Liriodendrin alleviates myocardial ischemia‑reperfusion injury via partially attenuating apoptosis, inflammation and mitochondria damage in rats.

in International journal of molecular medicine by Bo Li, Wei-Wei Yang, Bo-Chen Yao, Qing-Liang Chen, Li-Li Zhao, Yan-Qiu Song, Nan Jiang, Zhi-Gang Guo

TLDR

  • Liriodendrin, a natural product, exhibits cardioprotective effects by reducing biomarkers of myocardial damage, oxidative stress, and inflammatory response, as well as alleviating hypoxia-induced mitochondrial injury.

Abstract

Myocardial ischemia‑reperfusion (I/R) injury may lead to dysfunction of signaling pathways related to cell apoptosis, inflammation, oxidative stress, and mitochondrial damage. The present study investigated the defensive effect of liriodendrin, as a natural product isolated from, on reperfusion injury in rats and the underlying mechanisms involved in this process. Anrat model of I/R constructed by ligation of the left anterior descending artery, as well as anmodel using H9C2 cells under hypoxic conditions, was established to assess the cardioprotective effects of liriodendrin. The biomarkers of myocardial damage, oxidative stress, and inflammatory response were measured with enzyme‑linked immunosorbent assay (ELISA). Gene and protein expression were detected by reverse transcription‑quantitative PCR (RT‑qPCR) and western blotting. Mitochondrial morphology was observed by electron microscopy. The levels of creatine kinase isoenzymes and cardiac troponin T were significantly elevated in the I/R compared with the sham group; liriodendrin mitigated this elevation. The liriodendrin group exhibited a significant reduction in myocardial tissue apoptosis, as indicated by immunohistochemical staining and western blotting. Additionally, ELISA indicated that the I/R group had higher levels of reactive oxygen species (ROS) compared with the liriodendrin group, while the liriodendrin group had higher levels of superoxide dismutase. Theexperiments demonstrated that liriodendrin ameliorated hypoxia‑induced injury to mitochondria and suppressed the activation of nuclear factor-κB and B-cell lymphoma-2 associated X protein (Bax). Therefore, the present study demonstrated that liriodendrin impeded ROS‑associated metabolic disorders, maintained mitochondrial homeostasis and partially alleviated cardiomyocyte apoptosis by inhibiting the Bax signaling pathway.

Overview

  • The study investigated the defensive effect of liriodendrin, a natural product, on reperfusion injury in rats and explored the underlying mechanisms.
  • The study used a rat model of I/R injury and a cell model using H9C2 cells under hypoxic conditions to assess the cardioprotective effects of liriodendrin.
  • The primary objective was to examine the impact of liriodendrin on biomarkers of myocardial damage, oxidative stress, and inflammatory response, as well as its effect on mitochondrial morphology and cell apoptosis.

Comparative Analysis & Findings

  • Liriodendrin significantly reduced the elevation of creatine kinase isoenzymes and cardiac troponin T in the I/R group compared to the sham group.
  • The liriodendrin group exhibited reduced myocardial tissue apoptosis, as indicated by immunohistochemical staining and western blotting.
  • Liriodendrin suppressed ROS levels, increased superoxide dismutase levels, and alleviated hypoxia-induced mitochondrial injury compared to the I/R group.

Implications and Future Directions

  • The study provides evidence for the therapeutic potential of liriodendrin in mitigating reperfusion injury and its underlying mechanisms.
  • Future studies should investigate the optimal dosage and duration of liriodendrin administration for cardioprotection.
  • Exploring the molecular mechanisms by which liriodendrin inhibits Bax signaling and ROS metabolism could lead to the development of more effective therapeutic strategies for reperfusion injury.
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