BERBERINE HYDROCHLORIDE COULD PROVE TO BE A PROMISING BULLET AGAINST CLOSTRIDIUM DIFFICILE INFECTION: A PRELIMINARY STUDY FROM SOUTH INDIA
Keywords:Berberine hydrochloride, Clostridium difficile, Clostridium difficile infection, Diarrhea, Minimum inhibitory concentrations, Pulsed-field gel electrophoresis
Objective: Recurrent Clostridium difficile infection (CDI) and the emergence of strains with reduced susceptibility to metronidazole and vancomycin
warrants alternative therapy. Hence, we tested the potential efficacy of the natural compound berberine hydrochloride (BBRHCl) against toxigenic
Methods: Three representative polymerase chain reaction confirmed, toxin-positive strains were included in the study. Pulsed-field gel electrophoresis
(PFGE) profile and antibiogram of the strains were analyzed along with 10 other toxin positive isolates. Efficacy of BBRHCl against toxigenic C. difficile
was determined using agar diffusion by punch well method.
Results: PFGE grouped the test strains into three clusters with unique susceptibility pattern toward standard antibiotics. BBRHCl was efficacious
against the test strains at a concentration ranging between 6.25 Î¼g/ml and 10 mg/ml. BBRHCl's breakpoint point inhibitory zone diameter was
equivalent (p<0.001) to the epidemiological cutoff values for teicoplanin, vancomycin and 2% black seed oil. Although the predicted concentration of
BBRHCl for breakpoint zone diameter equivalent to European Committee on Antimicrobial Susceptibility Testing's epidemiological cutoff value for
metronidazole was observed to fall outside the tested concentration range; it was still within the safe dosage for humans.
Conclusion: The present study is promising in considering BBRHCl as a potent substitute or adjunct not only for metronidazole, vancomycin and
teicoplanin but also for natural compounds like 2% black seed oil for managing resistant cases of CDI. Owing to BBRHCl's direct antibacterial and antiinflammatory
action, further investigations will aid in the proper characterization of the therapeutic effects of similar plant compounds, to develop
safe and effective drugs against the epidemiological outbreak of CDI.
Lv Z, Peng G, Liu W, Xu H, Su J. Berberine blocks the relapseof clostridium difficile infection in C57BL/6 mice afterstandard vancomycin treatment. Antimicrob Agents Chemother2015;59(7):3726-35.
Yan F, Wang L, Shi Y, Cao H, Liu L, Washington MK, et al. Berberinepromotes recovery of colitis and inhibits inflammatory responses incolonic macrophages and epithelial cells in DSS-treated mice. Am JPhysiol Gastrointest Liver Physiol 2012;302(5):G504-14.
Sharanappa R, Vidyasagar GM. Plant profile, phytochemistry andpharmacology of Argemone mexicana Linn: A review. Int J PharmPharm Sci 2014;6(7):45-53.
Sack RB, Froehlich JL. Berberine inhibits intestinal secretory responseof vibrio cholerae and Escherichia coli enterotoxins. Infect Immun1982;35(2):471-5.
Tan W, Li Y, Chen M, Wang Y. Berberine hydrochloride: Anticanceractivity and nanoparticulate delivery system. Int J Nanomedicine2011;6:1773-7.
Remppis A, Bea F, Greten HJ, Buttler A, Wang H, Zhou Q, et al.Rhizoma coptidis inhibits LPS-induced MCP-1/CCL2 production inmurine macrophages via an AP-1 and NFkappaB-dependent pathway.Mediators Inflamm 2010;2010:194896.
Liu F, Liang HL, Xu KH, Tong LL, Tang B. Supramolecular interactionof ethylenediamine linked beta-cyclodextrin dimer and berberinehydrochloride by spectrofluorimetry and its analytical application.Talanta 2007;74(1):140-5.
Pulse Net, Centre for Disease Control and Prevention (CDC). One-Day(24-26 h) Standardized Laboratory Protocol for Molecular Subtypingof Campylobacter jejuni by Pulsed Field Gel-Electrophoresis (PFGE).Atlanta: CDC; n.d. Available from: http://www.cdc.gov/pulsenet/protocols/campy_protocol.pdf. [Last cited on 2014 Mar 01].
Chakraborty R, Ballal M, Prabhu MM, Hande MH, Pazhani GP,Ramamurthy T. Characterization of clostridium difficile isolated fromdiarrheal patients in a tertiary-care hospital, Karnataka, South India. SAsian J Trop Med Public Health 2016;47(6):1221-30.
Schwalbe R, Steele-Moore L, Goodwin AC, editors. AntimicrobialSusceptibility Testing Protocols. New York: CRC Press; 2007.
CLSI. Methods for Antimicrobial Susceptibility Testing of AnaerobicBacteria; Approved Standard, CLSI Document M11-A7. 7th ed. Wayne,Pennsylvania: Clinical and Laboratory Standards Institute; 2007.
Aljarallah KM. Inhibition of clostridium difficile by natural herbalextracts. J Taibah Univ Med Sci 2016;11:427-31.
Erikstrup LT, Danielsen TK, Hall V, Olsen KE, Kristensen B,Kahlmeter G, et al. Antimicrobial susceptibility testing of clostridiumdifficile using eucast epidemiological cut-off values and disk diffusioncorrelates. Clin Microbiol Infect 2012;18(8):E266-72.
Fraga EG, Nicodemo AC, Sampaio JL. Antimicrobial susceptibility ofBrazilian clostridium difficile strains determined by agar dilution anddisk diffusion. Braz J Infect Dis 2016;20(5):476-81.
Tenover FC, Arbeit RD, Goering RV, Mickelsen PA, Murray BE,Persing DH, et al. Interpreting chromosomal DNA restriction patternsproduced by pulsed-field gel electrophoresis: Criteria for bacterialstrain typing. J Clin Microbiol 1995;33(9):2233-9.
Janezic S, Rupnik M. Molecular typing methods for clostridiumdifficile: Pulsed-field gel electrophoresis and PCR ribotyping. MethodsMol Biol 2010;646:55-65.
Yin SH, Du YQ, Liu B. Clinical study on acupuncture combinedwith medication in restoration of gastrointestinal functions forpostoperative patients with gastric cancer. Chin Acupunct Moxibustion2009;29:459-62.
Hu Y, Ma Y, Wang J, Zhu ZH. Early enteral infusion of traditionalChinese medicine preparation can effectively promote the recovery ofgastrointestinal function after esophageal cancer surgery. J Thorac Dis2011;3(4):249-54.
Nishimura N, Naora K, Hirano H, Iwamoto K. Effects of sho-saikoto(xiao chai hu tang), a Chinese traditional medicine, on the gastricfunction and absorption of tolbutamide in rats. Yakugaku Zasshi2001;121(2):153-9.
Wang JJ, Wang WH, Ruan XM. Effect of abdominal needling in treatingpost-cardio surgical operational gastrointestinal dysfunction. ZhongguoZhong Xi Yi Jie He Za Zhi 2008;28(4):310-3.
Ge HX, Xu CP, Chu LL, Yang XY, Liu K. Effects of injecting traditionalChinese herbs via nasojejunal tube on gastrointestinal recoveryfollowing esophageal cancer surgery. J Nurs Sci 2011;26:4-6.22. Brown D. Antibiotic resistance breakers: Can repurposeddrugs fill the antibiotic discovery void? Nat Rev Drug Discov2015;14(12):821-32.
Spigaglia P. Recent advances in the understanding of antibioticresistance in clostridium difficile infection. Ther Adv Infect Dis2016;3(1):23-42.
Kheir MM, Wang Y, Hua L, Hu J, Li L, Lei F, et al. Acute toxicity ofberberine and its correlation with the blood concentration in mice. FoodChem Toxicol 2010;48(4):1105-10.
Wang S, Setlow B, Setlow P, Li YQ. Uptake and levels of the antibioticberberine in individual dormant and germinating clostridium difficile and Bacillus cereus spores as measured by laser tweezers Ramanspectroscopy. J Antimicrob Chemother 2016;71(6):1540-6.
FehÃ©r C, Soriano A, Mensa J. A review of experimental and offlabeltherapies for clostridium difficile infection. Infect Dis Ther2017;6(1):1-35.
Menees S, Saad R, Chey WD. Agents that act luminally to treat Diarrhoeaand constipation. Nat Rev Gastroenterol Hepatol 2012;9(11):661-74.
Mehta J, Jandaik SU. Evaluation of phytochemicals and synergisticinteraction between plant extracts and antibiotics for efflux pumpinhibitory activity against Salmonella typhimurium strains. Int J PharmPharm Sci 2016;8(10):217-23.
Upadhyay A, Mooyottu S, Yin H, Nair MS, Bhattaram V,Venkitanarayanan K. Inhibiting microbial toxins using plant-derivedcompounds and plant extracts. Medicines 2015;2(3):186-211.
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