Essential Oil from Lippia origanoides (Verbenaceae): Haemostasis and Enzymes Activity Alterations

Author(s): Maria L. Teixeira, Silvana Marcussi, Danubia A. de C.S. Rezende, Maisa L. Magalhães, David L. Nelson, Maria das G. Cardoso*

Journal Name: Medicinal Chemistry

Volume 15 , Issue 2 , 2019


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Graphical Abstract:


Abstract:

Background: The search for natural inhibitors of snake venom toxins is essential to supplement or even replace the serum therapy. The aim of this work was to evaluate the pharmacological properties of essential oil from Lippia origanoides Kunth. (Verbenaceae).

Methods: The oil was extracted by hydrodistillation and the constituents were identified and quantified by GC-MS and GC-FID. The essential oil from L. origanoides was evaluated in hemolysis tests, on the activities of phospholipases A2 and serine proteases and in coagulation and thrombolysis induced by different snake venoms.

Results: The major constituents of essential oil were carvacrol, p-cymene, γ-terpinene, and thymol. The oil inhibited approximately 10 % of the phospholipase A2 activity induced by Bothrops atrox, Bothrops jararaca, Bothrops jararacussu and Bothrops moojeni venoms and was not cytotoxic against erythrocytes. However, previous incubation of the oil with B. jararacussu, B. moojeni, and Crotalus durissus terrificus (C.d.t.) venoms resulted in potentiation of hemolytic activity (30 % and 50 % for 0.6 µL mL-1 and 1.2 µL mL-1, respectively). The essential oil presented a procoagulant effect on human citrated plasma, potentiated the thrombolytic action of proteases and phospholipases A2 present in B. jararacussu venom, and serine protease activity induced by B. jararaca and Lachesis muta venoms. When pre-incubated with the C.d.t. venom, however, prothrombotic activity was observed.

Conclusion: The results obtained in this work amplify the pharmacological characterization of the essential oil from L. origanoides. However, new studies are fundamental to define the action mechanisms and determine pharmaceutical applications.

Keywords: Coagulation, natural products, oxygenated monoterpenes, hemostatic action, enzyme inhibitors, medicinal plants.

[1]
Carvalho, B.M.A.; Santos, J.D.L.; Xavier, B.M.; Almeida, J.R.; Resende, L.M.; Martins, W.; Marcussi, S.; Marangoni, S.; Stábeli, R.G.; Calderon, L.A.; Soares, A.M.; Da Silva, S.L.; Marchi-Salvador, D.P. Snake venom PLA2s inhibitors isolated from brazilian plants: synthetic and natural molecules. BioMed Res. Int., 2013, 2013, 1-8.
[2]
Silva, M.L.; Marcussi, S.; Fernandes, R.S.; Pereira, P.S.; Januário, A.H.; França, S.C.; Da Silva, S.L.; Soares, A.M.; Lourenço, M.V. Anti-snake venom activities of extracts and fractions from callus cultures of Sapindus saponaria. Pharm. Biol., 2012, 50(3), 366-375.
[3]
Diogo, L.C.; Fernandes, R.S.; Marcussi, S.; Menaldo, D.L.; Roberto, P.G.; Matrangulo, P.V.F.; Pereira, P.S.; França, S.C.; Giuliatti, S.; Soares, A.M.; Lourenço, M.V. Inhibition of snake venoms and phospholipases A2 by extracts from native and genetically modified Eclipta alba: isolation of active coumestans. Basic Clin. Pharmacol. Toxicol., 2009, 104(4), 293-299.
[4]
Marcussi, S.; Sant’Ana, C.D.; Oliveira, C.Z.; Rueda, A.Q.; Menaldo, D.L.; Beleboni, R.O.; Stabeli, R.G.; Giglio, J.R.; Fontes, M.R.M.; Soares, A.M. Snake venom phospholipase A2 inhibitors: medicinal chemistry and therapeutic potential. Curr. Top. Med. Chem., 2007, 7, 743-756.
[5]
Vásquez, J.; Jiménez, S.L.; Gómez, I.C.; Rey, J.P.; Henao, A.M.; Marín, D.M.; Romero, J.O.; Alarcón, J.C. Snakebites and ethnobotany in the Eastern region of Antioquia, Colombia - the traditional use of plants. J. Ethnopharmacol., 2013, 146(2), 449-455.
[6]
Sarrazin, S.L.F.; Silva, L.A.; Assunção, A.P.F.; Oliveira, R.B.; Calao, V.Y.P.; Silva, R.; Stashenko, E.E.; Maia, J.G.S.; Mourão, R.H.V. Antimicrobial and seasonal evaluation of the carvacrol-chemotype oil from Lippia origanoides Kunth. Molecules, 2015, 20, 1860-1871.
[7]
Agência Nacional de Vigilância Sanitária [ANVISA], Fundação Oswaldo Cruz: Farmacopeia Brasileira. 3rd ed. Agência Nacional de Vigilância Sanitária [ANVISA]: Brasília, 2010, 198-199.
[8]
Pimentel, F.A.; Cardoso, M.G.; Salgado, A.P.S.P.; Aguiar, P.M.; Silva, V.F.; Moraes, A.R.; Nelson, D.L. A convenient method for the determination of moisture in aromatic plants. Quim. Nova, 2006, 29(2), 373-375.
[9]
Adams, R.P. Identification of essential oils components by gas chromatography/mass spectroscopy, 4th ed.; Allured: Carol Stream, 2007.
[10]
Teixeira, M.L.; Cardoso, M.G.; Figueiredo, A.C.S.; Moraes, J.C.; Assis, F.A.; Andrade, J.; Nelson, D.L.; Gomes, M.S.; Souza, J.A.; Albuquerque, L.R.M. Essential oils from Lippia origanoides Kunth. and Mentha spicata L.: chemical composition, insecticidal and antioxidant activities. Am. J. Plant Sci., 2014, 5, 1181-1190.
[11]
Gutiérrez, J.M.; Avila, C.; Rojas, E.; Cerdas, L. An alternative in vitro method for testing the potency of the polyvalent antivenom produced in Costa Rica. Toxicon, 1988, 26, 411-413.
[12]
Price, M.F.; Wilkinson, I.D.; Gentry, L.O. Plate method for detection in phospholipase activity in Candida albicans. Sabouraudia, 1982, 20, 7-17.
[13]
Cintra, A.C.O.; De Toni, L.G.B.; Sartim, M.A.; Franco, J.J.; Caetano, R.C.; Murakami, M.T.; Sampaio, S.V. Batroxase, a new metalloproteinase from B. atrox snake venom with strong fibrinolytic activity. Toxicon, 2012, 60(1), 70-82.
[14]
Gremski, L.H.; Chaim, O.M.; Paludo, K.S.; Sade, Y.B.; Otuki, M.F.; Richardson, M.; Gremski, W.; Sanchez, E.F.; Veiga, S.S. Cytotoxic, thrombolytic and edematogenic activities of leucurolysin-a, a metalloproteinase from Bothrops leucurus snake venom. Toxicon, 2007, 50(1), 120-134.
[15]
Selistre, H.S.; Queiroz, L.S.; Cunha, O.A.B.; Souza, G.E.P.; Giglio, J.R. Isolation and characterization of hemorrhagic, myonecrotic and edema-inducing toxins from Bothrops insularis (jararaca ilhoa) snake venom. Toxicon, 1990, 28(3), 261-273.
[16]
Valentin, E.; Lambeau, G. What can venom phospholipases A2 tell us about the functional diversity of mammalian secreted phospholipases A2? Biochimie, 2000, 82(9-10), 815-831.
[17]
Zaqueo, K.D.; Kayano, A.M.; Domingos, T.F.S.; Moura, L.A.; Fuly, A.L.; Da Silva, S.L.; Acosta, G.; Oliveira, E.; Albericio, F.; Zanchi, F.B.; Zuliani, J.P.; Calderon, L.A.; Stábeli, R.G.; Soares, A.M. BbrzSP-32, the first serine protease isolated from Bothrops brazili venom: purification and characterization. Comp. Biochem. Physiol, Part A. Mol. Integr. Physiol., 2016, 195, 15-25.
[18]
Ferreira, D.F. Sisvar: a computer statistical analysis system. Cienc. Agrotec., 2011, 35(6), 1039-1042.
[19]
Guimaraes, C.L.S.; Moreira-Dill, L.S.; Fernandes, R.S.; Costa, T.R.; Hage-Melim, L.I.S.; Marcussi, S.; Carvalho, B.M.A.; Da Silva, S.L.; Zuliani, J.P.; Fernandes, C.F.C.; Calderon, L.A.; Soares, A.M.; Stabeli, R.G. Biodiversity as a source of bioactive compounds against snakebites. Curr. Med. Chem., 2014, 21(25), 2952-2979.
[20]
Koh, D.C.I.; Armugam, A.; Jeyaseelan, K. Snake venom components and their applications in biomedicine. Cell. Mol. Life Sci., 2006, 63(24), 3030-3041.
[21]
Parente, L. Pros and cons of selective inhibition of cyclooxygenase-2 versus dual lipoxygenase/cyclooxygenase inhibition: is two better than one? J. Rheumatol., 2001, 28(11), 2375-2382.
[22]
Asgary, S.; Naderi, G.A.; Ardekani, M.R.S.; Sahebkar, A.; Airin, A.; Aslani, S.; Kasher, T.; Emami, A.S. Chemical analysis and biological activities of Cupressus sempervirens var. horizontalis essential oils. Pharm. Biol., 2013, 51(2), 137-144.
[23]
Xavier, A.L.; Pita, J.C.; Brito, M.T.; Meireles, D.R.; Tavares, J.F.; Silva, M.S.; Maia, J.G.; Andrade, E.H.; Diniz, M.F.; Silva, T.G.; Pessoa, H.L.; Sobral, M.V. Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla. Z. Naturforsch. C. Biosci., 2015, 70(5-6), 129-137.
[24]
Dhananjaya, B.L.; Zameer, F.; Girish, K.S.; D’Souza, C.J.M. Anti-venom potential of aqueous extract of stem bark of Mangifera indica L. against Daboia russellii (Russell’s viper) venom. Indian J. Biochem. Biophys., 2011, 48(3), 175-183.
[25]
Moura, L.A.; Sanchez, E.F.; Bianco, E.M.; Pereira, R.C.; Teixeira, V.L.; Fuly, A.L. Antiophidian properties of a dolastane diterpene isolated from the marine brown alga Canistrocarpus cervicornis. Biomed. Prevent. Nutr., 2011, 1(1), 61-66.
[26]
Patiño, A.C.; López, J.; Aristizábal, M.; Quintana, J.C.; Benjumea, D. Efecto inhibitorio de extractos de Renealmia alpinia Rottb. Maas (Zingiberaceae) sobre el veneno de Bothrops asper (mapaná). Biomedica. Revista del Instituto Nacional de Salud, 2012, 32(3), 365-374.
[27]
Torres, A.M.; Camargo, F.J.; Ricciardi, G.A.; Ricciardi, A.I.; Dellacassa, E. Neutralizing effects of Nectandra angustifolia extracts against Bothrops neuwiedi snake venom. Nat. Prod. Commun., 2011, 6(9), 1393-1396.
[28]
Cunha, E.M.; Martins, A.O. Principais compostos químicos presente nos venenos de cobras dos gêneros Bothrops e Crotalus – uma revisão. Revista Eletrônica de Educação e Ciência, 2012, 2(2), 21-26.
[29]
Arafat, A.S.Y.; Arun, A.; Ilamathi, M.; Asha, J.; Sivashankari, P.R.; D’Souza, C.J.M.; Sivaramakrishnan, V.; Dhananjaya, B.L. Homology modeling, molecular dynamics and atomic level interaction study of snake venom 5′ nucleotidase. J. Mol. Model., 2014, 20, 2156-2165.
[30]
Alvarenga, E.S.; Silva, S.A.; Barosa, L.C.A.; Demuner, A.J.; Parreira, A.G.; Ribeiro, R.I.M.A.; Marcussi, S.; Ferreira, J.M.S.; Resende, R.R.; Granjeiro, P.A.; Silva, J.A.; Soares, A.M.; Marangoni, S.; Da Silva, S.L. Synthesis and evaluation of sesquiterpene lactone inhibitors of phospholipase A2 from Bothrops jararacussu. Toxicon, 2011, 57(1), 100-108.
[31]
Santos, J.I.; Santos-Filho, N.A.; Soares, A.M.; Fontesa, M.R.M. Crystallization and preliminary X-ray crystallographic studies of a Lys49-phospholipase A2 homologue from Bothrops pirajai venom complexed with rosmarinic acid. Acta Crystallogr. Sect. F: Struct. Biol. Commun., 2010, 66, 699-701.
[32]
Santos, J.I.; Cardoso, F.F.; Soares, A.M.; Silva, M.P.; Gallacci, M.; Fontes, M.R.M. Structural and functional studies of a bothropic myotoxin complexed to rosmarinic acid: new insights into Lys49-PLA2 inhibition. PLoS One, 2011, 6(12), e28521.
[33]
Ticli, F.K. Rosmarinic acid, a new snake venom phospholipase A2 inhibitor from Cordia verbenacea (Boraginaceae): antiserum action potentiation and molecular interaction. Toxicon, 2005, 46(3), 318-327.
[34]
Miranda, C.A.S.F.; Cardoso, M.G.; Mansanares, M.E.; Gomes, M.S.; Marcussi, S. Preliminary assessment of Hedychium coronarium essential oil on fibrinogenolytic and coagulant activity induced by Bothrops and Lachesis snake venoms. J. Venom. Anim. Toxins Incl. Trop. Dis., 2014, 20, 39-46.
[35]
Miranda, C.A.S.F.; Cardoso, M.G.; Marcussi, S.; Teixeira, M.L. Clotting and fibrinogenolysis inhibition by essential oils from species of the Asteraceae family. Braz. Arch. Biol. Technol., 2016, 59, e16150775.
[36]
Zelanis, A.; Huesgen, P.F.; Oliveira, A.K.; Tashima, A.K.; Serrano, S.M.T.; Overall, C.M. Snake venom serine proteinases specificity mapping by proteomic identification of cleavage sites. J. Proteomics, 2015, 113, 260-267.
[37]
Maia, H.N.; Nguyenb, H.T.N.; Koiwaia, K.; Kondoa, H.; Hironoa, I. Characterization of a Kunitz-type protease inhibitor (MjKuPI) reveals the involvement of MjKuPI positive hemocytes in the immune responses of kuruma shrimp Marsupenaeus japonicus. Dev. Comp. Immunol., 2016, 63, 121-127.
[38]
Safavi, F.; Rostami, A. Role of serine proteases in inflammation: Bowman-Birk protease inhibitor (BBI) as a potential therapy for autoimmune diseases. Exp. Mol. Pathol., 2012, 93(3), 428-433.


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Article Details

VOLUME: 15
ISSUE: 2
Year: 2019
Published on: 12 February, 2019
Page: [207 - 214]
Pages: 8
DOI: 10.2174/1573406414666180829150515
Price: $65

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