Protective effects of Genistein on the cognitive deficits induced by chronic sleep deprivation

Abstract

Sleep deprivation has been widely reported to cause cognitive dysfunction, and elevation in oxidative stress and inflammation in the body, including the brain, have been suggested as the main factors. Genistein (GE) is an isoflavone widely present in leguminous plants, and it was found to exert a wide spectrum of biological activities, including antioxidant, anti‐inflammatory, hepatoprotective, neuroprotective, and antimetastatic effects. In this study, the protective effect of GE on chronic sleep deprivation (CSD)‐induced cognitive dysfunction was investigated. The mice were subjected to the sleep interruption apparatus and continuously sleep deprived for 25 days. GE was orally administrated (10, 20, and 40 mg/kg) during the sleep deprivation process totally for 25 days. Cognitive behavioral tests were conducted to study the learning and memory using the object location recognition (OLR) task, novel object recognition (NOR) test, and the Morris water maze (MWM) task. Additionally, the cortex and hippocampus were dissected to measure the oxidative stress markers and the antioxidant element nuclear erythroid‐2‐related factor 2 (Nrf2) and its downstream targets, including glutamate cysteine ligase catalytic, glutamate cysteine ligase modifier, heme oxygenase 1, and quinone oxidoreductase 1, as well as nuclear factor kappa B (NF‐κB) p65, nitric oxide synthase (iNOS), and cyclooxygenase 2 (COX‐2) protein expression. Moreover, the pro‐inflammatory cytokines (TNF‐α, interleukin [IL]‐6, and IL‐1β) level was examined in the serum. The current results showed that GE could dose‐dependently ameliorate the cognitive deficits of CSD‐treated mice in the OLR, NOR, and MWM tasks. In addition, GE treatment significantly elevated the activities of total antioxidant capacity and superoxide dismutase and the level of glutathione and lowered the content of malondialdehyde in the cortex and hippocampus of CSD‐treated mice. Furthermore, GE administration effectively activated the antioxidant element Nrf2 and its downstream targets in the cortex and hippocampus of CSD‐treated mice. Moreover, GE treatment significantly suppressed CSD‐induced NF‐κB p65, iNOS, and COX‐2 activation in the cortex and hippocampus, as well as inhibited CSD‐induced pro‐inflammatory cytokines (TNF‐α, IL‐6, and IL‐1β) release in the serum. Taken together, all these results suggested that GE has substantial potential as a therapeutic intervention for the alleviation of CSD‐induced deleterious effects.

Genistein: A Potential Natural Lead Molecule for New Drug Design and Development for Treating Memory Impairment

“…Each included study focused on different types of MI models. For example, Rumman et al [ 19 ] focused on hypoxia-induced MI while Lu et al [ 20 ] scrutinized on chronic sleep deprivation (CSD)-induced memory deficits. Two studies employed a streptozotocin (STZ)-induced model of MI, where Pierzynowska et al [ 13 ] investigated a STZ-induced Alzheimer’s disease (AD) model while Rajput et al [ 21 ] focused on STZ-induced diabetes for an MI model.…”

“…The exploratory behaviour of the animals will be observed based on the sniffing or touching action of the object. The duration of contact with each of the object will be recorded to evaluate the recognition memory [ 19 , 20 ].…”

“…The objects used are two small plastic bottles, identical in size and shape but different in color. The method is divided into three phases: habituation, familiarization and test phases [ 20 ].…”

Genista tridentata L.: A Rich Source of Flavonoids with Anti-Inflammatory Activity

“…In vitro: LPS-stimulated macrophages [57] In vitro: homocysteine-induced endothelial cell inflammation [65] In vivo: cyclophosphamide -induced hepatotoxicity [66] In vivo: LPS-induced microglial activation in murine BV2 microglial cell line and primary microglial culture [67] In vivo: imiquimod-induced psoriasis-like lesions in mice [68] In vivo: DSS-induced murine colitis [69] In vivo: NASH mouse model [70] In vivo: chronic sleep deprivation [71] In vitro: barrier function of intestinal epithelial CaCo-2/TC-7 cells via TEER measurements [56] In vivo: mouse model of periodontitis [72] In vivo: high-fat high-fructose diet-induced NASH rats [73] In Considering all these pieces of evidence and the fact that several flavonoids were found in G. tridentata, we selected some significative examples to discuss their anti-inflammatory potential, and Table 4 summarizes the effect and mechanism of action of the selected flavonoids.…”

“…In fact, the results show that the anti-inflammatory activity of genistein 1e downregulated microRNA expression of liver inflammation [70] but also pro-inflammatory cytokines species such as IL-1β and TNF-α [70,73]. Another interesting example is its ability to attenuate NF-κB inflammatory signaling in the brain with consequent inhibition of pro-inflammatory cytokines release, which gives genistein 1e the possibility to become a new drug able to relieve chronic sleep deprivation's adverse effects [71]. Furthermore, there is some evidence supporting that genistein 1e can, through its anti-inflammatory activity, prevent cardiovascular diseases [74].…”