Open Access

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
  • View Affiliations

  • 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.
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September-2024
Volume 28 Issue 3

Print ISSN: 1792-0981
Online ISSN:1792-1015

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Spandidos Publications style
Wang Y, Wang Y, Li C, Liu D, Cai Y and Li Q: Anti‑epileptic mechanism of isopimaric acid from <em>Platycladi cacumen</em> based on network pharmacology, molecular docking and biological validation. Exp Ther Med 28: 348, 2024.
APA
Wang, Y., Wang, Y., Li, C., Liu, D., Cai, Y., & Li, Q. (2024). Anti‑epileptic mechanism of isopimaric acid from <em>Platycladi cacumen</em> based on network pharmacology, molecular docking and biological validation. Experimental and Therapeutic Medicine, 28, 348. https://doi.org/10.3892/etm.2024.12637
MLA
Wang, Y., Wang, Y., Li, C., Liu, D., Cai, Y., Li, Q."Anti‑epileptic mechanism of isopimaric acid from <em>Platycladi cacumen</em> based on network pharmacology, molecular docking and biological validation". Experimental and Therapeutic Medicine 28.3 (2024): 348.
Chicago
Wang, Y., Wang, Y., Li, C., Liu, D., Cai, Y., Li, Q."Anti‑epileptic mechanism of isopimaric acid from <em>Platycladi cacumen</em> based on network pharmacology, molecular docking and biological validation". Experimental and Therapeutic Medicine 28, no. 3 (2024): 348. https://doi.org/10.3892/etm.2024.12637