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

Autor: Wang MD; 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.; 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., Zhang S; 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.; 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., Liu XY; 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.; 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., Wang PP; 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.; 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., Zhu YF; 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.; 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., Zhu JR; 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.; 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., Lv CS; 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.; 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., Li SY; Eye Institute of Xiamen University, Department of Ophthalmology, Xiang'an Hospital, School of Medicine, Xiamen University, Xiamen, 361102, China. shiying_li@126.com., Liu SF; Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, 361000, China. liujiasuifeng@gmail.com., Wen L; 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. wenlei@xmu.edu.cn.; 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. wenlei@xmu.edu.cn.
Jazyk: angličtina
Zdroj: Acta pharmacologica Sinica [Acta Pharmacol Sin] 2023 Nov; Vol. 44 (11), pp. 2151-2168. Date of Electronic Publication: 2023 Jul 07.
DOI: 10.1038/s41401-023-01125-3
Abstrakt: 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-APP 751 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.
(© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)
Databáze: MEDLINE
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