Cellular antioxidative, cytotoxic, and antileishmanial activities of Homalium letestui

Document Type : Original Research Article

Authors

1 Department Of Pharmacology and Toxicology, Faculty of Pharmacy, University of Uyo, Uyo, Nigeria

2 International Center for Chemical and Biological Sciences, University Of Karachi, Karachi, Pakistan

Abstract

Objective: Homalium letestui Pellegr (Flacourtiaceae) is used in traditional medicine in parts of Nigeria for the treatment of malaria, ulcer, and inflammatory diseases and as an aphrodisiac. This investigation was aimed to evaluate the cytotoxic, immunomodulatory, and antileishmanial properties of stem extract and fractions of Homalium letestui (H. letestui).
Materials and Methods: Cytotoxic activity against HeLa cells was done using sulphorhodamine (SRB) method and DNA interaction activity using gel electrophoresis. Immunomodulatory activity of the extract in whole blood, neutrophils, and macrophages was also investigated using luminol/lucigenin-based chemiluminescence assay. The extract and fractions were similarly screened for antileishmanial activity against promastigotes of Leishmania major in vitro. The GCMS analysis of the most active fraction against HeLa cells was carried out.
Results: The stem extract exerted prominent cytotoxic activity with the dichloromethane fraction exhibiting the most pronounced effect (GI50 -5.12±1.45 µg/ml, LC50- 57.3±2.33 µg/ml, TGI -12.6±0.87 µg/ml). The crude extract and the fractions did not interact with DNA when investigated using electrophoresis. The extract significantly ((pLeishmania major in vitro. GCMS analysis of active fraction revealed pharmacologically active compounds.
Conclusion: These results suggest that the stem extract/fractions of H. letestuipossess cytotoxic, immunomodulatory, and antileishmanial activities.

Keywords


Adams RP. 2001. Identification of Essential oils by Gas Chromatography Quadrupole Mass Spectrometry. Allured Publishing Corporation, Carol Stream, USA.
Anderson R, Gatner EMS, van Rensburg CE, Grabow G, Imkamp FH, Kok SK, van Rensburg J. 1981. In vitro and In vivo effect of dapsone on neutrophils and lymphocyte functions in normal individuals and patients with lepromatous leprosy. Antimicrob Agents Chemotherapy, 19: 495-503.
Atta-ur-Rahman, Choudhary MI, William JT. 1997. Bioassay techniques for drug development. Harward Academic Publisher, pp 67- 68.
Cho-Ngwa F, Abongwa M, Ngemenya MN, Nyongbela KN. 2010. Selective activity of extracts of Margaritaria discoidea and Homalium africanum on Onchocerca ochengi. BMC Complement Altern Med, 10: 62.
Chung PY, Chung LY, Ngeow YF, Goh SH,  Imiyabir Z. 2004. Antimicrobial activities of Malaysian plant species. Pharm Biol, 42: 292-300.
Desrivot J, Waikedre J, Cabalion P, Herrenknecht C, Bories C, Hocquemiller R, Fournet A. 2007. Antiparasitic activity of some New Caledonian medicinal plants. J Ethnopharmacol, 112: 7-12.
Ekabo OA, Farnsworth NR, Santisuk T, Reutrakul V. 1993. A phytochemical investigation of Homalium ceylanicum. J  Nat Prod, 56: 699-707.
Falah S, Katayama T, Suzuki T. 2008. Chemical constituents from Gmelina arborea bark and their antioxidant activity. J Wood Sci, 54: 483-489.
Gnananath K, Kumar GP, Reddy CR, Kumar BN, Kumar RV. 2012. Evaluation of anthelmintic activity in the bark of Homalium zeylanicum. Int Res J Pharm, 3: 436-437.
Haklar G, Ozveri ES, Yuksel M, Aktan A, Yalcin AS. 2001. Different kinds of reactive oxygen and nitrogen species were detected in colon and breast tumors. Cancer Lett, 165: 219 -224.
Halliwell B., Gutteridge JMC. 1999. Free Radicals in Biology and Medicine, 3rd ed. Oxford: Oxford University Press.
Helfand S, Werkmeister J, Roder J. 1982. Chemiluminescence response of human natural killer cells. I. The relationship between target cell binding, chemiluminescence, and cytolysis. J Exp Med, 156: 492-505.
Houghton P, Fang R, Techatanawat I,  Steventon G, Hylands PJ, Lee CC. 2007. The sulphorhodamine (SRB) assay and other approachesto testing plant extracts and derived compounds for activities related to reputed anticancer activity. Methods, 42: 377-387.
Hutchinson T, Daziel JM. 1963. Flora of West Tropical Africa, Vol 2. Crown Agents for overseas government. London.
Ishikawa T, Nishigaya K, Takami K, Uchikoshi H,  Chen IS, Lih T. 2004. Isolation of salicin derivatives from Homalium cochinchinensis and their antiviral activities. J Nat Prod, 67: 659-663.
Ismail M, Bagalkotkar G, Iqbal S, Adamu HA. 2012. Anticancer properties and phenolic contents of sequentially prepared extracts from different parts of selected medicinal plants indigenous to Malaysia. Molecules17: 5745-5756.
Keay RWJ. 1989. Trees of Nigeria. A revised version of Nigerian trees (Vol 1 and 2), Keay RWJ, Onoche CFA, Stanfield DP (eds). Clarendon Press: Oxford.
Mansour OC, Evison BJ, Sleebs BE, Watson KG ,Nudelman A, Rephaeli A., Buck DP, Collins JG, Bilardi RA, Phillips DR, Cutts SM. 2010. New Anthracenedione derivatives with improved biological activity by virtue of stable drug-DNA adduct formation. J Med Chem, 53: 6851-6866.
Mbwambo ZH, Kapingu MC, Moshi MJ,  Machumi F, Apers S, Cos P, Ferreira D, Jannie P, Marais JP, Dirk Berghe V, Maes L, Vlietinck A, Pieters L. 2006. Antiparasitic activity of some xanthones and biflavonoids from the root bark of Garcinia liwingstonei. J Nat Prod,69:369-372.

Madan S, Pannakal S, Ganapaty S, Singh GN and Kumar Y. 2009. Phenolic glucosides from Flacourtia indica. Nat Prod Commun, 4: 381-384

Mosaddik MA, Banbury L, Forster P, Booth R, MarkhamJ, LeachD, Waterman PG. 2004. Screening of some Australian Flacourtiaceae species for in vitro antioxidant, cytotoxic and antimicrobial activity. Phytomedicine, 11: 461-466.
Murakami Y, Hirata A, Ito S, Shoji M, Tanaka S, Yasui T, Machino M , Fujisawa S. 2007. Re-evaluation of Cyclooxygenase-2-inhibiting Activity of Vanillin and Guaiacol in Macrophages Stimulated with Lipopolysaccharide. Anticancer Res, 27: 801-808.
Nappez C, Battu S, Beneytout JL. 1996. Trans, trans-2,4-decadienal: cytotoxicity and effect on glutathione level in human erythroleukemia (HEL) cells. Cancer Lett, 99: 115-119.
Okokon JE, Ita BN, Udokpoh AE. 2006. Antimalarial activity of Homaliumletestui.Phytotherapy Res, 20: 949-951.
Okokon JE,Antia BS, Ita BN. 2007. Antidiabetic effects of Homalium Letestui (Flacourtiaceae) in streptozotocin induced diabetic rats.Res J Med Plant,1: 134-138.
Okokon JE, Dar A, Choudhary MI. 2012. Chemical constituents and analgesic activity of Telfaria occidentalis. Phytopharmacology,3: 359-366.
Pachute AP, Tyagi S, Mishra A, Shakya A.,Kumar D, Patel VK. 2011. Preliminary evaluation of anticancer activity of Flacourtia indica Merr. Bot Res Int, 4: 43-47.
Pattnaik S, Subramanyam VR, Bapaji M, Kole CR. 1997. Antibacterial andantifungal activity of aromatic constituents of essential oils. Microbios, 89:39-46.
Pedraza-Chaverri J, Cardenas-Rodriguez N, Orozco- Ibarra M, Perez-Rojas JM. 2008. Medicinal properties of mangosteen (Garcinia mangostana). Food Chem Toxicol, 46: 3227-3239.
Raja Rajeswari N, RamaLakshmi S, Muthuchelian K. 2011. GC-MS analysis of bioactive components from the ethanolic leaf extract of Canthium dicoccum (Gaertn.) Teijsm & Binn.J Chem Pharm Res,3:792-798.
Salvador MJ, Carvalho J, Wisniewski A, Kassuya C, Santos EP, Riva D, Stefanello ME. 2011. Chemical composition and cytotoxic activity of the essential oil from the leaves of Casearia Lasiophylla. Brazilian J Pharmacognosy,21: 864-868.
Setzer WN, Stokes SL, Penton AF, Takaku S, Haber WA, Hansell E, Caffrey CR, McKerrow JH. 2007. Cruzain Inhibitory Activity of Leaf Essential Oils of Neotropical Lauraceae and Essential Oil Components. Nat Prod Commun, 2: 1203-1210.
Silva SL, Chaar J, Figueiredo P, Yano T. 2008. Cytotoxic evaluation of essential oil from Casearia sylvestris Sw on human cancer cells and erythrocytes. Acta Amazonica, 38: 107-112
Soobrattee MA, Neergheen VS, Luximon-Ramma A, Aruoma OI, Bahorun T, 2005. Phenolics as potential antioxidant therapeutic agents: mechanism and actions. Mutat Res, 579: 200-213.
Suksamrarn S, Komutiban O, Ratananukul P, Chimnoi N, Lartpornmatulee N, Suksamrarn A. 2006. Cytotoxic prenylated xanthones from the young fruit of Garcinia mangostana. Chem Pharm Bull, 54: 301-305.
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Tian B, Hua, Y. 2005. Concentration dependence of prooxidant and antioxidant effects of aloin and aloe-emodin on DNA. Food Chem, 91: 413-418.
Tyag SN, Rakshit V, Singh A, Raghvendra P,Saxena A, Patel BD. 2010. In vitro antioxidant activity of methanolic and aqueous extract of Flacourtia indica Merr. Am-Euras J Sci Res, 5: 201-206.
Zhang J, Tao L, Liang Y, Chen L, Mi Y, Zheng L, Wang F,  She Z, Lin Y, To KK, Fu L. 2010. Anthracenedione Derivatives as Anticancer Agents Isolated from Secondary Metabolites of the Mangrove Endophytic Fungi. Mar Drugs, 8: 1469 -1481.