Polygonati Rhizoma Polysaccharides Improve Cognitive and Emotional Functions of Ovariectomy-AD Model Rats Through Modulating ERα/PI3K/Akt Pathway
10.13422/j.cnki.syfjx.20251802
- VernacularTitle:黄精多糖调控ERα/PI3K/Akt信号通路改善去卵巢-阿尔茨海默病模型大鼠的认知和情绪功能障碍
- Author:
Gengchao ZHANG
1
;
Li YANG
2
;
Yuan ZHANG
2
;
Tao ZHOU
2
Author Information
1. Medical School， Hubei Minzu University， Enshi 445000， China
2. Huanggang Hospital of Traditional Chinese Medicine（TCM） & Huanggang Hospital of TCM Affiliated to Hubei University of Chinese Medicine， Huanggang 438000，China
- Publication Type:Journal Article
- Keywords:
Polygonati Rhizoma polysaccharide;
Alzheimer's disease;
cognitive dysfunction;
estrogen-receptor α （ERα）/phosphoinositide 3kinase （PI3K）/protein-kinase-B （Akt） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(9):154-162
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveThis study aims to investigate the effectiveness and mechanisms of Polygonati Rhizoma polysaccharides （PRP） on improving cognitive and emotional functions in the ovariectomy （OVX）-Alzheimer's disease （AD） model rats. MethodsAfter being randomly divided into blank group， model group， estradiol group （0.18 mg·kg-1·d-1）， low-PRP group （200 mg·kg-1）， medium-PRP group （400 mg·kg-1）， and high-PRP group （800 mg·kg-1）， 60 SPF female Sprague-Dawley （SD） rats were subjected to OVX. One week later， vaginal smear examination as well as D-galactose intraperitoneal injection （150 mg·kg-1·d-1， once daily， for eight weeks） were adopted to establish the OVX-AD model， and drug intervention was initiated nine weeks after surgery. Upon completion of the treatment course， cognitive and emotional functions， as well as hippocampal CA3 region damage were assessed in all rats by open-field test， new object recognition test， Morris water maze test， and transmission electron microscopy. Indicators of inflammation ［interleukin-6 （IL-6）， tumor-necrosis-factor-α （TNF-α）， interleukin-1β （IL-1β））， oxidative-stress （superoxide-dismutase （SOD）， glutathione-peroxidase （GSH-Px）］ were measured by enzyme-linked immunosorbent assay （ELISA） and biochemical methods. The mRNA and protein expression levels of estrogen-receptor α （ERα）/phosphoinositide 3kinase （PI3K）/protein-kinase-B （Akt） signaling pathway， apoptosis ［Bcl-2 associated X protein （Bax）， B-cell lymphoma/leukemia-2 （Bcl-2）］ and the indicators of pathological sedimentary proteins ［amyloid β-protein1-42 （Aβ1-42）， microtubule-associated protein Tau， phosphorylated site 404 of microtubule-associated protein Tau ［p-Tau （Ser404）］ were detected by using real-time polymerase chain reaction （Real-time PCR） and western blot analysis. ResultsCompared with those in blank group， the rats in model group exhibited marked ultra-structural damage to hippocampal CA3 neurons， along with the reduction of activity time and shuttle frequency in central area， the index and exploration frequency of new object recognition， and the platform crossings and time spent in target quadrant， as well as the prolonged latency （P<0.05， P<0.01）. Furthermore， the contents and expression levels of IL-6， TNF-α， IL-1β， Bax， Aβ1-42， Tau， and p-Tau （Ser404） were significantly increased， and the activity and expression of SOD， GSH-Px， ERα， PI3K， Akt， and Bcl-2 were significantly decreased （P<0.05， P<0.01）. Compared to those in model group， the rats in estradiol group and groups with different doses of PRP noticeably presented with amelioration of neuronal damage， along with increased activity time and shuttle frequency in the central zone， elevated new object recognition index and exploration frequency， shortened latency， prolonged activity time， and increased platform crossings in the target quadrant （P<0.05， P<0.01）. What is more， the contents and expression levels of IL-6， TNF-α， IL-1β， Bax， Aβ1-42， Tau， and p-Tau （Ser404） were significantly reduced， whereas the activity and expression levels of SOD， GSH-Px， ERα， PI3K， Akt， and Bcl-2 were markedly elevated （P<0.05， P<0.01）. ConclusionPRP can improve the cognitive and emotional functions of AD model rats， and its mechanisms are probably related to modulating the ERα/PI3K/Akt pathway as well as inhibiting Aβ， Tau， neuro-inflammation， oxidative stress， and apoptosis， resulting in alleviation of neuronal damage.
