echinacoside and Neurodegenerative-Diseases

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.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid beta-Protein Precursor; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Cognitive Dysfunction; Disease Models, Animal; Glycosides; Mice; Mice, Transgenic; Neurodegenerative Diseases; NF-E2-Related Factor 2; Phosphatidylinositol 3-Kinases; PPAR gamma; Presenilin-1; Proto-Oncogene Proteins c-akt; Signal Transduction

We have investigated the protective effects of echinacoside (ECH), one of the phenylethanoid glycosides, on H(2)O(2)-induced cytotoxicity in the rat pheochromocytoma cell line (PC12 cells). Our data show that application of ECH to H(2)O(2)-injured PC12 cells (HIPCs) increased cell viability and decreased the apoptotic ratio. Flow cytometry (FCM) and laser scanning confocal microscopy (LSCM) analysis suggested that ECH exerted its inhibitory effects on the formation of reactive oxygen species (ROS) and the accumulation of intracellular free Ca(2+) ([Ca(2+)]i). In addition, ECH elevated the mitochondrial membrane potential (MMP) in HIPCs. Furthermore, Western blot analysis revealed that ECH prevented an H(2)O(2)-induced increase of the Bax/Bcl-2 ratio by down-regulating Bax protein expression and upregulating Bcl-2 protein expression. In summary, ECH showed significant neuroprotective effects on HIPCs through the mitochondrial apoptotic pathway, and could be a potential candidate for intervention in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Topics: Animals; Antioxidants; Apoptosis; bcl-2-Associated X Protein; Blotting, Western; Calcium; Cell Survival; Echinacea; Flow Cytometry; Glycosides; Intracellular Membranes; Membrane Potentials; Mitochondria; Neurodegenerative Diseases; Neuroprotective Agents; PC12 Cells; Phenylethyl Alcohol; Phytotherapy; Plant Extracts; Proto-Oncogene Proteins c-bcl-2; Rats; Reactive Oxygen Species