Phoradendron bathyoryctum Eichler relieves acute nociceptive pain stimulus and carrageenan-induced inflammation in mice
DOI:
https://doi.org/10.17533/udea.vitae.v32n1a356558Keywords:
Phoradendron bathyoryctum, anti-nociceptive, anti-inflammatory, Randall-Selitto, writhing test, hot plate, plethysmometer.Abstract
Background: The genus Phoradendron belongs to the Santalaceae family and possesses several species with antitumor, cytotoxic, and immunomodulatory activity, where pain and inflammation are common symptoms. It is used in venereal and liver diseases in Paraguayan folk medicine. In addition, it claims to have tonic properties for the heart and central nervous system. Previous studies have shown that crude extract of Phoradendron bathyoryctum Eichler (Pb) has anxiolytic and antidepressant activity.
Objective: This work aimed to determine the anti-nociceptive and anti-inflammatory activity ofPb using acute models in mice.
Methods: the anti-nociceptive activity of Pb was evaluated using mechanical pressure (Randall-Selitto test), acetic acid (writhing test), and heat (hot plate test) noxious stimulus in mice. The anti-inflammatory activity was assessed through carrageenan-induced plantar edema in mice previously treated with Pb.
Results: Presences of high polarity alkaloids, steroids/ free triterpenoids, leucoanthocyanidins, and tannins were detected in phytochemical studies. Oral doses of 30 (p<0.01) and 300 (p<0.001) mg/kg of Pb denoted a significant dose-dependent increase in pain threshold, using the Randall-Selitto and Writhing test (30; p<0.05; and 300; p<0.01. In addition, consistent with the above anti-nociceptive effect, an increase in the reaction latency time after oral administration of Pb at a dose of 300 mg/kg (p<0.05) in the hot plate test was denoted. Finally, a significant reduction of edema (30 mg/kg; p<0.01) induced by 1% carrageenan was evidenced, demonstrating a potential anti-inflammatory activity of Pb compared to the positive edema control. Interestingly, the anti-edematous activity of Pb showed a similar intensity response compared to the group treated with 10 mg/kg indomethacin (p<0.01).
Conclusion: This work revealed that the crude extract of Pb can increase pain threshold, be compatible with an analgesic effect, and reduce edema (anti-inflammatory) induced by Carrageenan in mice. Further pharmacological and chemical studies are being conducted to elucidate molecular mechanisms and components involved in the observed effects.
Downloads
References
Woolf CJ. What is this thing called pain? J Clin Invest. 2010;120(11):3742–4. DOI: https://doi.org/10.1172/JCI45178.3742
Rojas-Corrales MO, Casas J, Moreno-Brea MR, Gibert-Rahola J, Micó JA. Anti-nociceptive effects of tricyclic antidepressants and their noradrenergic metabolites. Eur Neuropsychopharmacol. 2003;13(5):355–63. DOI: https://doi.org/10.1016/S0924-977X(03)00017-8
Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: A Cochrane review. J Neurol Neurosurg Psychiatry. 2010;81(12):1372–3. DOI: https://doi.org/10.1136/jnnp.2008.144964
Hellión-Ibarrola MDC, Montalbetti Y, Heinichen OY, Ibarrola DA. Anxiolytic and Antidepressant-like Effect of the Hydro-alcoholic Extract of Phoradendron Bathyoryctum Eichler (santalaceae) (ka’avo Tyre’y) In Mice. J Appl Pharm Sci. 2021;11(6):062–9. DOI: https://doi.org/10.7324/JAPS.2021.110607
Sarker DS, Latif Z, Gray IA. Methods in Biotechnology. Natural Products Isolation. 2da ed. John Walkers, editor. Totowa New Jersey: Humana Press; 2005. 332 p.
Real Decreto M de AP y A, Presidencia CEE. Real decreto 1201/2005. Boe. 2005;252:34367–91.
Singh N, Bansal Y, Bhandari R, Marwaha L, Singh R, Chopra K, et al. Resveratrol protects against ICV collagenase-induced neurobehavioral and biochemical deficits. J Inflamm (United Kingdom). 2017;14(1):1–15. DOI: https://doi.org/10.1186/s12950-017-0158-3
Lapa AJ, Souccar C, Lima-Landman MT, De Lima TC. Métodos de avaliação da atividade farmacológica de plantas medicinais. Programa I. Lapa AJ, editor. Sao Paulo: CYTED; 2002. 60–69 p.
Lucena JEX, Bispo MD, Nunes RS, Cavalcanti SCH, Teixeira-Silvia F, Marçal RM, et al. Efeito antinociceptivo e anti-inflamatório do extrato aquoso da entrecasca de Coutarea hexandra Schum. (Rubiaceae). Brazilian J Pharmacogn. 2006;16(1):67–72. DOI: https://doi.org/10.1590/S0102-695X2006000100012
Qnais EY, Abu-Dieyeh M, Abdulla FA, Abdalla SS. The anti-nociceptive and anti-inflammatory effects of Salvia officinalis leaf aqueous and butanol extracts. Pharm Biol. 2010;48(10):1149–56. DOI: https://doi.org/10.3109/13880200903530763
Porto CRC, Soares LAL, Souza TP, Petrovick PR, Lyra IL, Araújo Júnior RF, et al. Anti-infl ammatory and anti-nociceptive activities of Phyllanthus niruri spray-dried standardized extract. Rev Bras Farmacogn [Internet]. 2013;23(1):138–44. DOI: http://dx.doi.org/10.1590/S0102-695X2013005000004.
Kim HS, Kwon OK, Park JW, Jeong HG, Oh SR, Lee HK, et al. Anti-inflammatory activities of methanol extract of Mastixia arborea c.b. clarke as to mouse macrophage and paw edema. Biosci Biotechnol Biochem. 2013;77(12):2356–61. DOI: https://doi.org/10.1271/bbb.130429
de Moura Sperotto ND, Steffens L, Veríssimo RM, Henn JG, Péres VF, Vianna P, et al. Wound healing and anti-inflammatory activities induced by a Plantago australis hydroethanolic extract standardized in verbascoside. J Ethnopharmacol. DOI: 2018;225(July):178–88. https://doi.org/10.1016/j.jep.2018.07.012
Aydede M. Does the IASP definition of pain need updating? Pain Reports. 2019;4(5):1–7. DOI: https://doi.org/10.1097/PR9.0000000000000777
Maallo AMS, Moulton EA, Sieberg CB, Giddon DB, Borsook D, Holmes SA. A lateralized model of the pain-depression dyad. Neurosci Biobehav Rev [Internet]. 2021;127(June):876–83. DOI: https://doi.org/10.1016/j.neubiorev.2021.06.003
Sudo RT, Neto ML, Monteiro CES, Amaral R V., Resende ÂC, Souza PJC, et al. Anti-nociceptive effects of hydro-alcoholic extract from Euterpe oleracea Mart. (Açaí) in a rodent model of acute and neuropathic pain. BMC Complement Altern Med. 2015;15(1):1–8. DOI: https://doi.org/10.1186/s12906-015-0724-2
Gregory N, Harris A, Robinson C, Dougherty P, Fuchs P, Sluka K. An overview of animal models of pain: disease models and outcome measures. J Pain. 2014;14(11):1–26. DOI: https://doi.org/10.1016/j.jpain.2013.06.008.An
Webb CM, Steeds CE. The anatomy and physiology of pain. Clin Integr care [Internet]. 2022;14(c):100115. DOI: https://doi.org/10.1016/j.intcar.2022.100115
Hryciw G, De Preter CC, Wong J, Heinricher MM. Physiological properties of pain-modulating neurons in rostral ventromedial medulla in female rats, and responses to opioid administration. Neurobiol Pain [Internet]. 2021;10:100075. DOI: https://doi.org/10.1016/j.ynpai.2021.100075
Ontiveros-Rodríguez JC, Rojas-Rojas FU, Alonso-Castro AJ, Salazar-Gómez A. American mistletoes as a promising source of bioactive compounds. Stud Nat Prod Chem. 2023 Jan 1;78:237–53. DOI: https://doi.org/10.1016/B978-0-323-91253-2.00020-0
Bastos IVGA, de Oliveira TB, Rodrigues MD, Militão GCG, da Silva TG, Turatti ICC, et al. Use of GC/MS to identify chemical constituents and cytotoxic activity of the leaves of Phoradendron mucronatum and Phoradendron microphyllum (Viscaceae). An Acad Bras Cienc. 2017;89(2):991–1001. DOI: https://doi.org/10.1590/0001-3765201720160586
Vasconcellos CLC, Vitório KCD, Andrade PA, Cambuí ÉVF, Lira AF, Cavalcante SCH, et al. Anti-nociceptive, anti-inflammatory, and antioxidant properties of Phoradendron piperoides leaves. Pharm Biol. 2009;47(7):645–52. DOI: https://doi.org/10.1080/13880200902917065
Gedalovich E, Kuijt J, Carpita NC. Chemical composition of viscin, an adhesive involved in dispersal of the parasite Phoradendron californicum (Viscaceae). Physiol Mol Plant Pathol. 1988;32(1):61–76. DOI: https://doi.org/10.1016/S0885-5765(88)80006-7
Lutz TM, Kimna C, Casini A, Lieleg O. Bio-based and bio-inspired adhesives from animals and plants for biomedical applications. Mater Today Bio [Internet]. 2022;13(January):100203. DOI: https://doi.org/10.1016/j.mtbio.2022.100203
Rangel-Méndez JA, Valencia-Chan LS, Peraza-Sánchez SR, Moo-Puc RE. Season affects active metabolite composition and cytotoxic effect in Phoradendron wattii methanol extracts. Nat Prod Res [Internet]. 2022;36(17):4466–9. DOI: https://doi.org/10.1080/14786419.2021.1984466.
Yazbek PB, Tezoto J, Cassas F, Rodrigues E. Plants used during maternity, menstrual cycle and other women’s health conditions among Brazilian cultures. J Ethnopharmacol [Internet]. 2016;179:310–31. DOI: http://dx.doi.org/10.1016/j.jep.2015.12.054
Dias KS, Almeida DS, Silva ABL, Marques MS, Menezes, Igor A, Santos TC, et al. Avaliação dos efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso da Phoradendron piperoides (Kunt.) Trel. (Viscaceae). Brazilian J Pharmacogn. 2007;17(3):373–7. DOI: DOI: https://doi.org/10.1590/S0102-695X2007000300012
McCarson KE. Models of Inflammation: Carrageenan- or Complete Freund’s Adjuvant (CFA)–Induced Edema and Hypersensitivity in the Rat. Curr Protoc Pharmacol. 2015;70(1):5.4.1-5.4.9. DOI: https://doi.org/10.1002/0471141755.ph0504s70
Bannon AW, Malmberg AB. Models of nociception: hot-plate, tail-flick, and formalin tests in rodents. Curr Protoc Neurosci. 2007;Chapter 8:8.9.1-8.9.16. DOI: https://doi.org/10.1002/0471142301.ns0809s41
Petrus M, Peier AM, Bandell M, Hwang SW, Huynh T, Olney N, et al. A role of TRPA1 in mechanical hyperalgesia is revealed by pharmacological inhibition. Mol Pain. 2007;3:1–8. DOI: https://doi.org/10.1186/1744-8069-3-40
Kamau PM, Li H, Yao Z, Han Y, Luo A, Zhang H, et al. Potent CaV3.2 channel inhibitors exert analgesic effects in acute and chronic pain models. Biomed Pharmacother [Internet]. 2022;153(May):113310. DOI: https://doi.org/10.1016/j.biopha.2022.113310
Simões RR, Coelho I dos S, Junqueira SC, Pigatto GR, Salvador MJ, Santos ARS, et al. Oral treatment with essential oil of Hyptis spicigera Lam. (Lamiaceae) reduces acute pain and inflammation in mice: Potential interactions with transient receptor potential (TRP) ion channels. J Ethnopharmacol [Internet]. 2017;200(February):8–15. DOI: http://dx.doi.org/10.1016/j.jep.2017.02.025
Brito TG da S, Silva APSA da, Cunha RX da, Fonseca CSM da, Araújo TF da S, Campos JK de L, et al. Anti-inflammatory, hypoglycemic, hypolipidemic, and analgesic activities of Plinia cauliflora (Mart.) Kausel (Brazilian grape) epicarp. J Ethnopharmacol [Internet]. 2021;268(October 2020):113611. DOI: https://doi.org/10.1016/j.jep.2020.113611
Duarte DB, Vasko MR, Fehrenbacher JC. Models of inflammation: Carrageenan air pouch. Curr Protoc Pharmacol. 2016;72(March):5.6.1-5.6.9. DOI: https://doi.org/10.1002/0471141755.ph0506s72
Fehrenbacher JC, Vasko MR, Duarte DB. Models of inflammation: Carrageenan- or complete freund’s adjuvant (CFA)-induced edema and hypersensitivity in the rat. Curr Protoc Pharmacol. 2012;56(March):5.4.1-5.4.7. DOI: https://doi.org/10.1002/0471141755.ph0504s56
Wang Z, Hwang SH, Guillen Quispe YN, Gonzales Arce PH, Lim SS. Investigation of the antioxidant and aldose reductase inhibitory activities of extracts from Peruvian tea plant infusions. Food Chem [Internet]. 2017;231:222–30. DOI: http://dx.doi.org/10.1016/j.foodchem.2017.03.107
Deuis JR, Dvorakova LS, Vetter I. Methods used to evaluate pain behaviors in rodents. Front Mol Neurosci. 2017;10(September):1–17. DOI: https://doi.org/10.3389/fnmol.2017.00284

Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Mariela Ortiz Rivas, Olga Heinichen, Wilfrido Arrua, Rosa Degen de Arrua, Derlis A. Ibarrola D., Maria del Carmen Hellion-Ibarrola

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Copyright Notice and Open Access Statement
The Journal Vitae works under the Open Access license, and the published manuscripts remain available for the public, both on the Journal's website and in databases, under the Creative Commons license, "Noncommercial Attribution" and "Share alike" systems, adopted in Colombia. Hence, when the authors agree to publish in the Journal Vitae, they will not have the right to economic retributions on publications and reproductions through different diffusion media. The documents are freely available to the internet public, permitting users to read, download, copy, distribute, print, search, or link to the full texts and pass them as data to software. The only constraint on reproduction and distribution, should be to give authors control over the integrity of their work and the right to be appropriately acknowledged and cited.
Authors declare that:
-
They are the intellectual property owners and are responsible for all the information stated in the article.
-
This manuscript has not been submitted or published in other printed or digital media. They accept the responsibility for the judgments, opinions, and points of view expressed in the published article and, therefore, they exonerate Universidad de Antioquia and Journal Vitae from any process.
-
They exempt Universidad de Antioquia and Journal Vitae from settling conflicts or disputes related to the authorship of the referred article.
-
They accept the revision of the original manuscript by suitable personnel, and they bind themselves to perform the corrections appointed or suggested by the assessors.
-
Therefore, they know the editorial process and will not bind the Editorial Board of the Journal to assume any obligations regarding the volume and issue in which the article is published.
-
They transfer the rights of publication, reprinting, and distribution of the article from the moment of its approval, in print and digital format, without the right to economic rewards, and under the licensing conditions considered relevant by Journal Vitae.
-
They fully authorize Universidad de Antioquia and Journal Vitae to submit the published material to the diverse databases and indexing systems where the Journal can be found to comply with the requirements of the regulatory authorities to maintain the national classification of journals.
-
They will assume the article publication costs established for the current issue, and they will make the payment as soon as they are informed about the volume and the issue in which the final version of the article is published.
-
After the article is published, you can share digital or printed copies in a noncommercial manner. You will be able to use the paper in your institution or company for educational or research purposes, including the use in course programs.
Conflict of interest: Authors are responsible for recognizing and disclosing any financial or other benefits that could be perceived to bias their work, acknowledging all financial support and any personal connections with potential sponsors. Examples of such conflicts include receiving research funds or honoraria, serving on advisory boards, stock ownership, or employment and consulting arrangements. Authors without such connections should clearly state that they have no financial support or personal relationships that could be perceived to bias their work. All conflicts of interest should be disclosed on the author's identification page of the manuscript.