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Article

Chemical Characterization and Biological Activity of Varronia curassavica Jacq. Essential Oil (Boraginaceae) and In Silico Testing of α-Pinene

by
José Thyálisson da Costa Silva
1,
Viviane Bezerra da Silva
2,
Sabrina Bezerra da Silva
3,
Maria Ivaneide Rocha
3,
Adrielle Rodrigues Costa
3,
Jailson Renato de Lima Silva
3,
Marcos Aurélio Figueirêdo dos Santos
4,
Maria Elizete Machado Generino
4,
Jeovane Henrique de Souza
3,
Maraiza Gregorio de Oliveira
3,
Clara Mariana Gonçalves Lima
5,*,
Raimundo Luiz Silva Pereira
5,
Renata Ferreira Santana
6,
Isaac Moura Araujo
5,
Maria Flaviana Bezerra Morais-Braga
1,
Talha Bin Emran
7,8,9,
Henrique Douglas Melo Coutinho
5,* and
José Weverton Almeida-Bezerra
1
1
Cariri Applied Mycology Laboratory, Regional University of Cariri, Crato 63105-000, CE, Brazil
2
Applied Ecology and Phytochemistry Laboratory, Federal University of Pernambuco, Recife 50740-600, PE, Brazil
3
Plant Ecophysiology Laboratory, Regional University of Cariri, Crato 63105-000, CE, Brazil
4
Applied Botany Laboratory, Regional University of Cariri, Crato 63105-000, CE, Brazil
5
Laboratory of Microbiology and Molecular Biology, Regional University of Cariri, Crato 63105-000, CE, Brazil
6
Department of Food Science and Engineering, Southwestern Bahia State University, Itapetinga 45083-900, BA, Brazil
7
Department of Pathology and Laboratory Medicine, Warren Alpert Medical School, Brown University, Providence, RI 02912, USA
8
Legorreta Cancer Center, Brown University, Providence, RI 02912, USA
9
Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Dhaka 1207, Bangladesh
*
Authors to whom correspondence should be addressed.
Analytica 2024, 5(4), 499-511; https://doi.org/10.3390/analytica5040034
Submission received: 29 June 2024 / Revised: 31 July 2024 / Accepted: 30 September 2024 / Published: 3 October 2024
(This article belongs to the Topic Discovery of Bioactive Compounds from Natural Organisms and Their Molecular Mechanisms against Diseases)
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Abstract

:
Multidrug-resistant bacteria have complicated the treatment of gastrointestinal diseases; their microbial resistance stems from the indiscriminate use of medications and the transfer of resistance genes. Varronia curassavica Jacq., a plant traditionally used to treat rheumatic and gastrointestinal diseases in underserved populations, has sparked interest as a potential source of antimicrobial compounds. This study aimed to investigate the chemical composition and antibacterial effects of V. curassavica essential oil and to evaluate its toxicity in Drosophila melanogaster. The essential oil was extracted through hydrodistillation and its chemical composition was determined using GC-MS. Antibacterial tests were performed with microdilution. The results showed the presence of major compounds including α-pinene and β-caryophyllene. The essential oil did not show relevant MIC, but it enhanced the effects of the antibiotics, gentamicin, norfloxacin, and oxacillin. It exhibited no toxicity and did not affect geotaxis, even at high concentrations. The in silico analysis of α-pinene revealed low toxicity; however, its permeability to the BBB shows that caution is needed in its application. These results indicate that the essential oil of V. curassavica shows promising potential in enhancing pharmaceuticals to prevent increased bacterial resistance. In addition, it demonstrated safe aspects when tested on D. melanogaster.

1. Introduction

Multidrug-resistant bacteria (MDR) pose a significant threat to public health, as the increasing resistance of these bacteria renders antibiotics ineffective in eliminating them or preventing their multiplication in the human body. This results in various serious health complications for individuals, potentially leading to death and, consequently, increasing the number of fatalities caused by bacterial infections. In recent decades, several factors have contributed to the evolution of bacteria, culminating in the emergence of super-resistant strains. These changes occurred due to mutations, recombinations, and various genetic modifications, including the presence of efflux pumps, in addition to inadequate and uncontrolled exposure to antibiotics [1,2,3,4,5].
MDR bacterial strains are common, especially in hospital settings, where infections frequently occur due to the presence of many microorganisms, affecting people with compromised immune systems and spreading rapidly. Bacterial strains such as Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa are of particular relevance due to their potent resistance mechanisms [6,7,8,9]. Thus, the use of medicinal plants as treatments for diseases has been a practice advocated by traditional populations throughout history, becoming more common in regions with limited access to healthcare services and scarce medications because of their easy accessibility and low cost [10,11].
The therapeutic activities of medicinal and aromatic plants are considered an effective complement to treatments and health maintenance, especially when associated with essential oils that are extracted from plant materials. As an alternative in combating bacterial infections, the use of essential oils has attracted more attention in research due to their complex composition (derived from plants’ secondary metabolites) and diverse biological activities, such as antiparasitic, antioxidant, anti-inflammatory, antibacterial, and antifungal [12,13,14,15].
Notably, the Boraginaceae family possesses various important medicinal properties that are of clinical relevance, with promising applications as therapeutic supplements [16,17,18]. Varronia curassavica Jacq. is one of the standout species, valued both pharmaceutically for its medicinal activities and economically due to the essential oil extracted from its leaves. It is popularly used in various forms, such as teas, extracts, decoctions, ointments, and tinctures, and is especially recognized for its anti-inflammatory effects, as well as for treating rheumatic diseases, myalgia, arthritis, and stomach ulcers [19,20].
Research on the ethnopharmacological application of V. curassavica has highlighted the plant’s potential biological effects as an antimicrobial, demonstrating efficacy in controlling pathogenic microorganisms. Additionally, the essential oil of this plant does not exhibit toxicity. Thus, this study aimed to quantify the chemical composition of the essential oil of V. curassavica, evaluate its antibacterial efficacy and drug-enhancing potential, examine its in vivo toxicity levels in the model organism Drosophila melanogaster, and perform an in silico analysis of the major phytochemical.

2. Materials and Methods

2.1. Botanical Material Collection

The botanical material, the leaves of V. curassavica, was collected in the municipality of Jardim, Ceará, Brazil, at coordinates latitude −7.554917 W and longitude −39.306611 S, during January/2022. A voucher specimen of the collected plant material was deposited in the Herbarium Caririense Dárdano de Andrade Lima—HCDAL, at the Universidade Regional do Cariri—URCA, under voucher number 15.291. Additionally, the research was registered in the Sistema Nacional de Gestão do Patrimônio Genético e do Conhecimento Tradicional Associado (SisGen), with code AEFC723, and in the Sistema de Autorização e Informação em Biodiversidade (SisBio), with permit number 82789-1.

2.2. Essential Oil Extraction

For the extraction of the essential oil, the collected leaves of V. curassavica were naturally dried and manually crushed to increase the surface area for solvent contact. Subsequently, they were placed in a 5 L volumetric flask with 2 L of distilled water and subjected to constant boiling for 2 h, coupled with the Clevenger system. Each extraction utilized 200 g of leaves. After each extraction, the resulting oil was stored in an amber-colored bottle, at a refrigeration temperature of 4 °C.

2.3. Phytochemical Analysis of Essential Oil by Gas Chromatography

The gas chromatography (GC) analysis was conducted using an Agilent Technologies 6890N GC-FID system (Agilent Technologies, Santa Clara, CA, USA), which was equipped with a DB-5 capillary column (30 m × 0.32 mm; 0.50 mm) and linked to an FID detector. The temperature program involved initial heating to 60 °C (1 min), followed by an increase to 180 °C, at a rate of 3 °C per minute. The injector and detector were both maintained at 220 °C, with a split ratio of 1:10. Helium served as the carrier gas, at a flow rate of 1.0 mL/min. The injected volume of V. curassavica essential oil was 1 μL, diluted in chloroform (1:10). Two replicates of the samples were processed using the same method. Component relative concentrations were calculated based on GC peak areas, without the utilization of correction factors.
Constituent identification relied on several methods, including retention index (RI) determination, using a reference set of n-alkanes (C7–C30) under the same experimental conditions. This identification was further validated through comparison with mass spectra library searches (NIST and Wiley) and referenced mass spectra literature [21]. The relative quantities of individual components were then calculated based on their respective gas chromatography (GC) peak areas, as measured by the flame ionization detector (FID) response.

2.4. Antibacterial Activity

2.4.1. Strains, Culture Media, and Drugs

To assess antibacterial activity and minimum inhibitory concentration (MIC), standard and multidrug-resistant bacterial strains were employed. Standard strains included Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 25853, and Staphylococcus aureus ATCC 25923, while the multidrug-resistant strains encompassed E. coli 06, P. aeruginosa 24, and S. aureus 10 (Table 1) [22]. Brain Heart Infusion (BHI, Merck KGaA, Darmstadt, Germany) culture medium was utilized in accordance with the manufacturer’s recommendations.
After the bacterial strains had grown, the samples were diluted in test tubes containing 3 mL of sterile saline solution (0.9% NaCl) and agitated using a vortex device. Turbidity was then compared to the McFarland standard of 0.5 scale (equivalent to 1.5 × 108 colony-forming units/mL) [23]. The antibiotics used for biological testing and to assess the potential enhancing activity of EOVC were gentamicin, oxacillin and norfloxacin, all diluted in distilled water.

2.4.2. Minimum Inhibitory Concentration (MIC)

To determine the minimum inhibitory concentration (MIC) of the essential oil responsible for inhibiting the complete growth of bacterial strains, the methodology used in [24] was adopted. A 1000 µL solution was prepared, consisting of 100 µL of inoculum and 900 µL of liquid BHI culture medium, mixed in Eppendorf tubes and then applied to a 96-well plate, with 100 µL of the solution added to each well. Subsequently, EOVC was added, with a range of concentrations, from 0.5 to 512 µg/mL. The plates were numbered and incubated for 24 h, at 37° C.
After the 24 h incubation period, 20 μL of liquid resazurin was added to each well. Resazurin undergoes a redox reaction in the presence of bacterial growth. Following a 1 h reaction period, the plates were analyzed based on the bioindicator coloration. The persistence of violet coloration indicated no bacterial growth, while a change to light pink coloration indicated bacterial growth.

2.4.3. Activity Modifying the Action of Antibiotics

To evaluate the modifying effect of the essential oil, the MIC results of multidrug-resistant bacteria were utilized to determine the sub-inhibitory concentration (MIC/8). This concentration was then combined with antibiotics in different proportions, ranging from 0.1 to 512 µg/mL. For the tests, 1162 µL of 10% BHI and 150 µL of inoculum were used. The control tube, on the other hand, consisted of 1350 µL of BHI and 150 µL of bacterial suspension [25]. The tests followed the microdilution methodology in wells, with antibiotic concentrations (0.5 to 512 µg/mL) dissolved in 100 µL in each well, up to the penultimate well. The plates were then incubated for 24 h at 37 °C and conducted in triplicate.

2.5. Toxicity Test with Drosophila melanogaster

2.5.1. Breeding and Storage of D. melanogaster

The species D. melanogaster was maintained in cornmeal composed of 1% w/v brewer’s yeast, 2% w/v sucrose, 1% w/v powdered milk, and 0.08% w/v methylparabenonipage. The flies remained at room temperature (25 °C) and relative humidity (60–70%) over a 12 h light/dark photoperiod [26].

2.5.2. Toxicological Tests

The groups received different dosages of 100, 500, and 1000 µg/mL of the oil, which was dissolved in ethanol (1%) and mixed with the fly diet over a 5-day exposure period. The test was conducted in triplicate, and every 24 h period, the count of dead flies was recorded until the end of the experiment [26].

2.5.3. Negative Geotaxis Assessment

To assess changes in the locomotor activity of the flies, the Negative Geotaxis test was performed. This test evaluated whether the essential oil was effective in reducing the flight height to no more than 6 cm in a vertical vial within a 5 s period. The tests were conducted five times, with each vial containing 20 adult flies, and these were compared to the control group [26].

2.6. In Silico Prediction of ADMET

To perform the in silico prediction of the major compound, identified as α-Pinene (42.26%), pkCSM, which was developed by the Biosig Lab at the University of Melbourne (Victoria, Australia), was used. This server was used for ADMET predictions of the compound, predicting the pharmacokinetic properties of ADMET (absorption, distribution, metabolism, and toxicity), which was the main focus [27].

2.7. Statistical Analysis

All assays were conducted in triplicate. The results were analyzed using GraphPad Prism version 6 (Graph Pad Software Inc., San Diego, CA, USA), employing a one-way analysis of variance (ANOVA), followed by Tukey’s post-hoc test. Significance was considered at p < 0.05.

3. Results

3.1. Chemical Composition

Based on the results obtained from the GC-MS analysis, it was possible to analyze the chemical composition of the essential oil that was extracted from the leaves of Varronia curassavica, as presented in Table 2. The investigation identified 11 chemical components, representing 94.66% of the oil’s composition. Most of its composition consisted of oxygenated monoterpenes (45.08%) and oxygenated sesquiterpenes (43.25%). The main component among the monoterpenes was α-pinene (42.26%), while the main sesquiterpene identified was β-caryophyllene (22.08%).

3.2. Antibacterial Activity

The evaluation of the antibacterial activity, which was conducted on the essential oil of the V. curassavica leaves, against standard strains of E. coli, P. aeruginosa, and S. aureus did not exhibit significant antimicrobial activity. When assessing the minimum inhibitory concentration (MIC), the results obtained exceeded 512 μg/mL, a concentration considered clinically irrelevant. Similar results were observed against multidrug-resistant strains of these bacteria (E. coli 06, P. aeruginosa 24, and S. aureus 10), with MIC values also exceeding 512 μg/mL, indicating no antibacterial activity.

3.3. Activity Modifying the Action of Antibiotics

As shown in Figure 1, the EOVC results showed a potential enhancing effect when combined with the antibiotics, demonstrating efficient modification potential. There was a significant decrease in the MIC of the referenced antibiotics (gentamicin, norfloxacin, and oxacillin) against the bacterial strains. Gentamicin, when combined with EOVC, significantly reduced the MIC against all bacteria, including P. aeruginosa 24 (MIC = 8 μg/mL); E. coli 06 (MIC = 1.58 μg/mL); and S. aureus 10 (MIC = 3.17 μg/mL). EOVC positively influenced this action.
The combination of EOVC with oxacillin did not exhibit a positive modifying action against P. aeruginosa 24 (MIC = 1024 μg/mL) or E. coli 06 (Figure 1), which are both classified as Gram-negative bacteria. However, it reduced the cell viability of S. aureus 10 (MIC = 0.5 μg/mL), classified as Gram-positive, indicating that the enhanced action directly affected its bactericidal action.
Additionally, norfloxacin showed significant reductions when combined with the essential oil, significantly lowering the MIC against both E. coli 06 (MIC = 20.15 μg/mL) and S. aureus 10 (MIC = 16 μg/mL). However, the effect on P. aeruginosa 24 was not significant and it depended on the dose, as it exhibited a synergistic effect at higher concentrations compared to the others.

3.4. Toxicity against Drosophila melanogaster

As shown in Figure 2, the results of the toxicity tests after the ingestion of the essential oil through the diet of the model organism, Drosophila melanogaster, demonstrated that there were no significant changes in mortality when compared to the control test. The test results indicated very low or even no changes, suggesting that these organisms were not affected in a way that would increase their mortality, even at higher concentrations, such as 1000 µg/g, over the course of 5 days of exposure, highlighting low toxicity in the in vivo tests.
Furthermore, as depicted in Figure 3, it was investigated whether EOVC affected the locomotor system of these flies by observing if there were significant changes in the negative geotaxis of D. melanogaster. The results obtained indicated that there were no alterations in the basic functioning of the locomotor system. This indicated that the essential oil has low levels of toxicity regarding the mobility of D. melanogaster; however, it is necessary to consider the possible cytotoxicity and genotoxicity action.

3.5. In Silico Analysis (pkCMS)

The molecular analysis of α-Pinene (Table 3) revealed significant properties related to this molecule. The number of rotatable bonds in the molecule indicated a low molecular flexibility in this compound. Additionally, the aqueous partition coefficient (logP) showed characteristics associated with lipophilicity, falling within the recommended parameters for drugs.
Table 4 displays the ADMET (absorption, distribution, metabolism, and toxicity) properties of α-Pinene. In terms of absorption and distribution, intestinal absorption showed favorable results, as well as permeability across the blood–brain barrier (BBB), which can also be seen positively. Additionally, α-Pinene is neither a substrate nor an inhibitor of permeability glycoproteins (P-gp), which are associated with active efflux from cells.
A positive aspect regarding the metabolism of the compound is that it does not inhibit cytochrome P450 (CYP) enzymes, which play a crucial role in drug metabolism. Therefore, the inhibition of these enzymes can result in side effects or drug interactions. Furthermore, α-Pinene does not present toxicological concerns, as shown in the table, suggesting that it has a good application when used in isolation.

4. Discussion

Various ethnopharmacological uses and applications of V. curassavica are employed in the treatment of gastrointestinal diseases, in addition to its promising anti-inflammatory and antimicrobial activity, which is influenced by terpenoids [19,28]. Phytochemical studies have identified α-pinene and β-caryophyllene as the main components, with variations of 56.69–25.32% and 21.78–12.52%, respectively [20,29,30,31,32]. However, other studies have found discrepancies, identifying sesquiterpenes as predominant, with β-caryophyllene comprising 25.4–23.26% [33,34] and shyobunol representing 27.46–24.24% of the total [35].
The observed percentage change can be affected by seasonal variations; environmental conditions and the specific plant parts used [36]. Collecting and extracting essential oil at different times of the year; and changes in abiotic factors [37], such as soil and seasonality, can influence the variation of some of the chemically active compounds present [38,39]. Other factors that can cause variations include plant age [32]; photosynthetically active radiation; the choice of drying process [40]; variations caused by air, high temperatures, parasitic herbivory [41]; and changes in light and different seasons [19].
Studies have shown that EOVC exhibits varied antibacterial activities, which may be positive or insignificant. The efficacy of the oil against different bacterial strains is directly influenced by the phytochemicals present. In previous experiments, ß-caryophyllene, which was identified as the major compound (25.4%), presented a MIC of 64 μg/mL against S. aureus, Bacillus cereus, and E. coli [33]. Another study found that Tricyclene (23.9%) has a MIC of 170 μg/mL against S. aureus 6538 [42]. Furthermore, sabinene (31.99%) was shown to be effective against E. coli and S. aureus [43], highlighting the need for caution regarding phytochemistry.
Essential oils can affect electron transport, DNA, and protein synthesis, and can influence the absorption and inhibition of essential enzymes, culminating in cell death [44,45]. This effect can be attributed to the ability of oils to cross the outer membranes of bacterial cells and the inner cytoplasmic membranes, resulting in the disintegration of cellular structures and increased permeability to other compounds [46]. However, essential oils can also have a bacteriostatic effect, temporarily inhibiting the reproduction of bacteria, such as V. curassavica, which has bacteriostatic action against Gram-positive bacteria [28].
The use of EOVC in conjunction with antibiotics may enhance the therapeutic effect of the latter. Research indicates that the compound responsible for this synergistic action may be partially linked to α-pinene [47], as this compound presents promising biological activities, such as antibacterial activity against E. coli and S. aureus [48,49]. Specifically, E. coli is sensitive to α-pinene at concentrations ranging from 98 to 512 μg/mL (MIC) [50,51] and S. aureus with 68.6 ± 7.9 μg/mL (IC50) [52]. Furthermore, analyses of isolated α-pinene have shown that it can damage membrane proteins [53].
The prediction made in this study suggests a high probability of distribution beyond the blood–brain barrier (BBB), which has been confirmed by in vivo tests performed by Satou et al. [54], in which α-pinene demonstrated significant transport to the brain. This is considered positive due to the neuroprotective effect of the compound, which modulates anti-inflammatory gene expression and reduces neuroinflammation, in addition to potentially restoring the BBB function in tested rats [55,56]. By effectively modulating the NF-κB pathway, which results in a promising anti-inflammatory effect, α-pinene can also act through the Nrf2/HO-1 regulatory pathway, exhibiting antioxidant action; this pathway is crucial in defending against damage caused by oxidative stress, increasing the activity of antioxidant enzymes [57,58,59].
The sesquiterpene compound, β-caryophyllene, has been shown to have significant antimicrobial activity and was effective against bacterial resistance, particularly against S. aureus, with a minimum inhibitory concentration (MIC) of 32 μg/mL. Furthermore, β-caryophyllene potentiates the effect of norfloxacin on other pathogenic strains [60,61]. Studies have indicated that it acts as an antibiofilm agent against Streptococcus mutans [62] and may cause changes in the cell membrane, such as the formation of pores that lead to the leakage of intracellular contents, as previously observed in Bacillus cereus [63].
The cytotoxic and genotoxic evaluation is of great importance, since the absence of toxicity in D. melanogaster exposed to EOVC can be compared with the results of tests on herbivorous insects, such as Tetranychus urticae and Myzus persicae, which also did not show toxicity [34]. However, the cytotoxic analysis of fibroblasts revealed the need for caution in its application, since a mean lethal concentration (LC50) of 138.1 μg/mL was demonstrated [31], which may increase with the age of the plant [32].

5. Conclusions

The results of this study indicate that the essential oil of Varronia curassavica is predominantly composed of monoterpenes, with an emphasis on α-Pinene, followed by sesquiterpenes, such as β-Caryophyllene. In vitro tests revealed that the essential oil of V. curassavica does not have antibacterial activity on its own, but it did demonstrate potential to increase the efficacy of drugs such as gentamicin, oxacillin, and norfloxacin. In addition, the toxicity tests did not indicate harmful effects on Drosophila melanogaster.
The presence of α-Pinene suggests the need for caution in applications due to its metabolic interactions and ability to cross the blood–brain barrier (BBB). Despite this, the study had limitations: it highlighted the need to investigate potential cytotoxic and genotoxic actions and for a detailed analysis of the molecular interactions between phytochemicals and drugs, including how these interactions can affect biological activity, especially in relation to antibacterial action.

Author Contributions

Conceptualization, J.W.A.-B., C.M.G.L. and J.T.d.C.S.; methodology, V.B.d.S., J.R.d.L.S. and R.L.S.P.; formal analysis, V.B.d.S., A.R.C., C.M.G.L. and H.D.M.C.; investigation, M.F.B.M.-B., M.G.d.O., I.M.A., R.F.S. and M.A.F.d.S.; resources, S.B.d.S., M.F.B.M.-B. and I.M.A.; data curation, M.I.R., M.A.F.d.S. and M.E.M.G.; writing—original draft preparation, S.B.d.S., M.I.R., A.R.C., M.E.M.G., J.H.d.S., M.G.d.O., R.L.S.P. and J.W.A.-B.; writing—review and editing, J.T.d.C.S., R.F.S. and T.B.E.; visualization, J.R.d.L.S., J.H.d.S., R.F.S., H.D.M.C. and T.B.E.; supervision, A.R.C.; project administration, J.T.d.C.S. and T.B.E. All authors have read and agreed to the published version of the manuscript.

Funding

This study did not receive funding for its implementation.

Data Availability Statement

Data are contained within the article.

Acknowledgments

The authors extend their appreciation to the Researchers Supporting Project, number (RSPD2024R620), King Saud University, Riyadh, Saudi Arabia. The authors would like to thank the Laboratório de Micologia Aplicada do Cariri (LMAC), Laboratório de Microbiologia e Biologia Molecular (LMBM), and Universidade Regional do Cariri (URCA).

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Freires, M.S.; Junior, O.M.R. Bacterial Resistance to Indiscriminate Use of Azithromycin versus COVID-19: An Integrative Review. Res. Soc. Dev. 2022, 11, e31611125035. [Google Scholar] [CrossRef]
  2. Makabenta, J.M.V.; Nabawy, A.; Li, C.H.; Schmidt-Malan, S.; Patel, R.; Rotello, V.M. Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections. Nat. Rev. Microbiol. 2021, 19, 23–36. [Google Scholar] [CrossRef]
  3. EFSA (European Food Safety Authority); ECDC (European Centre for Disease Prevention and Control). The European Union Summary Report on Antimicrobial Resistance in zoonotic and indicator bacteria from humans, animals and food in 2018/2019. EFSA J. 2021, 19, 1–179. [Google Scholar] [CrossRef]
  4. Arbab, S.; Iqbal, M.K.; Hussain, T.; Yasmeen, R.; Bano, R.; Abbas, G. Antimicrobial drug resistance against Escherichia coli and its harmful effect on animal health. Vet. Med. Sci. 2022, 8, 1780–1786. [Google Scholar] [CrossRef] [PubMed]
  5. Huemer, M.; Mairpady Shambat, S.; Brugger, S.D.; Zinkernagel, A.S. Antibiotic resistance and persistence—Implications for human health and treatment perspectives. EMBO Rep. 2020, 21, e51034. [Google Scholar] [CrossRef] [PubMed]
  6. Avershina, E.; Shapovalova, V.; Shipulin, G. Fighting antibiotic resistance in hospital-acquired infections: Current state and emerging technologies in disease prevention, diagnostics and therapy. Front. Microbiol. 2021, 12, 707330. [Google Scholar] [CrossRef]
  7. Teixeira, A.R.; Figueiredo, A.F.C.; França, R.F. Resistência bacteriana relacionada ao uso indiscriminado de antibióticos. Rev. Saúde Foco 2019, 11, 853–875. [Google Scholar]
  8. Christaki, E.; Marcou, M.; Tofarides, A. Antimicrobial resistance in bacteria: Mechanisms, evolution, and persistence. J. Mol. Evol. 2020, 88, 26–40. [Google Scholar] [CrossRef]
  9. Jian, Z.; Li, Y.; Xiao, X.; Zhang, S.; Zhao, Y.; Zhang, L.; Dong, L.; Wang, Y. Antibiotic resistance genes in bacteria: Occurrence, spread, and control. J. Basic Microbiol. 2021, 61, 1049–1070. [Google Scholar] [CrossRef]
  10. Ribeiro, D.A.; Macedo, D.G.; Oliveira, L.G.S.; Santos, M.O.; Almeida, B.V.; Macedo, J.G.F.; Macêdo, M.J.F.; Souza, R.K.D.; Araújo, T.M.S.; Almeida-Souza, M.M. Conservation priorities for medicinal woody species in a cerrado area in the Chapada do Araripe, northeastern Brazil. J. Environ. Sustain. 2019, 21, 61–77. [Google Scholar] [CrossRef]
  11. Rodrigues, F.C.; Santos, A.T.L.; Machado, A.J.T.; Bezerra, C.F.; Freitas, T.S.; Coutinho, H.D.M.; Morais-Braga, M.F.B.; Almeida-Bezerra, J.W.; Duarte, A.E.; Kamdem, J.P.; et al. Chemical composition and anti-Candida potencial of the extracts of Tarenaya spinosa (Jacq.) Raf. (Cleomaceae). Comp. Immunol. Microbiol. Infect. Dis. 2019, 64, 14–19. [Google Scholar] [CrossRef] [PubMed]
  12. Bortoluzzi, M.M.; Schmitt, V.; Mazur, C.E. Effect of herbal medical plants on anxiety: A brief review. Res. Soc. Dev. 2020, 9, e02911504. [Google Scholar] [CrossRef]
  13. Nuță, D.C.; Limban, C.; Chiriță, C.; Chifiriuc, M.C.; Costea, T.; Ioniță, P.; Nicolau, L.; Zarafu, I. Contribution of essential oils to the fight against microbial biofilms—A review. Processes 2021, 9, 537. [Google Scholar] [CrossRef]
  14. Alves, N.V.; Peres, M.M.; Lopes, L.A.; Rodrigues, T.G.L. Potencial farmacológico dos óleos essenciais: Uma atualização. In Práticas Integrativas e Complementares: Visão Holística e Multidisciplinar. Ed. Científica Digit. 2022, 13, 144–160. [Google Scholar] [CrossRef]
  15. Tariq, S.; Wani, S.; Rasool, W.; Shafi, K.; Bhat, M.A.; Prabhakar, A.; Shalla, A.H.; Rather, M.A. A comprehensive review of the antibacterial, antifungal and antiviral potential of essential oils and their chemical constituents against drug-resistant microbial pathogens. Microb. Pathog. 2019, 134, 103580. [Google Scholar] [CrossRef]
  16. Martim, J.K.; Maranho, L.T.; Costa-Casagrande, T.A. Role of the chemical compounds present in the essential oil and in the extract of Cordia verbenacea DC as an anti-inflammatory, antimicrobial and healing product. J. Ethnopharmacol. 2021, 265, 113300. [Google Scholar] [CrossRef]
  17. Jabbar, A.A.; Abdullah, F.O.; Hassan, A.O.; Galali, Y.; Hassan, R.R.; Rashid, E.Q.; Salih, M.I.; Aziz, K.F. Ethnobotanical, Phytochemistry, and Pharmacological Activity of Onosma (Boraginaceae): An Updated Review. Molecules 2022, 27, 8687. [Google Scholar] [CrossRef]
  18. Nigussie, G.; Ibrahim, F.; Neway, S. A Phytopharmacological Review on a Medicinal Plant: Cordia africana Lam. J. Trop. Pharm. Chem. 2021, 5, 254–263. [Google Scholar] [CrossRef]
  19. Toghlobi, G.S.S.; Arantes, R.A.; Knudsen, B.G.; Tabach, R.; Pereira, M.A.A.; Carvalho, R.G.; Ferraz, R.R.N.; Rodrigues, F.S.M. Usos clínicos do fitoterápico da erva-baleeira (Varronia curassavica jacq.): Revisão da literatura. Int. J. Health Manag. Rev. 2022, 8, 1–10. [Google Scholar] [CrossRef]
  20. Marques, A.P.S.; Bonfim, F.P.G.; Dantas, W.F.C.; Puppi, R.J.; Marques, M.O.M. Chemical composition of essential oil from Varronia curassavica Jacq. accessions in different seasons of the year. Ind. Crops Prod. 2019, 140, 111656. [Google Scholar] [CrossRef]
  21. Adams, R.P. Identification of Essential Oil Components by Gas Chromatography/Mass Spectrometry, 5th ed.; Texensis Publishing: Gruver, TX, USA, 2017. [Google Scholar]
  22. Almeida, R.S.; Freitas, P.R.; Araújo, A.C.J.; Alencar Menezes, I.R.; Santos, E.L.; Tintino, S.R.; Moura, T.F.; Ribeiro-Filho, J.; Ferreira, V.A.; Silva, A.C.A.; et al. GC-MS profile and enhancement of antibiotic activity by the essential oil of Ocotea odorífera and safrole: Inhibition of Staphylococcus aureus efflux pumps. Antibiotics 2020, 9, 247. [Google Scholar] [CrossRef] [PubMed]
  23. Fernandes, P.A.D.S.; Pereira, R.L.S.; Santos, A.T.L.D.; Coutinho, H.D.M.; Morais-Braga, M.F.B.; Silva, V.B.; Costa, A.R.; Generino, M.E.M.; Oliveira, M.G.; Menezes, S.A.; et al. Phytochemical analysis, antibacterial activity and modulating effect of essential oil from Syzygium cumini (L.) skeels. Molecules 2022, 27, 3281. [Google Scholar] [CrossRef]
  24. Almeida-Bezerra, J.W.; Cruz, R.P.; Pereira, R.L.S.; Silva, V.B.; Sousa, D.D.O.B.; Neto, J.X.D.S.; Souza, L.A.L.; Araújo, N.M.S.; Silva, R.G.G.; Lucetti, D.L.; et al. Caryocar coriaceum fruits as a potential alternative to combat fungal and bacterial infections: In vitro evaluation of methanolic extracts. Microb. Pathog. 2023, 181, 106203. [Google Scholar] [CrossRef] [PubMed]
  25. Coutinho, H.D.; Costa, J.G.; Lima, E.O.; Falcão-Silva, V.S.; Siqueira-Júnior, J.P. Enhancement of the antibiotic activity against a multiresistant Escherichia coli by Mentha arvensis L. and chlorpromazine. Chemotherapy 2008, 54, 328–330. [Google Scholar] [CrossRef] [PubMed]
  26. Costa, A.R.; Lima-Silva, J.R.; Oliveira, T.J.S.; Silva, T.G.; Pereira, P.S.; Oliveira-Borba, E.F.; Brito, E.S.; Ribeiro, P.R.V.; Almeida-Bezerra, J.W.; Júnior, J.T.C.; et al. Phytochemical profile of Anacardium occidentale L. (cashew tree) and the cytotoxic and toxicological evaluation of its bark and leaf extracts. S. Afr. J. 2020, 135, 355–364. [Google Scholar] [CrossRef]
  27. Azzam, K.A.L. SwissADME and pkCSM webservers predictors: An integrated online platform for accurate and comprehensive predictions for in silico ADME/T properties of artemisinin and its derivatives. Complex Use Miner. Resour. 2023, 325, 14–21. [Google Scholar] [CrossRef]
  28. Bristot, S.F.; Della-Colle, M.P.; Rossato, A.E.; Citadini-Zanette, V. Uso medicinal de Varronia curassavica Jacq. “erva-baleeira”(Boraginaceae): Estudo de caso no sul do Brasil. Braz. J. Anim. Environ. Res. 2021, 4, 170–182. [Google Scholar] [CrossRef]
  29. Sciarrone, D.; Rigano, F.; Carnovale, C.; Cimino, F.; Dugo, P. Quali-quantitative characterization of the volatile constituents in Cordia verbenacea DC essential oil exploiting advanced chromatographic approaches and nuclear magnetic resonance analysis. J. Chromatogr. A 2017, 1524, 246–253. [Google Scholar] [CrossRef]
  30. Silva, K.P.; de Carvalho Santos, T.A.; Moutinho, B.L.; da Silva, R.S.; dos Santos Pinto, V.; Blank, A.F.; Corrêa, C.B.; Scher, R.; Fernandes, R.P.M. Using Varronia curassavica (Cordiaceae) essential oil for the biocontrol of Phytomonas serpens. Ind. Crops Prod. 2019, 139, 111523. [Google Scholar] [CrossRef]
  31. Pereira, P.S.; de Oliveira, L.G.; de Lima, V.F.; da Silva, M.A.F.; Rodrigues, I.A.; Almeida, E.M. Cytotoxicity of essential oil Cordia verbenaceae against Leishmania brasiliensis and Trypanosoma cruzi. Molecules 2021, 26, 4485. [Google Scholar] [CrossRef]
  32. Farias, J.P.; Barros, A.L.A.N.; Araújo-Nobre, A.R.; Sobrinho-Júnior, E.P.C.; Alves, M.M.D.M.; Carvalho, F.A.D.A.; Rodrigues, K.A.F.; Andrade, I.M.; Silva-Filho, F.A.; Moreira, D.C.; et al. Influence of Plant Age on Chemical Composition, Antimicrobial Activity and Cytotoxicity of Varronia curassavica Jacq. Essential Oil Produced on an Industrial Scale. Agriculture 2023, 13, 373. [Google Scholar] [CrossRef]
  33. Rodrigues, F.F.G.; Costa, J.G.M.; Rios, K.A.; Carvalho, M.G.; Carvalho, F.A.A. Chemical composition, antibacterial and antifungal activities of essential oil from Cordia verbenacea DC leaves. Pharmacogn. Res. 2012, 4, 161–165. [Google Scholar] [CrossRef] [PubMed]
  34. Andrade, F.P.; Venzon, M.; Dôres, R.G.R.; Franzin, M.L.; Martins, E.F.; Araújo, G.J.; Fonseca, M.C.M. Toxicity of Varronia curassavica Jacq. essential oil to two arthropod pests and their natural enemy. Neotrop. Entomol. 2021, 50, 835–845. [Google Scholar] [CrossRef] [PubMed]
  35. Castro-Nizio, D.A.; Blank, A.F.; de Andrade Brito, F.; Gagliardi, P.R.; Alves, E.; Arrigoni-Blank, M.D.F. A comparative study of the antifungal activity of essential oils of Varronia curassavica Jacq. obtained by different distillation methods. Biosci. Res. 2020, 36, 1856–1865. [Google Scholar] [CrossRef]
  36. Rodrigues, F.A.F.; Silva, G.C.D.; Santana, M.F.; Bazzolli, D.M.S.; Rossi, C.C.; Diaz, M.A.N. Essential oils isolated from popular medicinal plants and spices as alternative antimicrobial and antibiofilm compounds against the pig pathogen Actinobacilluspleuro pneumoniae. Ciência Rural 2023, 53, 1–10. [Google Scholar] [CrossRef]
  37. Li, Y.; Kong, D.; Fu, Y.; Sussman, M.R.; Wu, H. The effect of developmental and environmental factors on secondary metabolites in medicinal plants. Plant Physiol. Biochem. 2020, 148, 80–89. [Google Scholar] [CrossRef]
  38. Oliveira, B.M.; Melo, C.R.; Santos, A.C.; Nascimento, L.F.; Nízio, D.A.; Cristaldo, P.F.; Blank, A.F.; Bacci, L. Essential oils from Varronia curassavica (Cordiaceae) accessions and their compounds (E)-caryophyllene and α-humulene as an alternative to control Dorymyrmex thoracius (Formicidae: Dolichoderinae). Environ. Sci. Pollut. Res. Int. 2019, 26, 6602–6612. [Google Scholar] [CrossRef]
  39. Matias, E.F.F.; Santos, K.K.A.; Almeida, T.S.; Costa, J.G.M.; Coutinho, H.D.M. Seasonal variation, chemical composition and biological activity of the essential oil of Cordia verbenacea DC (Boraginaceae) and the sabinene. Ind. Crops Prod. 2016, 87, 45–53. [Google Scholar] [CrossRef]
  40. Tonial, C.H.; Rodrigues, M.F.; Bosse, M.A.; Sousa, I.M.; Lima, J.D.; Cunha, M.A.A.; Foglio, M.A.; Marques, M.O.M.; Marchese, J.A. Technical and economic evaluation of cultivation and obtaining of Varronia curassavica Jacq. essential oil. Ind. Crops Prod. 2020, 154, 112650. [Google Scholar] [CrossRef]
  41. Lima, F.J.A.; Sousa, R.O.; Artur, F.; Araújo-Mendes, M.R.; Val, A.D.B. Characterization of the growth and production of essential oil from “erva baleeira” (Varronia curassavica Jaqc). Res. Soc. Dev. 2021, 10, e5810716204. [Google Scholar] [CrossRef]
  42. Meccia, G.; López, S.; Gutiérrez, J.; Echeverría, J.; Suárez, L.; Porras, N.; Delgado, G.; Stashenko, E.; Bazzocchi, I.L. Chemical composition and antibacterial activity of the essential oil of Cordia verbenacea from the Venezuelan Andes. Nat. Prod. Commun. 2009, 4, 1119–1122. [Google Scholar] [CrossRef] [PubMed]
  43. Carvalho, V.R.A.; Freitas, P.R.; Alencar Menezes, I.R.; Tintino, S.R.; Santos, E.L.; Lima, M.A.; Coutinho, H.D.M.; Junior, W.J.F.L. Antibiotic-Modifying Activity and Chemical Profile of the Essential Oil from the Leaves of Cordia verbenacea DC. J. Essent. Oil Bear. Plants 2017, 20, 337–345. [Google Scholar] [CrossRef]
  44. Bhavaniramya, S.; Vishnupriya, S.; Al-Aboody, M.S.; Vijayakumar, R.; Baskaran, D. Role of essential oils in food safety: Antimicrobial and antioxidant applications. Grain Oil Sci. Technol. 2019, 2, 49–55. [Google Scholar] [CrossRef]
  45. Mutlu-Ingok, A.; Tasir, S.; Seven, A.; Akgun, N.; Karbancioglu-Guler, F. Evaluation of the single and combined antibacterial efficiency of essential oils for controlling Campylobacter coli, Campylobacter jejuni, Escherichia coli, Staphylococcus aureus, and mixed cultures. Flavour Fragr. J. 2019, 34, 280–287. [Google Scholar] [CrossRef]
  46. Rao, J.; Chen, B.; McClements, D.J. Improving the efficacy of essential oils as antimicrobials in foods: Mechanisms of action. Annu. Rev. Food Sci. Technol. 2019, 10, 365–387. [Google Scholar] [CrossRef] [PubMed]
  47. Freitas, P.R.; Araújo, A.C.J.; Santos-Barbosa, C.R.; Muniz, D.F.; Silva, A.C.A.; Rocha, J.E.; Oliveira-Tintino, C.D.M.; Ribeiro-Filho, J.; Silva, L.E.; Confortin, C.; et al. GC-MS-FID and potentiation of the antibiotic activity of the essential oil of Baccharis reticulata (ruiz & pav.) pers. and α-pinene. Ind. Crops Prod. 2020, 145, 112106. [Google Scholar] [CrossRef]
  48. Allenspach, M.; Steuer, C. α-Pinene: A never-ending story. Phytochemistry 2021, 190, 112857. [Google Scholar] [CrossRef]
  49. Eduardo, L.S.; Silva, R.O.; Silva, K.M.; Moreira, G.O.; Costa, J.G.M.; Coutinho, H.D.M.; Almeida, V.M.; Menezes, I.R.A.; Tintino, S.R. Antibacterial activity and time-kill kinetics of positive enantiomer of α-pinene against strains of Staphylococcus aureus and Escherichia coli. Curr. Top. Med. Chem. 2018, 18, 917–924. [Google Scholar] [CrossRef]
  50. Yang, C.; Hu, D.-H.; Feng, Y. Antibacterial activity and mode of action of the Artemisia capillaris essential oil and its constituents against respiratory tract infection-causing pathogens. Mol. Med. Rep. 2015, 11, 2852–2860. [Google Scholar] [CrossRef]
  51. Leite-Sampaio, N.F.; Nogueira, C.E.S.; Silva, A.F.M.; Sampaio, B.L.; Andrade, L.N.; Fernandes, P.C.; Rocha, J.E.; Oliveira, M.R.; Quintans-Júnior, L.J.; Coutinho, H.D.M.; et al. Potentiation of the Activity of Antibiotics against ATCC and MDR Bacterial Strains with (+)-α-Pinene and (-)-Borneol. BioMed Res. Int. 2022, 2022, 8217380. [Google Scholar] [CrossRef]
  52. Utegenova, G.A.; Pallavi, R.; Fukin, A.M.; Kondratenko, E.; Bagryanskaya, I.Y.; Atazhanova, G.A.; Adekenov, S.M.; Zibareva, L.N.; Desenko, S.M.; Sharma, R.; et al. Chemical composition and antibacterial activity of essential oils from Ferula L. species against methicillin-resistant Staphylococcus aureus. Molecules 2018, 23, 1679. [Google Scholar] [CrossRef] [PubMed]
  53. Melkina, O.E.; Plyuta, V.A.; Khmel, I.A.; Zavilgelsky, G.B. The mode of action of cyclic monoterpenes (−)-limonene and (+)-α-pinene on bacterial cells. Biomolecules 2021, 11, 806. [Google Scholar] [CrossRef] [PubMed]
  54. Satou, T.; Murakami, S.; Hayashi, S.; Koike, K.; Sengoku, T. Mouse brain concentrations of α-pinene, limonene, linalool, and 1,8-cineole following inhalation. Flavour Fragr. J. 2016, 32, 36–39. [Google Scholar] [CrossRef]
  55. Khoshnazar, M.; Parvardeh, S.; Bigdeli, M.R. Alpha-pinene exerts neuroprotective effects via anti-inflammatory and anti-apoptotic mechanisms in a rat model of focal cerebral ischemia-reperfusion. J. Stroke Cerebrovasc. Dis. 2020, 29, 104977. [Google Scholar] [CrossRef] [PubMed]
  56. Rahayu, M.; Mahardika, A.M.; Fattah, F.A.; Krisnadi, D. Alpha-pinene attenuates microglial NF-κB activation and iNOS expression in gp120-induced neuroinflammation. Malang Neurol. J. 2021, 7, 80–84. [Google Scholar] [CrossRef]
  57. Rahimi, K.; Ghanbari, A.; Badi, H.N.; Asadi, F.; Sadeghi, S.; Azadi, H. The effects of alpha-pinene on the Nrf2-HO1 signaling pathway in gastric damage in rats. Mol. Biol. Rep. 2023, 50, 8615–8622. [Google Scholar] [CrossRef]
  58. Zhou, J.-Y.; Tang, F.-D.; Mao, G.-G.; Bian, R.-L. Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells. Acta Pharmacol. Sin. 2004, 25, 480–484. [Google Scholar]
  59. Yanaka, A. Role of NRF2 in protection of the gastrointestinal tract against oxidative stress. J. Clin. Biochem. Nutr. 2018, 63, 18–25. [Google Scholar] [CrossRef]
  60. Santos, E.L.; de Lima, M.A.; de Almeida, R.S.; de Menezes, I.R.A.; Tintino, S.R.; Rodrigues, M.A.V.; Rocha, J.E.; Júnior, W.J.F.L. Phytochemical characterization and antibiotic potentiating effects of the essential oil of Aloysia gratissima (Gillies & Hook.) and beta-caryophyllene. S. Afr. J. Bot. 2021, 143, 1–6. [Google Scholar] [CrossRef]
  61. Santos, E.L.; de Lima, M.A.; de Almeida, R.S.; de Menezes, I.R.A.; Tintino, S.R.; Rodrigues, M.A.V.; Rocha, J.E.; Júnior, W.J.F.L. Enhanced antibacterial effect of antibiotics by the essential oil of Aloysia gratissima (Gillies & Hook.) Tronc. and its major constituent beta-caryophyllene. Phytomed. Plus 2021, 1, 100100. [Google Scholar] [CrossRef]
  62. Yoo, H.-J.; Jwa, S.-K. Inhibitory effects of β-caryophyllene on Streptococcus mutans biofilm. Arch. Oral Biol. 2018, 88, 42–46. [Google Scholar] [CrossRef] [PubMed]
  63. Moo, C.L.; Yang, S.K.; Osman, M.A.; Yuswan, M.H.; Loh, J.Y.; Lim, W.M.; Lim, S.H.E.; Lai, K.S. Antibacterial Activity and Mode of Action of β-caryophyllene on Bacillus cereus. Pol. J. Microbiol. 2020, 69, 49–54. [Google Scholar] [CrossRef] [PubMed]
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Figure 1. Minimum inhibitory concentration activity to enhance the action of antibiotics against multidrug-resistant strains. Ns—not significant; ****—p < 0.0001; and ***—p < 0.001.
Figure 1. Minimum inhibitory concentration activity to enhance the action of antibiotics against multidrug-resistant strains. Ns—not significant; ****—p < 0.0001; and ***—p < 0.001.
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Figure 2. Toxic effect of the V. curassavica essential oil against D. melanogaster.
Figure 2. Toxic effect of the V. curassavica essential oil against D. melanogaster.
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Figure 3. Results of the assessment of negative geotaxis in Drosophila melanogaster. ns—not significant.
Figure 3. Results of the assessment of negative geotaxis in Drosophila melanogaster. ns—not significant.
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Table 1. Multidrug-resistant strains and drug resistance profile.
Table 1. Multidrug-resistant strains and drug resistance profile.
Multi-Resistant Bacterial StrainsOrigin/SourceResistance ProfileReference
Escherichia coli 06UrineCephalexin, cefoxitin, cefadroxil, ceftriaxone, cefepime, and ampicillin/sulbactam.[23]
Pseudomonas aeruginosa 24Urine cultureAmikacin, imipenem, ciprofloxacin, levofloxacin, piperacillin/tazobactam, ceftazidime, merpenem, and cefepime.
Staphylococcus aureus 10Rectal swab cultureCefadroxil, cephalexin, cephalothin, oxacillin, penicillin, ampicillin, amoxicillin, moxifloxacin, ciprofloxacin, levofloxacin, ampicillin/sulbactam, amoxilin/clavulanic acid, erythromycin, clarithromycin, azithromycin, and clindamycin.
Table 2. Chemical composition (%) of Varronia curassavica essential oil.
Table 2. Chemical composition (%) of Varronia curassavica essential oil.
ComponentsRI(%)
α-Pinene97642.26
β-Pinene9802.82
β-Elemene13751.13
β-Caryophyllene142822.08
α-humulene14602.77
Zingiberene14921.16
Biciclogermacrene149613.24
cis-α-Bisabolene17782.87
Nerolidol19613.26
Caryophyllene oxide20231.92
Juniper Camphor22051.15
Hydrocarbon Monoterpene 45.08
Oxygenated Monoterpene 1.15
Hydrocarbon Sesquiterpene 43.25
Oxygenated Sesquiterpene 5.18
Total (%)94.66%
RI—retention index.
Table 3. Molecular properties of the major compound in the essential oil, α-Pinene.
Table 3. Molecular properties of the major compound in the essential oil, α-Pinene.
DescriptorValue
Molecular formulaC10H16
Molecular weight136.238
LogP2.9987
Number of rotatable bonds0
Number of hydrogen acceptors0
Number of hydrogen donors0
Surface area63.322
LogP—octanol/water partition coefficient.
Table 4. ADMET properties (absorption, distribution, metabolism, and toxicity) of the compound α-Pinene.
Table 4. ADMET properties (absorption, distribution, metabolism, and toxicity) of the compound α-Pinene.
PropertyModel NamePredicted Value
AbsorptionWater solubility−3.733 mol/L
Caco2 permeability1.38 × 10−6 cm/s
Intestinal absorption (human)96.041
Skin permeability (log Kp)−1.827
P-glycoprotein substrateNo
P-glycoprotein I inhibitorNo
P-glycoprotein II inhibitorNo
DistributionVDss (human)0.667 L/kg
Fraction unbound (human)0.425
BBB permeability0.791
CNS permeability−2.201
MetabolismCYP2D6 substrateNo
CYP3A4 substrateNo
CYP1A2 inhibitorNo
CYP2C19 inhibitorNo
CYP2C9 inhibitorNo
CYP2D6 inhibitorNo
CYP3A4 inhibitorNo
ExcretionTotal clearance0.043 mL/min/kg
Renal OCT2 substrateNo
ToxicityAMES toxicityNo
Max. tolerated dose (human)0.48 mg/kg/day
hERG I inhibitorNo
hERG II inhibitorNo
Oral rat acute toxicity (LD50)1.77 mol/kg
Oral rat chronic toxicity (LOAEL)2.262
HepatotoxicityNo
Skin sensitizationNo
T.Pyriformis toxicity0.45 ug/L
Minnow toxicity1.159 mM
BBB—blood–brain barrier; CYP—Cytochrome-P; hERG—human ether-go-go gene.
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Silva, J.T.d.C.; Silva, V.B.d.; Silva, S.B.d.; Rocha, M.I.; Costa, A.R.; Silva, J.R.d.L.; Santos, M.A.F.d.; Generino, M.E.M.; Souza, J.H.d.; Oliveira, M.G.d.; et al. Chemical Characterization and Biological Activity of Varronia curassavica Jacq. Essential Oil (Boraginaceae) and In Silico Testing of α-Pinene. Analytica 2024, 5, 499-511. https://doi.org/10.3390/analytica5040034

AMA Style

Silva JTdC, Silva VBd, Silva SBd, Rocha MI, Costa AR, Silva JRdL, Santos MAFd, Generino MEM, Souza JHd, Oliveira MGd, et al. Chemical Characterization and Biological Activity of Varronia curassavica Jacq. Essential Oil (Boraginaceae) and In Silico Testing of α-Pinene. Analytica. 2024; 5(4):499-511. https://doi.org/10.3390/analytica5040034

Chicago/Turabian Style

Silva, José Thyálisson da Costa, Viviane Bezerra da Silva, Sabrina Bezerra da Silva, Maria Ivaneide Rocha, Adrielle Rodrigues Costa, Jailson Renato de Lima Silva, Marcos Aurélio Figueirêdo dos Santos, Maria Elizete Machado Generino, Jeovane Henrique de Souza, Maraiza Gregorio de Oliveira, and et al. 2024. "Chemical Characterization and Biological Activity of Varronia curassavica Jacq. Essential Oil (Boraginaceae) and In Silico Testing of α-Pinene" Analytica 5, no. 4: 499-511. https://doi.org/10.3390/analytica5040034

APA Style

Silva, J. T. d. C., Silva, V. B. d., Silva, S. B. d., Rocha, M. I., Costa, A. R., Silva, J. R. d. L., Santos, M. A. F. d., Generino, M. E. M., Souza, J. H. d., Oliveira, M. G. d., Lima, C. M. G., Pereira, R. L. S., Santana, R. F., Araujo, I. M., Morais-Braga, M. F. B., Emran, T. B., Coutinho, H. D. M., & Almeida-Bezerra, J. W. (2024). Chemical Characterization and Biological Activity of Varronia curassavica Jacq. Essential Oil (Boraginaceae) and In Silico Testing of α-Pinene. Analytica, 5(4), 499-511. https://doi.org/10.3390/analytica5040034

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