Hydroxysafflor Yellow A Exerts Neuroprotective Effects via HIF-1α/BNIP3 Pathway to Activate Neuronal Autophagy after OGD/R
Ruheng Wei,
Lijuan Song,
Zhuyue Miao,
Kexin Liu,
Guangyuan Han,
Haifei Zhang,
Dong Ma,
Jianjun Huang,
Hao Tian,
Baoguo Xiao,
Cungen Ma
Affiliations
Ruheng Wei
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Lijuan Song
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Zhuyue Miao
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Kexin Liu
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Guangyuan Han
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Haifei Zhang
Department of Neurology, First Affiliated Hospital, Shanxi Datong University, Datong 037009, China
Dong Ma
Shanxi Health Commission Key Laboratory of Nervous System Disease Prevention and Treatment, Datong 037003, China
Jianjun Huang
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Hao Tian
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
Baoguo Xiao
Institute of Neurology, Huashan Hospital, Fudan University, Shanghai 200433, China
Cungen Ma
The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Jinzhong 030619, China
In the process of ischemic stroke (IS), cellular macroautophagy/autophagy and apoptosis play a vital role in neuroprotection against it. Therefore, regulating their balance is a potential therapeutic strategy. It has been proved that hydroxysafflor yellow A (HSYA) has anti-inflammatory and antioxidant effects, which can both protect neurons. By exploring bioinformatics combined with network pharmacology, we found that HIF1A and CASP3, key factors regulating autophagy and apoptosis, may be important targets of HSYA for neuroprotection in an oxygen glucose deprivation and reperfusion (OGD/R) model. In this study, we explored a possible new mechanism of HSYA neuroprotection in the OGD/R model. The results showed that OGD/R increased the expression of HIF1A and CASP3 in SH-SY5Y cells and induced autophagy and apoptosis, while HSYA intervention further promoted the expression of HIF1A and inhibited the level of CASP3, accompanied by an increase in autophagy and a decrease in apoptosis in SH-SY5Y cells. The inhibition of HIF1A diminished the activation of autophagy induced with HSYA, while the inhibition of autophagy increased cell apoptosis and blocked the neuroprotective effect of HSYA, suggesting that the neuroprotective effect of HSYA should be mediated by activating the HIF1A/BNIP3 signaling pathway to induce autophagy. These results demonstrate that HSYA may be a promising agent for treating IS.
