Effect of two active compounds obtained from the essential oil of Cordia verbenacea on the acute inflammatory responses elicited by LPS in the rat paw
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BACKGROUND AND PURPOSE: alpha-Humulene and trans-caryophyllene are sesquiterpene compounds identified in the essential oil of Cordia verbenacea which display topical and systemic anti-inflammatory effects in different experimental models. However, the molecular mechanisms through which they exert their anti-inflammatory activity still remain unclear. Here, we evaluate the effects of alpha-humulene and trans-caryophyllene on the acute inflammatory responses elicited by LPS. EXPERIMENTAL APPROACH: The biological activities of alpha-humulene and trans-caryophyllene were investigated in a model of acute inflammation in rat paw, induced by LPS and characterized by paw oedema, neutrophil recruitment, cytokine production, activation of MAP kinases and NF-kappaB and up-regulated expression of kinin B(1) receptors. KEY RESULTS: Treatment with either alpha-humulene or trans-caryophyllene effectively reduced neutrophil migration and activation of NF-kappaB induced by LPS in the rat paw. However, only alpha-humulene significantly reduced the increase in TNF-alpha and IL-1beta levels, paw oedema and the up-regulation of B(1) receptors following treatment with LPS. Both compounds failed to interfere with the activation of the MAP kinases, ERK, p38 and JNK. CONCLUSIONS AND IMPLICATIONS: Both alpha-humulene and trans-caryophyllene inhibit the LPS-induced NF-kappaB activation and neutrophil migration, although only alpha-humulene had the ability to prevent the production of pro-inflammatory cytokines TNF-alpha and IL-1beta and the in vivo up-regulation of kinin B(1) receptors. These data provide additional molecular and functional insights into the beneficial effects of the sesquiterpenes alpha-humulene and trans-caryophyllene isolated from the essential oil of Cordia verbenacea as agents for the management of inflammatory diseases.
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α-Humulene from Cordia verbenacea reduces the increase of TNF-α and IL-1β levels in rat paw after LPS treatment or in carrageenan-injected rats.
“Some authors showed that from the essential oil of Cordia verbenacea, only α-humelene was able to reduce significantly the increase of TNF-α and IL-1β levels in the subcutaneous tissue of the rat paw after LPS treatment [113] or in carrageenan-injected rats”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [113]
α-Humulene and trans-caryophyllene inhibit LPS-induced NF-kB activation and neutrophil migration in the rat paw but are unable to inhibit LPS-induced MAP kinase activation.
“α-Humulene and trans-caryophyllene, the main constituents of Cordia verbenacea inhibited the LPS-induced NF-kB activation and neutrophil migration in the rat paw, however unable to inhibit LPS-induced MAP kinase activation [113].”
From Antioxidant and Anti-Inflammatory Activities of Essential Oils: A Short Review (2010) · cites this paper as [113]
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Pharmacology of Natural Volatiles and Essential Oils in Food, Therapy, and Disease Prophylaxis
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“Furthermore, inflammation was greatly attenuated by oral treatment an hour before lipopolysaccharide (LPS) was used as an inducer, evidently by the same mechanism as above (Medeiros et al., 2007).”
BackgroundMethodSantos, A. G., Santos, D. S., Santos, I. R., Lima, R. R., Pereira, A., de Moura, L. S., de Carvalho, R. N., Lameira, O. A., & Gomes‐Leal, W. (2012) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2012/918174 · Cited by 54 · see citing works
“α-humulene, other sesquiterpene present in the COR, reduces eosinophil recruitment and release of several proinnflammatory substances in an experimental model of airways allergic inflammation [40] or following LPS injection in the rat paw [41].”
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“Some studies have demonstrated the inhibitory effect of BCP on neutrophil migration through an indirect method, such as the reduction of myeloperoxidase (MPO) [7] [15] [16] [38].”
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Nizio, D. A. D. C., Brito, F. D. A., Sampaio, T. S., Melo, J. D. O., da Silva, F. L. S., Gagliardi, P. R., Arrigoni-Blank, M. D. F., dos Anjos, C. S., Alves, P. B., Wisniewski, A., et al. (2015) · Industrial Crops and Products · doi:10.1016/j.indcrop.2015.07.026 · Cited by 38 · see citing works
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“These constituents were evaluated by several authors and, interestingly, an anti-inflammatory activity for such constituents was shown.([30,46,47])”
Backgroundde Oliveira, B. M. S., Melo, C. R., Santos, A. C. C., Nascimento, L. F. D. A., Nizio, D. A. D. C., Cristaldo, P. F., Blank, A. F., & Bacci, L. (2019) · Environmental Science and Pollution Research · doi:10.1007/s11356-018-4044-1 · Cited by 36 · see citing works
Pinho‐da‐Silva, L., Mendes-Maia, P. V., Teófilo, T. M., Barbosa, R., Ceccatto, V. M., Coelho‐de‐Souza, A. N., Cruz, J. S., & Leal‐Cardoso, J. H. (2012) · Molecules · doi:10.3390/molecules171011965 · Cited by 36 · see citing works
“trans-Caryophyllene also has a well-documented anti-inflammatory activity [7,8].”
BackgroundHumulene Inhibits Acute Gastric Mucosal Injury by Enhancing Mucosal Integrity
Yeo, D., Hwang, S.-J., Song, Y., & Lee, H. (2021) · Antioxidants · doi:10.3390/antiox10050761 · Cited by 35 · see citing works
“In many aromatic plants, α-humulene is often present with its ring-opened isomer, β-caryophyllene, which has anti-cancer and anti-inflammatory activities [24,25].”
BackgroundGina Meccia, C., Rojas, L. B., Velasco, J., Díaz, T., Usubillaga, A. N., Arzola, J. C., & Ramos, S. (2009) · Natural Product Communications · doi:10.1177/1934578x0900400821 · Cited by 34 · see citing works
“of the sesquiterpenes, α-humulene and transcaryophyllene [11,12].”
ResultThe Clinical Translation of α-humulene – A Scoping Review
Dalavaye, N., Nicholas, M., Pillai, M., Erridge, S., & Sodergren, M. H. (2024) · Planta Medica · doi:10.1055/a-2307-8183 · Cited by 33 · see citing works
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“[60] described that trans-caryophyllene showed p tent anti-inflammatory in rats by significa tly decreasing the migrat on of neutrophils as well as increasi g the NF-κB-induced stimulation by lipopolysaccharides.”
BackgroundDougnon, G., & Ito, M. (2021) · Pharmaceuticals · doi:10.3390/ph14070651 · Cited by 32 · see citing works
Min, H., Kim, M. S., Jang, D. S., Park, E., Seo, E. K., & Lee, S. K. (2009) · International Immunopharmacology · doi:10.1016/j.intimp.2009.03.005 · Cited by 32 · see citing works
Kumari, R., & Agrawal, S. B. (2010) · Acta Physiologiae Plantarum · doi:10.1007/s11738-010-0637-0 · Cited by 30 · see citing works
“Medeiros et al. (2007) reported that a-humulene and (-)-trans-caryophyllene might be useful as important tools for the management and/or treatment of inflammatory diseases. a-humulene also has antitumorous property (Tundis et al. 2009). b-selinene has antimalarial, antiinfertility, antidementia,…”
BackgroundMarques, A. P. S., Bonfim, F. P. G., Dantas, W. F. C., Puppi, R. J., & Marques, M. O. M. (2019) · Industrial Crops and Products · doi:10.1016/j.indcrop.2019.111656 · Cited by 30 · see citing works
Gandolfo, E. S., & Hanazaki, N. (2014) · Urban Ecosystems · doi:10.1007/s11252-014-0345-4 · Cited by 30 · see citing works
“…as Polydoro et al. (2004) and Kadarian et al. (2002) for A. satureoides, Coelho-de-Souza et al. (2004) for P. catleyanum, and Sertie et al. (1991), Medeiros et al. (2007) and Passos et al. (2007) for V. curassavica (formerly Cordia verbenaceae); the latter known widely along the Brazilian coast…”
Antiprotozoal activity of essential oils derived fromPiperspp. grown in Colombia
Pinto, S. M. L., Pino-Benitez, N., Stashenko, E. E., Martı́nez, J. R., & Escobar, P. (2013) · Journal of Essential Oil Research · doi:10.1080/10412905.2013.820669 · Cited by 30 · see citing works
“It is an important chemical component of many EOs from some aromatic plants such as Cordia verbenacea (31), Copaiba tree (32), Syzygium aromaticum (33) and Piper spp.”
BackgroundPatents of drugs extracted from Brazilian medicinal plants
Balbani, A. P. S., Silva, D. H. S., & Montovani, J. C. (2009) · Expert Opinion on Therapeutic Patents · doi:10.1517/13543770902824180 · Cited by 29 · see citing works
Review of Recent Studies and Research Analysis for Anti-oxidant and Anti-aging Materials
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Citrus hystrix Extracts Protect Human Neuronal Cells against High Glucose-Induced Senescence
Pattarachotanant, N., & Tencomnao, T. (2020) · Pharmaceuticals · doi:10.3390/ph13100283 · Cited by 27 · see citing works
Mahajan, E., Singh, S., Diksha, Kaur, S., & Sohal, S. K. (2022) · Toxicon · doi:10.1016/j.toxicon.2022.09.016 · Cited by 27 · see citing works
Monitoring of biotransformation of hop aroma compounds in an in vitro digestion model
Heinlein, A., & Buettner, A. (2012) · Food & Function · doi:10.1039/c2fo30061c · Cited by 27 · see citing works
Differential Expression of Inflammation-Related Genes in Children with Down Syndrome
Silva, C. R. S., Biselli, J. M., Zampieri, B. L., Silva, W. A., de Souza, J. E. S., Bürger, M. C., Goloni‐Bertollo, E. M., & Pavarino, É. C. (2016) · Mediators of Inflammation · doi:10.1155/2016/6985903 · Cited by 24 · see citing works
Gomes, M. V. D. S., da Silva, J. D., Ribeiro, A. F., Cabral, L. M., & de Sousa, V. P. (2019) · Revista Brasileira de Farmacognosia · doi:10.1016/j.bjp.2019.01.009 · Cited by 24 · see citing works
Elsayed, H. E., El-Deeb, E. M., Taha, H., Taha, H. S., Elgindi, M. R., & Moharram, F. A.-E. (2023) · Frontiers in Chemistry · doi:10.3389/fchem.2023.1120432 · Cited by 24 · see citing works
“It possessed different biological effects such as anti-inflammatory (Medeiros et al., 2007) and anticarcinogenic (Langhasova et al.”
Dornelles, F. N., Santos, D. S., Dyke, T. E. V., Calixto, J. Β., Júnior, E. L. B., & Campos, M. M. (2009) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.109.155762 · Cited by 24 · see citing works
“The induction of this receptor has been associated with generation of inflammatory cytokines, neutrophil migration, and activation of several signaling pathways (Passos et al., 2004; Medeiros et al., 2007).”
BackgroundSharma, P., Manjusha, Rani, S., Malhotra, H., nitesh, N., Deswal, S., & Singh, S. (2015) · Asian Pacific Journal of Reproduction · doi:10.1016/s2305-0500(15)30004-x · Cited by 23 · see citing works
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Biologia floral e sistema reprodutivo da erva-baleeira (Varronia curassavica Jacq.)
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Therapeutic Potential of Essential Oils Against Ulcerative Colitis: A Review
Li, J., Zhang, X., Luan, F., Duan, J., Zou, J., Sun, J., Shi, Y., Guo, D., Wang, C., & Wang, X. Q. (2024) · Journal of Inflammation Research · doi:10.2147/jir.s461466 · Cited by 20 · see citing works
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Cordia verbenacea and secretion of mast cells in different animal species
de Oliveira, D. M. C., Luchini, A. C., Seito, L. N., Gomes, J. C., Lopez, M. E. C., & Stasi, L. C. D. (2011) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2011.03.046 · Cited by 19 · see citing works
“In this latter oil, the anti-inflammatoryproperty wasmainly attributed to -humulene and (−)-trans-caryophyllene (Fernandes et al., 2007; Medeiros et al., 2007; Passos et al., 2007).”
BackgroundInfluentialToxicity of Varronia curassavica Jacq. Essential Oil to Two Arthropod Pests and Their Natural Enemy
Andrade, F. P., Venzon, M., das Dôres, R. G. R., Franzin, M. L., Martins, E. F., de Araújo, G. J., & Fonseca, M. C. M. (2021) · Neotropical Entomology · doi:10.1007/s13744-021-00906-x · Cited by 18 · see citing works
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Swiderski, J., Sakkal, S., Apostolopoulos, V., Zulli, A., & Gadanec, L. K. (2023) · Nutrients · doi:10.3390/nu15112562 · Cited by 18 · see citing works
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In Silico Study of Anti-Insomnia Mechanism for Suanzaoren Prescription
Gao, J., Wang, Q., Huang, Y., Tang, K., Yang, X. L., & Cao, Z. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00925 · Cited by 18 · see citing works
Tonial, C. H., Rodrigues, M. F. F., Bosse, M. A., Sousa, I. M. D. O., de Lima, J. D., da Cunha, M. A. A., Foglio, M. A., Marques, M. O. M., & Marchese, J. A. (2020) · Industrial Crops and Products · doi:10.1016/j.indcrop.2020.112650 · Cited by 18 · see citing works
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“Anti-inflammatory activity of the tested extracts may be ascribed to polyphenols, flavonoids, and sesquiterpene.((25)) For example, it has been clearly established that flavonoids such as kaempferol act as regulators of NO synthase expression and NO release by concanavalin A (ConA)-stimulated splenocytes.”
BackgroundUsing Varronia curassavica (Cordiaceae) essential oil for the biocontrol of Phytomonas serpens
Silva, K. P., SANTOS, T. A. D. C., Moutinho, B. L., da Silva, R. S., Pinto, V. S. D. S. C., Blank, A. F., Corrêa, C. B., Scher, R., & Fernandes, R. P. M. (2019) · Industrial Crops and Products · doi:10.1016/j.indcrop.2019.111523 · Cited by 17 · see citing works
3D Printed Bigel: A Novel Delivery System for Cannabidiol-Rich Hemp Extract
Gościniak, A., Kocaj, F., Stasiłowicz-Krzemień, A., Szymański, M., Karpiński, T. M. M., & Cielecka‐Piontek, J. (2024) · Gels · doi:10.3390/gels10120770 · Cited by 16 · see citing works
da Silva, J. D., Gomes, M. V. D. S., Cabral, L. M., & de Sousa, V. P. (2019) · Journal of Drug Delivery Science and Technology · doi:10.1016/j.jddst.2019.101173 · Cited by 16 · see citing works
Rashid, N. A., Hussan, F., Hamid, A., Ridzuan, N. R. A., Halim, S. A. S. A., Jalil, N. A. A., Najib, N. H. M., Teoh, S. L., & Budin, S. B. (2020) · EXCLI journal · doi:10.17179/excli2020-2355 · Cited by 16 · see citing works
“In addition, α-caryophyllene and β-caryophyllene were found to inhibit the lipopolysaccharide (LPS)-induced NF-kB activation and neutrophil migration in animal models of inflammation (Medeiros et al., 2007).”
BackgroundGhazwani, M., Hani, U., Alqarni, M. H., & Alam, A. (2023) · Gels · doi:10.3390/gels9070550 · Cited by 15 · see citing works
“Anti-inflammatory [2], anti-carcinogenic [3], anti-bacterial [4], anti-oxidative [5], and analgesic [6] properties are amongst its reported biological effects.”
BackgroundYu, M.-H., Chae, I.-G., Jung, Y.-T., Jeong, Y.-S., Kim, H.-I., & Lee, I. (2011) · Journal of Life Science · doi:10.5352/jls.2011.21.3.375 · Cited by 13 · see citing works
Mendes, A. D. R., Lacerda, T. H. S., Rocha, S. M., & Martins, E. R. (2014) · Revista Brasileira de Plantas Medicinais · doi:10.1590/s1516-05722014000200015 · Cited by 13 · see citing works
Santos, A. V., Defaveri, A. C. A. E., Bizzo, H. R., Gil, R. A. D. S. S., & Sato, A. (2013) · In Vitro Cellular & Developmental Biology - Plant · doi:10.1007/s11627-013-9528-6 · Cited by 13 · see citing works
“…Janeiro 22290-240 Rio de Janeiro, Brazil e-mail: alicesato@unirio.br of cancer cells as well as strong antioxidant activity (Fernandes et al. 2007; Medeiros et al. 2007; Quispe-Condori et al. 2007; Roldão et al. 2008; Michielin et al. 2009, 2011) Based on its active component, the sesquiterpene…”
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Silva, V. B. G., da Fonsêca, B. M. B., de Aguiar, J. C. R. D. O. F., Navarro, D. M. D. A. F., de Oliveira, A. M., Napoleão, T. H., Correia, M. T. D. S., Lima, V. L. D. M., Costa, W. K., & da Silva, M. V. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116443 · Cited by 12 · see citing works
Fermentative α-Humulene Production from Homogenized Grass Clippings as a Growth Medium
Langsdorf, A., Drommershausen, A., Volkmar, M., Ulber, R., & Holtmann, D. (2022) · Molecules · doi:10.3390/molecules27248684 · Cited by 12 · see citing works
Matias, E. F. F., Alves, E. F., Silva, M. K. D. N., Carvalho, V. R. D. A., Medeiros, C. R., dos Santos, F. A. V., Bitu, V. D. C. N., de Souza, C. E. S., Figueredo, F. G., de Menezes, I. R. A., et al. (2015) · European Journal of Integrative Medicine · doi:10.1016/j.eujim.2015.03.007 · Cited by 12 · see citing works
Fu, J., Gao, Y., & Xing, X. (2022) · Molecules · doi:10.3390/molecules27144631 · Cited by 11 · see citing works
“In addition, both of these compounds were found to exhibit anti-inflammatory [33,34], analgesic [26,35], antifungal [36,37], and antibacterial activities [28,38,39].”
Background
- Authors
- Medeiros, R., Passos, G. F., Vitor, C. E., Koepp, J., Mazzuco, T. L., Pianowski, L. F., Campos, M. M., & Calixto, J. B.
- Affiliations
- Universidade Federal de Santa Catarina (BR)
- Pontifícia Universidade Católica do Rio Grande do Sul (BR)
- Venue
- British Journal of Pharmacology
- Publisher
- Wiley
- Published
- 2007-07
- Volume
- 151
- Issue
- 5
- Pages
- 618-627
- ISSN
- 0007-1188 (ISSN-L)
- 1476-5381
- PMC
- PMC2013990
- OpenAlex
- W1984871487
- Cited by
- 167
- References
- 46
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 11 · 2022: 10 · 2021: 12 · 2020: 12 · 2019: 11 · 2018: 11 · 2017: 6 · 2016: 9 · 2015: 16 · 2014: 8 · 2013: 6 · 2012: 6
- FWCI
- 2.23
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- British Journal of Pharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Sesquiterpenes and Asteraceae Studies
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Phytochemistry and Biological Activities
- Keywords
- Cordia verbenacea, α-humulene, β-caryophyllene, sesquiterpenes, essential oils, anti-inflammatory activity, acute inflammation, lipopolysaccharide, paw edema, neutrophil migration, NF-κB, mitogen-activated protein kinase, TNF-α, IL-1β, kinin B1 receptor, inflammatory cytokines
- MeSH terms
- Polycyclic Sesquiterpenes, Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Nucleus, Cytosol, Edema, Foot, Lipopolysaccharides, Male, Peroxidase, Neutrophils, Oils, Volatile, Sesquiterpenes, Tumor Necrosis Factor-alpha, Blotting, Western, Up-Regulation, NF-kappa B, Rats, Wistar, Reverse Transcriptase Polymerase Chain Reaction, Neutrophil Infiltration, Mitogen-Activated Protein Kinases, Electrophoretic Mobility Shift Assay, Cordia, Receptor, Bradykinin B1, Rats, Interleukin-1beta
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