<i>In silico</i> anti-inflammatory activity of lavender (<i>Lavandula officinalis</i>) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction

Bouchra Sarah Boukhatem; Abd-Elmouneim Belhadj; Bouchra Sarah Boukhatem; Abd-Elmouneim Belhadj

doi:10.3934/Allergy.2023009

AIMS Allergy and Immunology

2023, Volume 7, Issue 2: 132-153. doi: 10.3934/Allergy.2023009

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Research article

In silico anti-inflammatory activity of lavender (Lavandula officinalis) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction

Laboratory of Biomaterials and Transport Phenomena (LBMPT), Faculty of Technology, University of Médéa, 26000, Médéa, Algeria

Received: 02 December 2022 Revised: 20 February 2023 Accepted: 14 March 2023 Published: 03 April 2023

Advanced investigations are in action worldwide to find medications with improved safety profiles. Natural resources are essential in the creation of innovative treatments and drugs that have fewer side effects. The essential oil (EO) of lavender (Lavandula officinalis) is well-known in alternative and complementary therapies for its use as wound-healing and antimicrobial ingredients. However, the exact pharmacological and anti-inflammatory aspects of naturally produced lavender essential oil (LEO) compounds are still unknown. As a consequence, it is essential to explain LEO drug molecular docking experiments with cyclo-oxygenase enzymes (COX-1 and COX-2). An attempt was developed in this study to discover the anti-inflammatory activity of LEO bioactive components. The online DockThor server was used for in silico molecule docking simulation. Interaction studies of LEO compound binding poses with COX were performed to get an understanding of the interacting amino acids and their inter-molecular bondings. Based on physicochemical attributes and toxicity, the docked compounds with the greatest binding affinities were also investigated for drug similarity utilizing the admetSAR tool and PASS platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that electrostatic interactions and H-bonds make the main causative factor in inter-molecular connections associated with anti-inflammatory action. Seven top-ranked compounds were selected by virtual screening. Molecular docking revealed that limonene has the highest negative binding affinity (−8.536 kcal/mol) in complex with COX-1, followed by α-terpineol (−8.535 kcal/mol) and p-cymene (−8.515 kcal/mol), while two approved anti-inflammatory drugs (celecoxib and betamethasone) produced −8.191 and −8.041 kcal/mol respectively. Similarly, these terpenes can be documented as promising drug candidates based on qualifying Lipinski's rule five. The selected terpenes showed excellent drug-like properties and a percentage of human oral absorption. Besides, it was found to be safe for the human body in toxicological risk assessment. This work gives insight into the anti-inflammatory mechanism of action of LEO terpenes. LEO drugs' pharmacokinetic data and molecular docking patterns may open the way for the development of new COX inhibitors with anti-inflammatory capability and improved pharmacokinetic and pharmacodynamic properties.
- anti-inflammatory drugs,
- cyclo-oxygenase enzymes,
- Lavandula officinalis,
- essential oil compounds,
- molecular docking,
- toxicity
Citation: Bouchra Sarah Boukhatem, Abd-Elmouneim Belhadj. In silico anti-inflammatory activity of lavender (Lavandula officinalis) essential oil bioactive compounds: Molecular docking analysis of COX-1 and COX-2, and ADMET prediction[J]. AIMS Allergy and Immunology, 2023, 7(2): 132-153. doi: 10.3934/Allergy.2023009

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Abstract

Advanced investigations are in action worldwide to find medications with improved safety profiles. Natural resources are essential in the creation of innovative treatments and drugs that have fewer side effects. The essential oil (EO) of lavender (Lavandula officinalis) is well-known in alternative and complementary therapies for its use as wound-healing and antimicrobial ingredients. However, the exact pharmacological and anti-inflammatory aspects of naturally produced lavender essential oil (LEO) compounds are still unknown. As a consequence, it is essential to explain LEO drug molecular docking experiments with cyclo-oxygenase enzymes (COX-1 and COX-2). An attempt was developed in this study to discover the anti-inflammatory activity of LEO bioactive components. The online DockThor server was used for in silico molecule docking simulation. Interaction studies of LEO compound binding poses with COX were performed to get an understanding of the interacting amino acids and their inter-molecular bondings. Based on physicochemical attributes and toxicity, the docked compounds with the greatest binding affinities were also investigated for drug similarity utilizing the admetSAR tool and PASS platforms. Molecular docking studies exploring the bioactive principle targeted action revealed that electrostatic interactions and H-bonds make the main causative factor in inter-molecular connections associated with anti-inflammatory action. Seven top-ranked compounds were selected by virtual screening. Molecular docking revealed that limonene has the highest negative binding affinity (−8.536 kcal/mol) in complex with COX-1, followed by α-terpineol (−8.535 kcal/mol) and p-cymene (−8.515 kcal/mol), while two approved anti-inflammatory drugs (celecoxib and betamethasone) produced −8.191 and −8.041 kcal/mol respectively. Similarly, these terpenes can be documented as promising drug candidates based on qualifying Lipinski's rule five. The selected terpenes showed excellent drug-like properties and a percentage of human oral absorption. Besides, it was found to be safe for the human body in toxicological risk assessment. This work gives insight into the anti-inflammatory mechanism of action of LEO terpenes. LEO drugs' pharmacokinetic data and molecular docking patterns may open the way for the development of new COX inhibitors with anti-inflammatory capability and improved pharmacokinetic and pharmacodynamic properties.

Conflict of interest

The authors declare no conflict of interest.

Author contributions

B.S.B.: original draft preparation; A.B.: review and editing. All authors have read and agreed to the published version of the manuscript.

References

[1]	Bancos S, Bernard MP, Topham DJ, et al. (2009) Ibuprofen and other widely used non-steroidal anti-inflammatory drugs inhibit antibody production in human cells. Cell Immunol 258: 18-28. https://doi.org/10.1016/j.cellimm.2009.03.007
[2]	Day RO, Graham GG (2013) Non-steroidal anti-inflammatory drugs (NSAIDs). BMJ 346: f3195. https://doi.org/10.1007/978-3-0348-0620-6_52-2
[3]	Wehling M (2014) Non-steroidal anti-inflammatory drug use in chronic pain conditions with special emphasis on the elderly and patients with relevant comorbidities: management and mitigation of risks and adverse effects. Eur J Clin Pharmacol 70: 1159-1172. https://doi.org/10.1007/s00228-014-1734-6
[4]	Crofford LJ (2013) Use of NSAIDs in treating patients with arthritis. Arthritis Res Ther 15: 1-10. https://doi.org/10.1186/ar4174
[5]	Williams CS, Mann M, DuBois RN (1999) The role of cyclooxygenases in inflammation, cancer, and development. Oncogene 18: 7908-7916. https://doi.org/10.1038/sj.onc.1203286
[6]	Lucotti S, Cerutti C, Soyer M, et al. (2019) Aspirin blocks formation of metastatic intravascular niches by inhibiting platelet-derived COX-1/thromboxane A 2. J Clin Invest 129: 1845-1862. https://doi.org/10.1172/JCI121985
[7]	Morita I (2002) Distinct functions of COX-1 and COX-2. Prostag Oth Lipid M 68: 165-175. https://doi.org/10.1016/S0090-6980(02)00029-1
[8]	Warner TD, Mitchell JA (2004) Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J 18: 790-804. https://doi.org/10.1096/fj.03-0645rev
[9]	Dogné JM, Supuran CT, Pratico D (2005) Adverse cardiovascular effects of the coxibs. J Med Chem 48: 2251-2257. https://doi.org/10.1021/jm0402059
[10]	Wallace JL (2001) Pathogenesis of NSAID-induced gastroduodenal mucosal injury. Best Pract Res Cl Ga 15: 691-703. https://doi.org/10.1053/bega.2001.0229
[11]	Laine L (2003) Gastrointestinal effects of NSAIDs and coxibs. J Pain Symptom Manag 25: 32-40. https://doi.org/10.1016/S0885-3924(02)00629-2
[12]	Gierse J, Nickols M, Leahy K, et al. (2008) Evaluation of COX-1/COX-2 selectivity and potency of a new class of COX-2 inhibitors. Eur J Pharmacol 588: 93-98. https://doi.org/10.1016/j.ejphar.2008.03.057
[13]	Farzaneh V, Carvalho IS (2015) A review of the health benefit potentials of herbal plant infusions and their mechanism of actions. Ind Crop Prod 65: 247-258. https://doi.org/10.1016/j.indcrop.2014.10.057
[14]	Reddy DN (2019) Essential oils extracted from medicinal plants and their applications. Natural Bio-active Compounds . Singapore: Springer Nature 237-283. https://doi.org/10.1007/978-981-13-7154-7_9
[15]	Tasneem S, Liu B, Li B, et al. (2019) Molecular pharmacology of inflammation: Medicinal plants as anti-inflammatory agents. Pharmacol Res 139: 126-140. https://doi.org/10.1016/j.phrs.2018.11.001
[16]	Cavanagh HMA, Wilkinson JM (2002) Biological activities of lavender essential oil. Phytother Res 16: 301-308. https://doi.org/10.1002/ptr.1103
[17]	Lis-Balchin MT (2012) Lavender. Handbook of Herbs and Spices . Cambridge: Woodhead Publishing 329-347. https://doi.org/10.1533/9780857095688.329
[18]	Silva GL, Luft C, Lunardelli A, et al. (2015) Antioxidant, analgesic and anti-inflammatory effects of lavender essential oil. An Acad Bras Cienc 87: 1397-1408. https://doi.org/10.1590/0001-3765201520150056
[19]	Cardia GFE, Silva-Filho SE, Silva EL, et al. (2018) Effect of lavender (Lavandula angustifolia) essential oil on acute inflammatory response. Evid Based Complement Altern Med 2018: 1413940. https://doi.org/10.1155/2018/1413940
[20]	Feixiong C, Weihua L, Yadi Z, et al. (2012) Admetsar: a comprehensive source and free tool for assessment of chemical ADMET properties. J Chem Inf Model 52: 3099-3105. https://doi.org/10.1021/ci300367a
[21]	Goel RK, Singh D, Lagunin A, et al. (2011) PASS-assisted exploration of new therapeutic potential of natural products. Med Chem Res 20: 1509-1514. https://doi.org/10.1007/s00044-010-9398-y
[22]	Homnan N, Thongpraditchote S, Chomnawang M, et al. (2020) In vitro anti-inflammatory effects of Thai herb essential oils. Pharm Sci Asia 47: 153-163. https://doi.org/10.29090/psa.2020.02.019.0020
[23]	Kim KN, Ko YJ, Yang HM, et al. (2013) Anti-inflammatory effect of essential oil and its constituents from fingered citron (Citrus medica L. var. sarcodactylis) through blocking JNK, ERK and NF-κB signaling pathways in LPS-activated RAW 264.7 cells. Food Chem Toxicol 57: 126-131. https://doi.org/10.1016/j.fct.2013.03.017
[24]	Yu L, Yan J, Sun Z (2017) D-limonene exhibits anti-inflammatory and antioxidant properties in an ulcerative colitis rat model via regulation of iNOS, COX-2, PGE2 and ERK signaling pathways. Mol Med Rep 15: 2339-2346. https://doi.org/10.3892/mmr.2017.6241
[25]	Yoon WJ, Lee NH, Hyun CG (2010) Limonene suppresses lipopolysaccharide-induced production of nitric oxide, prostaglandin E2, and pro-inflammatory cytokines in RAW 264.7 macrophages. J Oleo Sci 59: 415-421. https://doi.org/10.5650/jos.59.415
[26]	Sousa OV, Silvério MS, Del-Vechio-Vieira G, et al. (2008) Antinociceptive and anti-inflammatory effects of the essential oil from Eremanthus erythropappus leaves. J Pharm Pharmacol 60: 771-777. https://doi.org/10.1211/jpp.60.6.0013
[27]	Ogunwande IA, Avoseh ON, Olasunkanmi KN, et al. (2019) Chemical composition, anti-nociceptive and anti-inflammatory activities of essential oil of Bougainvillea glabra. J Ethnopharmacol 232: 188-192. https://doi.org/10.1016/j.jep.2018.12.017
[28]	Suh HR, Chung HJ, Park EH, et al. (2016) The effects of Chamaecyparis obtusa essential oil on pain-related behavior and expression of pro-inflammatory cytokines in carrageenan-induced arthritis in rats. Biosci Biotech Bioch 80: 203-209. https://doi.org/10.1080/09168451.2015.1075864
[29]	Rufino AT, Ribeiro M, Sousa C, et al. (2015) Evaluation of the anti-inflammatory, anti-catabolic and pro-anabolic effects of E-caryophyllene, myrcene and limonene in a cell model of osteoarthritis. Eur J Pharmacol 750: 141-150. https://doi.org/10.1016/j.ejphar.2015.01.018
[30]	Siddappa MK, Satyanarayan ND, Yarbagi M, et al. (2016) Anti-proliferative and ADMET screening of novel 3-(1 H-indol-3-yl)-1, 3-diphenylpropan-1-one derivatives. Cogent Chem 2: 1172542. https://doi.org/10.1080/23312009.2016.1172542
[31]	Guimarães AC, Meireles LM, Lemos MF, et al. (2019) Antibacterial activity of terpenes and terpenoids present in essential oils. Molecules 24: 2471. https://doi.org/10.3390/molecules24132471
[32]	Zengin H, Baysal AH (2014) Antibacterial and antioxidant activity of essential oil terpenes against pathogenic and spoilage-forming bacteria and cell structure-activity relationships evaluated by SEM microscopy. Molecules 19: 17773-17798. https://doi.org/10.3390/molecules191117773
[33]	Baccouri B, Rajhi I (2021) Potential antioxidant activity of terpenes. Terpenes and Terpenoids Recent Advances . London: IntechOpen 53-62. https://doi.org/10.5772/intechopen.96638
[34]	de Cássia da Silveira e Sá R, Andrade LN, de Sousa DP (2013) A review on anti-inflammatory activity of monoterpenes. Molecules 18: 1227-1254. https://doi.org/10.3390/molecules18011227
[35]	Zarlaha A, Kourkoumelis N, Stanojkovic TP, et al. (2014) Cytotoxic activity of essential oil and extracts of Ocimum basilicum against human carcinoma cells. Molecular docking study of isoeugenol as a potent cox and lox inhibitor. Dig J Nanomater Biostructures 9: 907-917.
[36]	Refaey MS, Abouelela ME, El-Shoura EA, et al. (2022) In vitro anti-inflammatory activity of Cotula anthemoides essential oil and in silico molecular docking of its bioactives. Molecules 27: 1994. https://doi.org/10.3390/molecules27061994

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