Protective effects of Lycium barbarum polysaccharide on ovariectomy-induced cognition reduction in aging mice

Abstract

Women experience cognitive decline as they age due to the decrease in estrogen levels following meno- pause. Currently, effective pharmaceutical treatments for age-related cognitive decline are lacking; however, several Traditional Chinese medicines have shown promising effects. Lycium barbarum polysaccharides (LBPs) were found to exert a wide variety of biological activities, including anti-inflam- matory, antioxidant and anti-aging effects. However, to the best of our knowledge, the neuroprotective actions of LBP on cognitive impairment induced by decreased levels of estrogen have not yet been determined. To evaluate the effects of LBP on learning and memory impairment in an animal model of menopause, 45 female ICR mice were randomly divided into the following three groups: i) Sham; ii) ovariectomy (OVX); and iii) OVX + LBP treatment. The results of open-field and novel object recognition tests revealed that mice in the OVX group had learning and memory impairments, and lacked the ability to recognize and remember new objects. Notably, these deficits were attenuated following LBP treatment. Immunohistochemical staining confirmed the protective effects of LBP on hippocampal neurons following OVX. To further investigate the underlying mechanism of OVX in mice, mRNA sequencing of the hippocampal tissue was performed, which revealed that the Toll-like receptor 4 (TLR4) inflam- matory signaling pathway was significantly upregulated in the OVX group. Moreover, reverse transcription-quantitative PCR and immunohistochemical staining demonstrated that OVX induced hippocampal injury, upregulated the expression levels of TLR4, myeloid differentiation factor 88 and NF-κB, and increased the expression of TNF-α, IL-6 and IL-1β inflam- matory factors. Conversely, LBP treatment downregulated the expression levels of mRNAs and proteins associated with the TLR4/NF-κB signaling pathway, decreased the inflammatory response and reduced neuronal injury in mice that underwent OVX. In conclusion, the findings of the present study indicated that oral LBP treatment may alleviate OVX-induced cogni- tive impairments by downregulating the expression levels of mRNAs and proteins associated with the TLR4/NF-κB signaling pathway, thereby reducing neuroinflammation and damage to the hippocampal neurons. Thus, LBP may represent a potential agent for the prevention of learning and memory impairments in patients with accelerated aging caused by estrogen deficiency.