Coadministration of hydroxysafflor yellow A with levodopa attenuates the dyskinesia.
Levodopa (L-DOPA) is used as the most effective drug available for the symptomatic treatment of Parkinson's disease (PD). However, long-term treatment of L-DOPA frequently causes complications, including abnormal involuntary movements such as dyskinesia and response fluctuations in PD patients. In the present work, we investigated whether hydroxysafflor yellow A (HSYA) ameliorates L-DOPA-induced dyskinesia and motor fluctuations in the 6-hydroxydopamine-lesioned rat model of PD. Valid PD rats were treated daily with vehicle, HSYA alone, L-DOPA, or a combination of HSYA plus L-DOPA for 21days, respectively. L-DOPA (8mg/kg) and benserazide (15mg/kg) were treated intraperitoneally. HSYA was administrated intraperitoneally at a dose of 10mg/kg. The abnormal involuntary movements and rotational behavior were evaluated. The expression of the dopamine D3 receptor in the striatum was also assayed. The results demonstrated that daily administration of L-DOPA to PD rats for 21days induced a steady expression of dyskinesia. Coadministration of HSYA with L-DOPA significantly ameliorated L-DOPA-induced dyskinesia. The combination treatment also prevented the shortening of the motor response duration that defines wearing off motor fluctuations. HSYA also inhibited the increase of expression of the dopamine D3 receptor in the striatum. These findings demonstrated that HSYA provided anti-dyskinetic relief against L-DOPA in a preclinical model of PD via regulating the expression of the dopamine D3 receptor. The combination of L-DOPA and HSYA also reduced the likelihood of wearing off development, and may thus support the utility of such compounds for the improved treatment of PD.
School of Pharmacy, Yantai University, Yantai, Shandong 264005, PR China; State key laboratory of Long-acting and Targeting Drug Delivery Technologies (luye Pharma Group Ltd.), Yantai, Shandong 264003, PR China.
Tian
T
Wang
School of Pharmacy, Yantai University, Yantai, Shandong 264005, PR China.
Si-jin
SJ
Duan
School of Life Science, Yantai University, Yantai, Shandong 264005, PR China.
Shu-yun
SY
Wang
School of Life Science, Yantai University, Yantai, Shandong 264005, PR China.
Yan
Y
Lu
School of Life Science, Yantai University, Yantai, Shandong 264005, PR China.
Qing
Q
Zhu
School of Pharmacy, Yantai University, Yantai, Shandong 264005, PR China.
Li-jie
LJ
Wang
School of Life Science, Yantai University, Yantai, Shandong 264005, PR China. Electronic address: pharmacology533@163.com.
Bing
B
Han
D018663:Adrenergic Agents / Q000633:toxicity; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects*; D001058:Apomorphine / Q000494:pharmacology; D002599:Chalcone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D007980:Levodopa / Q000009:adverse effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D000857:Olfaction Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000188:drug therapy* / Q000209:etiology; D011809:Quinones / Q000627:therapeutic use*; D051381:Rats; D050637:Receptors, Dopamine D3 / Q000378:metabolism; D013997:Time Factors
D018663:Adrenergic Agents; D000978:Antiparkinson Agents; D011809:Quinones; D050637:Receptors, Dopamine D3; C085278:hydroxysafflor yellow A; D007980:Levodopa; D002599:Chalcone; D016627:Oxidopamine; D001058:Apomorphine
Coadministration; Dyskinesia; Hydroxysafflor yellow A; Levodopa