Therapeutic effects of hydroxysafflor yellow A on focal cerebral ischemic injury in rats and its primary mechanisms.
The therapeutic effects of hydroxysafflor yellow A (HSYA), extracted from Carthamus tinctorius. L, on focal cerebral ischemic injury in rats and its related mechanisms have been investigated. Focal cerebral ischemia in rats were made by inserting a monofilament suture into internal carotid artery to block the origin of the middle cerebral artery and administrated by HSYA via sublingular vein injection in doses of 1.5, 3.0, 6.0 mg kg(-1) at 30 min after the onset of ischemia, in comparison with the potency of nimodipine at a dose of 0.2 mg kg(-1). Then, 24 h later, the evaluation for neurological deficit scores of the rats were recorded and postmortem infarct areas determined by quantitative image analysis. At the end of the experiment, blood samples were taken to determine plasma 6-Keto-PGF1alpha/TXB2 by radioimmunoassays and blood rheological parameters. The effects exerted by HSYA on thrombosis formation by artery vein by-pass method and ADP-induced platelet aggregation in vivo and in vitro were investigated, respectively. The results indicated that more than 30% of the area of ischemic cerebrum was observed in the ischemic model group. HSYA dose-dependently improved the neurological deficit scores and reduced the cerebral infarct area, and HSYA bore a similarity in potency of the therapeutic effects on focal cerebral ischemia to nimodipine. The inhibition rates of thrombosis formation by HSYA at the designated doses were 20.3%, 43.6% and 54.2%, respectively, compared with saline-treated group. Inhibitory activities of HSYA were observed on ADP-induced platelets aggregation in a dose-dependent manner, and the maximum inhibitory aggregation rate of HSYA was 41.8%. HSYA provided a suppressive effect on production of TXA2 without significant effect on plasma PGI2 concentrations. Blood rheological parameters were markedly improved by HSYA, such as whole blood viscosity (from 21.71 +/- 4.77 to 11.61 +/- 0.90 mPa.s), plasma viscosity (from 2.73 +/- 0.53 to 1.42 +/- 0.07 mPa.s), deformability (from 0.66 +/- 0.26 to 0.77 +/- 0.33) and aggregation of erythrocyte (from 3.24 +/- 0.41 to 2.57 +/- 0.30), but no significant effect of HSYA on homatocrit was found (from 51.38 +/- 4.68% to 49.91 +/- 2.32%). HSYA appears to be a good potential agent to treat focal cerebral ischemia, and the underlying mechanisms exerted by HSYA might be involved in its inhibitory effects on thrombosis formation and platelet aggregation as well as its beneficial action on regulation of PGI2/TXA2 and blood rheological changes in rats.
Zhu
Hai-Bo
HB
Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
Zhang
Ling
L
Wang
Zheng-Hua
ZH
Tian
Jing-Wei
JW
Fu
Feng-Hua
FH
Liu
Ke
K
Li
Chang-Ling
CL
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000662:veterinary; D002599:Chalcone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000097:blood; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000662:veterinary; D011809:Quinones / Q000494:pharmacology*; D051381:Rats; D020521:Stroke / Q000188:drug therapy / Q000662:veterinary
D011809:Quinones; C085278:hydroxysafflor yellow A; D002599:Chalcone; D011464:Epoprostenol