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Article

Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways

by
Maria Lúcia de Azevedo Oliveira
1,2,
Rubiamara Mauricio de Sousa
2,
Eder Alves Barbosa
3,
Ony Araújo Galdino
2,
Duanny Lorena Aires Dantas
2,
Ingrid Reale Alves
4,
Raphaelle Sousa Borges
4,
Nayara Costa de Melo Castelo Branco
4,
Artemis Socorro do Nascimento Rodrigues
4,
Gisele Custódio de Souza
5,
Saulo Victor e Silva
6,
Gabriel Araujo-Silva
7,
Jefferson Romáryo Duarte da Luz
4,7,8,* and
Maria das Graças Almeida
1,2
1
Post-Graduation Program in Pharmaceutical Sciences, Health Sciences Center, Federal University of Rio Grande do Norte, R. Gen. Gustavo Cordeiro de Farias, s/n—Petrópolis, Natal 59012-570, RN, Brazil
2
Multidisciplinary Research Laboratory, Department of Clinical and Toxicological Analysis, Health Sciences Center, Federal University of Rio Grande do Norte, R. Gen. Gustavo Cordeiro de Farias, s/n—Petrópolis, Natal 59012-570, RN, Brazil
3
Laboratory of Synthesis and Analysis of Biomolecules (LSAB), Institute of Chemistry, Darcy Ribeiro University Campus, University of Brasilia, Brasília 70910-900, DF, Brazil
4
Department of Biological and Health Sciences—DCBS, Federal University of Amapá (UNIFAP), Rodovia Rod. Josmar Chaves Pinto, km 02—Jardim Marco Zero, Macapá 68903-419, AP, Brazil
5
College of Natural Sciences, Amapá State University (UEAP), Av. Presidente Vargas, s/n—Centro, Macapá 68900-070, AP, Brazil
6
Department of Food Science and Nutrition, University of Antofagasta, Antofagasta 02800, Chile
7
Organic Chemistry and Biochemistry Laboratory, Amapá State University (UEAP), Av. Presidente Vargas, s/n—Centro, Macapá 68900-070, AP, Brazil
8
College of Biological Sciences, Federal University of Amapá (UNIFAP), Rodovia BR 156, Universidade, Oiapoque 68980-000, AP, Brazil
*
Author to whom correspondence should be addressed.
Molecules 2025, 30(22), 4335; https://doi.org/10.3390/molecules30224335 (registering DOI)
Submission received: 28 September 2025 / Revised: 29 October 2025 / Accepted: 5 November 2025 / Published: 7 November 2025
(This article belongs to the Special Issue Natural Compounds for Disease and Health, 3rd Edition)

Abstract

Momordica charantia L. (Cucurbitaceae) has been widely recognized for its pharmacological potential, although studies on its leaves remain scarce. In this study, the hydroethanolic leaf extract (MCHLE) was chemically characterized by LC–MS/MS, revealing the presence of octopamine, ferulate, vitexin-2-O-rhamnoside, and other bioactive phenolics. Toxicological evaluation in Wistar rats demonstrated that both acute (2000 mg/kg) and repeated oral administration (up to 400 mg/kg for 28 days) caused no clinical or behavioral signs of toxicity. Notably, treatment significantly reduced glucose and cholesterol levels, in addition to attenuating lipid peroxidation and enhancing antioxidant defenses. In vivo, MCHLE inhibited leukocyte and neutrophil infiltration in the LPS-induced peritonitis model, with efficacy comparable to dexamethasone. It also reduced TNF-α secretion and nitric oxide generation in peritoneal fluids. In vitro assays with LPS-stimulated RAW 264.7 macrophages confirmed these effects, showing dose-dependent inhibition of TNF-α, IL-1β, and NO production. Gene expression analysis further demonstrated downregulation of TNF-α and MAPK, with marked suppression of NF-κB transcripts. Collectively, these results suggest that MCHLE exerts anti-inflammatory activity by targeting both mediator release and upstream signaling pathways, while maintaining a favorable safety profile, supporting its potential for further investigation as a promising source of bioactive compounds.
Keywords: Momordica charantia; cytokines; nitric oxide; acute toxicity; peritonitis model; RAW 264.7 macrophages; anti-inflammatory activity Momordica charantia; cytokines; nitric oxide; acute toxicity; peritonitis model; RAW 264.7 macrophages; anti-inflammatory activity

Share and Cite

MDPI and ACS Style

Oliveira, M.L.d.A.; Sousa, R.M.d.; Barbosa, E.A.; Galdino, O.A.; Dantas, D.L.A.; Alves, I.R.; Sousa Borges, R.; Castelo Branco, N.C.d.M.; Nascimento Rodrigues, A.S.d.; de Souza, G.C.; et al. Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways. Molecules 2025, 30, 4335. https://doi.org/10.3390/molecules30224335

AMA Style

Oliveira MLdA, Sousa RMd, Barbosa EA, Galdino OA, Dantas DLA, Alves IR, Sousa Borges R, Castelo Branco NCdM, Nascimento Rodrigues ASd, de Souza GC, et al. Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways. Molecules. 2025; 30(22):4335. https://doi.org/10.3390/molecules30224335

Chicago/Turabian Style

Oliveira, Maria Lúcia de Azevedo, Rubiamara Mauricio de Sousa, Eder Alves Barbosa, Ony Araújo Galdino, Duanny Lorena Aires Dantas, Ingrid Reale Alves, Raphaelle Sousa Borges, Nayara Costa de Melo Castelo Branco, Artemis Socorro do Nascimento Rodrigues, Gisele Custódio de Souza, and et al. 2025. "Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways" Molecules 30, no. 22: 4335. https://doi.org/10.3390/molecules30224335

APA Style

Oliveira, M. L. d. A., Sousa, R. M. d., Barbosa, E. A., Galdino, O. A., Dantas, D. L. A., Alves, I. R., Sousa Borges, R., Castelo Branco, N. C. d. M., Nascimento Rodrigues, A. S. d., de Souza, G. C., Silva, S. V. e., Araujo-Silva, G., Duarte da Luz, J. R., & Almeida, M. d. G. (2025). Momordica charantia L. (Cucurbitaceae) Leaf Extract from Phytochemical Characterization and Toxicity Evaluation to Modulation of Pro-Inflammatory Cytokines and MAPK/NFκB Pathways. Molecules, 30(22), 4335. https://doi.org/10.3390/molecules30224335

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