Pinostrobin alleviates chronic restraint stress‑induced cognitive impairment by modulating oxidative stress and the function of astrocytes in the hippocampus of rats

Abstract

Chronic stress has been recognized to induce the alterations of neuronal and glial cells in the hippocampus, and is thus implicated in cognitive dysfunction. There is increasing evidence to indicate that natural compounds capable of exerting neuroprotective and antioxidant activities, may function as potential therapeutic agents for cognitive impairment. The present study examined the neuroprotective effects of pinostrobin from Boesenbergia rotunda (L.) against chronic restraint stress (CRS)-induced cognitive impairment associated with the alterations of oxidative stress, neuronal density and glial fibrillary acidic protein (GFAP) of astrocytes in the hippocampus. For this purpose, male Wistar rats were administered once daily with pinostrobin (20 and 40 mg/kg, per os ) prior to exposure to CRS (6 h/day) for 21 days. The cognitive behaviors, the concentration of malondialdehyde, and the activities of superoxide dismutase and catalase were determined. Histologically, the alterations in astrocytic GFAP and excitatory amino acid transporter 2 (EAAT2) in the hippocampus were examined. The results revealed that pinostrobin potentially attenuated cognitive impairment in the Y-maze and in novel object recognition tests, with a reduction in oxidative stress. Furthermore, pinostrobin effectively increased neuronal density, as well as the immunoreactivities of GFAP and EAAT2 in the hippocampus. Taken together, these findings indicate that treatment with pinostrobin alleviates chronic stress-induced cognitive impairment by exerting antioxidant effects, reducing neuronal cell damage, and improving the function of astrocytic GFAP and EAAT2. Thus, pinostrobin may have potential for use as a neuroprotective agent to protect against chronic stress-induced brain dysfunction and cognitive deficits.

Sodium Hydrosulfide Reverts Chronic Stress–Induced Cardiovascular Alterations by Reducing Oxidative Stress

“…In our study, CRS increased lipid peroxidation, which reflects the increasing ROS production. This finding is in concordance with previous studies demonstrating that oxidative stress markers are increased in the hippocampus, 13,14 penile tissue, 10 brain, 63 serum, 13 and hearts 12 of animals with chronic stress. Indeed, the activity of superoxide dismutase and catalase, antioxidant enzymes, is decreased during chronic stress.…”

“…Indeed, the activity of superoxide dismutase and catalase, antioxidant enzymes, is decreased during chronic stress. 10,13,14 Conversely, the glutathione system is implicated in modulating oxidative stress because glutathione is a major antioxidant in the cellular defense against ROS. When the GSH 2 :GSSG ratio is decreased, it usually reflects an alteration in the redox environment.…”

“…In this regard, chronic stress-induced impairments have been attributed to impaired endothelial nitric oxide synthetize (eNOS) 10,11 and increased reactive oxygen species (ROS) and lipid peroxidation in the serum 12 and brain of stressed animals. 13,14 Given that chronic stress is a significant risk factor for cardiovascular diseases in patients, [15][16][17] it is crucial to explore potential therapeutic agents that can reverse chronic stressinduced cardiovascular alterations, such as H 2 S, a gasotransmitter involved in cardiovascular regulation. 18 H 2 S is synthesized by 3 different enzymes in mammals, including the cystathionin g-lyase (CSE), 19 cystathionin b-synthetase (CBS), 20 and 3-mercaptopyruvate sulfurtransferase (3-MST).…”

“…In this regard, chronic stress–induced impairments have been attributed to impaired endothelial nitric oxide synthetize (eNOS) 10,11 and increased reactive oxygen species (ROS) and lipid peroxidation in the serum 12 and brain of stressed animals. 13,14…”

Research Progress on the Pharmacological Effects and Molecular Mechanisms of Pinostrobin

“…66 Pinostrobin alleviates chronic stress-induced cognitive impairment by exerting antioxidant effects, reducing neuronal cell damage, and improving the function of astrocytes glial fibrillary acidic protein (GFAP) and excitatory amino acid transporter 2 (EAAT2). 67 Pinostrobin is an antioxidant that lacks significant toxicity, which makes it promising for the treatment of neurodegenerative diseases such as PNS repair after injury, Alzheimer's disease (AD) and Parkinson's disease (PD).…”