| Summary: | 碩士 === 國防醫學院 === 藥學研究所 === 91 === Magnolol was investigated in this study. Its physico-chemical properties and intraocular pressure (IOP) lowering effect were measured. This study established an animal model of NMDA (N-methyl-D- aspartate)-induced neuroretinities, and a vitreous pharmacokinetic model of fluorescein. For further assessing the neuroprotection effect of magnolol, we compared the pharmacokinetic parameters of vitreous and blood-retina-barrier (BRB) with or without pre-administration of magnolol.
An HPLC analytical method was established to determine the solubility and distribution coefficient of magnolol in pH 7.4 phosphate buffer. The solubility and distribution coefficient were 16.2 μg/mL and 4.44 ± 0.01 (Log P), respectively. The IOP effect of magnolol was determined by topical administration of magnolol suspension (50 μL, 0.5%) into the eyes of New Zealand rabbits using IOP recovery method. As the result, there was no significant effect on IOP for the topical use of magnolol.
Excess NMDA damages the ganglion cell of retina. According to this mechanism, by intra-vitreous injection of NMDA, we established the animal model of NMDA-induced neuroretinities. The fluorescein levels in plasma and vitreous after IV bolus injection of sodium fluorescein (25 mg/kg body weight) were measured by HPLC method and Fluorotron Master®, respectively. The time courses of fluorescein in plasma and vitreous were fit the established pharmacokinetic models to obtain pharmacokinetic parameters, including kin (the rate constant of fluorescein from blood to vitreous), kout (the rate constant of fluorescein from vitreous to blood), MRT (the mean resident time of fluorescein in vitreous), and permeability coefficient of BRB.
The kin, MRT, and permeability coefficient of fluorescein in pre-administration magnolol group were markedly lower than that of the group without dosing magnolol. Thus, the results might suggest that magnolol protects the ganglion cell of retina from the damage of excess NMDA, and reduces the penetration ability of fluorescein across the BRB. In conclusion, the higher kout was obtained in pre-administration magnolol. It revealed that magnolol could maintain the function of the outward active transport of BRB. Overall of the study, magnolol had a neuroprotection effect on retina ganglion cell, and maintained the integrity and function of BRB.
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