CINNAMOMUM VERUM (TRUE CINNAMON) LEAF ESSENTIAL OIL AS AN EFFECTIVE THERAPEUTIC ALTERNATIVE AGAINST ORAL AND NON-ORAL BIOFILM INFECTIONS: A BRIEF REVIEW Leaf Essential Oil, Biofilms, Infections, Natural antimicrobial agent

Medicinal plants play a major role as an alternative therapeutic agents for various disease conditions including cardiac and hepatic diseases, microbial infections and non-communicable disease such as diabetes mellitus. With the excessive use of synthetic antimicrobial drugs, micro-organisms become more virulent and resistant to available antimicrobial therapeutic agents. Further majority (around 60%-80%) of human microbial infections are biofilm associated infections and various resistance mechanisms of biofilms make it more difficult to eradicate or treat biofilm infections using available antimicrobial therapeutics. Further, biofilm structure acts as a physical barrier and prevent penetration of antimicrobial agents towards the biofilm core. Currently, scientists pay their attention to invent novel effective antimicrobial agents with less side effects for these biofilm infections. Phytochemicals have identified as a potential alternative antimicrobial strategy in biofilm control and eradication. Cinnamomum verum is a native Sri Lankan medicinal plant that has been widely used as a culinary spice, exhibits many medicinal benefits especially activity against microbial infectious diseases. Essential oils extracted from leaf and bark of C. verum have been used as a safe and effective antimicrobial agents against various infections for centuries. This review analyses the available scientific literature evidences on appositeness of true cinnamon leaf essential oil as an alternative antimicrobial strategy to control microbial biofilm infections with medical importance.

which is exhibiting a resistance to vancomycin [2], Pseudomonas aeruginosa [3], Streptococcus pneumoniae, a common respiratory pathogen with multidrug resistance [4], multidrugresistant Mycobacterium tuberculosis [5], which are causing an increase in the prevalence of tuberculosis; and virulent strains of Escherichia coli [6].
Azoles are group antifungal drugs used widely as a treatment of Candidiasis since they cause few side effects in human body. Resistance to azoles arises during long-term exposure to the drug as well as low-level prophylactic treatment regimens [7].

Cinnamon species
There are different types of Cinnamon species all over the world. Among them, true cinnamon/ ceylon cinnamon/ Cinnamomum verum is native to Sri Lanka and belongs to the family Lauraceae.

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Lankan plant and can be also found in tropical

True Cinnamon/ Ceylon Cinnamon/ Cinnamomum verum.
Other than culinary uses, in Ayurveda medicine, Cinnamon is considered a remedy for various disease conditions including respiratory, gastro-intestinal, endocrinal and gynecological ailments [13,14]. Almost every part of the cinnamon tree, specially the bark and leaves have some medicinal or culinary use. The essential oils obtained from barks and leaves, vary significantly in chemical composition, which suggests that they might vary in their pharmacological effects as well [15].

Chemical composition
Cinnamon oil is extracted by leaves or bark of Cinnamon tree. Based on the part of the tree used for extraction, chemical composition of the extracted oil is vastly varying. Both cinnamon leaf and bark essential oils contain cinnamaldehyde and Eugenol as their key constituents but the leaf oil has higher levels of eugenol, and the bark oil has higher levels of cinnamaldehyde. Both contain trace amounts of 43 other chemical compounds including bicyclogermacrene, α-phellanderene, ß-carryophyllene, aromadendrene, p-cymene α-copaene, α-amorphene and 1, 8-cineole [16,17, 18].

Oral microbiota
The oral cavity is considered a complex antibiotic therapy, as well as dental treatments [19]. Due to the polymicrobial character of the oral ecosystem, local infections are usually caused by different types of microorganisms and even the interaction of more than one species, such as dental caries, periodontal disease and other fungal infections [20,21]. and dental biofilms. These include: Streptococcus gordonii, Streptococcus oralis, Streptococcus mitis, Streptococcus mutans and Streptococcus sanguinis [22]. The dental biofilm is a complex, polymicrobial structure that favors the survival of microorganisms that contribute, due to its relation of mutualism, allowing the expression of genes in order to favor communication between them, the evasion of the immune system, as well as the production of a specialized habitat for each microorganism present [22].

Biofilm formation
Biofilms are surface attached microbial communities. These communities are embedded in an extracellular matrix with host origin or microbial origin [23,24]. These biofilms can be either monospecies biofilms which involve one microbial species or multi-species/polymicrobial biofilms. The vast majority of human microbiota exist as multispecies biofilms [25]. Biofilm formation is a complex and dynamic process and it considered to occur in four main stages.
First the microbial cell adhere to the biotic or abiotic surface (initial attachment). As soon as planktonic microbial cells attach to a surface, there is a rapid alteration in the gene expression responsible for exo-polysaccharide (EPS)/extracellular polymeric substances production and maturation [26]. Then the attached microorganisms undergo irreversible attachment and form microcolonies on attached surfaces followed by biofilm maturation and dispersion of microbial cells which may then further colonize new areas [23,27]. Even though the basic structure and development of microbial biofilms were well studied, the exact underlying processes of the transition of pathogenic microorganisms from planktonic to surface attached biofilm cells is still not well defined [27]. Importantly, sessile and planktonic microorganisms display distinct characteristics between these two states.
On the other hand, oral biofilm formation such as caries and periodontal diseases [29].
Among these secondary colonizers, Candida species is considered as a major contributor. PÁGINA 560
Since biofilms exhibit greater resistance to antimicrobials compared to suspension grown planktonic cells [34], different types of   such as Escherichia coli and Bacillus subtilis [45].

Formation of cytotoxic intracellular Reactive
Oxygen Species (ROS) is another antibacterial mechanism of action of eugenol containing C.
verum leaf EO which causes lipid peroxidation and increases cell permeability by damaging the cell envelope [45,46].

Cytotoxicity of C. verum Oil
Cinnamon has been used as a spice and as a traditional herbal medicine for centuries in At 100μl/ml, the percentages of surviving cells were 61% for cinnamon that was the maximum post-exposure survival rate for oils tested [49].