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

Yaowared Chulikhit,Rakvajee Wongpradit,Orawan Monthakantirat,Waraporn Putalun,Wichitsak Sukhano,Supawadee Daodee,Hiroshi Noguchi,Charinya Khamphukdee,Kaoru Umehara,Kinzo Matsumoto

doi:10.3390/molecules26113442

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.

Highlights

Accumulated evidence over the last 30 years has demonstrated that the estrogen hormone modulates cognitive function in female rodents and primates, including humans [1]
In order to establish whether Pueraria mirifica (PM) extract modulates OVX-induced cognitive impairments, the spatial and non-spatial memory performances of OVX mice were elucidated by the Y-maze test and novel ORT, respectively
The mouse model of OVX used in the present study showed clearly atrophic changes in the uterus, a decrease in the circulating level of E2, and cognitive deficits in a manner that may be reversed by Hormone replacement therapy (HRT) with 17β-estradiol

Summary

Introduction

Accumulated evidence over the last 30 years has demonstrated that the estrogen hormone modulates cognitive function in female rodents and primates, including humans [1]. Modulation by estrogens initially targets the ovary and uterus through which estrogens play a role in the sexual differentiation of various brain functions, including the regulation of reproduction and some cognitive functions. With aging, circulating estrogen levels markedly decrease and appear to contribute to age-related decline in learning and memory function in females [2]. These estrogen-dependent effects on cognition function throughout the lifespan have been attributed to classic genomic mechanisms, including processes such as hormone binding to specific receptors, alterations in gene transcription, and the initiation of organ-specific effects in target areas in the brain and peripheral organs [3]. The decrease induced in estrogen levels by menopause or ovariectomy may increase the incidence of inflammatory pathologies, and decrease neurogenesis and neuronal plasticity [5]

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