Protective roles of isoastilbin against Alzheimer's disease via Nrf2‑mediated antioxidation and anti‑apoptosis

Abstract

By analyzing the L-glutamic acid (L-Glu)-induced apoptosis of PC12 cells and an AlCl3 combined with D-galactose (D-gal)-developed Alzheimer's disease (AD) mouse model, the protective effects of isoastilbin (IAB) against AD were systematically investigated in the present study. Pre-incubation with IAB for 3 h prior to treatment with 25 mM L-Glu decreased cell viability and inhibited apoptosis, suppressed the accumulation of intracellular reactive oxygen species, and restored mitochondrial membrane potential in PC12 cells induced by L-Glu. In mice with AD, the reduced escape latency time in the water maze test, suppressed chronic movement in the center area of an open field test and enhanced ability to seek hidden food in a Y maze test indicated that abnormal behaviors had improved after 28 days of treatment with IAB. Furthermore, IAB reduced the deposition of amyloid β (Aβ) and the expression of phosphorylated-Tau in the mouse brain and enhanced the serum levels of Aβ. IAB ameliorated the oxidative stress via modulating the levels of associated enzymes and improved the functioning of the central cholinergic system, as indicated by an increase in acetylcholine and choline acetyltransferase concentrations. The expression levels of acetylcholine esterase were reduced in the mouse brain in response to IAB pre-treatment. In cells and brain tissue, IAB regulated the expression levels of pro- and anti-apoptotic proteins and enhanced the nuclear levels of NF-E2p45-related factor 2 (Nrf2); subsequently, IAB further enhanced the expression of superoxide dismutase 1, catalase, and heme oxygenase-1 and -2. The findings of the present study indicated that the protection of IAB against AD is at least partially associated with its antioxidation and anti-apoptotic properties.

Neuroprotective Effect of Tricyclic Pyridine Alkaloids from Fusarium lateritium SSF2, against Glutamate-Induced Oxidative Stress and Apoptosis in the HT22 Hippocampal Neuronal Cell Line

“…It is a pro-apoptotic cytokines that combines with the apoptotic protease activating factor 1 (Apaf-1), sequentially recruits caspase-9. An executioner caspase-3 in mitochondria-mediated apoptosis is activated by activation of caspase-9 in glutamate-treated HT22 cells [32]. In the present study, in the presence of glutamate, the expressions of cytochrome c and cleaved caspase-9, -3 increased, but these expressions were significantly attenuated when HT22 cells were treated with 4,6 -anhydrooxysporidinone.…”

“…The transcription factor Nrf2 and activated HO-1 through Nrf2 transactivation enhance activities of antioxidant enzyme such as SOD and CAT, resulting in the enhancement of cellular antioxidant function, and inhibits the depolarization of mitochondrial membrane [ 32 ]. In the present study, in the presence of glutamate, the Nrf2 and HO-1 decreased, but these reductions were significantly enhanced when HT22 cells were co-treated with 4,6′-anhydrooxysporidinone, which may be involved in the protective effect of 4,6′-anhydrooxysporidinone against toxicity in glutamate-treated HT22 cells.…”

Systems pharmacology-based approach to investigate the mechanisms of Danggui-Shaoyao-san prescription for treatment of Alzheimer’s disease

“…Figure 5 a shows the significantly enriched terms ( q < 0.05) in biological process (BP) and molecular function (MF) categories. Obviously, most of the biological processes are related with AD, such as the negative regulation of inflammatory response (BP, GO:0050728) [ 48 ] and oxidation reduction process (BP, GO:0055114) [ 49 ]. Previous literature has revealed that anti-inflammatory drugs could significantly reduce the incidence of AD [ 48 ].…”

“…Previous literature has revealed that anti-inflammatory drugs could significantly reduce the incidence of AD [ 48 ]. Moreover, accumulating evidence demonstrates that anti-oxidations are potentially promising strategies for safe and efficient treatment of AD [ 49 ]. Similarly, it is worthy to note that a great number of targets are associated with a variety of MF terms, which plays a role in the pathogenesis of AD.…”

Hirsutanol A exhibits neuroprotective activities against sevoflurane‐induced neurotoxicity in aged rats

“…The transcription factor, Nrf2, has been found to play a critical role in neurological disorders like Alzheimer's disease (Fao, Mota, & Rego, 2019). Interestingly, several studies have evidenced that Nrf2 activation is involved in neuroprotective functions against a variety of neurotoxic agents (Su et al, 2016; Yu, Yuan, Chu, Wang, & Bi, 2019). Interestingly, Nrf2 activation has also been reported to provide protection against sevoflurane‐induced neurotoxicity, both in vitro and in vivo (Huang, Huang, & Ning, 2017; Tian et al, 2017).…”