Integrated WGCNA and Network Pharmacology Explore the Potential Mechanisms of D-Limonene in Alleviating Traumatic Brain Injury.

Overview

1. Department of Anatomy and Histology & Embryology, Faculty of Basic Medical Science, Kunming Medical University, Kunming 650500, China; (H.J.); (X.L.); (H.L.); (Z.G.); (X.Y.)

Abstract

D-limonene (D-Lim) is a monocyclic monoterpene and the principal component of citrus essential oils; however, the potential mechanisms underlying its neuroprotective effects in traumatic brain injury (TBI) remain incompletely elucidated. By integrating network pharmacology, weighted gene co-expression network analysis (WGCNA), molecular docking, and experimental validation, this study systematically investigated the potential mechanisms through which D-Lim exerts neuroprotective activity. Database analyses and in vivo experiments showed that the anti-inflammatory and neuroprotective effects produced by D-Lim may be related to the p38 MAPK/NF-κB signaling axis and activation of the PI3K/AKT signaling pathway. Molecular docking and RT-PCR experiments indicated interactions between D-Lim and potential target proteins, including Icam1, Kdr, and Dpp4. HE and Nissl staining demonstrated that D-Lim ameliorated TBI-induced neuronal injury. Moreover, D-Lim had no observable effects on major organs and showed no peripheral toxicity, suggesting its favorable applicability for TBI intervention. Following early intervention with D-Lim, the inflammatory response induced by TBI was attenuated, which may be associated with the activation or modulation of the p38 MAPK, PI3K/AKT, and NF-κB p65 signaling pathways. These results indicate a potential acute protective role for D-Lim under prophylactic or early-intervention conditions, provide insights into TBI intervention, and establish a theoretical basis for potential preventive strategies.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Data links

• ncbi.nlm.nih.gov/geo, NCBI; found in the text, “4.1. WGCNA”

Data Availability Statement

All the data processing and analysis codes can be provided by the corresponding author upon reasonable request.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 6 authors, 5 keywords, 15 MeSH terms, 4 funders, 76 references.

Cite

This paper

Jiang, H., Luo, X., Li, H., Guo, Z., Yan, X., & Li, P. (2026). Integrated WGCNA and Network Pharmacology Explore the Potential Mechanisms of D-Limonene in Alleviating Traumatic Brain Injury. International journal of molecular sciences, 27(14), 6143. https://doi.org/10.3390/ijms27146143

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