloids in green and black tea. J Agric Food Chem 52:2807–2815

    Article  PubMed  Google Scholar 

  • Ellman GL (1959) Tissue sulfhydryl groups. Arch Biochem Biophys 82:70–77

    Article  CAS  PubMed  Google Scholar 

  • Engels C, Gräter D, Esquivel P, Jiménez VM, Gänzle MG, Schieber A (2012) Characterization of phenolic compounds in jocote (Spondias purpurea L.) peels by ultra high-performance liquid chromatography/electrospray ionization mass spectrometry. Food Res Int 46:557–562

    Article  CAS  Google Scholar 

  • Habig WH, Pabst MJ, Jakoby WB (1974) Glutathione S-transferases. The first enzymatic step in mercapturic acid formation. J Biol Chem 249:7130–7139

    CAS  PubMed  Google Scholar 

  • Han X, Shen T, Lou H (2007) Dietary polyphenols and their biological significance. Int J Mol Sci 8:950–988

    Article  PubMed Central  CAS  Google Scholar 

  • Haslam E (1996) Natural polyphenols (vegetable tannins) as drugs: possible modes of action. J Nat Prod 59:205–215

    Article  CAS  PubMed  Google Scholar 

  • Hellström J, Sinkkonen J, Karonen M, Mattila P (2007) Isolation and structure elucidation of procyanidin oligomers from saskatoon berries (Amelanchier alnifolia). J Agric Food Chem 55:157–164

    Article  PubMed  Google Scholar 

  • Hvattum E, Ekeberg D (2003) Study of the collision-induced radical cleavage of flavonoid glycosides using negative electrospray ionization tandem quadrupole mass spectrometry. J Mass Spectrom 38:43–49

    Article  CAS  PubMed  Google Scholar 

  • Jacobs BP, 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

    Article  PubMed  Google Scholar 

  • Jin Y, Xiao Y-S, Zhang F-F, Xue X, Xu Q, Liang X-M (2008) Systematic screening and characterization of flavonoid glycosides in Carthamus tinctorius L. by liquid chromatography/UV diode-array detection/electrospray ionization tandem mass spectrometry. J Pharm Biomed Anal 46:418–430

    Article  CAS  PubMed  Google Scholar 

  • Kerhoas L, Aouak D, Cingöz A, Routaboul J-M, Lepiniec L, Einhorn J, Birlirakis N (2006) Structural Structural characterization of the major flavonoid glycosides from Arabidopsis thaliana seeds. J Agric Food Chem 54:6603–6612

    Article  CAS  PubMed  Google Scholar 

  • Kind PR, King EJ (1954) Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J Clin Pathol 7:322–326

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Latté KP, Kolodziej H (2004) Antioxidant properties of phenolic compounds from Pelargonium reniforme. J Agric Food Chem 52:4899–4902

    Article  PubMed  Google Scholar 

  • Lee S-J, Lim K-T (2008) Glycoprotein of Zanthoxylum piperitum DC has a hepatoprotective effect via anti-oxidative character in vivo and in vitro. Toxicol In Vitro 22:376–385

    Article  CAS  PubMed  Google Scholar 

  • Li J, Li J, Li S, He B, Mi Y, Cao H, Zhang C, Li L (2012) Ameliorative effect of grape seed proanthocyanidin extract on thioacetamide-induced mouse hepatic fibrosis. Toxicol Lett 213:353–360

    Article  CAS  PubMed  Google Scholar 

  • Määttä KR, Kamal-Eldin A, Törrönen AR (2003) High-Performance liquid chromatography (HPLC) analysis of phenolic compounds in berries with diode array and electrospray ionization mass spectrometric (ms) detection: Ribes species. J Agric Food Chem 51:6736–6744

    Article  PubMed  Google Scholar 

  • Muriel P, Rivera-Espinoza Y (2008) Beneficial drugs for liver diseases. J Appl Toxicol 28:93–103

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  • Procházková D, Boušová I, Wilhelmová N (2011) Antioxidant and prooxidant properties of flavonoids. Fitoterapia 82:513–523

    Article  PubMed  Google Scholar 

  • Ramachandra Setty S, Quereshi AA, Viswanath Swamy AHM, Patil T, Prakash T, Prabhu K, Veeran Gouda A (2007) Hepatoprotective activity of Calotropis procera flowers against paracetamol-induced hepatic injury in rats. Fitoterapia 78:451–454

    Article  CAS  PubMed  Google Scholar 

  • Ramos S (2008) Cancer chemoprevention and chemotherapy: dietary polyphenols and signalling pathways. Mol Nutr Food Res 52:507–526

    Article  CAS  PubMed  Google Scholar 

  • Reddy KR (2007) Silymarin for the treatment of chronic liver disease. Gastroenterol Hepatol 3:825–826

    Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Sánchez-Rabaneda F, Jáuregui O, Casals I, Andrés-Lacueva C, Izquierdo-Pulido M, Lamuela-Raventós RM (2003) Liquid chromatographic/electrospray ionization tandem mass spectrometric study of the phenolic composition of cocoa (Theobroma cacao). J Mass Spectrom 38:35–42

    Article  PubMed  Google Scholar 

  • Shin MO, Yoon S, Moon JO (2010) The proanthocyanidins inhibit dimethylnitrosamine-induced liver damage in rats. Arch Pharm Res 33:167–173

    Article  CAS  PubMed  Google Scholar 

  • Srivastava A, Shivanandappa T (2010) Hepatoprotective effect of the root extract of Decalepis hamiltonii against carbon tetrachloride-induced oxidative stress in rats. Food Chem 118:411–417

    Article  CAS  Google Scholar 

  • Truchado P, Ferreres F, Tomas-Barberan FA (2009) Liquid chromatography–tandem mass spectrometry reveals the widespread occurrence of flavonoid glycosides in honey, and their potential as floral origin markers. J Chromatogr A 1216:7241–7248

    Article  CAS  PubMed  Google Scholar 

  • Wagner H, Ulrich-Merzenich G (2009) Synergy research: approaching a new generation of phytopharmaceuticals. Phytomedicine 16:97–110

    Article  CAS  PubMed  Google Scholar 

  • Wang B-J, Liu C-T, Tseng C-Y, Wu C-P, Yu Z-R (2004) Hepatoprotective and antioxidant effects of Bupleurum kaoi Liu (Chao et Chuang) extract and its fractions fractionated using supercritical CO2 on CCl4-induced liver damage. Food Chem Toxicol 42:609–617

    Article  CAS  PubMed  Google Scholar 

  • Williamson EM (2001) Synergy and other interactions in phytomedicines. Phytomedicine 8:401–409

    Article  CAS  PubMed  Google Scholar 

  • Winterbourn CC, Hawkins RE, Brian M, Carrell RW (1975) The estimation of red cell superoxide dismutase activity. J Lab Clin Med 85:337–341

    CAS  PubMed  Google Scholar 

  • Zanetti G (1979) Rabbit liver glutathione reductase. Purification and properties. Arch Biochem Biophys 198:241–246

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Professor Juha-Pekka Salminen, department of chemistry, university of Turku, Finland is acknowledged for the use of the HPLC–MS instrument during this study.

Conflict of interest

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacognosy, Faculty of Pharmacy, Ain-Shams University, Cairo, 11566, Egypt

    Eman Al-Sayed

  2. Laboratory of Organic Chemistry and Chemical Biology, Department of Chemistry, University of Turku, 20014, Turku, Finland

    Olli Martiskainen

  3. Department of Pharmacoloy, Theodor Bilharz Research Institute, Giza, 12411, Egypt

    Sayed H. Seif el-Din, Abdel-Nasser A. Sabra & Naglaa M. El-Lakkany

  4. Department of Pathology, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Olfat A. Hammam

Authors
  1. Eman Al-Sayed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Olli Martiskainen
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sayed H. Seif el-Din
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Abdel-Nasser A. Sabra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Olfat A. Hammam
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Naglaa M. El-Lakkany
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eman Al-Sayed.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 15 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Sayed, E., Martiskainen, O., Seif el-Din, S.H. et al. Protective effect of Pelargonium graveolens against carbon tetrachloride-induced hepatotoxicity in mice and characterization of its bioactive constituents by HPLC–PDA–ESI–MS/MS analysis. Med Chem Res 24, 1438–1448 (2015). https://doi.org/10.1007/s00044-014-1218-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00044-014-1218-3

Keywords

Search

Navigation