ICARIIN PROTECTS NEURONS FROM ISCHEMIC BRAIN INJURY BY UP-REGULATING SIRTL-MEDIATED PGC-1Α EXPRESSION

Qiang Zhou^{1, #}, Yuxia Xiao^{2, #}, Xin Wen³, Shurui Li⁴, Xilian Feng³, Qiong Wang⁵, Jingjing Zhang⁶, Naijia Liu³, Feng Zhao^{5, *} 

¹Integrated Chinese Medicine Treatment Area, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, Gansu Province, China - ²Changjiaxiang TCM Clinic, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, Gansu Province, China - ³Department of Acupuncture and Moxibustion, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, Gansu Province, China - ⁴Department of Disinfection, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, Gansu Province, China - ⁵Department of Neurology, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, Gansu Province, China - ⁶Department of Otolaryngology and Head Surgery, Affiliated Hospital of Gansu University of Traditional Chinese Medicine, Lanzhou 730020, Gansu Province, China

Objective: To analyze the protective effect of icariin on neurons from ischemic brain injury by up-regulating the expression of PGC-1α mediated by Sirt1. 

Methods: The mouse middle cerebral artery ischemia model was made by the suture method, which was divided into a sham operation group (only the common carotid artery was isolated without ligation), a model group, and low (50 mg/kg), medium (100 mg/kg) and high (200 mg/kg) dose icariin groups. We observed the changes in the neurological function and the number of dopaminergic neurons in the substantia nigra of the mice in each group. Western blot was used to detect the PGC-1α and Sirt1 proteins in the cerebral cortex of each group. Expression; Sirt1 inhibitor Ⅲ was used to treat cells and PGC-1α plasmid transfection technology to detect the survival and apoptosis rate of dopaminergic neurons in the substantia nigra of the mouse brain. Western blot was used to detect the effect of Sirt1 inhibitor on the expression of PGC-1α protein influences. 

Results: After treatment for 3 d and 7 d, the neurological scores of the mice is the low, medium, and high dose icariin groups were significantly lower than the model group, and the difference was statistically significant (P<0.05). Compared with the sham operation group, the number of dopaminergic neurons in the substantia nigra of mice in the model group was significantly reduced (P<0.05), and the number of dopaminergic neurons in the substantia nigra of mice in the low, medium, and high-dose icariin groups was significantly more than in the model group (P<0.05). The expression of PGC-1α and Sirt1 protein in the cortex of mice in the low, medium, and high dose icariin groups was significantly higher than that in the model group (P<0.05). The Sirt1 inhibitor group and PGC-1α interference group significantly reduced icariin and increased the survival rate of dopaminergic neurons in the substantia nigra of mice (P<0.05). Also, the Sirt1 inhibitor group and PGC-1α interference group significantly increased icariin and reduced the apoptosis rate of dopaminergic neurons in the substantia nigra of mice (P<0.05). Finally, the Sirt1 inhibitor group blocked the increase of PGC-1α protein expression in the mouse cortex by icariin, compared with the control group, and the difference was statistically significant (P<0.05). 

Conclusion: Icariin has a protective effect on ischemic brain injury neurons, and the mechanism of action may be related to the up-regulation of Sirt1-mediated PGC-1α expression, suggesting that icariin may become a new type of ischemic brain injury protection agent.