Costunolide attenuates oxygen‑glucose deprivation/reperfusion‑induced mitochondrial‑mediated apoptosis in PC12 cells

Meng,Lanqing; Ma,Huixia; Meng,Jinni; Li,Tingting; Zhu,Yafei; Zhao,Qipeng

doi:10.3892/mmr.2021.12050

Costunolide attenuates oxygen‑glucose deprivation/reperfusion‑induced mitochondrial‑mediated apoptosis in PC12 cells

Authors:
- Lanqing Meng
- Huixia Ma
- Jinni Meng
- Tingting Li
- Yafei Zhu
- Qipeng Zhao
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Affiliations: Department of Pharmacology, School of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China, Key Laboratory of Hui Ethnic Medicine Modernization, Ministry of Education, Ningxia Medical University, Yinchuan, Ningxia Hui Autonomous Region 750004, P.R. China
Published online on: March 30, 2021 https://doi.org/10.3892/mmr.2021.12050
Article Number: 411
Copyright: © Meng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study investigated the effect of costunolide (CT), a compound extracted from Aucklandia lappa Decne, to attenuate oxygen‑glucose deprivation/reperfusion (OGD/R)‑induced mitochondrial‑mediated apoptosis in PC12 cells. The present study used molecular docking technology to detect the binding of CT with mitochondrial apoptotic protein targets. A model of oxygen‑glucose deprivation for 2 h and reperfusion for 24 h in PC12 cells was used to mimic cerebral ischemic injury. Cell viability and damage were measured using the Cell Counting kit‑8 and lactate dehydrogenase (LDH) cytotoxicity assay kits. Cellular apoptosis was analyzed using flow cytometry. A fluorescence microscope determined intracellular [Ca²⁺] and mitochondrial membrane potential. Furthermore, immunofluorescence and Western blot analyses were used to detect the expression of apoptosis‑associated proteins. CT contains binding sites with Caspase‑3, Caspase‑9 and Caspase‑7. CT markedly enhanced cell viability, inhibited LDH leakage, increased intracellular [Ca²⁺], stabilized the mitochondrial membrane potential, increased the expression of Bcl‑2 and inhibited the expression of Apaf‑1, Bax, cleaved‑caspase‑7, cleaved‑caspase‑9 and cleaved‑caspase‑3. CT may markedly protect PC12 cells from damage caused by OGD/R, and its mechanism is associated with blocking the calcium channel and inhibiting mitochondrial‑mediated apoptosis.

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