Effects of Pueraria candollei var mirifica (Airy Shaw and Suvat.) Niyomdham on Ovariectomy-Induced Cognitive Impairment and Oxidative Stress in the Mouse Brain

Abstract

The effects of the phytoestrogen-enriched plant Pueraria mirifica (PM) extract on ovari-ectomy (OVX)-induced cognitive impairment and hippocampal oxidative stress in mice were investigated. Daily treatment with PM and 17β-estradiol (E2) significantly elevated cognitive behavior as evaluated by using the Y maze test, the novel object recognition test (NORT), and the Morris water maze test (MWM), attenuated atrophic changes in the uterus and decreased serum 17β-estradiol levels. The treatments significantly ameliorated ovariectomy-induced oxidative stress in the hippocampus and serum by a decrease in malondialdehyde (MDA), an enhancement of superoxide dismutase, and catalase activity, including significantly down-regulated expression of IL-1β, IL-6 and TNF-α proinflammatory cytokines, while up-regulating expression of PI3K. The present results suggest that PM extract suppresses oxidative brain damage and dysfunctions in the hippocampal antioxidant system, including the neuroinflammatory system in OVX animals, thereby preventing OVX-induced cognitive impairment. The present results indicate that PM exerts beneficial effects on cognitive deficits for which menopause/ovariectomy have been implicated as risk factors.

Effect of Yakae-Prajamduen-Jamod Traditional Thai Remedy on Cognitive Impairment in an Ovariectomized Mouse Model and Its Mechanism of Action

“…In the current study, estrogen deprivation for 6 weeks following OVX produced cognitive dysfunction, as shown by a decrease in spontaneous alternations in the Y-maze test, a failure to discriminate between novel and familiar objects in the NORT, and an increase in escape latency time and a decrease in time spent in the target quadrant in the MWMT. These learning and memory impairments are in agreement with those noted in previous finding [6,29,33].…”

“…In parallel, estrogen also increases antioxidant defenses by up-regulating several antioxidant enzymes, including peroxiredoxin 5, glutaredoxin, and manganese superoxide dismutase (MnSOD), thereby reducing free radicals and lowering oxidative damage to brain mitochondria [22,25]. Therefore, the estrogen loss induced by menopause or ovariectomy can exacerbate the effects of aging on cognitive decline [27][28][29]. From a basic science perspective, ovariectomy is the gold standard procedure for understanding estrogen deficiency through animal experiments.…”

“…Mitochondrial dysfunction is often closely associated with the overproduction of free radicals and reduced antioxidant enzyme activities [34,35]. The resulting oxidative stress has been widely associated with the development and progression of neuronal cell damage, which in turn leads to cognitive dys-function in estrogen-deficient postmenopausal women and Alzheimer's disease [29,[34][35][36].…”

“…The Y-maze test was conducted 1 h after drug treatment. The mice were placed on one arm, and the sequence of arm entries was observed and recorded manually over an 8 min testing period [29,39]. An alternation was defined as an entry into all three arms without a repeat entry.…”

“…The novel object recognition test (NORT) uses rodents' natural proclivity for exploring novelty to test recognition memory. The NORT was performed as described previously [29,39]. Briefly, 24 h before the test, mice were habituated to an empty examination box (50 × 50 × 40 cm high) for 10 min.…”