Welcome to International Network for Natural Sciences | INNSpub

Synergistic antimicrobial activity of black seed (Nigella sativa) with ciprofloxacin against multidrug resistant Salmonella typhimurium

Research Paper | December 1, 2020

| Download 9

Fazal-ur-Rehman, Abdul Hannan, Fiaz Ahmad, Maryam Khan, Saba Shamim

Key Words:

Int. J. Biosci.17( 6), 328-337, December 2020

DOI: http://dx.doi.org/10.12692/ijb/17.6.328-337


IJB 2020 [Generate Certificate]


Typhoid fever is an important cause of disease and death in south east and south central Asia.  Itis becoming resistant to more potent drugs such as fluoroquinolones and third generation cephalosporins. It was a descriptive experimental study in which preserved bacterial isolates of multi drug resistant (MDR) Salmonella typhimuirum (n=49) were used. The methods used for antibacterial effect was agar well diffusion method and disc diffusion method for black seed extract and ciprofloxacin respectively, agar dilution method for minimum inhibitory concentration (MIC), and microtitre checkerboard method for synergism. The antibacterial effect of ethanolic black seed extract by agar well diffusion method did not show any inhibition zone at 100 % concentration v/v. By agar dilution method, the MIC of ciprofloxacin was 0.25 µg/ml, 0.5 µg/ml and 1 µg/ml for 6 isolates (12 %), 2 µg/ml for 20 isolates (40 %), 4 µg/ml for 48 isolates (97 %), 8 µg/ml for 49 isolates (100 %). The extract inhibited 23 isolates (46 %) at 64 % concentration which was the highest concentration used by agar dilution method. The ciprofloxacin and ethanolic black seed extract exhibited synergism against two S. typhimurium isolates, indifference against 45 tested isolates, and not determinable against 2 isolates. A newly tried combination showed to be synergistic against two isolates, indifferent against 45 tested MDR S. typhimurium isolates and not determinable (ND) against 2 isolates.


Copyright © 2020
By Authors and International Network for
Natural Sciences (INNSPUB)
This article is published under the terms of the Creative
Commons Attribution Liscense 4.0

Synergistic antimicrobial activity of black seed (Nigella sativa) with ciprofloxacin against multidrug resistant Salmonella typhimurium

Ababutain IM. 2011. Antimicrobial activity of ethanolic extracts from some medicinal plant. Australian Journal of Basic and Applied Sciences 5(11), 678-683.

Amina B, Rachida A. 2013. Molecular composition and antibacterial effect of essential oil of Nigella sativa. African Journal of Biotechnology 12(20), 3006-3011. http://dx.doi.org/10.5897/AJB2013.12070

Abdelmalek M, Moussa A, Noureddine D, Saad A. 2012. Antibacterial activity of honey alone and in combination with Nigella sativa seeds against Pseudomonas aeruginosa infection. Asian Pacific Journal of Tropical Disease 2, S428-S430. http://dx.doi.org/10.1016/S2222-1808(12)60197-2

Aburjai T, Darwish RM, Al-Khalil S, Mahafzah A, Al-Abbadi A. 2001. Screening of antibiotic resistant inhibitors from local plant materials against two different strains of Pseudomonas aeruginosa. Journal of Ethnopharmacology 76, 39-44. http://dx.doi.org/10.1016/S0378-8741(01)00206-9

Ali NH, Kazmi SU, Faizi S. 2007. Activity of synergistic combination Amoxy-cassia against Salmonella. Pakistan Journal of Pharmaceutical Sciences 20, 140-145.

Capoor MR, Nair D. 2010. Quinolone and cephalosporin resistance in enteric fever. Journal of Global  Infectious Diseases 2(3), 258-262. http://dx.doi.org/10.4103/0974-777X.68529

Cheesman MJ, Ilanko A, Blonk B, Cock IE. 2017. Developing new antimicrobial therapies: are synergistic combinations of plant extracts/compounds with conventional antibiotics the solution? Pharmacognosy Reviews 11(22), 57–72. http://dx.doi.org/10.4103/phrev.phrev_21_17

Cooke FJ, Wain J. 2004. The emergence of antibiotic resistance in typhoid fever. Travel Medicine and Infectious Disease 2, 67-74. http://dx.doi.org/10.1016/j.tmaid.2004.04.005

Develi S, Evran B, Kalaz EB, Koḉak-Toker N, Erata GÖ. 2014. Protective effect of Nigella sativa oil against binge ethanol-induced oxidative stress and liver injury in rats. Chinese Journal of Natural Medicines 12, 495-499. .http://dx.doi.org/10.1016/S1875-5364(14)60077-7

Dulger B, Gonuz A. 2004. Antimicrobial activity of certain plants used in Turkish traditional medicine. Asian Journal of Plant Sciences 3, 104-107. http://dx.doi.org/10.3923/ajps.2004.104.107

Dyson ZA, Klemm EJ, Palmer S, Dougan G. 2019. Antibiotic resistance and typhoid. Clinical Infectious Diseases 68(2), S165–S170. http://dx.doi.org/10.1093/cid/ciy1111

Gilani AH, Atta-ur-Rahman. 2005. Trends in ethnopharmacology. Journal of Ethnopharmacology 100(1-2), 43-49. http://dx.doi.org/10.1016/j.jep.2005.06.001

Halawani E. 2009. Antibacterial activity of thymoquinone and thymohydroquinone of Nigella sativa L. and their interaction with some antibiotics. Advances in Biological Research 3(5-6), 148-152.

Hannan A, Saleem S, Chaudhary S, Barkaat M, Arshad MU. 2008. Anti bacterial activity of Nigella sativa against clinical isolates of methicillin resistant Staphylococcus aureus. Journal of Ayub Medical College Abbottabad 20, 72-74.

Harish BN, Menezes GA, Sarangapani K, Parija SC. 2008. A case report and review of the literature: ciprofloxacin resistant Salmonella enterica serovar Typhi in India. Journal of Infection in Developing Countries 2(4), 324-327. http://dx.doi.org/10.3855/jidc.229

Hosseinzadeh H, Bazzaz BF, Haghi MM. 2007. Antibacterial activity of total extracts and essential oil of Nigella sativa L. seeds in mice. Pharmacologyonline 2, 429-435.

Hosseinzadeh H, Jaafari MR, Khoel AR, Rahmani M. 2010. Anti-ischemic effect of Nigella sativa L. seed in male rats. Iranian Journal of Pharmaceutical Research 5(1), 53-58. http://dx.doi.org/10.22037/IJPR.2010.653

Hosseinzadeh H, Tafaghodi M, Mosavi MJ, Taghiabadi E. 2013. 2013. Effect of aqueous and ethanolic extracts of Nigella sativa seeds on milk production in rats. Journal of Acupuncture and Meridian Studies 6(1), 18-23. http://dx.doi.org/10.1016/j.jams.2012.07.019

Hu Z-Q, Zhao WH, Yoda Y, Asano N, Hara Y, Shimamura T. 2002. Additive, indifferent and antagonistic effects in combinations of epigallocatechin gallate with 12 non-β-lactam antibiotics against methicillin-resistant  Staphylococcus aureus. Journal of Antimicrobial Chemotherapy 50(6), 1051–1054. http://dx.doi.org/10.1093/jac/dkf250

Islam MH, Ahmad IZ, Salman MT. 2013. Antibacterial activity of Nigella sativa seed in various germination phases on clinical bacterial strains isolated from human patients. E3 Journal of Biotechnology and Pharmaceutical Research 4(1), 8-13.

Kabbashi AS, Garbi MI, El-Badri EO, Dahab MM, Koko WS, Abuzeid N. 2015. In vitro antimicrobial activity of ethanolic seeds extract of Nigella sativa (Linn) in Sudan. African Journal of Microbiology Research 9, 788-792.

Kamal A, Arif JM, Ahmad IZ. 2010. Potential of Nigella sativa L. seed during different phases of germination on inhibition of bacterial growth. E3 Journal of Biotechnology and Pharmaceutical Research 1(1), 009-013.

Kasper MR, Sokhal B, Blair PJ, Wierzba TF, Putnam SD. 2010. Emergence of multidrug-resistant Salmonella enterica serovar Typhi with reduced susceptibility to fluoroquinolones in Cambodia. Diagnostic Microbiology and Infectious Disease 66(2), 207-209. http://dx.doi.org/10.1016/j.diagmicrobio.2009.09.002

Lee J, Jang M, Seo J, Kim G. 2011. Evaluation for antibacterial effects of volatile flavors from Chrysanthemum indicum against food-borne pathogens and food spoilage bacteria. Journal of Food Safety 31, 140-148. http://dx.doi.org/10.1111/j.1745-4565.2010.00277.x

Lusby PE, Coombes AL, Wilkinson JM. 2005. Bactericidal activity of different honeys against pathogenic bacteria. Archives of Medical Research 36, 464-467. http://dx.doi.org/10.1016/j.arcmed.2005.03.038

Manchanda V, Bhalla P, Sethi M, Sharma V. 2006. Treatment of enteric fever in children on the basis of current trends of antimicrobial susceptibility of Salmonella enterica serovar typhi and paratyphi A. Indian Journal of Medical Microbiology 24(2), 101-106. http://dx.doi.org/10.4103/0255-0857.25182.

Martens E, Demain AL. 2017. The antibiotic resistance crisis, with a focus on the United States. The Journal of Antibiotics 70, 520–526. http://dx.doi.org/10.1038/ja.2017.30

Mayer I, Nagy E. 1999. Investigation of the synergic effects of aminoglycoside-fluoroquinolone and third-generation cephalosporin combinations against clinical isolates of Pseudomonas spp. Journal of Antimicrobial Chemotherapy 43, 651-657. http://dx.doi.org/10.1093/jac/43.5.651

Neuzil KM, Pollard AJ, Marfin AA. 2019. Introduction of typhoid conjugate vaccines in Africa and Asia. Clinical Infectious Diseases 68(1), S27-S30. https://dx.doi.org/10.1093/cid/ciy878

Salem ML. 2005. Immunomodulatory and therapeutic properties of the Nigella sativa L. seed. International immunopharmacology 5(13-14), 1749-1770. http://dx.doi.org/10.1016/j.intimp.2005.06.008.

Singh G, Marimuthu P, De Heluani CS, Catalan C. 2005. Chemical constituents and antimicrobial and antioxidant potentials of essential oil and acetone extract of Nigella sativa seeds. Journal of the Science of Food and Agriculture 85, 2297-2306. http://dx.doi.org/10.1002/jsfa.2255

Siriwong S, Teethaisong Y, Thumanu K, Dunkhunthod B, Eumkeb G. 2016. The synergy and mode of action of quercetin plus amoxicillin against amoxicillin-resistant Staphylococcus epidermidis. BMC Pharmacology and Toxicology 17(1), 39-53. http://dx.doi.org/10.1186/s40360-016-0083-8

Tavakkoli A, Ahmadi A, Razavi BM, Hosseinzadeh H. 2017. Black seed (Nigella sativa) and its constituent thymoquinone as an antidote or a protective agent against natural or chemical toxicities. Iranian Journal of Pharmaceutical Research (16), 2-23.

Veloira WG, Domenico P, Lipuma JJ, Davis JM, Gurzenda E, Kazzaa JA. 2003. In vitro activity and synergy of bismuth thiols and tobramycin against Burkholderia cepacia complex. Journal of Antimicrobial Chemotherapy 52, 915-919. http://dx.doi.org/10.1093/jac/dkg471

Visalli MA, Jacobs MR, Appelbaum PC. 1998. Determination of activities of levofloxacin, alone and combined with gentamicin, ceftazidime, cefpirome, and meropenem, against 124 strains of Pseudomonas aeruginosa by checkerboard and time-kill methodology. Antimicrobial Agents and Chemotherapy 42, 953-955.

Wikaningtyas P, Sukandar EY. 2016. The antibacterial activity of selected plants towards resistant bacteria isolated from clinical specimens, Asian Pacific Journal of Tropical Biomedicine 6(1), 16-19. http://dx.doi.org/10.1016/j.apjtb.2015.08.003

Wolfson JS, Hooper DC. 1985. The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrobial Agents and Chemotherapy 28(4), 581-586. http://dx.doi.org10.1128/aac.28.4.581

Yarnell E, Abascal K. 2011. Nigella sativa: holy herb of the middle East. Alternative and Complementary Therapies 17(2), 99-105. http://dx.doi.org/10.1089/act.2011.17203

Yimer EM, Tuem KB, Karim A, Najeeb Ur-Rehman, Anwar F. 2019. Nigella sativa L. (black cumin): a promising natural remedy for wide range of illnesses. Evidence-Based Complementary and Alternative Medicine 2019, 1-16. http://dx.doi.org/10.1155/2019/1528635