Echinacoside Improves Cognitive Impairment by Inhibiting Aβ Deposition Through the PI3K/AKT/Nrf2/PPARγ Signaling Pathways in APP/PS1 Mice

Abstract

Echinacoside (ECH), a phenylethanoid glycoside, has protective activity in neurodegenerative disease, including anti-inflammation and antioxidation. However, the effects of ECH in Alzheimer’s disease (AD) are not very clear. This present study investigates the role and mechanism of ECH in the pathological process of AD. APP/PS1 mice treated with ECH in 50 mg/kg/day for 3 months. Morris water maze, nesting test, and immunofluorescence staining used to observe whether ECH could improve AD pathology. Western blot used to study the mechanism of ECH improving AD pathology. The results showed that ECH alleviated the memory impairment of APP/PS1 mice by reducing the time of escape latency as well as increasing the times of crossing the platform and rescued the impaired ability to construct nests. In addition, ECH significantly reduced the deposition of senile plaques in the brain and decreased the expression of BACE1 in APP/PS1 mice through activating PI3K/AKT/Nrf2/PPARγ pathway. Furthermore, ECH decreased ROS formation, GP91 and 8-OHdG expression, upregulated the expression of SOD1 and SOD2 as well as activating the PI3K/AKT/Nrf2 signaling pathway. Moreover, ECH inhibited glia cells activation, pro-inflammatory cytokine IL-1β and TNF-α release, NLRP3 inflammasome formation through TXNIP/Trx-1 signaling pathway. In conclusion, this paper reported that ECH improved cognitive function, inhibited oxidative stress, and inflammatory response in AD. Therefore, we suggest that ECH may considered as a potential drug for AD treatment.

Profiling and characterization of the constituents of taibai ginseng using ultra‐high performance liquid chromatography‐quadrupole time of flight mass spectrometry

“…Compounds with high response values in the chemical profile, such as aucubin, exhibit neuroprotective, anti-neuroinflammatory, and antioxidant properties [57]. In addition, echinacoside has been reported to improve cognitive impairment by inhibiting Aβ deposition through the PI3K/AKT/Nrf2/PPARγ signaling pathways in APP/PS1 mice [58]. Acteoside, isoacteoside, and echinacoside exert neuroprotective effects on H 2 O 2 -induced apoptosis in PC12 cells via the Nrf2/ARE pathway [59].…”

Neuroprotective mechanism of human umbilical cord mesenchymal stem cell‐derived extracellular vesicles improving the phenotype polarization of microglia via the PI3K/AKT/Nrf2 pathway in vascular dementia

“…Following Nrf2 siRNA transfection and LY294002 treatment, genistein cannot stimulate HO‐1 to exert the neuroprotective effects on Ab25‐35‐treated SH‐SY5Y cells (Yi et al., 2021). Echinacoside reduces senile plaque deposition in brains by activating the PI3K/AKT/Nrf2/PPARγ pathway, which improves cognitive function and represses inflammatory response and oxidative stress in AD (Qiu & Liu, 2022). In brief, this study discovered for the first time that hUCMSC‐Evs alleviated the neurological injury of VaD rats by activating the PI3K/AKT/Nrf2 pathway.…”

Beneficial Effects of Echinacoside on Cognitive Impairment and Diabetes in Type 2 Diabetic db/db Mice

“…Echinacoside (ECH) is the most active component of C. tubulosa. Previous studies have shown ECH might be potentially promising for the treatment of depressive disorders, vascular dementia, cerebral ischemia, Parkinson's disease, and AD [28][29][30][31][32]. ECH can freely cross the blood-brain barrier, exhibiting neuroprotective, anti-oxidative, anti-neuroinflammatory properties, and regulating apoptosis and autophagy [33].…”