Synergic Effect of Curcuma longa L. Extract with Antimicrobials against Cuban Helicobacter pylori Isolates

Document Type : Original Research

Authors
O. Feliciano 1
Y. Ybalmea 2
A. Yglesias 2
A. Diaz 2
R. Llanes 3
O. Gutierrez 3
1 Research, Diagnostic and Reference Center. Pedro Kouri Tropical Medicine Institute.
2 Department of Research, Laboratories of Biopharmaceuticals and Chemistries Productions (LABIOFAM)
3 Research, Diagnostic and Reference Center. Pedro Kouri Tropical Medicine Institute
10.29252/iem.6.3.165
Abstract
Aims: Helicobacter pylori is a bacterium that colonizes the gastric mucosa and is the main cause of gastritis as well as ulcer and gastric cancer. Due to the clinical significance and international increase in H. pylori multidrug resistance, it is necessary to search for new strategies improving eradication rates. Natural compounds have been demonstrated to have antimicrobial effect and the ability to restore the efficacy of conventional drugs. The objective of this work was to evaluate the antimicrobial effect of the hydroalcoholic extract of Curcuma longa L. (Cu) against H. pylori isolates.

Materials & Methods: The minimum bactericidal concentration of the extract was determined by means of the MTT assay; also, the combination and dose reduction indices for levofloxacin (LVX), metronidazole (MET), and rifampicin (RIF) antimicrobial agents were determined by checkerboard format. Interaction analysis was performed using the CompuSyn program.

Findings: About 90% of H. pylori isolates studied (9/10) were sensitive to the hydroalcoholic extract. Synergism was observed in more than 50% of Cu-LVX, Cu-MET, and Cu-RIF combinations. Additionally, for different concentrations of the extract, reduction rates in antimicrobial agents were determined to be between 0.5 and 360 times.

Conclusions: The hydroalcoholic extract of turmeric showed a good potential to be used as an antimicrobial agent in the treatment of H. pylori infection, either alone or in combination with antibiotics used, suggesting the renewal of the effectiveness of conventional antimicrobials in reducing the phenomenon of antimicrobial resistance.

Keywords

Subjects

1. Kanna S, Maradey-Romero C, Fass R. Diagnostic tests for Helicobacter pylori. Gastroenterol Endosc News. 2013;11(Special edition):51-8.
2. Mahady GB, Pendland SL, Yun G, Lu ZZ. Turmerir (Curcuma longa) and curcumin inhibit growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 2002;22(6C):4179-4181.
3. Sarkar A, De R, Mukhopadhyay A. Curcumin as a potential therapeutic candidate for Helicobacter pylori associated diseases. World J Gastroenterol 2016;22(9):2736-2748. DOI: 10.3748/wjg.v22.i9.2736.
4. Otero W, Trespalacios AA, Otero L, Vallejo M, Torres M, Pardo R, et al. Guía práctica para el diagnóstico y tratamiento de la infección por Helicobacter pylori en adultos. Rev Col Gastroenterol 2015;30(1):17-33.
5. Fu L. Diagnóstico y resistencia antimicrobiana de Helicobacter pylori. Instituto de Gastroenterología, abril-septiembre 2018 [tesis de maestría]. Instituto de Medicina Tropical Pedro Kouri; 2018.
6. Kwiecien S, Magierowski M, Majka J, Ptak-Belowska A, Wojcik D, Sliwowski Z et al. Curcumin: A Potent Protectant against Esophageal and Gastric Disorders. Int. J. Mol. Sci. 2019;20:1477.
7. Regulación M 85-16. Requisitos para la licencia sanitaria de fabricación y comercialización de los preparados vegetales y medicamentos naturales en los centros de producción local. Cuba. MINSAP-CECMED. Abril 2016; páginas 1-14.
8. González RA, Vistel M. Caracterización fitoquímica de la Curcuma longa L. Rev. Cubana Quím. 2015;27(1):9-18.
9. Fernández A, Mendiola J, Acuña D, Caballero Y, Scull R, Gutiérrez Y. Actividad antimalárica y citotoxicidad de extractos hidroalcohólicos de seis especies de plantas usadas en la medicina tradicional cubana. Rev Cub Med Trop 2011;63(1):52-7.
10. Leyva M, Tacaronte JE, Marqueti MC, Scull R, Montada D, Rodriguez Y. Actividad insecticida de aceites esenciales de plantas en larvas de Aedes aegypti (díptera: Culicidae). Rev cub Med Trop 2008;60(1):78-82.
11. Llanes R, Feliciano O, Gutiérrez O, Gala A, Valdés L, Capó V, et al. Nuevos conocimientos sobre el diagnóstico y la resistencia antimicrobiana de Helicobacter pylori en Cuba. Revista Anales de la Academia de Ciencias de Cuba 2014;2(4):1-9.
12. Picazo JJ. Métodos básicos para el estudio de la sensibilidad a los antimicrobianos. Procedimientos de microbiología clínica 2000:1-54. Libro
13. Chou TC. Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies. Pharmacol Rev 2006;58(3):621–681.
14. Aşkar Ş, Deveboynu Şn. Investigation of In-Vitro Antibacterial Activity of Curcuma longa Commercial Extract. Eurasian JHS 2018;1(1):1-6.
15. Cos P, Vlietinck AJ, Bander Berghe D, Maes L. Anti-infective potential of natural products: How to develop a stronger in vitro proof-of-concept. Journal of Ethnopharmacology 2006;106:290–302.
16. Gibbons S. Phytochemicals for Bacterial Resistance – Strengths, Weaknesses and Opportunities. Planta Med 2008;74:594–602
17. Rai D, Singh JK, Roy N, Panda D. Curcumin inhibits FtsZ assembly: an attractive mechanism for its antibacterial activity. Biochem J 2008;410(1):147-155.
18. Patil TR, Patil ST, Patil S, Patil A. Effect of Non Antibiotic Antimicrobial Curcuma Longa on Helicobacter Pylori Infection. Int J Pharmacogn Chinese Med 2018,2(5):000150.
19. Mahady GB, Pendland SL, Yun G, Lu ZZ. Turmerir (Curcuma longa) and curcumin inhibit growth of Helicobacter pylori, a group 1 carcinogen. Anticancer Res 2002;22(6C):4179-4181
20. Mun SH, Joung DK, Kim YS, Kang OH, Kim SB, Seo YS et al. Synergistic antibacterial effect of curcumin against methicillin-resistant Staphylococcus aureus. Phytomedicine 2013;20: 714-718.
21. Maliziaa T, Tejadaa M, Marchettib F, Favinib P, Pizzarellic G, Campaa M. Synergic interactions of macrolides and proton-pump inhibitors against Helicobacter pylori: a comparative in-vitro study. Journal of Antimicrobial Chemotherapy 1998;41(Suppl. B):29.
22. Cheng A, Sheng WH, Liou JM, Wang HP, Wu MS, Lin JT. Comparative in vitro antimicrobial susceptibility and synergistic activity of antimicrobial combination against Helicobacter pylori isolates in Taiwan. Journal of Microbiology, Inmunology and Infection 2015;48:72-79.
23. Ranjbar R, Mohammadi A. Synergistic effects of combined curcumin and antibiotic in ameliorating an animal model of Helicobacter pylori infection. Biomedical Research 2018;29(8):1702-1707.
24. Sasidharan NK, Ravikumar S, Jacob J, Nambisan B. In Vitro Synergistic Effect of Curcumin in Combination with Third Generation Cephalosporins against Bacteria Associated with Infectious Diarrhea. Biomed Res Int. vol 2014; 561456, 8 pages.
25. Rangel-Castañeda I, Cruz-Lozano J, Zermeño-Ruiz M, Cortes-Zarate R, Hernández-Hernández L, Tapia-Pastrana G. Drug Susceptibility Testing and Synergistic Antibacterial Activity of Curcumin with Antibiotics against Enterotoxigenic Escherichia coli. Antibiotics 2019;8(43).
26. Judaki A, Rahmani A, Feizi J, Asadollahi K, Hafezi M. Curcumin in combination with triple therapy regimes ameliorates oxidative stress and histopathologic changes in chronic gastritis–associated Helicobacter pylori infection. Arq Gastroenterol 2017;54(3):177-182.
27. Hassana S, Berchova K, Majerova M, Pokorna M, Svajdlenkaa E. In vitro synergistic effect of Hibiscus sabdariffa aqueous extract in combination with standard antibiotics against Helicobacter pylori clinical isolates. Pharmaceutical Biology 2016;54(9)1736–1740.
28. Lodovico S, Napoli E, Campli E, Fermo P, Gentile D, Ruberto G. Pistacia vera L. oleoresin and levofloxacin is a synergistic combination against resistant Helicobacter pylori strains. Scientific Reports 2019;9:4646.
29. Zullo V, Hassan C, Giorgio F, Rosania R, Ierardi E. Mechanisms of Helicobacter pylori antibiotic resistance: An updated appraisal. World J Gastrointest Pathophysiol 2011;2:35-41.
Infection Epidemiology and Microbiology
Volume 6, Issue 3
August 2020
Pages 165-175