We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Bushen Yizhi Formula regulates the IRE1a pathway to alleviate endoplasmic reticulum stress in an Alzheimer's disease rat model.
- Authors
XIRU XU; YUAN FANG; BIAO ZHANG; SHICHAO TENG; XIANG WU; JING ZHANG; XIAOQUN GU; MEIXIA MA
- Abstract
Background: While the Bushen Yizhi Formula can treat Alzheimer's disease (AD), the yet to be ascertained specific mechanism of action was explored in this work. Methods: Different concentrations of the Bushen Yizhi Formula and amyloid-beta peptide (Aß) were used to treat rat pheochromocytoma cells (P12) and human neuroblastoma cells (SH-SY5Y). Cell morphological changes were observed to determine the in vitro cell damage. Cell Counting Kit (CCK)-8 assay and flow cytometry were employed to identify cell viability and apoptosis/cell cycle, respectively. Western blotting and immunohistochemistry were employed to measure the expressions of endoplasmic reticulum stress (ERS)-related proteins (GRP78 and CHOP), p-IRE1a, IRE1a, ASK1, p-JNK, JNK, Bax, Bcl-2, XBP-1, and Bim. Fura 2-acetoxymethyl ester (Fura-2/AM) was used to determine the intracellular calcium (Ca2+) concentration. Also, an AD model was constructed by injecting Aß into the CA1 area of the hippocampus in Sprague Dawley rats. AD model rats were gavaged with different concentrations of Bushen Yizhi Formula for 14 consecutive days. The Morris water maze experiment was conducted to test the learning and memory of rats. Hematoxylin & Eosin (H&E) and Terminal-deoxynucleotidyl Transferase (TdT)-mediated dUTP Nick-End Labeling (TUNEL) staining were done to determine histopathological changes in the brain. Results: Bushen Yizhi Formula relieved the Aß-induced effects including cell injury, decreased viability, increased apoptosis, G0/G1 phase cell cycle arrest, upregulation of GRP78, CHOP, p-IRE1a, p-JNK, Bax, XBP-1 and Bim, as well as down-regulation of Bcl-2. These results were also seen with IRE1a silencing. While Aß suppressed the learning and memory abilities of rats, the Bushen Yizhi Formula alleviated these effects of Aß. Brain nerve cell injury induced by Aß could also be treated with Bushen Yizhi Formula. Conclusion: Bushen Yizhi Formula could influence ERS through the IRE1a signaling pathway to achieve its therapeutic effects on AD.
- Subjects
ALZHEIMER'S disease; ENDOPLASMIC reticulum; CHINESE medicine; AMYLOID beta-protein; LABORATORY rats
- Publication
Biocell, 2023, Vol 47, Issue 7, p1595
- ISSN
0327-9545
- Publication type
Article
- DOI
10.32604/biocell.2023.027697