Ligustrazine induces viability, suppresses apoptosis and autophagy of retinal ganglion cells with ischemia/reperfusion injury through the PI3K/Akt/mTOR signaling pathway

ABSTRACT

Ligustrazine, an alkaloid monomer extracted from Chuanxiong Rhizoma, has the function of protecting nerve cells. However, the effect and mechanism of ligustrazine on retinal ischemia/reperfusion (I/R) injury still need to be clarified. In our study, retinal ganglion cells (RGC-5) were used to establish a retinal I/R injury model by anaerobic cultivation. Cell viability, autophagy, and apoptosis were evaluated by cell counting kit 8 assay, transmission electron microscopy, and TUNEL staining after treatment with ligustrazine, PI3K inhibitor Ly294002, and/or mTOR inhibitor rapamycin, respectively. Besides, the levels of PI3K/Akt/mTOR pathway and autophagy-related proteins were determined by western blot. Moreover, one-way ANOVA was adopted for inter-group comparisons of measurement data. Our results demonstrated that low-concentration ligustrazine significantly enhanced cell viability and suppressed cell autophagy and apoptosis of RGC-5 cells after I/R injury, suggesting the protective effect of low-concentration ligustrazine on retinal I/R injury. Moreover, the alleviating effect of ligustrazine on RGC-5 with retinal I/R injury was mechanistically associated with the activation of the PI3K/Akt/mTOR pathway. In conclusion, low-concentration ligustrazine has a significant protective effect on RGC-5 cells with retinal I/R injury by activating the PI3K/Akt/mTOR pathway.

Graphical abstract

KEYWORDS:

• Ligustrazine
• ischemia/reperfusion injury
• retinal ganglion cells
• autophagy
• PI3K/Akt/mTOR signaling pathway

Highlights

• Ligustrazine induces the viability of RGCs after retinal I/R injury

• Inhibition of PI3K or mTOR attenuated ligustrazine-induced cell viability

• Ligustrazine inhibited the apoptosis and autophagy of I/R RGCs by PI3K or mTOR

• Ligustrazine activates PI3K/Akt/mTOR pathway

Disclosure statement

The authors declare no conflict of interest.

Author contributions

Hong-yan Du designed research and wrote the paper; Hong-yan Du, Rong Wang, Jian-liang Li, Huang Luo, Xiao-yan Xie, Ran Yan, Yue-ling Jian, and Jin-ying Cai performed research and analyzed data.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

This study was financed by the [National Natural Science Foundation of China] under Grant [number 81704123]; and [Scientific Research Project of Guangdong Traditional Chinese Medicine Bureau] under Grant [number 20182109].