Ocotea quixos essential oil: A systematic review about the ethno- medicinal uses, phytochemistry and biological activity

Matteo Radice (E-mail: mradice@uea.edu.ec ) a , Joe Silva (E-mail: agi20140057@.edu.ec) a , Cristian Francisco Correa (E-mail: agi20140018@uea.edu.ec) a , Alejandro Moya (E-mail: agi20140039@uea.edu.ec) a , José Antonio Escobar (E-mail: jescobar@uea.edu.ec) a , , Amaury Pérez Martínez (E-mail: amperez@uea.edu.ec) a, b , ... etc. a Universidad Estatal Amazónica, Km 2 1⁄2 Via Napo (paso lateral), Puyo, Pastaza, Ecuador b Universidad de Camagüey “Ignacio Agramonte Loynaz”, Circunvalación Norte km 5 1⁄2, Camagüey, Camagüey, Cuba


Introduction
Recent reviews about research trends and scientific development clearly suggest that natural products will still be for a long time indispensable as sources of new drugs [1,2].

Materials and Methods
The present systematic review was achieved adopting the following electronic databases: Scifinder, Pubmed, ISI-Web of Science, Google Scholar, Scielo and Scopus. Data was independently extracted from six reviewers and the final papers selections were completed avoiding duplication of data. The following keywords were selected: Ocotea quixos, ishpingo, ishpink, canela amazónica. All key words were searched individually and in combination. The reviewers selected articles in English and Spanish language, finally data from patents, symposiums and congress abstracts was excluded.
The oldest selected articles is dated 1981 and some key papers for the first three chapters were also considered. As described in Fig. 1, the above-mentioned criteria allowed selecting 38 eligible articles. The second step allowed eliminating duplicated papers, resulting in 25 articles. Finally, two papers, which did not satisfy the selection methodology, were rejected because of the lack of clarity in their procedures. 3 aromatic volatile compounds. The genus Ocotea is widespread within the American continent and in Southern Africa [17]. In Ecuador O. quixos is known with different common names, including: cannelloni, canela amazónica and ishpink or ishpingo [18,19].
The species: O. quixos was considered for a long time as endemic for Ecuador; it belongs to the Lauraceae family and it is a perennial tree 2-5 m tall with leaf blade and white-greenish color flowers. Due to its persistent and characteristic smell of cinnamon it is usually named "American cinnamon" [20,21].
As described by Naranjo (1969), Naranjo et al., (1981) and Fernandez de Oviedo (1959), O. quixos was known since the Incas age for its aromatic properties [16,21,22] and the local anesthetic and disinfectant uses. The same authors reported that in 1540 Pizarro and Orellana started an expedition from de Andes to the Amazonian region looking for a famous "cinnamon trees" with the hope to identify Cinnamomum zeylanicum Blume trees, an appreciated and well-known spice that was very important for the European market. In addition, in the Humbolt and Bonpland's 1800 expedition the presence of cinnamon-smell trees was reported. Due to its typical fragrance, O. quixos dried chalices were described as "Flor de Canela" and it is traditionally used for infusions and beverages or as a spice or flavoring for foods [23]. Nowadays, O. quixos is an essential ingredient for the recipe of "Colada Morada", a typical beverage that local people used to drink during the Day of the Dead; the essential oil is also used for aromatherapy [24][25][26]. Moreover, O. quixos essential oil and spice (powdered chalices) were mentioned respectively as ingredients for cosmetics and tisanes, these products are part of the proposal of Mashi Numi, an Ecuadorian network of 14 community-based organizations / companies producing natural ingredients and medicinal plants [27].

Phytochemistry 2.2.1 Leaves
Sacchetti et al. (2006) have studied samples of Ocotea quixos leaves oil (OQLO) from Morona Santiago (Ecuador) by means of gas chromatography coupled to mass spectrometry (GC-MS), the above-mentioned essential oil contains sixty-one compounds, representing the 93.6% of the total detected. The main constituents were β-Caryophyllene (15.1%), trans-Cinnamyl acetate (11.4%), Sabinene (7.6%), Geranial (5.6%) and trans-Cinnamaldehyde (5.1%). The authors highlighted the presence of a predominant sesquiterpene fraction (35.6%) followed by 2 minor fractions: the oxygenated monoterpenes (24.8%) and the monoterpenic hydrocarbons (21.7%), respectively. The essential oil scent was defined as, sweet-spicy, persistent cinnamon-like, warm and with a soft lemonscented note. Trans-Cinnamyl acetate and cinnamaldehyde are the source of the cinnamon-like taste of the essential oil. The authors mentioned the high terpenic and sesquiterpenic abundance as responsible of slightly inferior odor profile, which can explain why a massive exploitation of O. quixos has never been observed [28]. Noriega and Dacarro (2008) have studied others samples of OQLO from Ecuador, these authors obtained sixty-two compounds which concern the 83.89% of the detected molecules. The β-Caryophyllene (19.0%) was found to be the main component, moreover, α-Humulene (14.3%), Eremophylene (11.4%) and Methyl cinnamate (7.0%) were also detected in relevant amount [29].
Finally, a preliminary study accomplished on the OQLO confirmed the presence of trans-Cinnamaldehyde into the essential oil and the presence of alkaloids, tannins coumarines flavonoids y quinones [33].
The composition of the mayor compounds reported by cited studies is detailed in Table 1.

Biological Activity 2.3.1 Antimicrobial and antifungal activity
The inhibitory effects of OQLO were examined using the in vitro agar well diffusion method [29]. The first one achieved a lower activity compared with the second one, reaching the 40% and 85% of activity, respectively [34]. Rolli et al. (2014) tested the phytotoxic activity of OQLO against Solanum lycopersicum seeds and seedlings, in order to find new potential natural herbicides. The OQLO was able to extend the germination time in a pre-emergence effects test but showed a low damage rate in a post-emergence effects test on the same species, in both assays essential oils were applied at 1 ml/l on S. lycopersicum plant [31].

Antioxidant activity
As reported by Bruni et al. (2004) and Amilia Destryana et al., (2014), the β-Carotene Linoleic Acid Bleaching Test and the DPPH Radical Scavenging Assay were performed on the OQCO and on the OQLO respectively. In the DPPH test, the oil revealed a promising scavenging effect, also in comparison with Trolox and T. vulgaris essential oil, respectively, a synthetic and a natural antioxidant. The assay showed that OQCO have stronger antioxidant activity than Trolox but weaker than T. vulgaris, which means in any case a remarkable result. The same assay was performed on OQLO in comparison with another anti-oxidant agent, butylated hydroxytoluene (BHT), showing an irrelevant antioxidant activity [30,34].
For both oils, the β-Carotene Linoleic Acid Bleaching Test showed negligible results.

Anti-inflammatory activity
OQLO was studied in order to appreciate the suppression of prostaglandin E2 (PGE2) by lipopolysaccharide (LPS-stimulated RAW264.7 Macrophage System) and the nitric oxide (NO) concentration, both pro-inflammatory predictive assays [30]. The results obtained showed that OQLO inhibited NO and PGE-2 production, suggesting promising usages as anti-inflammatory compound. By means of in vitro and in vivo models, similar studies were performed by Ballabeni et al. (2010) [17] on OQCO and its main components: trans-cinnamaldehyde and methyl cinnamate. Using dexamethasone as positive control, OQCO and trans-cinnamaldehyde were able to significantly reduced LPS-induced NO release from J774 macrophages, showing in addition a non-toxic concentration between 1 and 10 μg/ml. Methyl cinnamate was not effective. At the concentration of 10 μg/ml OQFC and transcinnamaldehyde exhibited a strong and quite strong ability to inhibit the nitrite (NO) production, showing the 66% and 30% of inhibition activity, respectively. Moreover, OQCO, but not transcinnamaldehyde and methyl cinnamate, was able to significantly increased the levels of CAMP in forskolin-stimulated SK-N-MC cells, suggesting that the phytocomplex presented synergic effects that are not ascribable to a single constituent of the essential oil. OQCO could also inhibit the LPS-induced COX-2 expression according to a dose-dependently (1-10 μg/ml) mechanism.

Antiplatelet and antithrombotic activities
The antiplatelet activity and the inhibition of clot in guinea pig and rat plasma by 24 different essential oil were recently screened [35]. OQLO showed potent antiplatelet activity against ADP, Arachidonic Acid and the Thromboxane A2 agonist U46619, moreover a good ability to destabilize clot retraction was observed. The findings seems to be associated to the presence of phenylpropanoids content, like trans-cinnamaldehyde and methyl cinnamate.
A similar study on OQCO and its main components was performed; the trans-cinnamaldehyde and the methyl cinnamate, were considered in rodent and human plasma, respectively. The study showed that OQCO, probably due to the presence of trans-cinnamaldehyde, owns a strong antithrombotic activity not accompanied by pro-hemorrhagic side effect. The findings were supported by the in vitro research on inhibition of arachidonic acid-U46619-, ADP-, phorbol12-myristate13-alcetate, collageninduced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma. Moreover, in in vivo study on mice, it was found that OQCO and trans-cinnamaldehyde could reduce the contraction induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring and prevented acute thrombosis induced by collagen-epinephrine intravenous injection [17].

Conclusions
Essential oils from O. quixos, obtained from leaves (OQLO) and from calices (OQCO), respectively showed interesting activity, especially as antiplatelet, antithrombotic and anti-inflammatory biocompound. Considering also the antioxidant, antifungal and antimicrobial activities, both oils and their main components may be an attractive and promising source of new functional fragrances.