Anthocyanins Reversed D-Galactose-Induced Oxidative Stress and Neuroinflammation Mediated Cognitive Impairment in Adult Rats

Abstract

Aging is a major factor involved in neurological impairments, decreased anti-oxidant activities, and enhanced neuroinflammation. D-galactose (D-gal) has been considered an artificial aging model which induces oxidative stress and inflammatory response resulting in memory and synaptic dysfunction. Dietary supplementation exerts valuable effects against oxidative stress and neuroinflammation. Polyphenolic flavonoids, such as anthocyanins, have been reported as an anti-inflammatory and anti-oxidant agents against various neurodegenerative diseases. Recently, our group reported anthocyanin neuroprotection of the developing rat brain against ethanol-induced oxidative stress and neurodegenaration and ethanol-induced neuronal apoptosis via GABA receptor intracellular signaling in prenatal rat hippocampus. Here, we examined the protective effect of anthocyanin neuroprotection against D-gal-induced oxidative and inflammatory response in the hippocampus and cortex regions and explore the potential mechanism of its action. Our results indicated that anthocyanins treatment significantly improved behavioral performance of D-gal-treated rats in Morris water maze and Y-maze tests. One of the potential mechanisms of this action was decreased expression of the receptor for advance glycation end product, reduced level of reactive oxygen species (ROS) and lipid peroxidation as well as markers of the Alzheimer's disease. Furthermore, the results also indicated that anthocyanins inhibited activated astrocytes and neuroinflammation via suppression of various inflammatory markers including p-NF- B, inducible nitric oxide synthase (iNOS), and tumor necrosis factor-alpha (TNF-α) in the hippocampus and cortex regions of D-gal-treated rats brain. Moreover, anthocyanins abrogated neuroapoptosis via C-jun N-terminal kinase (p-JNK) suppression and improved deregulated synaptic proteins including synaptophysin, synaptosomal-associated protein (SNAP)-23, SNAP-25, and phosphorylated CREB. This data suggests that anthocyanins could be a safe and promising anti-oxidant and anti-neuroinflammatory agent for age-related neurodegenerative diseases such as Alzheimer's disease.

Gintonin Attenuates D-Galactose-Induced Hippocampal Senescence by Improving Long-Term Hippocampal Potentiation, Neurogenesis, and Cognitive Functions

“…Brain aging is characterized by a progressive decline in cognitive functions and neurogenesis in the hippocampus [25]. Several studies have attempted to delay or retard brain aging; D-gal has been used to establish an experimental hippocampal aging model in rodents in an attempt to identify anti-brain aging agents [8][9][10][11]. Recent studies have focused on herbal medicines, determining their beneficial effects against brain aging because various herbs are used to improve brain health worldwide [1,3,8,9,15].…”

“…D-galactose (D-gal) has been used to induce aging in mice for brain aging or anti-aging pharmacological research because the D-gal-induced brain aging processes in mice resemble those in humans [8][9][10][11]. The molecular mechanisms of D-gal-induced brain aging involve the production of reactive oxygen species (ROS) and subsequent ROS-induced mitochondrial dysfunction [12].…”

“…Furthermore, a high dosage of D-gal inhibits the expression of nerve growth factors and their associated proteins, resulting in the degeneration of neurons and further impairment of long-term potentiation (LTP) and neurogenesis in the hippocampus, thereby causing memory dysfunctions [15]. Since chronic exposure to D-gal causes ROS production and mitochondrial dysfunctions, accelerating brain aging promotes age-related cognitive decline in experimental animals [9,11,13]. However, although ginseng extract provides benefits for brain function, little is known about the components of ginseng extract that can attenuate brain aging induced by D-gal.…”

Selenomethionine Ameliorates Neuropathology in the Olfactory Bulb of a Triple Transgenic Mouse Model of Alzheimer’s Disease

“…Neuroinflammation induced by excessive oxidative stress has been thought to play a pivotal role in brain host defense involved in neuronal loss of AD [45]. Chronic inflammation is characterized by longstanding microglia and astrocyte activation, which is followed by the sustained release of inflammatory mediators.…”

Flavonoid Hesperidin Induces Synapse Formation and Improves Memory Performance through the Astrocytic TGF-β1

“…Despite this information, flavonoid’s cellular targets and molecular mechanisms of action remain poorly understood, especially concerning their actions on non-neuronal cells. Glial cells are highly responsive to flavonoids (Matias et al, 2016), as these compounds may: (1) modulate the redox state of astrocytes through an up-regulation of antioxidant enzymes and genes (Bahia et al, 2008); (2) reduce neuroinflammation by controlling astrocyte reactivity and secretion of pro-inflammatory cytokines (Khan et al, 2016; Rehman et al, 2017); and (3) regulate the secretion of trophic factors by astrocytes (Xu et al, 2013a; Wang et al, 2014). …”