Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis.
10.19540/j.cnki.cjcmm.20221201.401
- Author:
Lei SHI
1
;
Chen-Chen JIANG
1
;
Jia-Jun LU
1
;
Zi-Xu LI
1
;
Wang-Jie LI
2
;
Xiu-Yun YIN
3
;
Zhuo CHEN
3
;
Xin-Ya ZHAO
3
;
Hui ZHANG
3
;
Hao-Ran HU
4
;
Lu-Tan ZHOU
1
;
Jun HAN
5
Author Information
1. Third-Grade Pharmacology Laboratory, National Administration of Traditional Chinese Medicine Wuhu 241002, China School of Pharmacy, Drug Research and Development Center, Wannan Medical College Wuhu 241002, China.
2. Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui Wuhu 241002, China Anhui Provincial Engineering Research Center for Polysaccharide Drugs Wuhu 241002, China.
3. Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui Wuhu 241002, China School of Pharmacy, Drug Research and Development Center, Wannan Medical College Wuhu 241002, China.
4. Third-Grade Pharmacology Laboratory, National Administration of Traditional Chinese Medicine Wuhu 241002, China Anhui Provincial Engineering Research Center for Polysaccharide Drugs Wuhu 241002, China.
5. Third-Grade Pharmacology Laboratory, National Administration of Traditional Chinese Medicine Wuhu 241002, China Anhui Provincial Engineering Laboratory for Screening and Re-evaluation of Active Compounds of Herbal Medicines in Southern Anhui Wuhu 241002, China Anhui Provincial Engineering Research Center for Polysaccharide Drugs Wuhu 241002, China School of Pharmacy, Drug Research and Development Center, Wannan Medical College Wuhu 241002, China.
- Publication Type:Journal Article
- Keywords:
PC12 cells;
ferritinophagy;
ferroptosis;
ligustilide;
oxygen-glucose deprivation/reperfusion(OGD/R)
- MeSH:
Animals;
Rats;
PC12 Cells;
Ferroptosis/genetics*;
Reactive Oxygen Species;
Transcription Factors;
Glutathione
- From:
China Journal of Chinese Materia Medica
2023;48(11):3046-3054
- CountryChina
- Language:Chinese
-
Abstract:
The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.
