Huangqin Decoction Exerts Beneficial Effects on Rotenone-Induced Rat Model of Parkinson's Disease by Improving Mitochondrial Dysfunction and Alleviating Metabolic Abnormality of Mitochondria
Li Gao, Min Cao, Guanhua Du, Xuemei Qin
Abstract
, has therapeutic effects on PD, but whether HQD has a therapeutic effect on PD has not been reported. In this study, the protective effects of HQD on rotenone-induced PD rats were evaluated by behavioral assays (open field, rotating rod, suspension, gait, inclined plate, and grid) and immunohistochemistry. The mechanisms of HQD on attenuation of mitochondrial dysfunction were detected by biochemical assays and mitochondrial metabolomics. The results showed that HQD (20 g/kg) can protect rats with PD by improving motor coordination and muscle strength, increasing the number of tyrosine hydroxylase (TH)-positive neurons in rats with PD. Besides, HQD can improve mitochondrial dysfunction by increasing the content of adenosine triphosphate (ATP) and mitochondrial complex I. Mitochondrial metabolomics analysis revealed that the ketone body of acetoacetic acid (AcAc) in the rotenone group was significantly higher than that of the control group. Ketone bodies have been known to be used as an alternative energy source to provide energy to the brain when glucose was deficient. Further studies demonstrated that HQD could increase the expression of glucose transporter GLUT1, the content of tricarboxylic acid cycle rate-limiting enzyme citrate synthase (CS), and the level of hexokinase (HK) in rats with PD but could decrease the content of ketone bodies [AcAc and β-hydroxybutyric acid (β-HB)] and the expression of their transporters (MCT1). Our study revealed that the decrease of glucose metabolism in the rotenone group was parallel to the increase of substitute substrates (ketone bodies) and related transporters, and HQD could improve PD symptoms by activating the aerobic glycolysis pathway.