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Hydroxysafflor Yellow A Improves Motor Dysfunction in the Rotenone-Induced Mice Model of Parkinson’s Disease

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Abstract

Dopamine D3 receptor (DRD3) is diminished in patients of Parkinson’s disease (PD). Brain-derived neurotrophic factor (BDNF) is responsible for regulating expression of the DRD3 in the brain. Our previous study showed that hydroxysafflor yellow A (HSYA) could increase BDNF content in the striatum of PD mice. This experiment aimed to evaluate whether HSYA can improve the motor dysfunction induced by rotenone through regulating the BDNF/TrkB/DRD3 signaling pathway in mice. Male C57/BL6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. Pole, rotarod and open field tests were investigated at 28 d. Then, tyrosine hydroxylase (TH) in substantia nigra was observed by immunohistochemistry. Dopamine content was detected by high-performance liquid chromatography. The expressions of BDNF, phospho-tropomyosin-related kinase B (p-TrkB), tropomyosin-related kinase B (TrkB), phospho-phosphoinositide 3-kinase (p-PI3K), phosphoinositide 3-kinase (PI3K), phospho-protein kinase B (p-AKT), protein kinase B (AKT), and DRD3 were assayed by western blotting. Behavioral tests showed that rotenone-challenged mice displayed motor dysfunction. However, treatment with HSYA improved motor dysfunction induced by rotenone. HSYA treatment increased not only the number of TH-containing dopaminergic neurons in substantia nigra, but also the dopamine content in the striatum in PD mice. Moreover, the expressions of BDNF, p-TrkB/TrkB, DRD3, p-PI3K/PI3K, p-AKT/AKT were significantly increased in rotenone plus HSYA group. Our results indicated that HSYA improved motor dysfunction in rotenone-induced PD model and the pharmacological action of HSYA was related to regulating BDNF/TrkB/DRD3 signaling pathway, at least, in part.

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Acknowledgements

This work was supported by the Joint Fund Project of the Education Department of Shandong Province (NO. ZR2014JL052) and Taishan Scholars Program of Shandong Province (NO. TSHW201502046). The authors are grateful to Prof. Lon Clark for his assistance in English language revision.

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    Authors and Affiliations

    1. School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, 264005, Yantai, Shandong, People’s Republic of China

      Tian Wang, Lijie Wang, Cuiting Li & Fenghua Fu

    2. Center of Mitochondria and Healthy Aging, School of Life Science, Yantai University, 264005, Yantai, Shandong, People’s Republic of China

      Bing Han, Zhenhua Wang, Ji Li, Yan Lv & Shuyun Wang

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    1. Tian Wang
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    Correspondence to Fenghua Fu.

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    Tian Wang and Lijie Wang have contributed equally to this work.

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    Wang, T., Wang, L., Li, C. et al. Hydroxysafflor Yellow A Improves Motor Dysfunction in the Rotenone-Induced Mice Model of Parkinson’s Disease. Neurochem Res 42, 1325–1332 (2017). https://doi.org/10.1007/s11064-017-2176-1

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