Pharmacological potential of <em>Populus nigra</em> extract as antioxidant, anti-inflammatory, cardiovascular and hepatoprotective agent

Nadjet Debbache-Benaida

Dina Atmani-Kilani

Valérie Schini-Keirth

Nouredine Djebbli

Djebbar Atmani

Objective

To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract.

Methods

Antioxidant and anti-inflammatory activities of the extract were assessed using respectively the ABTS test and the animal model of carrageenan-induced paw edema. Protection from hepatic toxicity caused by aluminum was examined by histopathologic analysis of liver sections. Vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries precontracted with high concentration of U46619.

Results

The results showed a moderate antioxidant activity (40%), but potent anti-inflammatory activity (49.9%) on carrageenan-induced mice paw edema, and also as revealed by histopathologic examination, complete protection against AlCl₃-induced hepatic toxicity. Relaxant effects of the same extract on vascular preparation from porcine aorta precontracted with high concentration of U46619 were considerable at 10^{g/L, and comparable (}P>0.05) between endothelium-intact (67.74%, IC₅₀=0.04 mg/mL) and -rubbed (72.72%, IC₅₀=0.075 mg/mL) aortic rings.

Conclusions

The extract exerted significant anti-inflammatory, hepatoprotective and vasorelaxant activities, the latter being endothelium-independent believed to be mediated mainly by the ability of components present in the extract to exert antioxidant properties, probably related to an inhibition of Ca^influx.

*Corresponding author: Djebbar Atmani, Laboratory of Applied Biochemistry, Faculty of Nature and Life Sciences, University of Bejaia, 06000 Algeria. Tel/Fax: +21334214762, E-mail: moc.oohay@inamtajd

Received 2013 Jun 25; Accepted 2013 Aug 20.

Abstract

Objective

To evaluate antioxidant, anti-inflammatory, hepatoprotective and vasorelaxant activities of Populus nigra flower buds ethanolic extract.

Methods

Results

Conclusions

Keywords: Populus nigra, Polyphenols, Anti-inflammatory activity, Hepatoprotection, Vasorelaxation

Abstract

Acknowledgments

We wish to thank the Ministry of Higher Education and Scientific Research of Algeria for sponsoring this work (CNEPRU Grant No. F00620100006).

Acknowledgments

Notes

Comments

Background

Endothelial dysfunction is a key physiopathological mechanism that contributes to several diseases. An impaired vasodilation mediated mainly by a deficiency in NO is the major reason of endothelial dysfunction. NO is also implicated in many physiologic processes such as anti-inflammatory and antioxidant. Therefore, search of potential NO synthase inhibitors is the need of time.

Research frontiers

The present research work describes antioxidant and anti-inflammatory activities of the ethanolic extract of P. nigra flower buds estimated by in vivo and in vitro models. Hepatic toxicity caused by aluminum was examined by histopathologic analysis, while vasorelaxant effect was estimated in endothelium-intact and -rubbed rings of porcine coronary arteries.

Related reports

Aluminum is a well known hepatotoxins to humans. Using natural antioxidants against metal-induced hepatotoxicity is a modern approach. It is reported that modulation of iNOS is important in the prevention of inflammation, and flavanoids are potent inhibitors of iNOS.

Innovations and breakthroughs

Traditionally, P. nigra is used in the treatment of many conditions related to endothelial dysfunction. Some in vitro antioxidant and anti-inflammatory activities are also reported. In the present study, authors have demonstrated vasorelaxant, in vivo anti-inflammatory and hepato-protective activities.

Applications

This study provides basis for the traditional use of P. nigra buds in the treatment of inflammatory pathologies. Other pharmacological effects such as hepato-protection and prevention of cardiovascular diseases could be explored.

Peer review

The authors have presented their findings effectively. Endothelium independent vasorelaxent effect was found to be correlated with the antioxidant activity of the plant extract which is due to the presence of flavanoids. Moreover, histopathological examination revealed complete protection against AlCl₃ induced hepatic toxicity. P. nigra extract was identified as a potential anti-inflammatory, hepatoprotective and vasorelaxent agent.

Notes

Footnotes

Foundation Project: Supported by Ministry of Higher Education and Scientific Research of Algeria (CNEPRU Grant No. F00620100006).

Conflict of interest statement: We declare that we have no conflict of interest.

Footnotes

References

1. Savoia C, Sada L, Zezza L, Pucci L, Lauri FM, Befani A, et al. et al. Vascular inflammation and endothelial dysfunction in experimental hypertension. Int J Hypertens. 2011 doi: 10.4061/2011/281240.] [
2. Schini-Kerth VB, Auger C, Kim J-H, Étienne-Selloum N, Chataigneau TNutritional improvement of the endothelial control of vascular tone by polyphenols: role of NO and EDHF. Pflugers Arch. 2010;459:853–862.[PubMed][Google Scholar]
3. Rubbo H, Radi R, Trujillo M, Telleri R, Kalyanaraman B, Barnes S, et al. et al. Nitric oxide regulation of superoxide and peroxynitrite-dependant lipid peroxidation. Formation of novel nitrogen-containing oxidized lipid derivatives. J Biol Chem. 1994;269:26066–26075.[PubMed]
4. Pashkow FJOxidative stress and inflammation in heart disease: Do antioxidants have a role in treatment and/or prevention? Int J Inflam. 2011 doi: 10.4061/2011/514623.] [[Google Scholar]
5. De Caterina R, Zampolli A, Del Turco S, Madonna R, Massaro MNutritional mechanisms that influence cardiovascular disease. Am J Clin Nutr. 2006;83(2):S421–S426.[PubMed][Google Scholar]
6. Dudonné S, Poupard P, Coutiére P, Woillez M, Richard T, Mérillon JM, et al. et al. Phenolic composition and antioxidant properties of poplar bud (Populusnigra) extract: individual antioxidant contribution of phenolics and transcriptional effects on skin aging. J Agric Food Chem. 2011;59(9):4527–4536.[PubMed]
7. Atmani D, Chaher N, Berboucha M, Ayouni K, Lounis H, Boudaoud H, et al. et al. Antioxidant capacity and phenol content of selected Algerian medicinal plants. Food Chem. 2009;112(2):303–309.[PubMed]
8. Akanitapichat P, Phraibung K, Nuchklang K, Prompitakkul SAntioxidant and hepatoprotective activities of five eggplant varieties. Food Chem Toxicol. 2010;48:3017–3021.[PubMed][Google Scholar]
9. Maksimoviĉ Z, Malenciĉ ND, Kovaceviĉ NPolyphenol contents and antioxidant activity of Maydis stigma extracts. Bioresour Technol. 2005;96(8):873–877.[PubMed][Google Scholar]
10. Vaghasiya Y, Dave R, Chanda SPhytochemical analysis of some medicinal plants from western region of india. Res J Med Plant. 2011;5(5):567–576.[PubMed][Google Scholar]
11. Oyedemi SO, Afolayan AJAntibacterial and antioxidant activities of hydroalcoholic stem bark extract of Schotia latifolia Jacq. Asian Pac J Trop Med. 2011;4(12):952–958.[PubMed][Google Scholar]
12. Bairagi SM, Aher AA, Nema N, Nimase PKAntiinflammatory evaluation of methanol extract and aqueous fraction of the bark of Bauhinia varriegata (leguminosae) Int J Res Pharm Chem. 2012;2(1):77–82.[PubMed][Google Scholar]
13. Pan R, Qiu S, Lu DX, Dong JCurcumin improves learning and memory ability and its neuroprotective mechanism in mice. Chin Med J (Engl) 2008;121(9):832–839.[PubMed][Google Scholar]
14. Anselm E, Chataigneau M, Ndiaye M, Chataigneau T, Schini-Kerth VBGrape juice causes endothelium-dependent relaxation via a redox-sensitive Src- and Akt-dependent activation of eNOS. Cardiovasc Res. 2007;73(2):404–413.[PubMed][Google Scholar]
15. Oyedemi SO, Bradley G, Afolayan AJ. In vitro and in vivo antioxidant activities of aqueous extract of Strychnos henningsii Gilg. Afr J Pharm Pharmacol. 2010;4(2):70–78.[PubMed]
16. Bankova VRecent trends and important developments in propolis research. Evid Based Complement Alternat Med. 2005;2(1):29–32.[Google Scholar]
17. Vardar-Ünlü G, Silici S, Ünlü MComposition and in vitro antimicrobial activity of Populus buds and poplar-type propolis. World J Microbiol Biotechnol. 2008;24:1011–1017.[PubMed][Google Scholar]
18. Von Kruedener S, Schneider W, Elstner EFEffects of extracts from Populus tremula L., Solidago virgaurea L and Fraxinus excelsior L. on various myeloperoxidase systems. Arzneimittelforschung. 1996;46(8):809–814.[PubMed][Google Scholar]
19. Bonaterra GA, Kelber O, Weiser D, Metz J, Kinscherf R. In vitro anti-proliferative effects of the willow bark extract STW 33-I. Arzneimittelforschung. 2010;60:330–335.[PubMed]
20. Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al. et al. Anti-inflammatory effect of zerumbone on acute and chronic inflammation models in mice. Fitoterapia. 2010;81(7):855–858.[PubMed]
21. Gan TJDiclofenac: an update on its mechanism of action and safety profile. Curr Med Res Opin. 2010;26(7):1715–1731.[PubMed][Google Scholar]
22. Mohammadirad A, Abdollahi MA systematic review on oxidant/antioxidant imbalance in aluminium toxicity. Int J Pharmacol. 2011;7(1):12–21.[PubMed][Google Scholar]
23. Fahaid Al-HCamel's milk protects against aluminum chloride-induced normocytic normochromic anemia, lipid peroxidation and oxidative stress in erythrocytes of white albino rats. Am J Biochem Biotechnol. 2009;5(3):126–136.[PubMed][Google Scholar]
24. Enas AKStudy of the possible protective and therapeutic influence of Coriander (Coriandrum sativum L.) against neurodegenerative disorders and Alzheimer's disease induced by aluminum chloride in cerebral cortex of male Albino rats. Nat Sci. 2010;8(11):202–213.[PubMed][Google Scholar]
25. Türkez H, Yousef MI, Geyikoglu FPropolis prevent aluminium-induced genetic and hepatic damages in rat liver. Food Cheml Toxicol. 2010;48(10):2741–2746.[PubMed][Google Scholar]
26. Han S, Lemire J, Appanna VP, Auger C, Castonguay Z, Appanna VDHow aluminum, an intracellular ROS generator promotes hepatic and neurological diseases: the metabolic tale. Cell Biol Toxicol. 2013;29(2):75–84.[PubMed][Google Scholar]
27. Zhang L, Li X, Gu Q, Zhu Y, Zhao H, Li Y, et al. et al. Effects of subchronic aluminum exposure on serum concentrations of iron and iron-associated proteins in rats. Biol Trace Elem Res. 2011;141(1–3):246–253.[PubMed]
28. Peto MVAluminium and iron in humans: bioaccumulation, pathology and removal. Rejuvenation Res. 2010;13(5):589–598.[PubMed][Google Scholar]
29. Hobbs AJ, Ignarro LJNitric oxide-cyclic GMP signal transduction system. Methods Enzymol. 1996;269:134–148.[PubMed][Google Scholar]
30. Dimmeler S, Fleming I, Fisslthaler B, Hermann C, Busse R, Zeiher AMActivation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation. Nature. 1999;399:601–605.[PubMed][Google Scholar]
31. Ryu JH, Ahn H, Kim JY, Kim YKInhibitory activity of plant extracts on nitric oxide synthesis in LPS-activated macrophages. Phytother Res. 2003;17:485–489.[PubMed][Google Scholar]
32. Stoclet JC, Chataigneau T, Ndiaye M, Oak MH, El Bedoui J, Chataigneau M, et al. et al. Vascular protection by dietary polyphenols. Eur J Pharmacol. 2004;500:299–313.[PubMed]
33. Schmitt CAH, Handler N, Heiss EH, Erker T, Dirsch VMNo evidence for modulation of endothelial nitric oxide synthase by the olive oil polyphenol hydroxytyrosol in human endothelial cells. Atherosclerosis. 2007;195(1):58–64.[PubMed][Google Scholar]
34. Huisman A, Van De Wiel A, Rabelink TJ, Van Faassen EEWine polyphenols and ethanol do not significantly scavenge superoxide nor affect endothelial nitric oxide production. J Nutr Biochem. 2004;15(7):426–432.[PubMed][Google Scholar]
35. Ng LC, Gurney AMStore-operated channels mediate Ca^{influx and contraction in rat pulmonary artery.}Circ Res. 2001;89(10):923–929.[PubMed][Google Scholar]
36. Wray S, Burdyga TSarcoplasmic reticulum function in smooth muscle. Physiol Rev. 2010;90(1):113–178.[PubMed][Google Scholar]
37. Saponara S, Carosati E, Mugnai P, Sgaragli G, Fusi FThe flavonoid scaffold as a template for the design of modulators of the vascular Ca(v) 1.2 channels. Br J Pharmacol. 2011;164:1684–1697.[Google Scholar]
38. Khushmatov ShS, Omonturdiev SZ, Eshbakova KA, Usmanov PB, Toshmatov ZORelaxant effect of the flavonoid pulicarin. Med Plant Res. 2012;2(5):21–25.[PubMed][Google Scholar]
39. Lee MY, Man RYThe phytoestrogen genistein enhances endothelium-independent relaxation in the porcine coronary artery. Eur J Pharmacol. 2003;481:227–232.[PubMed][Google Scholar]