Evaluation of pharmacological activities, cytotoxicity and phenolic composition of four Maytenus species used in southern African traditional medicine to treat intestinal infections and diarrhoeal diseases

BMC Complementary and Alternative Medicine

Jacobus N Eloff¹  Lyndy J McGaw¹  Aroke Shahid Ahmed² 

[1]Phytomedicine Programme, Department of Paraclinical Sciences, Faculty of Veterinary Science, University of Pretoria, Private Bag X04, Onderstepoort 0110, South Africa

[2]Permanent address: Federal Institute of Industrial Research, Oshodi, P.M.B 21023, Ikeja, Lagos, Nigeria

关键词: Cytotoxicity;    Diarrhoea;    Infections;    Gastrointestinal tract;    Maytenus;   

Others  :  1229964
DOI  :  10.1186/1472-6882-13-100

 received in 2012-12-10, accepted in 2013-05-10,  发布年份 2013

【 摘 要 】

Background

Microbial infections and resulting inflammation and oxidative stress are common pathogenesis of gastrointestinal tract (GIT) disorders. In South Africa, several species of the genus Maytenus are used in traditional medicine to treat various infectious diseases. Most of the previous work on this genus was focused on nonpolar extracts from the root and bark. In this study, leaf extracts of polar extracts of Maytenus peduncularis, Maytenus procumbens, Maytenus senegalensis and Maytenus undata were evaluated for antimicrobial, anti-inflammatory and antioxidant activities to determine their efficacy as therapeutic agents in GIT disorders.

Methods

Phenolic-enriched leaf extracts and fractions were prepared by extracting with acidified 70% methanol and solvent-solvent fractionation. The activities of the fractions against Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus faecalis as well as clinical isolates of Aspergillus fumigatus, Candida albicans and Cryptococcus neoformans were determined using a serial microplate dilution method. Antioxidant activities were determined using 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis(3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), hydroxyl (OH) radical scavenging and linoleic acid peroxidation inhibitory assays. The phenolic composition as well as the cytotoxicity against Vero cell lines of the crude extracts was evaluated using various standard protocols.

Results

The antimicrobial activities were concentrated in the non-polar fractions of hexane, dichloromethane and ethyl acetate (MICs 19–312 μg/ml). The crude extracts and polar fractions (butanol and water) had moderate to poor antimicrobial activity (MICs 312 to above 2500 μg/ml). The crude extracts and polar fractions had good antioxidant activity (EC₅₀ values varied from 1.22 to 607 μg/ml, 1.71 to 312 μg/ml and 23 to 284 μg/ml for DPPH, ABTS and OH respectively. Linoleic acid peroxidation inhibition EC₅₀ values of the crude extracts ranged between 27 and 39 μg/ml with relatively low toxicity against Vero cell lines (IC₅₀ values 87 to 187 μg/ml). Fractionation of a crude extract with low activity could lead to fractions with more potent activity.

Conclusion

This study justifies the traditional use of leaf crude extracts and fractions from these four plants to remedy gastrointestinal disorders resulting from infection, inflammation and oxidative stress complications. The study also provides rationale for the use of leaf extracts with same beneficial effects in place of unsustainable root and bark harvest.

【 授权许可】

   
2013 Ahmed et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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【 参考文献 】

• [1]Schulzke J-D, Troger H, Amasheh M: Disorders of intestinal secretion and absorption. Best Practice & Res Clin Gastroenter 2009, 23:395-406.
• [2]Sakunpak A, Panichayupakaranant P: Antibacterial activity of Thai edible plants against gastrointestinal pathogenic bacteria and isolation of a new broad spectrum antibacterial polyisoprenylated benzophenone, chamuangone. Food Chem 2012, 130:826-831.
• [3]Quigley EMM, Quera R: Small Intestinal Bacterial Overgrowth: Roles of Antibiotics, Prebiotics, and Probiotics. Gastroenter 2006, 130:S78-S90.
• [4]Kelly P: Infectious diarrhoea. Medicine 2011, 39(4):201-206.
• [5]Michelangeli F, Ruiz MC: Physiology and pathology of the gut in relation to viral diarrhoea. In Viral gastroenteritis. Edited by Desselberger U, Gray J. Amsterdam: Elservier Science BV; 2003:23-50.
• [6]Thapar N, Sanderson IR: Diarrhoea in children: an interface between developing and developed countries. Lancet 2004, 363:641-53.
• [7]Petri WA Jr, Miller M, Binder HJ, Levine MM, Dillingham R, Guerrant RL: Enteric infections, diarrhea, and their impact on function and development. J Clin Invest 2008, 118:1277-1290.
• [8]Cello JP, Day LW: Idiopathic AIDS enteropathy and treatment of gastrointestinal opportunistic pathogens. Gastroenter 2009, 136:1952-65.
• [9]WHO, World Health Report 2003: World Health Organization. Geneva, Switzerland: WHO Publications Office; 2003:1-50.
• [10]Pavlick KP, Laroux FS, Fuseler J, Wolf RE, Gray L, Hoffman J, Grisham MB: Role of reactive metabolites of oxygen and nitrogen in inflammatory bowel disease. Free Radic Biol Med 2002, 33(3):311-322.
• [11]Sebastian E, Winter SE, Keestra AM, Tsolis RM, Baumler AJ: The Blessings and Curses of Intestinal Inflammation. Cell Host Microbe 2010, 8:36-42.
• [12]Gorowara S, Sapru S, Ganguly NK: Role of intracellular second messengers and ROS in the pathophysiology of V. cholerae 0139 treated rabbit ileum. Biochim Biophys Acta 1998, 1407:21-30.
• [13]Grisham MB, Gaginella TS, von Ritter C, Tamai H, Be RM, Granger DN: Effects of neutrophil-derived oxidants on intestinal permeability, electrolyte transport, and epithelial cell viability. Inflammation 1990, 14:531-42.
• [14]Segui J, Gironella M, Sans M, Granell S, Gil F, Gimeno M: Superoxide dismutase ameliorates TNBS-induced colitis by reducing oxidative stress, adhesion molecule expression, and leukocyte recruitment into the inflamed intestine. J Leukoc Bio 2004, 76:537-44.
• [15]Anh NT, Cam PD, Dalsgaard A: Antimicrobial resistance of Shigella spp isolated from diarrhoeal patients between 1989 and 1998 in Vietnam. Southeast Asian J Tropical Medical Public Health 2001, 32:856-862.
• [16]Dimitrios PK, Russell EL: Antifungal drug resistance of pathogenic fungi. Lancet 2002, 359:1135-1144.
• [17]Periska T, Murad L, Decy S, Nunung M, Shinta K, Wasis S, Cyrus HS, Narain P, James RC, William KA, James HB, Andrew LC, Buhari AO: Antimicrobial resistance of bacterial pathogens associated with diarrhoeal patients in Indonesia. Amer J Tropical Medicine and Hygiene 2003, 68:666-670.
• [18]Chambers JR, Gong J: The intestinal microbiota and its modulation for Salmonella control in chickens. Food Res Int 2011, 44:3149-3159.
• [19]Bhat RB, Jacobs TV: Traditional herbal medicine in Transkei. J Ethnopharmacol 1995, 48:7-12.
• [20]Watt JM, Breyer-Brandwijk MG: The Medicinal and Poisonous Plants of Southern and Eastern Africa. 2nd edition. London: Livingstone; 1962.
• [21]Gonzalez AG, Bazzocchi IL, Moujir L, Jimenez IA: Ethnobotanical uses of Celastraceae: Bioactive metabolites studies. Nat Prod Chem 2000, 23:649-738.
• [22]Momtaz S, Hussein AA, Ostad SN, Abdollahi M, Lall N: Growth inhibition and induction of apoptosis in human cancerous HeLa cells by Maytenus procumbens. Food Chem Toxicol 2013, 51:38-45.
• [23]Muthaura CN, Rukunga GM, Chabra SC, Mungai GM, Njagi ENM: Traditional phytotherapy of some remedies used in treatment of malaria in Meru district of Kenya. S Afr J Bot 2007, 73:402-411.
• [24]da Silva G, Tamia M, Rocha J, Serrona R, Gomes ET, Sepodea B, Silva O: In vivo Anti-inflammatory effect and toxicological screening of Maytenus heterophylla and Maytenus senegalensis extracts. Hum Exp Toxicol 2010, 30(7):693-700.
• [25]Matu EN, van Staden J: Antibacterial and anti-inflammatory activity of some plants used for medical purposes in Kenya. J Ethnopharmacol 2003, 87:35-41.
• [26]Koné WM, Atindehou KK: Ethnobotanical inventory of medicinal plants used in traditional veterinary medicine in Northern Côte d’Ivoire (West Africa). S Afri J Bot 2008, 74:76-84.
• [27]McGaw LJ, Eloff JN: Ethnoveterinary use of Southern African plants and scientific evaluation of their medicinal properties. J Ethnopharmacol 2008, 119:559-574.
• [28]Naczk M, Shahidi F: Extraction and analysis of phenolics in food. J Chromatography A 2004, 1054:95-111.
• [29]Butler KM: Enterococcal Infection in Children. Seminar Pediat Infect Dis 2006, 17:128-139.
• [30]Balaban N, Rasooly A: Staphylococcal enterotoxins. Int J Food Microbiol 2000, 61:1-10.
• [31]Nataro JP, Kaper JB: Diarrhoeagenic Escherichia coli. Clin Microbiol Rev 1998, 11:142-201.
• [32]Garbati MA, Alasmari FA, Al-Tannir MA, Tleyjeh IM: The role of combination antifungal therapy in the treatment of invasive aspergillosis: a systematic review. Int J Infect Dis 2012, 16:e76-e81.
• [33]Jose RJ, Brown JS: Opportunistic and fungal infections of the lung. Medicine 2012, 40(6):335-339.
• [34]Zipfel PF, Skerka C, Kupka D, Luo S: Immune escape of the human facultative pathogenic yeast Candida albicans: The many faces of the Candida Pra1 protein. Int J Med Microb 2011, 301:423-430.
• [35]Talwar P, Chakrabarti A, Chawla A, Mehta S, Walia BNS, Kumar L, Chugh KS: Fundal diarrhoea: Association of different fungi and seasonal variation in incidence. Mycopathologia 1990, 110:101-105.
• [36]Franquet T, Giménez A, Hidalgo A: Imaging of opportunistic fungal infections in immunocompromised patient. Eur J Radiol 2004, 51:130-138.
• [37]Goldenberg S, Price N: Opportunistic fungal lung infections. Medicine 2008, 36(6):295-299.
• [38]Othman M, Loh HS, Wiart C, Khoo TJ, Lim KH, Ting KN: Optimal methods for evaluating antimicrobial activities from plant extracts. J Microbiol Methods 2011, 84:161-166.
• [39]Eloff JN: A sensitive and quick microplate method to determine the minimal inhibitory concentration of plant extracts for bacteria. Planta Med 1998, 64:711-713.
• [40]Brand-Williams W, Cuvelier ME, Berset C: Use of a free radical method to evaluate antioxidant activity. Lebensmittel Wissenschaftund Technologie 1995, 28:25-30.
• [41]Masoko P, Picard J, Eloff JN: The antifungal activities of twenty-four Southern Africa Combretum species (Combretaceae). S Afr J Bot 2007, 73:173-183.
• [42]Re R, Pellegrini N, Proteggente A, Pannala A, Yang M, Rice-Evans C: Antioxidant activity applying an improved ABTS radical cation decolourization assay. Free Radic Biol Med 1999, 26(9/10):1231-1237.
• [43]Smirnoff N, Cumbes OJ: Hydroxyl radical scavenging activity of compatible solutes. Phytochemistry 1999, 28:1057-1060.
• [44]Xanthopoulou MN, Fragopoulou E, Kalathara K, Nomikos T, Karantonis HC, Antonopoulou S: Antioxidant and anti-inflammatory activity of red and white wine extracts. Food Chem 2010, 120:665-672.
• [45]Xun S, Tian Jingdong T, Zhaonan Z, Xinyuan L: Chemiluminescence study on the peroxidation of linoleic acid initiated by the reaction of ferrous iron with hydrogen peroxide. Biophys Chem 1991, 40:161-167.
• [46]Mosmann T: Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983, 65:55-63.
• [47]Makkar HPS: Quantification of tannins in tree and foliage- a laboratory manual. The Netherland: Klumer Academic Press Dordrecht; 2003.
• [48]Heimler D, Vignolini P, Dini MD, Vincieri FF, Romani A: Antiradical activity and polyphenol composition of local Brassicaceae edible varieties. Food Chemy 2006, 99:464-469.
• [49]Vermerris W, Nicholson R: Phenolic Compounds Biochemistry. New York: Publisher Springer; 2006:151-196.
• [50]Abdel-Hameed ESS: Total phenolic contents and free radical scavenging activity of certain Egyptian Ficus species leaf samples. Food Chem 2009, 114(4):1271-1277.
• [51]Lyckander IM, Malterud KE: Lipophilic flavonoids from Orthosiphon spicatus as inhibitors of 15-lipoxygenase. Acta Pharm Nord 1992, 4:159-166.
• [52]Naik GH, Priyadarsini KI, Hari M: Free radical scavenging reactions and phytochemical analysis of triphala, an ayurvedic formulation. Curr Sci 2006, 90:1100-1105.
• [53]Zirihi GN, Mambu L, Guede-Guina F, Bodo B, Grellier P: In vitro antiplasmodial activity and cytotoxicity of 33 West African plants used for treatment of malaria. J Ethnopharmacol 2005, 98:281-285.
• [54]Marcos LA, Dupont HL: Advances in defining aetiology and new therapeutic approaches in acute diarrhea. J Infect 2007, 55:385-393.
• [55]Doughari JH, El-mahmood AM, Tyoyina I: Antimicrobial activity of leaf extracts of Senna obtusufolia L. Afr J Pharm Pharmacol 2008, 2:07-013.
• [56]Sharma A, Patel VK, Rawat S, Ramteke P, Verma R: Identification of antibacterial component of some Indian medicinal plants against Klebsiella pneumoniae. Int J Pharm Pharmaceut Sci 2010, 2:123-127.
• [57]Agarwal AK, Singh M, Gupta N, Saxena R, Puri A, Verma AK, Saxena RP, Dubey CB, Saxena KC: Management of giardiasis by an immunomodulatory herbal drug Pippali rassayana. J Ethnopharmacol 1994, 44:143-146.
• [58]Agrawal AK, Tripathi DM, Sahai R, Gupta N, Saxena RP, Puri A, Singh M, Misra RN, Dubey CB, Saxena KC: Management of giardiasis by a herbal drug ‘Pippali rasayana’: a clinical study. J Ethnopharmacol 1997, 56:233-236.
• [59]Chen JC, Chang YS, Wu SL, Chao DC, Chang CS, Li CC, Ho TY, Hsiang CY: Inhibition of Escherichia coli heat-labile enterotoxin-induced diarrhea by Chaenomeles speciosa. J Ethnopharmacol 2007, 113:233-239.
• [60]Bakker-Woudenberg IAJM, van Vianen W, van Soolingen D, Verbrugh HA, van Agtmael MA: Antimycobacterial agents differ with respect to their bacteriostatic versus bactericidal activities in relation to time of exposure, mycobacterial growth phase, and their use in combination. Antimicrob Agents Chemother 2005, 49:2387-2398.
• [61]Lindsey KL, Budesinsky M, Kohout L, van Stade J: Antibacterial activity of maytenoic acid isolated from the root-bark of Maytenus senegalensis (Lam.) Exell. S Afr J Bot 2006, 72:473-477.
• [62]Khalid SA, Friedrichsen GM, Christensen SB, El Tahir A, Satti GM: Isolation and characterization of pristimerin as the antiplasmodial and antileishmanial agent of Maytenus senegalensis (Lam.) Exell. ARKIVOC 2007, ix:129-134.
• [63]Kakkar P, Mehrotra S, Viswanathan PN: Interrelation of active oxygen species, membrane damage and altered calcium functions. Molecular cell Biochem 1992, 111(1–2):11-15.
• [64]Esterbauer H, Schaur RJ, Zollner H: Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. Free Radic Biol Med 1991, 11:81-128.
• [65]Stables MJ, Gilroy DW: Old and new generation lipid mediators in acute inflammation and resolution. Prog Lipid Res 2011, 50:35-51.
• [66]Gaginella ST, Kachur JF, Tamai H, Kershavarzian A: Reactive oxygen and Nitrogen metabolites as mediators of Secretory Diarrhea. Gastroenter 1995, 109:2019-2028.
• [67]Doughari JH: Antimicrobial activity of Tamarindus indica Linn. Trop J Pharmaceut Res 2006, 5:597-603.
• [68]Rackova L, Oblozinsky M, Kostalova D, Kettmann V, Bezakova L: Free radical scavenging activity and lipoxygenase inhibition of Mahonia aquifolium extract and isoquinoline alkaloids. J inflammation 2007, 4:15. BioMed Central Full Text
• [69]Muhammed I, El-Sayed KA, Mossa JS, Al-Said MS, El-Feraly FS, Clark AM, Hufford CD, Oh S, Mayer AMS: Bioactive 12-Olaenene triterpene and secotriterpene acids from Maytenus undata. J Nat Prod 2000, 63:605-610.
• [70]Bruins MJ, Cermak R, Kiers JL, van der Meulen J, van Amelsvoort JM, van Klinken BJ: In vivo and in vitro effects of tea extracts on enterotoxigenic Escherichia coli-induced intestinal fluid loss in animal models. J Paediat, Gastroenter Nutr 2006, 43:459-469.