Preliminary prospection of phytotherapic compounds from the essential oils from barks and leaves of Umburana (Commiphora Leptophloeos)Abstract
The potential of the biome caatinga (exclusive from northeastern Brazil) has been evaluated in recent research for application in the pharmaceutical industry. Among the species of medicinal plants from caatinga, one can highlight the Commiphora leptophloeos (umburana), which has been used as infusions and syrups by the regional population for inflammatory and infectious diseases. Essential oils from umburana leaves and barks were obtained in a Clevenger apparatus and analyzed by gas chromatography/mass spectrometry, and total phenolic and flavonoids were determined by spectrophotometric analysis. It was observed that a large part of the major compounds present in the essential oil is described as having antitumor activity, enabling research in investigational oncology with umburana (C. leptophloeos). In addition, some little explored components have been identified, such as cadinene, alpha-selinene, and elemenone. Despite being easily found in several plants, there are no clinical trials involving their biological activity in a well-defined isolated form, which could make exploring new studies possible. Furthermore, the presence of phenolic compounds and flavonoids allows future studies about the potential antimicrobial and antioxidant activity.
Keywords:
Commiphora leptophloeos; Medicinal plant; Gas chromatography; Essential oil
INTRODUCTION
Plants are used as a therapeutic resource by a large part of the population due to the great variety of chemical substances with antimicrobial, expectorant, antiseptic, anti-inflammatory, and hepatoprotective properties (Dutra et al., 2016). However, popular culture often induces the use of plants without any scientific evidence, in the form of essential oil, extracts, infusions, or patches to treat common infections. Bioprospecting studies involving various aspects of plant biology and phytochemistry are proving the traditional uses of several plants for therapeutic purposes (Trentin et al., 2011; Dutra et al., 2016).
Brazil has one of the greatest biodiversity on the planet with the potential to provide products of natural origin, by the extraction of plants, and their respective active principles, for application in foods and drugs. The biome caatinga (exclusive from northeastern Brazil, with an area of around 735,000 km2) has a great diversity of plants with high biological potential and great interest in the pharmaceutical industry, being a key point for the development of prospecting studies of plants, aiming to use as phytotherapics (Trentin et al., 2011).
Among the species of medicinal plants of the caatinga, Commiphora leptophloeos (Mart.) J.B. Gillett is a resinous angiosperm adapted to semi-arid and desert climates that survive in total sun exposure. It has been used in the form of infusions and syrups, by indigenous populations, for inflammatory and infectious diseases (Pereira et al., 2017; Silva et al., 2017). Some studies have demonstrated its anti-inflammatory and healing potential, as too against gastritis, ulcers, bronchitis, coughs, inflammation of the urinary tract, and anesthetic and cytotoxic activities (Dong et al., 2017).
The literature register that secondary metabolites found in these species and other plants of the same genus are condensed tannins, anthocyanins, flavonoids, saponins, alkaloids, albumins, and sesquiterpenes (Dong et al., 2017; Fang et al., 2018).
Few studies on the detailed chemical composition of its essential oil have been reported. Most of the published studies on the chemical composition (by gas chromatographic analyzes) are related to other similar species such as C. guidottii (Yeo et al., 2016), C. myrrha (Ahamad et al., 2017), and C. mukull (Rhourrhi-Frih et al., 2012).
Because of the above, this work aims to evaluate in more detail the chemical composition of the essential oils of the Umburana bark and leaves and to indicate the potential phytotherapy application.
MATERIAL AND METHODS
Samples and Reagents
Samples of bark and leaves of Commiphora leptophloeos were collected in the “Barra da Onça Settlement” located in the city of Poço Redondo, Sergipe, Northeast Brazil (GPS 9° 48‘ 23“ S 37° 41’ 08W”). The exsiccate of the plant material was deposited in the herbarium of Tiradentes University - Aracaju/SE.
The collection of biological material was according to the SISBio (Biodiversity Authorization and Information System), linked to the Chico Mendes Institute for Biodiversity Conservation (ICMBio), under registry number 62387-5. It was also registered in the National System management of Genetic heritage and Traditional Associated Knowledge (SISGEN) under number AD82169.
The plant materials (barks and leaves) were sanitized with deionized water, dried in an oven at 50 ºC for 48 hours, and ground in a stainless-steel knife mill. A mixture of n-alkanes (C7-C37) (Supelco Park, PA, USA) was used in the gas chromatograph coupled to quadrupole mass spectrometry (GC/qMS) to calculate the retention index. The carrier gas used was Helium (He) with purities higher than 99.999%, obtained from White Martins (Aracaju, SE).
Essential oil extraction
The essential oil of C. leptophloeos was obtained by hydrodistillation in a graduated Clevenger apparatus using a method adapted from Hou et al. (2019). 50 g of plant material (leaves and bark) and 500 mL of distilled water was used for the extraction. The temperature was raised to 100 °C until boiling, then reduced to 75 °C and held for 2 hours. After extraction, the oil was collected and filtered in anhydrous sodium sulfate and stored in a vial protected from light with aluminum foil for further chromatographic analysis.
GC/qMS analysis
The chromatographic analysis was performed by GC/qMS (SHIMADZU-GCMS-QP2010-Ultra, Japan), with automatic injector AOC- 20 (SHIMADZU, AOC- 20i, Japan), capillary column SLB-5 (equivalent to 5% phenyl methyl silicone) with 60 m x 0.25 mm x 0.25 μm. Helium (99.999%) was used as carrier gas with a linear velocity of 31 cm s-1.
Initially, 1 μL of the sample (1.000 mg L-1 in dichloromethane) was injected in splitless mode. The temperatures of the injector, the interface, and the ion source were 280 ºC, ionization energy by electron impact (70 eV), and spectra scanning in masses in the range of 35 to 450 Daltons. The analysis was performed in the temperature ramp, with the initial temperature of 40 °C for 2 min, heating at 4 °C min-1 until reaching the temperature of 300 °C, holding for 40 min.
Chromatography data were handled by the GCMS solution software, version 4.3. The identification of the compounds was performed by comparing the fragmentation profile of each compound with those present in the NIST 14 library (National Institute of Standards and Technology). Spectral similarity ≥ 80%, and Linear Temperature Programmed Retention Indices (LPTRI) with a maximum difference of 15 units for columns with similar polarities, were used as criteria for considering the compound tentatively identified. The retention index was automatically calculated by the software of the equipment, using a mixture of linear alkanes from seven to thirty- seven carbon atoms in the chain.
Total phenolic and flavonoids
The spectrophotometric analysis was performed in an equipment Shimadzu (model - 1900 UV-VIS, Japan) measured in triplicate in quartz cuvettes.
The total phenolic compounds of the essential oil were determined using the Folin-Ciocalteau reagent according to the methodology described by Djeridane et al. (2006). Five milligrams of each essential oil were weighed separately and transferred to volumetric flasks of 5 mL and completed their volume with methanol. After, 0.5 mL of this solution were added to test tubes, previously prepared with 2.5 mL of reagent Folin- Ciocalteau, distilled water (1:10) (v/v), and 2 mL of Na2CO3 solution 7.5 % (m/v). Subsequently, the test tubes with the samples were kept in a low-light environment and externally protected with aluminum foil for 2 hours. The absorbance was measured at 760 nm.
The flavonoid content was determined using the aluminum nitrate colorimetric method. as(Barbosa et al., 2019).
RESULTS AND DISCUSSION
Gas Chromatographic Analysis
The essential oil yield for the bark was 3.13% ± 0.30, while for the leaves it was 2.05% ± 0.24. These results may be justified by the resinous character of the plant. In addition, the extraction of the essential oil from leaves was more efficient when compared to the extraction performed by Da Silva et al. (2015) (Da Silva et al., 2015), which obtained only 0.08% oil using the same technique, but a higher amount of sample (150 g) and higher extraction time (4 h).
The chromatograms of the essential oils of barks and leaves of C. Leptophloeos can be viewed in Figure 1. It is possible to observe a different profile for each sample. In bark, the essential oil has highlighted the presence of compounds with lower boiling points, compared with the leaves essential oil.
Chromatogram analysis of the essential oil from C. leptophloeos barks (black) and leaves (pink) analyzed by GC/ qMS.
The complete identification of compounds can be found in the Supplementary Electronic Material (Table SI). This Table shows the tentatively identified compounds, retention time, chemical class of compounds, relative area (%), and retention index.
Figure 2 shows the distribution of relative area for each identified chemical class of compounds in both samples, while the main compounds (area % > 3 %) for at least one of the samples are presented in Figure 3.
Percentage area of the terpenes identified in the essential oil of barks and leaves from C. leptophloeos.
In the bark essential oil, 127 peaks were found, of which it was possible to identify 94 compounds (84.3%) and 29 remained without identification (15.7%). In the sample, sesquiterpenes present a larger percentage area (79.4%), followed by fatty acids (13.1%), aldehydes (3.1%), and esters (2.2%). Among the major compounds are β-caryophyllene, trans-α-bergamotene, α-selinene, δ-cadinene, β-elemenone, and hexadecenoic acid.
In the essential oil obtained from the leaves, 95 peaks were found, of which 83 compounds (87.3%) were tentatively identified and 12 were not identified (12.7%). In this sample, hydrocarbons correspond to 28.0%, sesquiterpenes 20.8%, and other classes are also present, such as sterols (19.1%), triterpenes (14.2%), fatty acids (6.3%), fatty alcohols (3.1%). Among the major compounds of leaf essential oil are β-elemenone, nonacosane, hentriacontane, γ-sitosterol, tritriacontane, lupeol, hexadecanoic acid, 5α-Stigmasta-7,16-dien-3β-ol.
Only one study was found in the literature (Da Silva et al., 2015), approaching the GC-MS analysis of essential oil of the C. leptophloeos leaves. In that work was observed the presence of only 55 compounds, with 46 tentatively identified compounds, being α-phellandrene, trans -caryophyllene, and β-phellandrene, the majors (Da Silva et al., 2015).
The antioxidant activity has been described in the literature for fatty acids (Elagbar et al., 2016) and gamma-sitosterol (Yoshida, Niki, 2003), a triterpene phytosterol present in the essential oil. Phytosterols have a well-known activity, being that one of the main, is the reduction of serum cholesterol and lipid levels (Styrczewska et al., 2015). In addition, triterpenes have been described as compounds that improve the quality of healing by regulating pro-and anti-inflammatory mediators, chemokines, growth factors, inducing granulation formation, re-epithelization, and wound contraction (Kim et al., 2013). Styrczewska et al. (2015) (Styrczewska et al., 2015). demonstrated the synergistic activity of cannabidiol with β-sitosterol inducing anti- inflammatory and collagen production activities, being phytosterol responsible for the matrix remodeling effect.
The essential oil of the leaves also presented lupeol as one of its major compounds, which presents involvement in the healing of cutaneous wounds by stimulating the migration of keratinocytes and increasing the contraction of fibroblasts in a collagen matrix (Beserra et al., 2018). Lupeol is a triterpene widely found in medicinal plants and has a varied pharmacological potency with anti-inflammatory, antioxidant, anti- infectious, antihyperglycemic, antiasthmatic, antiarthritic, cardioprotective, neuroprotective, hepatoprotective, and chemosensitizing effects (Badshah et al., 2016).
Wang et al. (2018) demonstrated the in vitro anti- cancer effect of lupeol by modifying cell viability, induction of apoptosis, migration, cell cycle arrest, and inactivation of Wnt-β-catenin signaling activity in human colorectal cancer cells. Other authors further suggest that this compound may be used in the future as an inhibitor of human osteosarcoma cell metastases (Hsu et al., 2019).
The γ-sitosterol, another phytosterol presented in leaves, has been described by its ability to increase the secretion of insulin in the presence of glucose (Sirikhansaeng et al., 2017) and anti-cancer activities interrupting the cell cycle causing apoptosis of cancer cells, being cytotoxic to cell lines the colon and liver (Endrini et al., 2014). Suttiarporn et al. (2015) also claim that phytosterol concentrations in the blood may increase the proliferation of antileukemic cells and suggest extraction of the compound for addition at higher doses in other foods and dietary supplements.
The identification and isolation of plant-derived antioxidant compounds may be a solution to treat a variety of lesions and diseases caused by oxidative stress, such as depression and hepatotoxicity (Mhalla et al., 2018).
Sesquiterpenes are the chemical class with the highest number of compounds in the essential oils of barks of C. Leptophloeos, being were found 63 sesquiterpenes (Table SI) corresponding to 67% of the total area of the chromatogram (considering the identified and unknown peaks).
As can be seen in Figures 1 and 3 the major compounds in sesquiterpenes were trans-α-bergamotene (10.8%), followed by trans-β-elemenone (5.3%), β-caryophyllene (5.1%) and α-selinene (4.4%). Already in the essential oil of leaves, 42 sesquiterpenes were found (Table SI) corresponding to only 18.5% (Figure 2) of the total area of the chromatogram. Although the essential oil of leaves of C. Leptophloeos presents many peaks of sesquiterpenes, the total percentual area was inferior when compared to the essential oil of the bark. The sesquiterpene that presented the highest relative area (Figure 4) was trans-β- Elemenone (6.3%).
Analytical curve for the analysis of phenols and flavonoids. a) Gallic acid with concentrations of 20, 40, 60, 80, 100 and 120 mg GAE g-1 analyzed at 765 nm, b) Quercitina with concentrations of 20, 40, 60, 80, 100 mg QE g-1 analyzed at 420 nm.
Govindarajan et al. (2018) identified the trans- β-elemenone compound as a major component in the essential oil of the pitanga leaves (Eugenia uniflora) and demonstrated efficacy against Anopheles subpictus, Aedes albopictus, and Culex tritaeniorhynchus larvae, as well as low toxicity for humans.
Another important compound of the essential oil, β-caryophyllene, is a bicyclic sesquiterpene with a cyclobutene ring also found in several plants, which has biological importance, anticonvulsive, antimalarial, antileishmanial, local anesthetic, spasmolytic and antimicrobial activities have been described (Fidyt et al., 2016). In addition, this compound has potential for the treatment of inflammatory diseases, atherosclerosis, ischemia, and cerebral inflammation (Viveros-Paredes et al., 2017; Hammad et al., 2018), as well as ischemic heart and liver lesions (Hammad et al., 2018).
As well as other compounds present in essential oil from C. leptophloeos that present anti-cancer activities, studies have already demonstrated that β-caryophyllene has chemo-preventive or antimutagenic properties, besides having an antioxidant role, being able to be desensitized chemo-resistant cancer cells when combined with other drugs (Di Giacomo et al., 2017 and 2018).
The trans-α-bergamotene compound has been identified as an active compound that can attract ectoparasites such as Melittobia digitata (wasps), serving as a trapping strategy, where pests are attracted away from the main crop (Yin, Wong 2019).
Li et al. (2017) found trans-α-bergamotene as one of the main compounds in the distilled fraction of basil oil and associated its presence with the ability of this oil in reducing inflammatory cytokines.
Several studies have identified the compounds α-selinene, cadinene, and elemenone, however, there is a deficiency of clinical trials demonstrating its isolated properties. Cadinene has recently been identified in the study by Zhu et al. (2019) which demonstrated its cytotoxicity and selectivity for the human liver cancer cell line. In general, studies have described such compounds as part of the class of sesquiterpenes with anti-inflammatory, bactericidal, antioxidant, and antitumor activities (Dutra et al., 2016; Fidyt et al., 2016; Viveros-Paredes et al., 2017).
Determination of phenolic and flavonoids compounds
The phenolic compounds have in their structure one or more hydroxyls directly connected to an aromatic ring. Flavonoids, inserted within phenolic compounds, are subdivided into flavonols, flavones, flavanones, anthocyanidins, and isoflavones according to their chemical structure (Singh et al., 2017; Gandhi et al., 2018).
For the analysis of phenolics compounds and flavonoids was constructed analytical curves which can be viewed in Figure 4.
The analytical curve for the quantification of the phenolic compounds showed a coefficient of determination of 0.9954 (Figure 4a), which reflects a high degree of linearity. The obtained polyphenols content, measured in mg GAE g-ˡ, was 60.02 ± 0.19 for barks and 62.56 ± 0.2 for leaves.
These values were higher than those presented by Pereira et al. (2017) (Pereira et al., 2017), which obtained
20.3 ± 0.78 mg GAE g-ˡ in its aqueous extract from barks obtained in Catimbau National Park (Pernambuco/ Brazil). Phenolic substances have a higher affinity for polar solvents such as ethyl alcohol (Tiwari et al., 2011), but high concentrations of these compounds were found in essential oil too.
The coefficient of determination obtained from the analytical curve for flavonoids was 0.9972 (Figure 4b). The total flavonoids of samples varied from 64.56 ± 0.2 mg QE g-ˡ in essential oil from barks, slightly higher than the leaves, 57.18 ± 0.17 mg QE g-ˡ.
The phenolic compounds tentatively identified by GC/qMS in the leaves correspond to only 2.15% of the area (eugenol, gamma-tocopherol, and α-tocopherol). In the bark sample, no phenolic compounds were identified. About f lavonoids, no component was tentatively identified in the samples by GC/qMS. The difficulty in identifying these classes of molecules is associated with the complexity of the sample since more than 10% of the area in both samples refers to unidentified compounds. For a more complete elucidation of these components, it is necessary to employ a methodology with greater separation power, such as comprehensive two-dimensional gas chromatography.
Phenolic compounds and flavonoids are described in the literature as they have important biological activities such as antioxidant (Rufino et al., 2009), immunomodulating (Talhaoui et al., 2016; Jarger, Parylak, Gage, 2018), anti-inflammatory (Oteiza et al., 2018), gastroprotective (Yousefian et al., 2018) and antimicrobial activity (Santos et al., 2015; Silva et al., 2016). The plant is responsible for the bactericidal activity against gram- positive bacteria E. faecalis, B. subtilis, M. luteus, and S. aureus, according to Pereira et al. (2017) (Pereira et al., 2017). This result may be promising for the evaluation of the bactericidal and bacteriostatic activity of these and other strains using the essential oil of Commiphora leptophloeos collected in the state of Sergipe.
CONCLUSIONS
In this work, several constituents of the essential oil of umburana (Commiphora leptophloeos) were tentatively identified, which present new biotechnological possibilities, indicating the beginning of great research involving plants of the caatinga biome of northeastern Brazil.
It was observed that the major compounds on the essential oil are known by their antitumor activity, creating the possibility of investigations in investigational oncology with the essential oil of umburana. Still, compounds little exploited, like cadinene, alpha-selinene, and elemenone, despite being easily found in several plants, have no clinical trials involving their biological activity in a well-defined isolated form, which could make possible the exploration in new studies.
The presence of phenolic compounds and flavonoids allows the exploration of studies with bactericidal activity investigation with strains of various bacteria, which helps in the possibility of new therapies against microbial resistance.
ACKNOWLEDGMENT
The author thanks CAPES and CNPq for the financial support.
REFERENCES
- Ahamad SR, Al-Ghadeer AR, Ali R, Qamar W, Aljarboa S. Analysis of inorganic and organic constituents of myrrh resin by GC-MS and ICP-MS: An emphasis on medicinal assets. Saudi Pharm J. 2017;25(5):788-794.
- Badshah H, Ali T, Rehman SU, Amin FU, Ullah F, Kim TH, et al. Protective effect of lupeol against lipopolysaccharide- induced neuroinflammation via the p38/c-Jun N-terminal kinase pathway in the adult mouse Brain. J Neuroimmune Pharmacol. 2016;11(1):48-60.
- Barbosa AM, Santos KS, Borges GR, Munizc AVCS, Mendonça FMR, Pinheiro MS, et al. Separation of antibacterial biocompounds from Hancornia speciosa leaves by a sequential process of pressurized liquid extraction. Sep Purif Technol. 2019;222:390-395.
- Beserra FP, Xue M, Maia GLA, Rozza AL, Pellizzon CH, Jackson CJ. Lupeol, a Pentacyclic triterpene, promotes migration, wound closure, and contractile effect In Vitro: Possible Involvement of PI3K/Akt and p38/ERK/MAPK Pathways. Molecules. 2018;23(11):2819.
- Da Silva RCS, Milet-Pinheiro P, Da Silva PCB, Da Silva AG, Da Silva MV, Navarro DMDAF, et al. (E)-Caryophyllene and α-Humulene: Aedes aegypti oviposition deterrents elucidated by gas chromatography-electrophysiological assay of Commiphora leptophloeos leaf oil. Plos One. 2015;10(12):e0144586.
- Djeridane A, Yousfi M, Nadjemi B, Boutassouna D, Stocker P, Vidal N. Antioxidant activity of some Algerian medicinal plants extracts containing phenolic compounds. Food Chem. 2006;97:654-660.
- Di Giacomo S, Abete L, Cocchiola RM, Mazzanti G, Eufemi M, Di Sotto A. Caryophyllane sesquiterpenes inhibit DNA- damage by tobacco smoke in bacterial and mammalian cells. Food Chem. Toxicol. 2018;111:393-404.
- Di Giacomo S, Di Sotto A, El-Readi M, Mazzanti G, Wink M. Chemosensitizing Properties of β-Caryophyllene and β-Caryophyllene Oxide in Combination with Doxorubicin in Human Cancer Cells. Anticancer Res. 2017;37(3):1191-1196.
- Dong L, Luo Q, Cheng LZ, Yan YM, Cheng YX, Wang SM. New terpenoids from Resina Commiphora. Fitoterapia. 2017;117:147-153.
- Dutra RC, Campos MM, Santos ARS, Calixto JB. Medicinal plants in Brazil: Pharmacological studies, drug discovery, challenges and perspectives. Pharmacol Res. 2016;112:4-29.
- Elagbar ZA, Naik RR, Shakya AK, Bardaweel SK. Fatty Acids Analysis, Antioxidant and Biological Activity of Fixed Oil of Annona muricata L. Seeds. J Chem. 2016;1-6.
- Endrini S, Rahmat A, Ismail P, Taufiq -Yap YH. Cytotoxic effect of γ-sitosterol from Kejibeling (Strobilanthes crispus) and its mechanism of action towards c-myc gene expression and apoptotic pathway. Med J Indones. 2014;23:203-208.
- Fang Y, Kang Y, Zou H, Cheng X, Xie T, Shi L, et al. β-elemene attenuates macrophage activation and proinflammatory factor production via crosstalk with Wnt/β-catenin signaling pathway. Fitoterapia . 2018;124:92-102.
- Fidyt K, Fiedorowicz A, Strządała L, Szumny A. β-caryophyllene and β-caryophyllene oxide-natural compounds of anticancer and analgesic properties. Cancer Med. 2016;5(10):3007-3017.
- Gandhi GR, Neta MTSL, Sathiyabama RG, Quintans JSS, Silva AMO, Araújo AAS, et al. Flavonoids as Th1/Th2 cytokines immunomodulators: A systematic review of studies on animal models. Phytomedicine. 2018;44:74-84.
- Govindarajan M, Rajeswary M, Senthilmurugan S, Vijayan P, Alharbi NS, Kadaikunnan S, et al. Curzerene, trans-β-elemenone, and γ-elemene as effective larvicides against Anopheles subpictus, Aedes albopictus, and Culex tritaeniorhynchus: toxicity on non-target aquatic predators. Environ Sci Pollut Res. 2018;25(11):10272-10282.
- Hammad FT, Ojha S, Azimullah S, Lubbad L. Does β-caryophyllene protect against renal dysfunction following ischemia-reperfusion injury in the rat? Int J Physiol Pathophysiol Pharmacol. 2018;10(6):63-171.
- Hou HS, Bonku EM, Zhai R, Zeng R, Hou YL,Yang ZH, et al. Extraction of essential oil from Citrus reticulate Blanco peel and its antibacterial activity against Cutibacterium acnes (formerly Propionibacterium acnes). Heliyon. 2019,5:1-6.
- Hsu MJ, Peng SF, Chuen FS, Tsia CH, Tsai FJ, Huang CY, et al. Lupeol suppresses migration and invasion via p38/MAPK and Pl3K/Akt signaling pathways in human osteosarcoma U-2 OS cells. Biosci Biotechnol Biochem. 2019;83(9):1-11.
- Jarger BN, Parylak SL, Gage FH. Mechanisms of dietary flavonoid action in neuronal function and neuroinflammation. Mol Asp Med. 2018;61:50-62.
- Kim WK, Song SY, Oh WK, Kaewsuwan S, Tran TL, Kim WS, et al. Wound-healing effect of ginsenoside Rd from leaves of Panax ginseng via cyclic AMP-dependent protein kinase pathway. Eur J Pharmacol. 2013;702(1-3):285-293.
- Li H, Ge Y, Zhou Y, Zhang X, Zhang J, Fu Q. Evaluation of the chemical composition, antioxidant and anti-inflammatory activities of distillate and residue fractions of sweet basil essential oil. J Food Sci Technol. 2017;54(7):1882-1890.
- Mhalla D, Bouassida KZ, Chawech R, Bouaziz A, Makni S, Jlaiel L, et al. Antioxidant, hepatoprotective and antidepressant effects of Rumex tingitanus extracts and identification of a new bioactive compound. Biomed Res Int. 2018;59:1-10.
- Oteiza PI, Fraga CG, Mills DA, Taft DH. Flavonoids and the gastrointestinal tract: local and systemic effects. Mol Asp Med . 2018;61:41-49.
- Pereira JJS, Pereira APC, Jandú JJB, Da Paz JÁ, Crovella S, Correia MTS, et al. Commiphora leptophloeos phytochemical and antimicrobial characterization. Front Microbiol. 2017;8: 52-62.
- Rhourrhi-Frih B, West C, Pasquier L, Chaimbault P, Lafosse M. Classification of natural resins by liquid chromatography- mass spectrometry and gas chromatography-mass spectrometry using chemometric analysis. J Chromatogr A. 2012;1256:177-190.
- Rufino MSM, Fernades FAN, Alves RE, Brito ES. Free radical-scavenging behaviour of some north-east Brazilian fruits in a DPPHradical dot system. Food Chem . 2009;114:693-695.
- Santos ATB, Araújo TFS, Silva LCN, Silva CB, Oliveira AFM, Araújo JM, et al. Organic extracts from Indigofera suffruticosa leaves have antimicrobial and synergic actions with erythromycin against Staphylococcus aureus Front Microbiol . 2015;6:1-7.
- Silva APSA, Silva LCN, Fonseca CSM, Araújo JM, Correia MTS, Cavalcanti MS, et al. Antimicrobial activity and phytochemical analysis of organic extracts from Cleome spinosa Jaqc. Front Microbiol . 2016;7:1-10.
- Silva RCS, Ferreira RLC, Da Silva JAA, Meunier IMJ, Berger R. Phytosociological aspects and growth of Commiphora leptophloeos in Brazilian Semiarid. Braz J Forest Res. 2017;37:11-18.
- Singh B, Singh JP, Kaur A, Singh N. Phenolic composition and antioxidant potential of grain legume seeds: a review. Food Res Int. 2017;101:1-6.
- Sirikhansaeng P, Tanee T, Sudmoon R, Chaveerach A. Major phytochemical as γ-sitosterol disclosing and toxicity testing in lagerstroemia species. Evid Based Complement Alternat Med. 2017;2017:1-10.
- Styrczewska M, Kostyn A, Kulma A, Majkowska-Skrobek G, Augustyniak D, Prescha A, et al. Flax fiber hydrophobic extract inhibits human skin cells inflammation and causes remodeling of extracellular matrix and wound closure activation. BioMed Res Int. 2015;2015:862391.
- Suttiarporn P, Chumpolsri W, Mahatheeranont S, Luangkamin S, Teepsawang S, Leardkamolkarn V. Structures of Phytosterols and Triterpenoids with Potential Anti-Cancer Activity in Bran of Black Non-Glutinous Rice. Nutrients. 2015;7(3):1672-1687.
- Talhaoui N, Veza T, Caravaca AMG, Fernández-Gutiérrez A, Galvez J, Carretero AS. Phenolic compounds and in vitro immunomodulatory properties of three Andalusian olive leaf extracts. J Funct Foods. 2016;22:270-277.
- Tiwari P, Kumar B, Kaur M, Kaur G, Kaur H. Phytochemical screening and Extraction: a review. Int Pharm Sci. 2011;1:98-106.
- Trentin DS, Giordani RB, Zimmer KR, Da Silva AG, Da Silva MV, Correia MTS, et al. Potential of medicinal plants from the Brazilian semi-arid region (Caatinga) against Staphylococcus epidermidis planktonic and biofilm lifestyles. J Ethnopharmacol. 2011;137(1):327-335.
- Viveros-Paredes JM, González-Castañeda RE, Gertsch J, Chaparro-Huerta V, López-Roa RI, Vázquez-Valls E, et al. Neuroprotective Effects of β-Caryophyllene against Dopaminergic Neuron Injury in a Murine Model of Parkinson’s Disease Induced by MPTP. Pharmaceuticals. 2017;10(3):60.
- Wang Y, Hong D, Qian Y, Tu X, Wang K, Yang X, et al. Lupeol inhibits growth and migration in two human colorectal cancer cell lines by suppression of Wnt-β-catenin pathway. Onco Targets Ther. 2018;11:9787-7999.
- Yeo SK, Ali AY, Hayward OA, Turnham D, Jackson N, Bowen ID, et al. β-bisabolene, a sesquiterpene from the essential oil extract of opoponax (Commiphora guidottii), exhibits cytotoxicity in breast cancer cell lines. Phytother Res. 2016;30(3):418-425.
- Yin JL, Wong WS. Production of santalenes and bergamotene in Nicotiana tabacum plants. Plos One . 2019;14(1):1-16.
- Yoshida Y, Niki E. Antioxidant effects of phytosterol and its components. J Nutr Sci Vitaminol. 2003;49(4):277-280.
- Yousefian M, Shakour N, Hosseinzadeh H, Hayes AW, Hadizadeh F, Karimi G. The natural phenolic compounds as modulators of NADPH oxidases in hypertension. Phytomedicine . 2018;55:200-2013.
- Zhu S, Qin DWS, Yang C, Li G, Cheng Y. Commiphora lactam A, a cytotoxic sesquiterpenoidal lactam from resina Commiphora. Fitoterapia . 2019;134:382-388.
SUPPLEMENTARY ELECTRONIC MATERIAL
