Forsythoside B attenuates memory impairment and neuroinflammation via inhibition on NF-κB signaling in Alzheimer’s disease

Abstract

Background Neuroinflammation is a principal element in Alzheimer’s disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. Methods APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. Results In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. Conclusions FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.

Aureonitol Analogues and Orsellinic Acid Esters Isolated from Chaetomium elatum and Their Antineuroinflammatory Activity

“…Microglia are resident immune cells in the central nervous system (CNS), and their activation plays a vital role in immune defense and homeostasis maintenance of the CNS . Infections, injuries, and inflammation overactivate microglia, − and subsequent oversecretion of various pro-inflammatory factors, such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), reactive oxygen species (ROS), and nitric oxide (NO), aggravate neurodegenerative diseases, such as Alzheimer’s disease, Parkinsonian disease, stroke, and spinal cord injury. − …”

Multiple Roles of Paeoniflorin in Alzheimer’s Disease

“…TCM monomer components are mainly divided into alkaloids, phenylpropanoids, flavonoids, saponins, terpenoids, glycosides, and so on. At present, the studies on the therapeutic mechanism of AD are mainly focused on berberine [ 14 – 16 ], evodiamine [ 17 ], icariin [ 18 , 19 ], forsythoside [ 20 ], ferulic acid [ 21 ], osthole [ 22 , 23 ], triptolide [ 24 ], resveratrol [ 25 ], and rhynchophylline and isorhynchophylline [ 26 ]. However, there has been a lack of systematic review and research on the relationship between a component of Radix Paeoniae and AD.…”

Metabolome analysis of genus Forsythia related constituents in Forsythia suspensa leaves and fruits using UPLC-ESI-QQQ-MS/MS technique

“…suspensa . Previous studies demonstrated their anti-inflammatory and antioxidant effects [ 13 , 14 ]. Knowledge of metabolites in herbal plants is very important.…”

“…Forsythiaside and forsythiaside A were isolated from air-dried fruits of F. suspensa. Previous studies demonstrated their anti-inflammatory and antioxidant effects [13,14]. Knowledge of metabolites in herbal plants is very important.…”