Astragaloside IV Ameliorates Cognitive Impairment and Neuroinflammation in an Oligomeric Aβ Induced Alzheimer’s Disease Mouse Model <i>via</i> Inhibition of Microglial Activation and NADPH Oxidase Expression

Abstract

Microglial activation and neuroinflammation induced by amyloid β (Aβ) play pivotal roles in Alzheimer's disease (AD) pathogenesis. Astragaloside IV (AS-IV) is one of the major active compounds of the traditional Chinese medicine Astmgali Radix. It has been reported that AS-IV could protect against Aβ-induced neuroinflammation and cognitive impairment, but the underlying mechanisms need to be further clarified. In this study, the therapeutic effects of AS-IV were investigated in an oligomeric Aβ (oAβ) induced AD mice model. The effects of AS-IV on microglial activation, neuronal damage and NADPH oxidase expression were further studied. Different doses of AS-IV were administered intragastrically once a day after intracerebroventricularly oAβ injection. Results of behavioral experiments including novel object recognition (NOR) test and Morris water maze (MWM) test revealed that AS-IV administration could significantly ameliorate oAβ-induced cognitive impairment in a dose dependent manner. ELISA results showed that increased levels of ROS, TNF-α, IL-1β and IL-6 in hippocampal tissues induced by oAβ injection were remarkably inhibited after AS-IV treatment. OAβ induced microglial activation and neuronal damage was significantly suppressed in AS-IV-treated mice brain, observed in immunohistochemistry results. Furthermore, oAβ upregulated protein expression of NADPH oxidase subunits gp91phox, p47phox, p22phox and p67phox were remarkably reduced by AS-IV in western blotting assay. These results revealed that AS-IV could ameliorate oAβ-induced cognitive impairment, neuroinflammation and neuronal damage, which were possibly mediated by inhibition of microglial activation and down-regulation of NADPH oxidase protein expression. Our findings provide new insights of AS-IV for the treatment of neuroinflammation related diseases such as AD.

Astragaloside IV supplementation attenuates cognitive impairment by inhibiting neuroinflammation and oxidative stress in type 2 diabetic mice

“…Multiple studies have demonstrated that excessive oxidative stress accompanied by impaired antioxidant capacity in T2DM encouraged the generation of ROS that further led to neuronal damage and cognitive dysfunction in T2DM (Valko et al, 2007 ; Gocmez et al, 2019 ; Michailidis et al, 2022 ). Furthermore, studies have shown that AS-IV exerts neuroprotective effects on AD and chronic cerebral hypoperfusion-induced dementia depending on the inhibition of oxidation stress (Kim et al, 2015 ; Chen et al, 2021 ). Consistent with the preceding studies, our current study showed that the activities of SOD were decreased, while the MDA levels were increased in T2DM mice.…”

“…Moreover, AS-IV has been proven to exert potent protective effects on diabetic nephropathy via inhibiting the expressions of inflammatory genes in a rat model of T2DM (Gui et al, 2013a ). Meanwhile, a previous study indicated that AS-IV was an effective anti-inflammatory agent in the treatment of an AD mouse model (Chen et al, 2021 ). In our study, the levels of TNF-α, IL-6, and IL-1β were increased in T2DM mice, while treatment with AS-IV exhibited a significantly anti-inflammatory prowess by decreasing the levels of those pro-inflammatory cytokines in T2DM mice.…”

Anti-Aging of the Nervous System and Related Neurodegenerative Diseases With Chinese Herbal Medicine

“…In addition, Astragaloside IV promotes mitochondrial autophagy, thus reducing the accumulation of damaged mitochondria and the production of mitochondrial reactive oxygen species. 14,[96][97][98][99][100][101][102][103] To conclude, the mechanism of Astragali Radix against aging-related neurodegenerative diseases mainly involves anti-neurotoxicity, anti-neuroinflammation and antioxidation. Astragali Radix is a dietary herb, applied with many potential signal regulations, including neurotransmitters and receptors, anti-inflammatory activity, inhibiting amyloid aggregation, inducing myelin repair and neurogenesis, and activating signal pathways related to neurological diseases.…”

Astragalus mongholicus Bunge (Fabaceae): Bioactive Compounds and Potential Therapeutic Mechanisms Against Alzheimer’s Disease

“… Chen et al (2021) used AβO-infused mice to explore the anti-neuroinflammation activity of AS-IV. They found that injection of AβO significantly upregulated expression of ROS, IL-1β, IL-6, and TNF-α, which are biomarkers of inflammation.…”