PÁGINA 556 Camila Maia Authors Review Article open access article under theCC-BYopen access article license: bjns.com.br. published inNovember 2020in DOI: ______9110 Gayan KanchanaWijesinghe–E-mail: A agent Keywords: biofilm infections withmedicalimportance. of true cinnamon essential oil as an alternative antimicrobial strategy to control microbial appositeness on evidences literature scientific available the analyses review This centuries. for verum of bark and leaf from extracted oils Essential diseases. infectious microbial against activity especially benefits medicinal many exhibits spice, culinary a as used widely been has that eradication. and control biofilm in strategy Currently, core. for these biofilm biofilm infections. Phytochemicals have the identified as towards a potential alternative antimicrobial agents antimicrobial scientists pay their attention to invent novel effective antimicrobial agents with less side effects of penetration prevent and barrier a physical as acts toeradicate structure Biofilm therapeutics. antimicrobial difficult available using it biofilms more treat or make biofilms of mechanisms associated resistance biofilm various are and infections infections microbial human of 60%-80%) (around majority the Further, organisms morebecome virulent and resistant to available antimicrobial therapeutic agents. disease such as diabetes mellitus. With the excessive use of synthetic antimicrobial drugs, micro- conditions including cardiac and hepatic diseases, microbial infections and non-communicable Medicinal play a major role as an alternative therapeutic agents for various disease Abstract 1 Piracicaba DentalSchool,StateUniversity ofCampinas,Brazil. Corresponding author: https://doi.org/10.31415/bjns.v3i2.119 - received on:October Article 15,2020;acceptedOctober 23,2020; have been used as a safe and effective antimicrobial agents against various infections : Gayan Kanchana Wijesinghe All authors contributed equally to the article. All authorscontributed equallytoThe authors declare thearticle. noconflict ofinterest Thisisan verum, 1 , Felipe Joia effective therapeuticalternativeagainstoralandnon-oralbiofilm Cinnamomum verum

infections: Abriefreview. : OpenAccess 1 , Janaina Priscila Barbosa

Brazilian JournalofNatural Sciences Brazilian Journalof Natural Sciences, Vol. 3,N.3,Online,ISSN:2595-0584–www. [email protected] –ORCID:https://orcid.org/0000-0003-3304- Leaf Essential Oil, Biofilms, Infections, Natural antimicrobial Natural Infections, Biofilms, Oil, Essential Leaf 1,A www.bjns.com.br (true cinnamon)leafessentialoilasan , Simone Busato de Feiria http://creativecommons.org/licenses/by/4.0 Cinnamomum verum 1 , Giovana Cláudia Boni

1 , Thaís Rossini de Oliveira is a native Sri Lankan medicinal Lankan Sri native a is ISSN 2595-0584-V.3- N.3 1 , José Francisco Höfling Revista Eletrônica Novembro 2020 1 , Flavia , Flavia C. 1 Though plants have provided western development ofmicrobial resistance [8]. less side effects, lower toxicity and decreased based on medicinal plants derivatives with remedies to combat these microorganisms their attention to develop new antimicrobial etiological agents, many scientists pay Due to this increasing multiresistance of regimens [7]. drug as well as low-level prophylactic treatment azoles arises during long-termexposure to the few side effects in human body. Resistance to as a treatment of Candidiasis since they cause Azole groupantifungal drugs are widelyused bacterial pathogens with multidrug resistance. strains virulent of and tuberculosis; of agent [4], pneumoniae [2], vancomycin Pseudomonas aeruginosa to resistance a exhibiting of nosocomialinfections, and which is aureus drugs. Methicillin-resistant of effective new antimicrobial therapeutic to an increasing need for the development microbial infections and mortality, which leads in the incidence of systemic and opportunistic resistance has resulted in a dramatic increase in immunocompromised patients. Such problem, especially when it comes to infections available antimicrobials has become a major [1]. Resistance world of organisms against problem in health care facilities in modern Anti-microbial resistance is an emerging Medicinal plants medicine with an abundance of medicines and Escherichia coli Mycobacterium tuberculosis WIJESINGHE (MRSA), causativea common agent , a common respiratory, a common pathogen , G.K.et-al [6] are few examples for - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 [3], Staphylococcus Streptococcus [5], causative [5],

antibiotics, some patients prefer to use herbal are not necessarily safer than synthetic Further, natural herbal antimicrobial products in vitro fewof plants, very ofthese have subjected to fungal infections. But, among these vast range medicine as treatments for bacterial and of plants worldwide are used in traditional antimicrobial As a compounds. result, hundreds reliable sourcesthe for discovery ofuseful used in traditional medicines continue to be treatments for a variety of infections, species Lankan plant and can be also found in tropical in found also be can and plant Lankan ( or truecinnamon( The main two varieties of cinnamon are Ceylon [11]. species spread in various regions of the world (Malabar cinnamon) arecinnamon othermajor and cinnamon) cinnamon), (Vietnamese (Indonesian C.cassia . family the to belongs and Lanka Sri to native cinnamon/ ceylon all over the world. Among them, true cinnamon/ There are different types of Cinnamon species Cinnamon species herbal medicines[10]. order to ensure safe and effective use of those the available evidence herbal for antibiotics in healthcare professionals should be aware on medicines due to various reasons. Thus, Cinnamom cassia Cinnamom screening [9]. (Chinese Cinnamon), Cinnamon verum ). Cinnamomum verum C. verumC. is a native Sri C. citriodorum C. loureiroi C. burmannii ) and cassia is

PÁGINA 557 PÁGINA 558 PÁGINA 558 well-drained soils and rarely reaches more than The cinnamon ( physical andchemicalproperties. Cinnamomum, Though all of thembelongs to samegenus, Seychelles, Tanzania, andUganda. such as Comoros, Ghana, Madagascar, Nigeria, Asia [12] and exotic to several African countries, resident and transient colonizers may undergo mycoplasmas, fungiandviruses.However, both and can many species harbor of bacteria, resident microbiota of the oral cavity is diverse to the oral microorganisms colonizing it. The atmospheres, which confers different habitats distribution of nutrients and different ecosystem with different ecological conditions, The oral cavity is considered acomplex Oral microbiota ß-carryophyllene, aromadendrene, p-cymene α-copaene, α-amorphene and 1,8-cineole [16,17, 18]. α-phellanderene, bicyclogermacrene, including compounds chemical other 43 of amounts trace contain Both cinnamaldehyde. of levels higher has oil bark the and eugenol, of levels higher has oil leaf keythe their Eugenolcinnamaldehydebut as and constituents contain oils essential bark extraction,for chemicalcompositionofthe extracted oil is vastly Both cinnamon leaf and varying. treethe used of part extractedthe is tree.on oil Cinnamon Based Cinnamon of byleavesbark or Chemical composition composition, whichsuggeststhatthey intheirpharmacological effects mightvary aswell[15]. chemical in significantly vary , and barks from obtained oils essential The use. culinary or [13, 14]. Almost every part of the cinnamon tree, specially the bark and leaves have some medicinal disease conditions including respiratory, gastro-intestinal, endocrinal and gynecological ailments uses, in AyurvedaOther than culinary medicine, Cinnamon is considered a remedy for various True Cinnamon/Ceylon Cinnamon/ variations depending on the individual’s diet, WIJESINGHE they are exhibiting different , G.K.et-al C. verum - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 ) grows in moist Cinnamomum verum. and are borneinclusters. greenish to yellow, with characteristic aroma are bisexual small The green. deep a other. Young leaves are red/pink and mature to veins are prominent and roughly parallel to each have smooth margins and are usually oval; the leaves simple thick The height. in meters 15 spp. Among these oral colonizers, 21]. [20, infections fungal other and disease species, such as dental caries, periodontal and even the interaction of more than one caused by different types of microorganisms oral ecosystem, local infections are usually the of character polymicrobial the to Due [19]. antibiotic therapy, as well as dental treatments immune conditions, saliva flow, treatments with are membranesin found both mucous Streptococcus

still not well defined [27]. Importantly, sessile Importantly, [27]. defined well not still is cells biofilm attached surface to planktonic transition of pathogenic microorganisms from studied, the exact underlying processes of the well were biofilms microbial of development and structure basic the though Even 27]. [23, biofilm colonize newareas which may then further by followed maturation and dispersion of microbial cells surfaces attached attachment and microcoloniesform on the Then attached microorganisms undergo irreversible [26]. maturation substances and production polymeric (EPS)/extracellular expression responsible exo-polysaccharidefor theresurface, is a rapid alteration in the gene a to attach cells microbial planktonic as soon (initial attachment). As or abiotic surface First the microbial cell adhere to the biotic considered toin occur four main stages. is a complexand dynamic process and it formation Biofilm [25]. biofilms multispecies The vast majority of humanmicrobiota exist as biofilms. multi-species/polymicrobial which involve one microbial species or biofilms monospecies be either can biofilms These 24]. [23, origin microbial or origin host microbial embedded in an extracellular matrix with attached surface communities. These communities are are Biofilms Biofilm formation each microorganism present [22]. them, the evasion of the immune system, as well as the production ofa specialized habitat for relation of mutualism, allowing the expression of genes in order to favor communicationbetween polymicrobial structure that favors the of microorganismssurvival that contribute, due to its mitis include: These biofilms. dental and , WIJESINGHE Streptococcus mutans , G.K.et-al - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 and Streptococcus sanguinis Streptococcus gordonii oral by adsorbingproteinssalivary surfaces on formed are Pellicles biofilm. non-oral other formation biofilm oral slightly differ from the formation process of hand, other the On characteristics betweenthese twostates. and planktonic microorganisms display distinct species isconsidered asamajorcontributor. colonizers,Among these secondary [29]. diseases periodontal and caries as such by otherspecies that may lead to diseases, promotes colonization conditions and further pioneer species modify localecological biofilm dental The microorganisms. other on molecules and similar receptorshost surface in multiple interactions both with participate and adhesin can molecules on their surface generally possess more than one type of period oftime. Oral within bacteria a short mediated stronger irreversible attachment mutans micro-organisms including formation, reversibly attached acidogenic and other host molecules. Afterthe pellicle glycoproteins, phosphor proteins, lipids pellicle. The major components ofpellicle are salivary enamel acquired the termed is film and glycoproteins. conditioning This surface [22]. The dental biofilm is a complex, a is biofilm dental The [22]. , Streptococcus oralis 2] neg adhesin-receptor undergo [28] , Streptococcus Streptococcus Candida

PÁGINA 559 PÁGINA 560 PÁGINA 560 krusei through biofilms of than flucytosine. Further, rates of drug diffusion single-species penetrates fluconazole Similarly, decreased. by penetration positively charged whereas aminoglycosides is readily, biofilms penetrate fluoroquinolones the extracellular matrix material. For example, nature of both the antimicrobial agent and the chemical on and biofilm the of thickness antimicrobial agent and would depend on the occur through adsorption or neutralization of would This exposure. escape biofilm such an extent that cells lying deep within a matrix components couldreduce access to extracellular biofilm Nevertheless, structure. biofilm the in channels water of presence by the assisted also is biofilms the into access Drug matrix. biofilm the penetrate to agents antimicrobial agents is often attributed to the failure of these to biofilms of resistance The Biofilms andtheir resistance infections. associated biofilm are 31] [26, joints. prosthetic and pacemakers catheters, catheters, peritonealand urinary dialysis valves, centrallenses, mechanical heart venous infections including infections in contact renal infections, and medical device related meningitis, osteomyelitis, rhinosinusitis, [30], fibrosis, dental caries, periodontitis, oral thrush chronicinfections, wound endocarditis, cystic 80%) of humaninfectious diseases including Available statistics reveal that the majority (60- Biofilm infections WIJESINGHE r fse ta toe hog biofilms through those than faster are Candida , G.K.et-al Candida glabrata biofilms more rapidly more biofilms - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 P. aeruginosa or Candida

with systemicinfections. recoverypoor ofthe patients and even deaths wellas as therapies of antimicrobial efficacy the causes prolonged hospitalization, reduction of the infections associated biofilm in-vivo microorganisms to in harsh conditions survive host defense mechanisms, whichenables are more resistant to routine antibiotics and species microbial producing biofilms These anti-biofilm remedies [9]. potential a as identified were phytochemicals infections. As aresult of those studies, many plants and biofilm these control to order in new find effective alternative antimicrobial strategies to scientists many by conducted polymicrobial resistance, many studies were and to effects side Due harmful availability, of [35]. lack agents antimicrobial and ofsynthetic natural use the or biofilms oral of removal mechanical include removal biofilm of methods Traditional infections. biofilm of strategies are used in control and treatment of types different [34], cells planktonic grown resistance greater to antimicrobials compared to suspension exhibit biofilms Since epidermidis of biofilms mixed-species while diffusion of antimicrobial drugs through of Candida parapsilosis . The difficulty in treating and controlling issignificantlyslow[32,33]. or C. albicans C. Candida tropicalis and S. , Anti-Bacterial activity of Cinnamon oil Penicillium viridicatum graminearum, Penicillium citrinum Aspergillus ochraceus, terreus, Fusarium moniliforme, Fusarium Aspergillus flavus, pathogenic fungi, antifungal effect of Cinnamon oil against Further, Singh [39] Fusarium spp., striafaciens michiganense Corynebacterium spp., many microbial species including the reported antimicrobial activity of Cinnamon oil against (1987) Suksrikarm Similarly of thosemolds[37,38]. and Penicillium flavus Aspergillus cinnamon against seven mycotoxigenic molds showed (1982) al., et cinnamon/ cassia (Chinese extract cinnamon of effect the investigated 2000 in Nir example, For plant. Cinnamon from antimicrobial activity of essential oils extracted Some publish evidence revealed the potential a great success[36]. based on natural herbal products is exhibiting Thus, the novel antifungal drug discovery rich source of biologically active compounds. metabolism of plant species, constituting a compounds originating from the secondary Essential oils are mixtures of various chemical Cinnamon oilasanantimicrobial agent P. citrinum Bacillus thermoacidurans WIJESINGHE Aspergillus ) against

spp.

spp. , Clostridium botulinum , Mucor and observed growthand observed inhibition M46, et al., , G.K.et-al

, Helicobacter pylori Aspergillus niger, Aspergillus spp. A. parasiticus

spp. P.roqueforti ,

[16]. 20) hwd the showed (2007) the effect ofChinese Canninghamella , and - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 , Salmonella Penicillium , , Pseudomonas A. ochraceus Cinnamonum Lactobacillus , , P.patulum Alternaria , Azzouz and

et al. spp.,

spp. spp. , , ,

gingivalis actinomycetemcomitans mutans and periodontal diseases, against major oral pathogens in caries cell membrane changes following 2h exposure observed they Importantly, respectively). mL mg/ 0.15 – 0.8 and mg/mL 0.63 - 0.21 (MIC antibacterial activity against the tested bacteria in relative amount) and cinnamon oil showed (82.5% oil cinnamon of component major the According to authors,cinnamaldehyde was studied by Zainal-Abidin Z. when the biofilm was treated with oil atthe MIC foranhour[41]. oil with treated was biofilm the when reduced was mass biofilm the of 50% least at dose- and exposure time-dependent. Further the findings, preventive effect of truecinnamonoil was in their to the According with treatment. biomasses biofilm established of casei. mutans forming biofilm oral using oil anti-plaque effects of et al. is well documented. Wiwattanarattanabut K. them, Among effect of biofilms. oral of controlling and physical approaches are employed in cariogenic oral plaques and different chemical for agent causative are biofilms microbialOral diseases [40]. agent in preventing bacterial-related oral therapeutic potential a as oil bark cinnamon to the (07 eaie te niirba and antimicrobial the examined (2017) , They observed a significant reduction significant a observed They , KPSK2 and clinical strain C. verum S. mitis C. verum and Fusobacterium nucleatum , oil. This finding suggested finding This oil. S. salivarius essential oil on oral plaques C. verum , , Aggregatibacter Porphyromonas et al., bark essential bark Streptococcus Streptococcus Lactobacillus (2013). was

PÁGINA 561 PÁGINA 562 PÁGINA 562 Linalool is another component of which causeeventual cell apoptosis [44]. with cellular macromolecular components levels of intacellular glutathione (GSH) and react This cytotoxic Quinone methide deplete the mediated P-450 conversion of eugenol into quinonemethide. cytochrome by caused is and according to them,the antifungal activity the anti- eugenol. Schmidt to explain the mode ofantimicrobial action of hypotheses developed by various scientists responsible for its bioactivity. There are few component of group ofphenylpropanes is the major active Phenolic eugenol compound belongs to the Cinnamon leafoil true of action antimicrobial of Mode etc [43]. on Prevotella S. mutans gingivalis including 2011 eugenol against some oral bacterial species in al. et demonstrated a high antibacterial activity of Moon by conducted Study Lactobacillus plantarumin-vitro niirba ptny 12–. mg/ml) (1.25–2.5 against cariogenic potency antimicrobial Cinnamon exhibited observations, the greatest as oil Cinnamon used an anti-microbial agent. According to their they study their In combination with chlorhexidine digluconate. on Antimicrobial effects of essential oils in Filoche

S. sobrinus WIJESINGHE Candida et al. , moderate antibacterial activity on

as well as weak antibacterial activity S. gordonii , Fusobacterium nucleatum odce a td i 2005 in study a conducted , S. sanguinis C. verum activityof , G.K.et-al et al. Streptococcus mutans and in 2007 researched on researched 2007 in leaf EO which is - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 and C. verumC. Porphyromonas biofilms[42]. S. anginosus C. verum leaf oil , and and

such as bacterial enzymes of some bacterial species bacterial cells. Further, eugenol can inhibit acids anddisruptthe plasma membrane of nonspecific and permeability by altering the membrane fatty integrity membrane cell bacterial species. Eugenol caninterfere with of actions of Cinnamon leaf EO on different al. Another review conducted by Marchese to thehyphalform[44]. including inhibition of germtubes and transition virulence mechanismsof This linalool can be contributing in controlling leaf EO, which contains in small amounts. antimicrobial activity of the oil in order to Unlu M. phytochemical agent. this important effects of cinnamonoil to ensure safe use of modern scientists researched onthe cytotoxic and effectsimmunomodulatory etc. Further, antioxidant, anticancer, cardiovascular, antimicrobial, hypo-lipemic, inflammatory, evidence suggest that cinnamon has anti- laboratory and animal of the world. The availablemany parts a traditional herbal medicine for centuries in Cinnamon has been used as a spice and as Cytotoxicity of the cellenvelope [45,46]. and increases cell permeability by damaging verum mechanism of action of eugenol containing Oxygen Species (ROS) is anotherantibacterial Formation ofcytotoxic intracellular Reactive [45]. in 2017 identified several other modes other several identified 2017 in leaf EO which causes lipid peroxidation Escherichia coli et al.

(00 ivsiae the investigated (2010) , C. verum in vivo and

Oil Bacillus subtilis Candida experimental spp. in vitroin C. et

El-Meleigy may prove to be a chemotherapeutic agent [48]. effect on the majorityofcancercells and thus inhibitory significant a had ACE that indicates of the majority ofthe cancerous cells which inhibition growth 35-85% in resulted treatment 1.28mg/mL ACE cinnamaldehyde), of µM 10.24 concentration (containing critical a cinnamaldehyde). At µM 1.28 (containing 0.16mg/ mL above just concentrations at cells they found,ACE was cytotoxic to cancerous cells. As as mousecelllines and primary of bark an of aqueous Cinnamon extract (ACE) from the effect cytotoxic the analyzed (2009) Another studyconductedby Singh treatment ofinfections andneoplasms[47]. its potential use as remedies for the topical oil ofCinnamon,indicating the possibilities of of the essential anticarcinogenic properties study showed the potential antimicrobial and higher than effect onnormalcell line. Their significantly were lines cell cancer on effect cytotoxic Importantly, experiments. their for cytotoxicity with less than 20 µg/mL IC bromide staining. They a strongobserved orange/ethidium acridine and examined assay MTT were by fibroblasts on oil essential oil. The cytotoxic and apoptotic effects of the of effect antimicrobial significant inhibitory concentration methods. They noticed krusei albicans, pneumoniae Streptococcus pyogenes 4 (ATCC) including, and 21bacterial (ATCC) against species efficacy its evaluate WIJESINGHE using disc diffusion and minimum C. verum

Candida parapsilosis et al., , Enterococcus faecalis, , G.K.et-al (2010) on various humanas well Staphylococcus aureus conducted a research - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 , Candida and Streptococcus species C

50 Candida Candida . values et al., verum ,

decreased. At100μL/mL,thepercentagesof 21) eemnn te fet o aqueous true Cinnamon extract onHL-60 cells as a of effects the determining (2013) A study conducted by Assadollahi for oilstested[49]. was thepost-exposure maximum rate survival cells weresurviving 61% for cinnamon that was cells surviving of number the μg/mL 25 to concentration increasing by while μL/mL, low concentration of essential oils from1-10 (colon normalcell) when cells subjected to namely, MRCs (lung normal cell) and CRL-1539 any deleterious effect ontwohumancells including cinnamon oil. They could not observe to study the cytotoxicity of fouressential oils tested ranging from 0.5to 1000mg/mL[18]. on experimental model at any concentration C. verum toxicity of experiment determination model for of al A recent study published by Wijesinghe treating promyelocytic leukemia [50]. single drug orbesides other medications for they introduce true cinnamon extract as a conclusion, a as Further 90.1%. by inhibited was extract, Cinnamon mg/L 0.01 with cells HL-60 of growth the exposure, of h 72 After as correlated with concentration and time. extract inhibited the growth ofHL-60 cells .According to their Cinnamon observations, model for Acute promyelocytic leukemia (APL) , 22) used (2020) ., leaf oil does not exhibit any toxic effect C. verumC. leaf EO and they foundthat Galleria mallonella larvae larvae et al., in-vivo et

PÁGINA 563 PÁGINA 564 PÁGINA 564 29: 525–52.DOI:10.1128/CMR.00058-15 2016; Rev. Microbiol. Clin. perspective. States and post-conjugate vaccine eras: A United resistant Streptococcus pneumoniaein pre- and epidemiological features of antibiotic- 4. Kim L, McGee L, Tomczyk S, Beall B. Biological 10.1186/2047-2994-3-32 DOI: 2014. Control. Infect. Resist. Antimicrob. A systematic review and meta-analysis. resistant Pseudomonas aeruginosa infections: of hospital-acquired resistant and multidrug- Menon V. Clinical and economic consequences 3. Nathwani D, Raman G, Sulham K, Gavaghan M, cid/cit178 10.1093/ DOI: 1779–88. 56: 2013; Pract. Clin. resistant aureusStaphylococcus infections? vancomycin in the treatment of methicillin- replace to time it Is VG. Fowler SJ, Hal Van 2. United States;CDC:Atlanta, GA,USA,2013. (CDC). Antibiotic Resistance Threats in the 1. Centers for Disease Control and Prevention REFERENCES Conflicts ofInterest: immunology, Piracicaba dentalschoolwere acknowledged. Acknowledgments: Funding: research onthisaspectaswell. etiological fungal tospecies for acidogenic oral conduct plaque formation, it important is very anti- specially observations, the Candida support to data published of lack are there strategy, control control. Though C. verum Conclusion WIJESINGHE biofilm effect,biofilm This research received noexternalfunding. essential oil C. verumC. , G.K.et-al All academic and non-academicmembersofthe Allacademic area ofmicrobiology and

The authorsdeclare noconflictofinterest. is a potential alternative antimicrobial strategy oral for and non-oral infection ex-vivo leaf oil is identified as a potential non-toxic, effective microbial biofilm non-toxic, effective microbial potential a as identified is oil leaf - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 and in-vivo toxicity of 2013; 38(1):44-50.PMID: 23645957 oil against Brucella melitensis. of selected Labiatae (Lamiaceae) essencial activity antibacterial The M. Safi A, Al-Mariri 8. Lancet, 2002;359(9312):1135–44. drug resistance of pathogenic fungi. The 7. Kontoyiannis, DP, & Lewis, RE. Antifungal 10.3389/ DOI: fcimb.2015.00074 2015. Microbiol. Infect. Cell. isolated strains O26:H11 from animal, food, and clinical samples. Front. coli Escherichia al. characterization of Shiga toxin-producing et J, Burgán AV, Bustamante AI, 6. Krüger A, Lucchesi PM, Sanso AM, Etcheverría 10.3201/eid2106.141873 DOI: 992–1001. 21: 2015; Dis. Infect. Emerg. patients with multidrug-resistant tuberculosis. tuberculosis and poor outcomesamong HM. Mirtskhulava Blumberg MJ, M, Acquired drug resistance in Mycobacterium Magee Kipiani N, Tukvadze RR, V, Kempker 5. C. verum leaf oil. Since Candida Iran J Med Sci, Med J Iran is the major Genetic 296–301. (4): 7 Prod.2013; Nat. Rec. reductaseenzyme. toward Plasmodium falciparumenoyl-ACP Welw. (Lauraceae) and their inhibitory activity from the stem bark of Cinnamomum zeylanicum HK, Mustafa Ali SAA, MS, et al. Constituents 14. Nkanwen E, Awouafack M, Bankeu J, Wabo (3): 803–12.DOI:10.1016/j.jep.2011.01.035 134 2011; Ethnopharmacol. J. extracts. plant Cameroonian spices and selected medicinal Fankam I, AG, Voukeng Tankeo M, S, Youns et B, al. Krusche Cytotoxicity V, of Kuete some 13. 10.1016/j. DOI: 66–70. 5(2): jtcme.2014.11.008 2015; Med. repellent activities. J. Trad. Complement. antifungal, nematicidal, acaracidal, and anticholesterol, antidiabetes, antibacterial, and a series of functions such as antioxidant, cells and prevention of Alzheimer’s disease, on the inhibition of angiogenesis in cancer of traditional applications to its novel effects S, Shahlari M. Cinnamon from the selection Hamidpour M, Hamidpour R, Hamidpour 12. jf405580c 10.1021/ DOI: 2516–21. (12): 62 2014; Chem. Food J. Agric. spectrometric method. mass fingerprinting injection (FIMS) flow a using burmannii, C. verum, C. cassia, and C. loureiroi) the four majorspecies of cinnamons (C. 11. Chen P, SunJ, Ford P. Differentiation of 241–6. DOI:10.1093/jac/dkg087 51(2): 2003; Chemotherapy. Antimicrobial of a review ofcontrolled clinical trials, Journal medicines for treatment of bacterial infections: 10. Karen W. Edzard Ernst,Herbal Martin, doi.org/10.31415/bjns.v3i1.89 Brief Review. bjns. 2020; 3(1):249. DOI: https:// essential oil and its medical applicability. A Feiria S, Boni G, Maia F, et al. de Busato J, Barbosa A, T,TeixeiraOliveira 9. WIJESINGHE , G.K.et-al - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 Melaleuca spp. f ak la ro ad ri o cinnamon of and root zeylanicum(cinnamomum Blum),grown in Sri leaf bark, of of essential AM: Acomparison oil constituents GS, Jayawardena AL, Senanayake UM, Mubarak ParanagamaPA,17. Jayatilake S, Wimalasena DOI: 1650–61. 45(9): 10.1016/j.fct.2007.02.031 2007; Toxicology. and their constituents. Food and Chemical chemical, cinnamon leaf and bark volatile oils, oleoresins of comparison antioxidant and antimicrobial studies of A CAN. Catalan S,deLampasonaMP,16. Singh G,Maurya 12583177 GC-MS. Zhong Yao Cai. 2002; 25: 257-8. PMID: cinnamomi byramulus cinnamomi and cortex on chemicalconstituents of essential oil from F,Chen Q, Shen 15. Luo studies Comparison J. ppat.1000713 2010; Pathog. https://doi.org/10.1371/journal.DOI: 1-8. 6(1): PLoS Individuals. Healthy in of the Oral Fungal Microbiome (Mycobiome) Cui F, Sikaroodi M, Naqvi PK, Mukherjee RJ, A, Jurevic MA, Ghannoum et 21. al. Characterization tim.2005.09.006 10.1016/j. DOI: 589–95. 13: 2005; Microbiol. Communities in Sickness and in Health. Trends Microbial Oral RJ. Lamont HF, Jenkinson 20. Santos: Santos; 2005. 19. Marsh P, MV. Martin Microbiologia oral. 4a. https://doi. DOI: org/10.1590/0074-02760200349 e200349. 115: 2020; Cruz. Galleria mellonella model. determination of the in-vivo toxicity with virulence factors of Candida species and of Cinnamomumverum leaf essential oil on Effect al. et JP F,Barbosa Joia SNB, Feiria de 18. Wijesinghe GK, Maia FC, de Oliveira TR, DOI: 10.4038/jnsfsr.v29i3-4.2613 Lanka. J Natl Sci Found Sri. 2010, 29: 147-153. 192. Mem. Inst. Oswaldo

PÁGINA 565 PÁGINA 566 PÁGINA 566 : 7-0 DI https://doi.org/10.1038/ DOI: nrmicro2381 471-80. cell–cell 8: of role 2010; Microbiology. Reviews Nature key distance. the and biofilm development multispecies Oral NS. Jakubovics S, Periasamy RJ, Jr Palmer PE, Kolenbrander 28. DOI: https://doi.org/10.1186/s12866-014-0253-z 253. 14: 2014; Microbiol. BMC studies. up ofan experimental system for molecular VS, set- formation: biofilm in steps early Exploring Brözel C, Senechal Costaglioli P, Le C, Bonneu M, et al. Barthe M, Crouzet 27. 2018; 4(12):e01067. Heliyon. prevention. and treatment its on implantable devices and approaches to EJ, Mah TF, formation Suuronen biofilm Bacterial EI. Alarcon CD, McTiernan Z, Khatoon 26. DOI: 10.1111/1462-2920.13594 385–92. 13: 2016; Microbiol. Environ systems. M, Burmølle model biofilm multispecies experimental now: KW, Lee Kelvin Kjelleberg S,Rice SA, Lee KWK, et al. All together CH, Tan 25. v3i2.99 https://doi.org/10.31415/bjns. 2020; DOI: bjns. 3(2):342. Review. Brief A microrganisms. and its applicability to combat resistant of alternative anti-human diseases, antimicrobial agent, an as (stone-breaker) L. niruri Busato de Feiria S, Boni G, et al. F,OliveiraT, Maia G, J, 24. Wijesinghe Barbosa 10.1159/000494757 aureus. of Pseudomonas aeruginosa and Staphylococcus Formation Biofilm and B, Adhesion, Growth, Gayani A, Influence of Laboratory Culture Media Dilhari on in vitro GK, Kottegoda N, Samaranayake L, Weerasekera M. Wijesinghe 23. DOI: 10.1128/JB.187.21.7193-7203.2005 7193-203. 187(21): 2005; Bacteriol. J. Biofilm. and Streptococcussanguinis in the Dental Coexistence between Streptococcusmutans 22. Kreth J, Merritt J, Shi W, Qi F. Competition and WIJESINGHE Med Princ Pract. 2019; 28: 28–35. DOI: , G.K.et-al - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 Phyllanthus Medical Association.2018;81(1):7–11. associated infections. Journal ofthe Chinese F, Jalil S, Andleeb Imran M, W,Nawaz MA, et al. Bacterial Ahmad biofilm and M, Jamal 31. 554–60. DOI:10.1159/000484718 and 26: 2017; Pract. Princ Med albicans tropicalis. Candida Candida of Formation Biofilm Sweeteners on the Growth, Adhesion, and et al. CP,N, GunasekaraKottegoda GK, N, Fernando 30. Weerasekera MM, Jayarathna TA, Wijesinghe DOI: 10.1128/mmbr.66.3.486-505.2002 486-505. 66(3): 2002; Rev. Biol Mol Microbiol Communication amongoral bacteria. Blehert RN, DS, Egland PG, Foster JS,Palmer RJJ. Andersen PE, Kolenbrander 29. albicans. Medical Mycology. 2012; 50: 33–42. 50: Mycology.2012; Medical albicans. Anti- against multi-drug resistant isolates of Candida I. Ahmad combination with A, amphotericin B or fluconazole Malik candidal activity of essential oils alone and in SMA, Khan biofilms. 36. oral of control the Periodontology 2000.2011;55: 143–66. in therapy Photodynamic JM. Goodson NS, Soukos 35. DOI: 1494–500. 3(9): 2008; 10.1038/nport.2008.141 Protoc. Nat its and method biofilms application to antifungal susceptibility testing. fungal of plate-based formation the well for 96 reproducible FL, Mowat E,Ramage G, et al. A simple and P,Uppuluri CG, PierceWormley 34. TristanAR, 1008. 999– 55: 2006; Microbiol. Med J resistance. chemical compositionand role in drug of Candida albicans and Candida tropicalis: matrix Biofilm LJ. Douglas MA, Al‐Fattani 33. 10.1016/j. DOI: 1213–9. 5: micinf.2003.08.009 2003; Infect. Microbes of biofilms. aeruginosa resistance Pseudomonas Antimicrobial E. Drenkard 32. The Effect of Nutritive and Non-Nutritive and Nutritive of Effect The O: https://doi.org/10.1080/097206 421–429. 10(5), DOI: 2007; Plants. Bearing Isolates Oil Clinical 38 of Candida albicans. Journal ofEssential against Oils Eugenol-Containing Essential Various and Eugenol of Activity V,Antifungal Gochev T,Girovaal. G, et Buchbauer K, Wlcek L, Jirovetz E, Schmidt 44. Biol. 2011;56:907–16. and antibiotics against oral bacteria. Arch Oral between clove oil and its major compounds 43. Moon SE, Kim HY, Cha JD. Synergistic effect DOI: 221–5. 10.1111/j.1399-302X.2005.00216.x 20(4): 2005; Immunology. and chlorhexidine digluconate. Oral Microbiology effects of essential oils in combination with 42. Filoche SK, Soma K, Sissons CH. Antimicrobial herbs. J.Clin.Diagn.Res.2017;11:30–35. effects plaque of essential oils extracted from culinary anti-cariogenic vitro In T. Srithavaj S, Choonharuangdej K, Wiwattanarattanabut 41. Journal. 2013;42(4):12-16. Pathogens. The Open Conference Proceedings Anti- Bacterial Activity ofCinnamon Oil on Oral I. Jantan WAW, Mustapha A, Majid FA, Majid Abdul S, Mohd-Said Z, Zainal-Abidin 40. Printing, Thailand. 39. Suksrikarm B, 1987. Herb and Spice. Amorn 10.4315/0362-028X- DOI: 45.14.1298 1982; 1301. – Protection. 1298 Food 45: of Journal agents. plant components and commercial antifungal Comparative antimycotic effects of selected herbs, spices, LB. Bullerman MA, Azzouz 38. of Helicobacter. 2000;5:94–7. effect the of cinnamon extract on Helicobacter pylori. trial M, Controlled Tabak I. E, Stermer Neeman I, Potasman Y, Nir 37. DOI: 10.3109/13693786.2011.582890 WIJESINGHE , G.K.et-al - Braz. J.Nat.Sci.–eletronic journal-ISSN:2595-0584V.3 -N.3 Food and Chemical Toxicology. 2010; 48(11): 2010; Toxicology.Chemical and Food zeylanicumCinnamomum Blume (Lauraceae). activity and in vitro cytotoxicity of essential oil from antimicrobial Composition, N. Vural HS, GV,Zeytinoglu Unlu E, Ergene M, Unlu 47. 398. DOI:10.1016/j.jare.2017.05.007 activity of pyochelin. J Adv Res. 2017; 8(4):393- of role The reactive oxygen species in the antimicrobial SM. Lee YL, Cheow KS, Ong 46. 668– 689. DOI:10.1080/1040841X.2017.1295225 43(6), 2017; Microbiology. in Reviews eugenol: A mechanistic viewpoint. Critical of eugenol and essential oils containing Daglia M, Nabavi SF, et al. IE, Orhan E, Coppo R, Barbieri A, Marchese 45. 0X.2007.10643575 10.4103/2277-9175.108001 DOI: 25. 2013; 2. Res. Biomed Adv cells. HL-60 leukemia myeloid acute in process apoptotic The effect of aqueous cinnamonextract on the NH, Roudbari K, AR,MotamediM,EzatpourB,et al. Khalatbary Parivar V, Assadollahi 50. Environmental Sanitation.2010;5(2):143-59. Bacterial Cells. Journal of Applied Sciences in of Cytotoxicity RA, Four Essential Oils on SomeHumanAnd EE. Arafa El-Kholany ME, NA, Ahmed Ebrahim MA, El-Meleigy 49. 1174–9. 47(12): 2009; Biology. Pharmaceutical lines. with bark commercial cinnamaldehyde onvarious cell zeylanicum Cinnamomum from of analysis cytotoxic effect of aqueous cinnamon extract Comparative RK. Ghanekar AR, 48. Singh R, Koppikar SJ, Paul P, Gilda S, Paradkar 3274–80. DOI:10.1016/j.fct.2010.09.001 Antimicrobial activity

PÁGINA 567