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Volume 17
Issue 12
10.3390/ph17121671
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Article

Antinociceptive Potential of Ximenia americana L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways

by
Renata Torres Pessoa
1,
Lucas Yure Santos da Silva
1,
Isabel Sousa Alcântara
1,
Tarcísio Mendes Silva
1,
Eduardo dos Santos Silva
1,
Roger Henrique Sousa da Costa
1,
Aparecida Barros da Silva
1,
Jaime Ribeiro-Filho
1,2,
Anita Oliveira Brito Pereira Bezerra Martins
1,
Henrique Douglas Melo Coutinho
3,
Jean Carlos Pereira Sousa
4,
Andréa Rodrigues Chaves
4,
Ricardo Neves Marreto
5 and
Irwin Rose Alencar de Menezes
1,*
1
Laboratory of Pharmacology and Molecular Chemistry, Department of Chemical Biology, Regional University of Cariri (URCA), Rua Coronel Antônio Luis 1161, Pimenta, Crato 63105-000, Ceará, Brazil
2
Oswaldo Cruz Foundation (FIOCRUZ), Fiocruz Ceará, R. São José, S/N—Precabura, Eusébio 61773-270, Ceará, Brazil
3
Laboratory of Microbiology and Molecular Biology, Department of Biological Chemistry, Regional University of Cariri (URCA), Crato 63105-000, Ceará, Brazil
4
Institute of Chemistry, Federal University of Goiás, Goiânia 74001-970, Goiás, Brazil
5
Faculty of Pharmacy, Federal University of Goiás, Goiânia 74605-170, Goiás, Brazil
*
Author to whom correspondence should be addressed.
Pharmaceuticals 2024, 17(12), 1671; https://doi.org/10.3390/ph17121671
Submission received: 6 November 2024 / Revised: 28 November 2024 / Accepted: 7 December 2024 / Published: 11 December 2024
(This article belongs to the Special Issue The 20th Anniversary of Pharmaceuticals — Multi-Targeted Natural Products as Therapeutics)
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Abstract

Background/Objectives: This study evaluated the antinociceptive effect of the Ximenia americana L. bark extract (HEXA) and its primary component, caffeic acid (CA), through in vivo assays. Methods: The antinociceptive properties were assessed using abdominal writhing, hot plate, and Von Frey tests. Additionally, the study investigated the modulation of various pain signaling pathways using a pharmacological approach. Results: The results demonstrated that all doses of the HEXA significantly increased latency in the hot plate test, decreased the number of abdominal contortions, reduced hyperalgesia in the Von Frey test, and reduced both phases of the formalin test. Caffeic acid reduced licking time in the first phase of the formalin test at all doses, with the highest dose showing significant effects in the second phase. The HEXA potentially modulated α2-adrenergic (52.99%), nitric oxide (57.77%), glutamatergic (33.66%), vanilloid (39.84%), cyclic guanosine monophosphate (56.11%), and K+ATP channel-dependent pathways (38.70%). Conversely, CA influenced the opioid, glutamatergic (53.60%), and vanilloid (34.42%) pathways while inhibiting nitric oxide (52.99%) and cyclic guanosine monophosphate (38.98%). Conclusions: HEXA and CA exhibit significant antinociceptive effects due to their potential interference in multiple pain signaling pathways. While the molecular targets remain to be fully investigated, HEXA and CA demonstrate significant potential for the development of new analgesic drugs.
Keywords: natural compounds; HPLC; nociception; anti-inflammatory; mechanism of action; pain natural compounds; HPLC; nociception; anti-inflammatory; mechanism of action; pain
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MDPI and ACS Style

Pessoa, R.T.; Santos da Silva, L.Y.; Alcântara, I.S.; Silva, T.M.; Silva, E.d.S.; da Costa, R.H.S.; da Silva, A.B.; Ribeiro-Filho, J.; Pereira Bezerra Martins, A.O.B.; Coutinho, H.D.M.; et al. Antinociceptive Potential of Ximenia americana L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways. Pharmaceuticals 2024, 17, 1671. https://doi.org/10.3390/ph17121671

AMA Style

Pessoa RT, Santos da Silva LY, Alcântara IS, Silva TM, Silva EdS, da Costa RHS, da Silva AB, Ribeiro-Filho J, Pereira Bezerra Martins AOB, Coutinho HDM, et al. Antinociceptive Potential of Ximenia americana L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways. Pharmaceuticals. 2024; 17(12):1671. https://doi.org/10.3390/ph17121671

Chicago/Turabian Style

Pessoa, Renata Torres, Lucas Yure Santos da Silva, Isabel Sousa Alcântara, Tarcísio Mendes Silva, Eduardo dos Santos Silva, Roger Henrique Sousa da Costa, Aparecida Barros da Silva, Jaime Ribeiro-Filho, Anita Oliveira Brito Pereira Bezerra Martins, Henrique Douglas Melo Coutinho, and et al. 2024. "Antinociceptive Potential of Ximenia americana L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways" Pharmaceuticals 17, no. 12: 1671. https://doi.org/10.3390/ph17121671

APA Style

Pessoa, R. T., Santos da Silva, L. Y., Alcântara, I. S., Silva, T. M., Silva, E. d. S., da Costa, R. H. S., da Silva, A. B., Ribeiro-Filho, J., Pereira Bezerra Martins, A. O. B., Coutinho, H. D. M., Sousa, J. C. P., Chaves, A. R., Marreto, R. N., & de Menezes, I. R. A. (2024). Antinociceptive Potential of Ximenia americana L. Bark Extract and Caffeic Acid: Insights into Pain Modulation Pathways. Pharmaceuticals, 17(12), 1671. https://doi.org/10.3390/ph17121671

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