Inhibiting Effect of Lycium Barbarum Extracts on Sub-RPE Deposit Formation in High-fat Diet and Oral Hydroquinone Model Mice
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Graphical Abstract
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Abstract
OBJECTIVE To investigate the inhabiting effect of lycium barbarum extracts on sub-RPE deposit formation in high-fat diet and oral hydroquinone (HQ) model mice. METHODS 40 eight-month-old C57BL/6 female mice, 8 were fed normal diet as aging control group; 32 were fed a high-fat diet for 6 months followed by HQ (0.8%) in the drinking water for 3 months. Model mice were randomly divided into model control group (8 mice) and 3 treatment groups (8 mice each group). Lycium barbarum extracts were given through different dose lavage one time every day(high:3.75g/kg/d, middle:2.50g/kg/d, low:1.25g/kg/d) for 3 months. At the end of the experimental period, the mice were killed and the eyes were immediately removed. Transmission electron microscopy was used to observe sub-RPE deposit formation and Bruch membrane (BrM) thickness, semiquantitative grading of deposit severity was performed; The mRNA and protein expression of cathepsin B(Cat B)and cystatin C(Cys C)were detected by real-time PCR and western blot respectively. RESULTS Mice fed a high-fat diet and HQ showed RPE damage was severe, formation of sub-RPE deposits was increasing, in addition, BrM was typically thickened,the severity in model control group was statistically greater than in the aging control group. Lycium barbarum extracts could reduce RPE damage, inhibit sub-RPE deposit formation and thickening of BrM. Compared with the aging control group, the mRNA and protein expression of Cat B and Cys C were significantly higher in the model control group. Expression of Cat B and Cys C were down regulated by the lycium barbarum extracts, and the effect was enhanced as the dosage was increased in a dose dependent manner, there was an especially significant reduction of Cys C expression.CONCLUSION Lycium barbarum extracts could reduce RPE damage, and inhibit sub-RPE deposit formation and thickening of BrM in high-fat diet and oral HQ mice model. The mechanism may be to reduce generation of ROS, down regulate the expression of Cat B and Cys C, and comprehensive actions of Cat B and Cys C shift to the function of Cat B.
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