hydroxysafflor-yellow-a and Parkinsonian-Disorders

Hydroxysafflor yellow A (HSYA) has been shown to have neuroprotective effects in cerebral infarction. However, its underlying roles in apoptosis and inflammation in Parkinson's disease (PD) are unknown.. The present study investigates the effects and underlying mechanisms of HSYA on dopaminergic (DA) neurodegeneration, inflammation, and apoptosis.. The PD model was established by 2 μL of 6-hyroxydopamine (6-OHDA) (3 μg/μL) striatal injection in C57BL/6J mice with different doses of HSYA (2, 4, or 8 mg/kg).. Administration of HSYA significantly reduced the Apomorphine (APO)-induced rotation, decreased from 122.5 ± 15.1 (6-OHDA group) to 47.2 ± 14.3 (8 mg/kg HSYA group). HSYA partially restored a deficit in the SN and STR of PD mice brains in TH. Furthermore, western blot analysis revealed that HSYA reduced inflammatory proteins, including iNOS, COX-2 and NF-κB and attenuated the elevation of DA neuronal apoptosis observed in PD. These findings indicate that HSYA protects against 6-OHDA induced DA neurodegeneration partly by regulating the MAPK inflammatory signalling pathway and apoptosis which highlight its therapeutic potential in the treatment of PD.

Topics: Animals; Apoptosis; Chalcone; Corpus Striatum; Dopamine; Dopaminergic Neurons; Dose-Response Relationship, Drug; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Oxidopamine; Parkinsonian Disorders; Quinones; Signal Transduction

Autophagy is an intracellular degradation process that is involved in α-synuclein (α-syn) homeostasis and Parkinson's disease (PD). The purpose of this study was to investigate whether hydroxysafflor yellow A (HSYA) could promote α-syn clearance via regulating autophagy in PD mice. Male C57BL/6 mice were intraperitoneally treated with HSYA. Thirty minutes later, they were intragastrically administered with rotenone at a dose of 30 mg/kg. The hanging wire test was performed at 14 and 28 days. Then, autophagosomes and ultrastructural changes were examined by transmission electron microscopy. The expression of tyrosine hydroxylase (TH), α-syn, JNK1, p-JNK1, Bcl-2, p-Bcl-2, Beclin1, autophagy-related proteins (Atg) 7 and 12-5, and the LC3-II/LC3-I ratio were investigated by western blot. The hanging time of HSYA-treated PD mice was significantly increased compared with that of rotenone-induced PD mice (p < 0.05 or p < 0.01). Compared with rotenone-induced PD mice, treatment with HSYA augmented the formation of autophagosomes. The expression of TH, p-JNK1/JNK1, Beclin1, Atg7, Atg12-5, p-Bcl-2/Bcl-2, and the LC3-II/LC3-I ratio were significantly increased, whereas the expression of α-syn was reduced in the rotenone plus HSYA group. These results indicate that HSYA promoted α-syn clearance via regulating autophagy in rotenone-induced PD mice.

Topics: alpha-Synuclein; Animals; Autophagy; Brain; Chalcone; Male; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Parkinsonian Disorders; Quinones; Rotenone; Uncoupling Agents

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.

Topics: Animals; Chalcone; Dopamine; Male; Mice; Mice, Inbred C57BL; Motor Skills Disorders; Parkinsonian Disorders; Pigments, Biological; Quinones; Random Allocation; Rotarod Performance Test; Rotenone