INTEGRATED NETWORK PHARMACOLOGY ANALYSIS IDENTIFIES MOLECULAR TARGETS AND SIGNALING PATHWAYS THAT MAY BE MODULATED BY CANNABIDIOL IN SICKLE CELL DISEASE
- 1Universidade Federal do Oeste da Bahia (UFOB), Barreiras, BA, Brazil
Abstract
Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic inflammation, oxidative stress, hemolysis, and recurrent episodes of pain and vascular occlusion. These mechanisms contribute significantly to disease morbidity and underscore the need for therapeutic strategies capable of modulating these changes. In this context, cannabidiol (CBD) has attracted interest due to its anti-inflammatory and immunomodulatory properties; however, its molecular mechanisms of action in SCD remain poorly understood. Thus, this study aimed to identify molecular targets shared between CBD and SCD, as well as the main biological pathways potentially modulated by the compound, using a network pharmacology approach. Human targets of CBD were obtained from the SwissTargetPrediction, ChEMBL, BindingDB, and Comparative Toxicogenomics Database (CTD) databases, while genes associated with SCD were retrieved from GeneCards (Relevance Score ≥10), DisGeNET (Association Score ≥0.1), and CTD, considering only genes with direct evidence. The genes from each database were integrated into separate lists for CBD and SCD. After standardizing gene symbols according to the HUGO Gene Nomenclature Committee (HGNC) and removing duplicates, an intersection analysis was performed between the sets, retaining only the shared genes for subsequent analyses. These genes were used to construct a protein-protein interaction (PPI) network in STRING and to perform a functional enrichment analysis in g:Profiler, using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome, with statistical significance assessed using the g:SCS method, with an adjusted p-value <0.05. A total of 89 genes were identified that were shared between CBD targets and genes associated with SCD. The PPI network revealed potential connectivity among these genes, highlighting AKT1, IL6, TNF, NFKB1, RELA, STAT3, MAPK1, JAK2, ICAM1, and HMOX1 as recurring genes in the main enriched pathways. Functional analysis revealed significant enrichment in processes related to responses to chemical stimuli, oxidative stress, intracellular signal transduction, regulation of cell death, and cell migration. The main enriched pathways included PI3K-Akt, AGE-RAGE, and Lipid and Atherosclerosis (KEGG), as well as Signaling by Interleukins, Cytokine Signaling in the Immune System, and MAPK family signaling cascades (Reactome). The results suggest that CBD may modulate key mechanisms in the pathophysiology of SCD, particularly those related to inflammation, the immune response, oxidative stress, and endothelial activation. The intersection of these signaling pathways reinforces CBD’s potential as a modulator of biological processes involved in disease progression, and network pharmacology has enabled the identification of genetic elements that may be involved in CBD’s effects on SCD, providing insights for experimental and clinical studies aimed at evaluating its therapeutic efficacy.
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BibTeX
@article{filho2026integrated,
title = {{INTEGRATED NETWORK PHARMACOLOGY ANALYSIS IDENTIFIES MOLECULAR TARGETS AND SIGNALING PATHWAYS THAT MAY BE MODULATED BY CANNABIDIOL IN SICKLE CELL DISEASE}},
author = {Manoel FERREIRA DE MAGALHÃES FILHO and Larissa Paola RODRIGUES VENANCIO},
journal = {Hematology, Transfusion and Cell Therapy},
year = {2026},
month = oct,
doi = {10.1016/j.htct.2026.106665},
url = {https://doi.org/10.1016/j.htct.2026.106665},
note = {CC BY},
}
RIS
TY - JOUR
TI - INTEGRATED NETWORK PHARMACOLOGY ANALYSIS IDENTIFIES MOLECULAR TARGETS AND SIGNALING PATHWAYS THAT MAY BE MODULATED BY CANNABIDIOL IN SICKLE CELL DISEASE
AU - Manoel FERREIRA DE MAGALHÃES FILHO
AU - Larissa Paola RODRIGUES VENANCIO
PY - 2026
DA - 2026/10/23
JO - Hematology, Transfusion and Cell Therapy
DO - 10.1016/j.htct.2026.106665
UR - https://doi.org/10.1016/j.htct.2026.106665
AB - Sickle cell disease (SCD) is an inherited hemoglobinopathy characterized by chronic inflammation, oxidative stress, hemolysis, and recurrent episodes of pain and vascular occlusion. These mechanisms contribute significantly to disease morbidity and underscore the need for therapeutic strategies capable of modulating these changes. In this context, cannabidiol (CBD) has attracted interest due to its anti-inflammatory and immunomodulatory properties; however, its molecular mechanisms of action in SCD remain poorly understood. Thus, this study aimed to identify molecular targets shared between CBD and SCD, as well as the main biological pathways potentially modulated by the compound, using a network pharmacology approach. Human targets of CBD were obtained from the SwissTargetPrediction, ChEMBL, BindingDB, and Comparative Toxicogenomics Database (CTD) databases, while genes associated with SCD were retrieved from GeneCards (Relevance Score ≥10), DisGeNET (Association Score ≥0.1), and CTD, considering only genes with direct evidence. The genes from each database were integrated into separate lists for CBD and SCD. After standardizing gene symbols according to the HUGO Gene Nomenclature Committee (HGNC) and removing duplicates, an intersection analysis was performed between the sets, retaining only the shared genes for subsequent analyses. These genes were used to construct a protein-protein interaction (PPI) network in STRING and to perform a functional enrichment analysis in g:Profiler, using Gene Ontology (GO), the Kyoto Encyclopedia of Genes and Genomes (KEGG), and Reactome, with statistical significance assessed using the g:SCS method, with an adjusted p-value <0.05. A total of 89 genes were identified that were shared between CBD targets and genes associated with SCD. The PPI network revealed potential connectivity among these genes, highlighting AKT1, IL6, TNF, NFKB1, RELA, STAT3, MAPK1, JAK2, ICAM1, and HMOX1 as recurring genes in the main enriched pathways. Functional analysis revealed significant enrichment in processes related to responses to chemical stimuli, oxidative stress, intracellular signal transduction, regulation of cell death, and cell migration. The main enriched pathways included PI3K-Akt, AGE-RAGE, and Lipid and Atherosclerosis (KEGG), as well as Signaling by Interleukins, Cytokine Signaling in the Immune System, and MAPK family signaling cascades (Reactome). The results suggest that CBD may modulate key mechanisms in the pathophysiology of SCD, particularly those related to inflammation, the immune response, oxidative stress, and endothelial activation. The intersection of these signaling pathways reinforces CBD’s potential as a modulator of biological processes involved in disease progression, and network pharmacology has enabled the identification of genetic elements that may be involved in CBD’s effects on SCD, providing insights for experimental and clinical studies aimed at evaluating its therapeutic efficacy.
SN - 2531-1379
SN - 2531-1387
ER -