Genistein Improves 3-NPA-Induced Memory Impairment in Ovariectomized Rats: Impact of Its Antioxidant, Anti-Inflammatory and Acetylcholinesterase Modulatory Properties

Abstract

Huntington’s disease (HD) is a progressive neurodegenerative disorder. The pre-motor symptomatic stages of the disease are commonly characterized by cognitive problems including memory loss. 3-Nitropropionic acid (3-NPA) is a mitochondrial toxin that produces selective lesions in the brain similar to that of HD and was proven to cause memory impairment in rodents. Phytoestrogens have well-established neuroprotective and memory enhancing effects with fewer side effects in comparison to estrogens. This study investigated the potential neuroprotective and memory enhancing effect of genistein (5, 10 and 20 mg/kg), a phytoestrogen, in ovariectomized rats challenged with 3-NPA (20 mg/kg). These potential effects were compared to those of 17β-estradiol (2.5 mg/kg). Systemic administration of 3-NPA for 4 consecutive days impaired locomotor activity, decreased retention latencies in the passive avoidance task, decreased striatal, cortical and hippocampal ATP levels, increased oxidative stress, acetylcholinesterase (AChE) activity, cycloxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) expressions. Pretreatment with genistein and 17β-estradiol attenuated locomotor hypoactivity, increased retention latencies in the passive avoidance task, increased ATP levels, improved the oxidative stress profile, attenuated the increase in AChE activity and decreased the expression of COX-2 and iNOS. Overall, the higher genistein dose (20 mg/kg) was the most effective. In conclusion, this study suggests neuroprotective and memory enhancing effects for genistein in a rat model of HD. These effects might be attributed to its antioxidant, anti-inflammatory and cholinesterase inhibitory activities.

Neuroprotective Mechanisms of Calycosin Against Focal Cerebral Ischemia and Reperfusion Injury in Rats

“…Accumulating evidence has shown that phytoestrogens exert beneficial effects in a variety of neurodegenerative disorders, including acute ischemic stroke [8-10] Due to a structural similarity to the mammalian estrogen, phytoestrogens can selectively bind estrogen receptors (ERs) to regulate relevant gene expression and produce estrogenic and/or anti-estrogenic effects. Calycosin, as an isoflavone phytoestrogen isolated from Astragalus membranaceus , is found to possess various potential pharmacological activities.…”

Spectroscopic and molecular docking study on the structure–affinity relationship and mechanism in the interaction of genistein and its derivatives with bovine serum albumin

“…The emission spectrum of the BSA overlaps with the absorption spectrum of these compounds, as shown in Figure 5. According to equations (6)(7)(8), the values of E, J (λ), R 0 and r 0 can be calculated, which are listed in Table 4. The values of r 0 were 2.56, 1.81, 2.65, 2.64, 2.69 nm for GEN, GEN1, GEN2, GEN3 and GEN4, respectively, which were all much smaller than the academic value (7 nm).…”

“…Genistein, a major isoflavone in soybean, possesses many biological and pharmacological activities including estrogenic, antioxidant, anti‐inflammatory and antibacterial properties, anticancer activity . However, the clinical use of genistein is limited due to its poor water solubility and low bioavailability .…”

“…[5] Genistein, a major isoflavone in soybean, possesses many biological and pharmacological activities including estrogenic, antioxidant, anti-inflammatory and antibacterial properties, anticancer activity. [6][7][8] However, the clinical use of genistein is limited due to its poor water solubility and low bioavailability. [9] Many researchers have focused on designing and synthesizing genistein derivatives over recent years, and some derivatives have shown antiproliferative activity in cancer cells at much lower concentrations than genistein.…”

Synthesis and Biological Evaluation of Novel Genistein Amino Acid Ester Derivatives as Potential Anti‐Tumor Agents

“…Genistein (5,7,4’‐trihydroxyisoflavone), mainly found in legumes, displays antitumor, anti‐inflammatory, antioxidant, anti‐osteoporotic, antimicrobial properties and its antitumor activity has always been the focus of research. Although genistein possesses various biological activities, its poor solubility and low bioavailability limited its potential in clinical treatment , .…”