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14-05-2023 | Analgesics in Dentistry | Original Article

Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen

Authors: Bushra Arooj, Sajid Asghar, Mohammad Saleem, Syed Haroon Khalid, Muhammad Asif, Tahir Chohan, Ikram Ullah Khan, Hafiz Muhammad Zubair, Hafiza Sidra Yaseen

Published in: Inflammopharmacology | Issue 4/2023

Abstract

Inflammation is the core contributor in the pathogenesis of various acute and chronic illness including appendicitis, bronchitis, arthritis, cancer and neurological diseases. NSAIDs, commonly used medications for inflammatory diseases, on prolonged use cause GI bleeding, ulcers and many more issues. Plant-based therapeutic agents including essential oils in combination with low-dose synthetic drugs have been shown to produce synergistic effects and reduce complications of synthetic drugs. This study was designed to evaluate the anti-inflammatory, analgesic and anti-pyretic properties of Eucalyptus globulus essential oil alone and in combination with flurbiprofen. GC–MS analysis was performed to screen chemical composition of oil. In vitro anti-inflammatory assay (membrane stabilization assay) and in vivo inflammatory acute (carrageenan and histamine-induced paw oedema) and chronic (cotton pellet-induced granuloma and Complete Freund’s adjuvant-induced arthritis) models were performed to check anti-inflammatory properties. Acetic acid-induced algesia and yeast-induced pyrexia models were performed to check analgesic and anti-pyretic properties. qRT-PCR was performed to study the effect of treatments on the expression of inflammatory biomarkers. GC–MS analysis of E. globulus essential oil showed the presence of eucalyptol along with other active biomolecules. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better in vitro membrane stabilization effects as compared with groups treated with 500 mg/kg of E. globulus oil and 10 mg/kg of Flurbiprofen alone. 500 + 10 mg/kg of oil-drug combination showed significantly (p < 0.05) better anti-inflammatory, analgesic and antipyretic effects as compared to 500 mg/kg of E. globulus oil alone in all in vivo models. When comparison was done between 500 + 10 mg/kg of oil-drug combination-treated and 10 mg/kg Flurbiprofen-treated group, the former group showed significantly (p < 0.05) better anti-inflammatory and anti-pyretic effects, but there were non-significant differences in the analgesic model. Animal group treated with 10 mg/kg of Flurbiprofen showed significantly (p < 0.05) better anti-inflammatory and analgesic effects than group treated with 500 mg/kg of oil alone while, there were non-significant differences in anti-pyretic effects. qRT-PCR analysis showed significant (p < 0.05) down-regulation in the expression of IL-4 and TNF-α in serum samples of animals treated with 500 + 10 mg/kg of oil-drug combination as compared to the diseased control (arthritic) group. Overall, the current research demonstrates that Eucalyptus globulus essential oil in combination with flurbiprofen showed better anti-inflammatory, analgesic and anti-pyretic effects than oil and flurbiprofen alone which is attributed to the down-regulation of pro-inflammatory biomarkers (IL-4 and TNF-α). Further studies are required to formulate a stable dosage form and to check the anti-inflammatory efficacy in different inflammatory disorders.

Adriana Estrella G-R, María Eva G-T, Alberto H-L, María Guadalupe V-D, Azucena C-V, Sandra O-S, Noé A-V, Francisco Javier L-M (2021) Limonene from Agastache mexicana essential oil produces antinociceptive effects, gastrointestinal protection and improves experimental ulcerative colitis. J Ethnopharmacol 280:114462. https://doi.org/10.1016/j.jep.2021.114462CrossRefPubMed

Andleeb F, Asif M, Yaseen HS (2022) Exploration of molecular mechanisms responsible for anti-inflammatory and anti-angiogenic attributes of methanolic extract of Viola betonicifolia. Inflammopharmacology 30:1459–1474CrossRefPubMed

Asif M, Mahrukh Saadullah M, Yaseen HS, Saleem M, Yousaf HM, Khan IU, Yaseen M, Shams MU (2020a) Evaluation of in vivo anti-inflammatory and anti-angiogenic attributes of methanolic extract of Launaea spinosa. Inflammopharmacology 28:993–1008. https://doi.org/10.1007/s10787-020-00687-6CrossRefPubMed

Asif M, Saleem M, Saadullah M, Yaseen HS, Al Zarzour R (2020b) COVID-19 and therapy with essential oils having antiviral, anti-inflammatory, and immunomodulatory properties. Inflammopharmacology 28:1153–1161. https://doi.org/10.1007/s10787-020-00744-0CrossRefPubMedPubMedCentral

Boukhatem MN, Sudha T, Darwish NHE, Chader H, Belkadi A, Rajabi M, Houche A, Benkebailli F, Oudjida F, Mousa SA (2020) A new eucalyptol-rich lavender (Lavandula stoechas L.) essential oil: emerging potential for therapy against inflammation and cancer. Molecules. https://doi.org/10.3390/molecules25163671CrossRefPubMedPubMedCentral

Chandorkar N, Tambe S, Amin P, Madankar C (2021) A systematic and comprehensive review on current understanding of the pharmacological actions, molecular mechanisms, and clinical implications of the genus Eucalyptus. Phytomedicine Plus 1:100089. https://doi.org/10.1016/j.phyplu.2021.100089CrossRef

Cronstein BN, Montesinos MC, Weissmann G (1999) Salicylates and sulfasalazine, but not glucocorticoids, inhibit leukocyte accumulation by an adenosine-dependent mechanism that is independent of inhibition of prostaglandin synthesis and p105 of NFkappaB. Proc Natl Acad Sci U S A 96:6377–6381. https://doi.org/10.1073/pnas.96.11.6377CrossRefPubMedPubMedCentral

De Cicco P, Maisto M, Tenore GC, Ianaro A (2020) Olive leaf extract, from Olea Europaea L., reduces palmitate-induced inflammation via regulation of murine macrophages polarization. Nutrients 12:3663CrossRefPubMedPubMedCentral

Fujiwara N, Kobayashi K (2005) Macrophages in inflammation. Curr Drug Targets-Inflamm Allergy 4:281–286CrossRefPubMed

Furman D, Campisi J, Verdin E, Carrera-Bastos P, Targ S, Franceschi C, Ferrucci L, Gilroy DW, Fasano A, Miller GW, Miller AH, Mantovani A, Weyand CM, Barzilai N, Goronzy JJ, Rando TA, Effros RB, Lucia A, Kleinstreuer N, Slavich GM (2019) Chronic inflammation in the etiology of disease across the life span. Nat Med 25:1822–1832. https://doi.org/10.1038/s41591-019-0675-0CrossRefPubMedPubMedCentral

Gunathilake K, Ranaweera K, Rupasinghe HV (2018) In vitro anti-inflammatory properties of selected green leafy vegetables. Biomedicines 6:107CrossRefPubMedPubMedCentral

Ho C-L, Li L-H, Weng Y-C, Hua K-F, Ju T-C (2020) Eucalyptus essential oils inhibit the lipopolysaccharide-induced inflammatory response in RAW2647 macrophages through reducing MAPK and NF-κB pathways. BMC Complement Med Ther 20:200. https://doi.org/10.1186/s12906-020-02999-0CrossRefPubMedPubMedCentral

Hu XQ, Sun Y, Lau E, Zhao M, Su SB (2016) Advances in synergistic combinations of chinese herbal medicine for the treatment of cancer. Curr Cancer Drug Targets 16:346–356. https://doi.org/10.2174/1568009616666151207105851CrossRefPubMedPubMedCentral

Khodabakhsh P, Shafaroodi H, Asgarpanah J (2015) Analgesic and anti-inflammatory activities of Citrus aurantium L. blossoms essential oil (neroli): involvement of the nitric oxide/cyclic-guanosine monophosphate pathway. J Nat Med 69:324–331. https://doi.org/10.1007/s11418-015-0896-6CrossRefPubMed

Kong X, Wan H, Su X, Zhang C, Yang Y, Li X, Yao L, Lin N (2014) Rheum palmatum L. and Coptis chinensis Franch., exert antipyretic effect on yeast-induced pyrexia rats involving regulation of TRPV1 and TRPM8 expression. J Ethnopharmacol 153:160–168CrossRefPubMed

de Lavor ÉM, Fernandes AWC, de Andrade Teles RB, Leal AEBP, de Oliveira Júnior RG, Gamae Silva M, de Oliveira AP, Silva JC, de Moura Fontes Araújo MT, Coutinho HDM, de Menezes IRA, Picot L, da Silva Almeida JRG (2018) essential oils and their major compounds in the treatment of chronic inflammation: a review of antioxidant potential in preclinical studies and molecular mechanisms. Oxidative Med Cell Longev 2018:6468593. https://doi.org/10.1155/2018/6468593CrossRef

Lin TC, Wang SH, Huang CC, Lai YC, Song TY, Tsai MS (2018) Anti-fatigue, antioxidation, and anti-inflammatory effects of eucalyptus oil aromatherapy in swimming-exercised rats. Chin J Physiol 61:257–265. https://doi.org/10.4077/cjp.2018.bag572CrossRefPubMed

Mahdi HJ, Khan NAK, Asmawi MZB, Mahmud R, Vikneswaran A, Murugaiyah L (2018) In vivo anti-arthritic and anti-nociceptive effects of ethanol extract of Moringa oleifera leaves on complete Freund’s adjuvant (CFA)-induced arthritis in rats. Integr Med Res 7:85–94CrossRefPubMed

Marcum ZA, Hanlon JT (2010) Recognizing the risks of chronic nonsteroidal anti-inflammatory drug use in older adults. Ann Longterm Care 18:24–27PubMedPubMedCentral

Martins AOBPB, Rodrigues LB, Cesário FRAS, de Oliveira MRC, Tintino CDM, Castro FFE, Alcântara IS, Fernandes MNM, de Albuquerque TR, da Silva MSA, de Sousa Araújo AA, Júniur LJQ, da Costa JGM, de Menezes IRA, Wanderley AG (2017) Anti-edematogenic and anti-inflammatory activity of the essential oil from Croton rhamnifolioides leaves and its major constituent 1,8-cineole (eucalyptol). Biomed Pharmacother 96:384–395. https://doi.org/10.1016/j.biopha.2017.10.005CrossRefPubMed

de Morais Oliveira-Tintino CD, Pessoa RT, Fernandes MNM, Alcântara IS, da Silva BAF, de Oliveira MRC, Martins AOBPB, da Silva MdS, Tintino SR, Rodrigues FFG (2018) Anti-inflammatory and anti-edematogenic action of the Croton campestris A. St.-Hil (Euphorbiaceae) essential oil and the compound β-caryophyllene in in vivo models. Phytomedicine 41:82–95CrossRef

Mworia JK, Kibiti CM, Ngugi MP, Ngeranwa JN (2019) Antipyretic potential of dichloromethane leaf extract of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in rats models. Heliyon 5:e02924CrossRefPubMedPubMedCentral

Mworia JK, Kibiti CM, Ngeranwa JJ, Ngugi MP (2021) Anti-inflammatory potential of dichloromethane leaf extracts of Eucalyptus globulus (Labill) and Senna didymobotrya (Fresenius) in mice. Afr Health Sci 21:397–409CrossRefPubMedPubMedCentral

Nagarkar B, Jagtap S (2017) Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model. BMC Complement Altern Med 17:1–12CrossRef

Naghizadeh B, Mansouri MT, Ghorbanzadeh B (2016) Ellagic acid enhances the antinociceptive action of carbamazepine in the acetic acid writhing test with mice. Pharm Biol 54:157–161CrossRefPubMed

Nakamura T, Yoshida N, Yamanoi Y, Honryo A, Tomita H, Kuwabara H, Kojima Y (2020) eucalyptus oil reduces allergic reactions and suppresses mast cell degranulation by downregulating IgE-FcεRI signalling. Sci Rep 10:1–15CrossRef

Nathan C (2002) Points of control in inflammation. Nature 420:846–852CrossRefPubMed

Pillinger MH, Capodici C, Rosenthal P, Kheterpal N, Hanft S, Philips MR, Weissmann G (1998) Modes of action of aspirin-like drugs: salicylates inhibit erk activation and integrin-dependent neutrophil adhesion. Proc Natl Acad Sci U S A 95:14540–14545. https://doi.org/10.1073/pnas.95.24.14540CrossRefPubMedPubMedCentral

Ploeger HE, Takken T, De Greef M, Timmons BW (2009) The effects of acute and chronic exercise on inflammatory markers in children and adults with a chronic inflammatory disease: a systematic review. Exerc Immunol Rev 15:6–41PubMed

Ratthé C, Ennaciri J, Garcês Gonçalves DM, Chiasson S, Girard D (2009) Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect mechanism. Mediat Inflamma 2009:193970. https://doi.org/10.1155/2009/193970CrossRef

Rosato A, Altini E, Sblano S, Salvagno L, Maggi F, de Michele G, Carocci A, Clodoveo ML, Corbo F, Fracchiolla G (2021) Synergistic activity of new diclofenac and essential oils combinations against different candida spp. Antibiotics (Basel). https://doi.org/10.3390/antibiotics10060688CrossRefPubMed

Saleem M, Iftikhar A, Asif M, Hussain K, Shah PA, Saleem A, Akhtar MF, Tanzeem M, Yaseen HS (2021) Asphodelus tenuifolius extracts arrested inflammation and arthritis through modulation of TNF-α, NF-κB, ILs, and COX-2 activities in in vivo models. Inflammopharmacology 29:483–497CrossRefPubMed

Shabbir A, Batool SA, Basheer MI, Shahzad M, Sultana K, Tareen RB, Iqbal J (2018) Ziziphora clinopodioides ameliorated rheumatoid arthritis and inflammatory paw edema in different models of acute and chronic inflammation. Biomed Pharmacother 97:1710–1721CrossRefPubMed

Shala AY, Gururani MA (2021) Phytochemical properties and diverse beneficial roles of eucalyptus globulus labill.: a review. Horticulturae 7:450CrossRef

Shao J, Yin Z, Wang Y, Yang Y, Tang Q, Zhang M, Jiao J, Liu C, Yang M, Zhen L, Hassouna A, White WL, Lu J (2020) Effects of different doses of eucalyptus oil from eucalyptus globulus labill on respiratory tract immunity and immune function in healthy rats. Front Pharmacol. https://doi.org/10.3389/fphar.2020.01287CrossRefPubMedPubMedCentral

Silva J, Abebe W, Sousa S, Duarte V, Machado M, Matos F (2003) Analgesic and anti-inflammatory effects of essential oils of Eucalyptus. J Ethnopharmacol 89:277–283CrossRefPubMed

Sokeng SD, Talla E, Sakava P, Fokam Tagne MA, Henoumont C, Sophie L, Mbafor JT, Tchuenguem Fohouo F-N (2020) Anti-inflammatory and analgesic effect of arachic acid ethyl ester isolated from propolis. BioMed Res Int 2020:1–8CrossRef

Sugimoto M, Toda Y, Hori M, Mitani A, Ichihara T, Sekine S, Kaku S, Otsuka N, Matsumoto H (2016) Topical anti-inflammatory and analgesic effects of multiple applications of S(+)-flurbiprofen plaster (SFPP) in a rat adjuvant-induced arthritis model. Drug Dev Res 77:206–211. https://doi.org/10.1002/ddr.21314CrossRefPubMedPubMedCentral

Takaki I, Bersani-Amado L, Vendruscolo A, Sartoretto S, Diniz S, Bersani-Amado C, Cuman R (2008) Anti-inflammatory and antinociceptive effects of Rosmarinus officinalis L. essential oil in experimental animal models. J Med Food 11:741–746CrossRefPubMed

Tanzeem MU, Asghar S, Khalid SH, Asif M, Ullah MS, Khan IU, Khalid I, Faran SA, Rehman A, Gohar UF, Hussain T (2019) Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis. Pak J Pharm Sci 32:2787–2793PubMed

Yehya AHS, Asif M, Abdul Majid AMS, Oon CE (2023) Polymolecular botanical drug of Orthosiphon stamineus extract (C5OSEW5050ESA) as a complementary therapy to overcome gemcitabine resistance in pancreatic cancer cells. J Tradit Complement Med 13:39–50. https://doi.org/10.1016/j.jtcme.2022.10.002CrossRefPubMed

Zhang L, Liang X, Ou Z, Ye M, Shi Y, Chen Y, Zhao J, Zheng D, Xiang H (2020) Screening of chemical composition, anti-arthritis, antitumor and antioxidant capacities of essential oils from four Zingiberaceae herbs. Ind Crop Prod 149:112342CrossRef

Zhu L, Zhang Z, Xia N, Zhang W, Wei Y, Huang J, Ren Z, Meng F, Yang L (2020) Anti-arthritic activity of ferulic acid in complete Freund’s adjuvant (CFA)-induced arthritis in rats: JAK2 inhibition. Inflammopharmacology 28:463–473CrossRefPubMed

Zuo X, Gu Y, Wang C, Zhang J, Zhang J, Wang G, Wang F (2020) A systematic review of the anti-inflammatory and immunomodulatory properties of 16 essential oils of herbs. Evid-Based Complement Altern Med 2020:8878927. https://doi.org/10.1155/2020/8878927CrossRef

Title: Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen
Authors: Bushra Arooj
Sajid Asghar
Mohammad Saleem
Syed Haroon Khalid
Muhammad Asif
Tahir Chohan
Ikram Ullah Khan
Hafiz Muhammad Zubair
Hafiza Sidra Yaseen
Publication date: 14-05-2023
Publisher: Springer International Publishing
Keywords: Analgesics in Dentistry
Cytostatic Therapy
Published in: Inflammopharmacology / Issue 4/2023
Print ISSN: 0925-4692
Electronic ISSN: 1568-5608
DOI: https://doi.org/10.1007/s10787-023-01237-6

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Anti-inflammatory mechanisms of eucalyptol rich Eucalyptus globulus essential oil alone and in combination with flurbiprofen

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