Anti‑epileptic mechanism of isopimaric acid from <em>Platycladi cacumen</em> based on network pharmacology, molecular docking and biological validation

Wang,Yan; Wang,Yun; Li,Chang; Liu,Dong; Cai,Yi; Li,Qifu

doi:10.3892/etm.2024.12637

Anti‑epileptic mechanism of isopimaric acid from Platycladi cacumen based on network pharmacology, molecular docking and biological validation

Authors:
- Yan Wang
- Yun Wang
- Chang Li
- Dong Liu
- Yi Cai
- Qifu Li
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Affiliations: Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China, Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China, Engineering Research Center of Tropical Medicine Innovation and Transformation of Ministry of Education, International Joint Research Center of Human‑Machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province, Hainan Key Laboratory for Research and Development of Tropical Herbs and Haikou Key Laboratory of Li Nationality Medicine, School of Pharmacy, Hainan Medical University, Haikou, Hainan 571199, P.R. China
Published online on: July 3, 2024 https://doi.org/10.3892/etm.2024.12637
Article Number: 348
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Platycladi cacumen (PC) is derived from the dry twigs and leaves of Platycladi orientalis (L.) Franco and exerts anti‑epileptic effects. However, its mechanism of action remains unknown. The present study explored the potential anti‑epileptic components and mechanisms of PC. The primary active components and targets of PC were analyzed using network pharmacology and a lipopolysaccharide (LPS)‑induced murine microglial cell line (BV2) was used to confirm anti‑epileptic effects by detecting reactive oxygen species (ROS), apoptosis, inflammatory markers, cell migration and signaling pathways. A total of 13 core active components showed druggable properties, of which deoxypicrop odophyllotoxin, hinokinin and isopimaric acid (IPA) were predicted to cross the blood‑brain barrier. In total, 255 potential targets of these three compounds were predicted using SwissTargetPrediction and Similarity Ensemble Approach websites and 150 were associated with epilepsy. In vitro experiments confirmed that IPA significantly inhibited LPS‑induced microglial oxidative stress and inflammation by decreasing the migration area, cellular ROS content, lactate dehydrogenase release and early phase of apoptosis. IPA also increased the mRNA expression of anti‑oxidative enzymes (superoxide dismutase‑1 and ‑2) and suppressed inflammatory cytokines (interleukin‑1β and tumor necrosis factor‑α). Furthermore, IPA phosphorylated AKT and mTOR proteins. Taken together, the present findings suggested that IPA is a potential anti‑epileptic compound derived from PC.