| Purpose: It is known that oxidative stress plays a pivotal role in age-related macular degeneration(AMD)pathogenesis.Alpha-mangostin is the main xanthone purified from mangosteen known as anti-oxidative properties.The aim of the study was to test the protective effect of alpha-mangostin against retinal light damage in mice.Methods: Totally 30 Balb/c mice,aged 6-8 weeks,were randomly divided into the control group,light-exposure group and ?-mangostin group.Every group contained10 mice.Mice from ?-mangostin group were treated with alpha-mangostin at the dose of 30mg/kg body weight by intragastric administration daily for 7 days,and then exposed to white light at the fifth day.The light-exposure group and ?-mangostin group were exposed to 5000±200Lux white light-emmiting diodes(LEDs)for continuously 1 hour to establish the mice model of retinal light damage.Flash-electroretinograme was recorded 72 hours after light exposure.The changes in retinal morphology of mice were observed by light microscopy.Compared the thinning of outer nuclear layer of three groups.Retinas were extracted to detect the activity of caspase-3,Superoxide Dismutase(SOD),Glutathione peroxidase(Gpx),and the content of malondialdhyde(MDA)and glutathione in the retinal homogenate.Immunofluorescence was used to determine the distribution of Nrf2 and the nuclear translocation of Nrf2.Western blot was used to detect the expression of HO-1 in total protein of retina in three groups,and the expression of Nrf2 in nuclear protein of retina in three groups.Results: Flash-electroretinogram showed that retinal dysfunction was less severe in?-mangostin group than in light-exposure group(p<0.05).Light microscopy test showed that retina structural damage was less severe in ?-mangostin group than in light-exposure group(p<0.05).Under the fluorescence microscope,we observed that t apoptotic cells were mainly distributed in outer nuclear layer.The number of apoptotic cells in light-exposure group was more than ?-mangostin group and normal group(P<0.05).The level of apoptic markers caspase-3 was markedly increased in light-exposure group.However,alpha-mangostin significantly prevented caspase-3activation induced by light damage(P<0.05).Light exposure to retina produced excessive lipid peroxides.Daily administration of alpha-mangostin(30mg/kg)significantly blocked the light-induced generation of MDA(P<0.05).The activity of SOD,Gpx and the content of GSH in light-exposure group reduced dramatically versus the normal group(P<0.05).?-mangostin supplement suppressed the reduction induced by light exposure(P<0.05).The expression of HO-1and Nrf2 increased after light exposure.The expression of HO-1 and Nrf2 in ?-mangostin group were significantly higher than that in normal group.Conclusion: Administration with alpha-mangostin suppressed light-induced loss of photoreceptor cells and retina dysfunction.We demonstrate that ?-mangostin can suppress oxidative damage and lipid peroxidation induced by intensive light.?-mangostin can protect retina against oxidative stress via enhancing Nrf2 transcriptional activity,translocating Nrf2 to nucleus and increasing the expression of HO-1.?-mangostin also can strengthen the endogenous defense system including SOD,Gpx and GSH.It is indicated that alpha-mangostin could be an a new approach to suspend the onset and development of AMD. |
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