ABSTRACT
To investigate the protective effects of ginkgo diterpene lactone meglumine injection (GDLMI) on cerebral focal ischemia reperfusion injury induced by middle cerebral artery occlusion (MCAO) in rats, and explore its possible mechanism. One hundred and forty male SD rats were randomly divided into sham operation group, model group, ginkgo biloba extract injection (Ginaton, 1.0 mL•kg⁻¹) group, nimodipine (0.4 mg•kg⁻¹) group, and GDLMI (5.2, 2.6, 1.3 mg•kg⁻¹) groups; All of rats received corresponding drugs by tail vein injection 4 days before operation (normal saline in model group and sham operation group). Except the sham operation group, the cerebral ischemic stroke model was established by MCAO method in right brain of the other rats. After 3 h of ischemia, all the animals received intravenous administration again. The neurobehavioral scores of rats after ischemia-reperfusion were evaluated and the infarct rate of brain tissue was observed by TTC staining. The super oxide dismutase (SOD), glutathione (GSH), malondialdehyde (MDA) and lactic acid (LA) contents in brain tissue homogenate and the concentration of Ca2+, glutamate (Glu) and aspartate (Asp), creatine phosphate kinase (CK-BB) and lactate dehydrogenase (LDH) content changes in cerebrospinal fluid were measured. As compared with the sham operation group, the cerebral infarction rate was increased significantly in the model group; the content of MDA and LA in the homogenate of brain tissue was increased, and the content of GSH and SOD was decreased; in cerebrospinal fluid, Ca2+ concentration was decreased, and the content of Glu and Asp, CK-BB and LDH increased significantly. As compared with the model group, the high and medium dose GDLMI groups can significantly reduce the cerebral infarction rate and improve the symptoms of neurological impairment; increase SOD and GSH activity, reduce MDA and LA content in serum; increase Ca2+ concentration in cerebrospinal fluid and decrease the content of neurotransmitter Glu and Asp as well as CK-BB and LDH. GDLMI could obviously improve neurologic impairment in model rats, and the mechanism may be related to recovering the blood brain barrier, scavenging free radicals, decreasing free Ca2+ inflow into the cells and the content of excitatory amino acid in cerebrospinal fluid to improve its protective effect on cerebral ischemia.
ABSTRACT
The left middle cerebral artery occlusion (MCAO) model was made by inserting the nylon thread plug into the internal carotid artery. The behavioral score, cerebral infarction area, brain water content, ethidium bromide (EB) spillover, coagulation four indices, occludin and MMP-9 expression in brain tissues were detected after 14 days of administration, to investigate whether the protective effect of ginkgo diterpene lactone meglumine injection (GDLMI) which had obvious protective effect on cerebral ischemic injury in the previous experiment was related to reducing the permeability of the blood-brain barrier (BBB) and reducing the risk of bleeding, and to explore its possible mechanism of action. The results showed that GDLMI could effectively alleviate the behavioral changes caused by MCAO at 24 h, reduce the behavioral score, improve the edema of brain tissue, reduce the EB overflow rate, reduce the bleeding tendency caused by long-term administration, significantly reduce the occlusion deficiency in ischemic brain tissue of model rats, and down-regulate MMP-9 expression. The above results indicate that GDLMI has obvious effect on cerebral ischemia, and the therapeutic effect of GDLMI may mainly depend on lowering the permeability of blood-brain barrier to improve brain edema.
ABSTRACT
To further evaluate the safety of ginkgo diterpene lactone meglumine injection in the clinical use in ischemic stroke patients. Clinical safety study was conducted in 82 clinical units and 6 300 cases were completed and included from June 2013 to December 2014 by using multicenter, prospective, open and uncontrolled design methods for clinical research. A total of 29 cases of adverse reactions were observed in the experiment. Adverse reaction ratio (ADR) was 0.46%, and about 86.21% (25 cases) of them was mild with transient response which could be alleviated or disappeared without intervention; about 13.79% (4 cases) was moderate, including 2 cases of headache, 1 case of dizziness and 1 case of rash; no serious adverse reactions were found. The adverse reactions occurred in this study were pre-known adverse reactions or common adverse reactions of Chinese medicine injection. The overall incidence of adverse reactions was low, and the risk was controllable.
ABSTRACT
Objective: To establish a high performance size exclusion chromatography (HPSEC) method for the determination of high molecular weight substances in ginkgo diterpene lactone extraction. Methods: The chromatographic column Phenomenex Biosep-SEC-S2000 (300 mm × 7.8 mm, 5 μm) was used with 0.05 mol/L sodium sulfate as the mobile phase at a flow rate of 0.7 mL/min, with refractive index detector (RID), and the temperature of the column was 30℃. High molecular weight substances in samples were calculated with area normalization method. Results: In the range of 2 500-84 400 of substance molecular weights, a linearity was achieved (r = 0.998 3). The average recovery rate was 96.8%, and RSD was 1.5%. The high molecular weight substances in five batches of ginkgo diterpene lactone extraction were not detected. Conclusion: This method is simple, quick, accurate, and suitable for the quality control of high molecular weight substances in ginkgo diterpene lactone extraction.