Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer’s disease mouse model through downregulating BACE1 and Aβ generation  

作　　者：Meng-dan Wang Shuo Zhang Xing-yang Liu Pan-pan Wang Yi-fan Zhu Jun-rong Zhu Chong-shan Lv Shi-ying Li Sui-feng Liu Lei Wen 

机构地区：[1]State Key Laboratory of Cellular Stress Biology,Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research,Institute of Neuroscience,Xiang’an Hospital,School of Medicine,Xiamen University,Xiamen,361102,China [2]Xiamen Key Laboratory for TCM Dampness Disease,Neurology&Immunology Research,Department of Traditional Chinese Medicine,Xiang’an Hospital,School of Medicine,Xiamen University,Xiamen,361102,China [3]Eye Institute of Xiamen University,Department of Ophthalmology,Xiang’an Hospital,School of Medicine,Xiamen University,Xiamen,361102,China [4]Zhongshan Hospital of Xiamen University,School of Medicine,Xiamen University,Xiamen,361000,China

出　　处：《Acta Pharmacologica Sinica》2023年第11期2151-2168,共18页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(82274301 and 81774377);the Natural Science Foundation of Fujian Province of China(Grant No.2021J01019);the National Key Research and Development Program of China(2016YFC1305903);the Program for New Century Excellent Talents in University of China(NCET-13-0505)(to LW).

摘　　要：Alzheimer’s disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson’s disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg^(−1)·d^(−1), i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 μM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aβ generation by inhibiting the β-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aβ plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aβ generation in early AD, which is a potential therapeutic intervention for early AD treatment.

关 键 词：early Alzheimer’s disease RETINOPATHY salvianolic acid B BACE1 AΒ proinflammatory cytokine 

分 类 号：R285.5[医药卫生—中药学]