Erzhi Pills Ameliorate Cognitive Dysfunction and Alter Proteomic Hippocampus Profiles Induced by D-galactose and Aβ Injection in Ovariectomized Alzheimer's Disease Model Rats

Overview

Journal Pharm Biol

Specialties Pharmacology
Pharmacy

Date 2021 Oct 21

PMID 34672897

Citations 8

Authors

Yongyan Xie

Bo Yan

Min Hou

Maofu Zhou

Chao Liu

Mengsheng Sun

Kun He

Cong Fang

Yaohui Chen

Liping Huang

Affiliations

Soon will be listed here.

Abstract

Context: Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear.

Objective: The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated.

Materials And Methods: An AD rat model was established by ovariectomy combined with d-galactose and Aβ injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERβ, Aβ, and p-tau was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins.

Results: Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERβ-positive cells (57.42, 39.83); Aβ (18.85, 36.83)- and p-tau (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3β and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated.

Discussion And Conclusion: Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.

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References

Bove R, Secor E, Chibnik L, Barnes L, Schneider J, Bennett D . Age at surgical menopause influences cognitive decline and Alzheimer pathology in older women. Neurology. 2013; 82(3):222-9. PMC: 3902759. DOI: 10.1212/WNL.0000000000000033. View

Gao H, Wang D, Wang X, Wang Z, Wang X, Wu Z . Effect of Erzhi Pill (二至丸) on improving cerebral nerve cell apoptosis in aging rats. Chin J Integr Med. 2010; 16(6):504-9. DOI: 10.1007/s11655-010-0565-2. View

Wu J, Wang Y, Zhang Z, Yu B . Herbal medicine in the treatment of Alzheimer's disease. Chin J Integr Med. 2014; 21(2):102-7. DOI: 10.1007/s11655-014-1337-y. View

Li L, Zhang L, Yang C . Multi-Target Strategy and Experimental Studies of Traditional Chinese Medicine for Alzheimer's Disease Therapy. Curr Top Med Chem. 2015; 16(5):537-48. DOI: 10.2174/1568026615666150813144003. View

Walton J . Cognitive deterioration and associated pathology induced by chronic low-level aluminum ingestion in a translational rat model provides an explanation of Alzheimer's disease, tests for susceptibility and avenues for treatment. Int J Alzheimers Dis. 2012; 2012:914947. PMC: 3423924. DOI: 10.1155/2012/914947. View

Gong Y, Hua N, Zang X, Huang T, He L . Melatonin ameliorates Aβ -induced Alzheimer's cognitive deficits in mouse model. J Pharm Pharmacol. 2017; 70(1):70-80. DOI: 10.1111/jphp.12830. View

Matsuo F, Andrade M, Loyola A, da Silva S, Silva M, Cardoso S . Pathologic significance of AKT, mTOR, and GSK3β proteins in oral squamous cell carcinoma-affected patients. Virchows Arch. 2018; 472(6):983-997. DOI: 10.1007/s00428-018-2318-0. View

Pike C . Sex and the development of Alzheimer's disease. J Neurosci Res. 2016; 95(1-2):671-680. PMC: 5120614. DOI: 10.1002/jnr.23827. View

Ibrahim W, Safar M, Khattab M, Agha A . 17β-Estradiol augments antidepressant efficacy of escitalopram in ovariectomized rats: Neuroprotective and serotonin reuptake transporter modulatory effects. Psychoneuroendocrinology. 2016; 74:240-250. DOI: 10.1016/j.psyneuen.2016.09.013. View

10.

Song L, Xiong H, Li J, Liao W, Wang L, Wu J . Sphingosine kinase-1 enhances resistance to apoptosis through activation of PI3K/Akt/NF-κB pathway in human non-small cell lung cancer. Clin Cancer Res. 2011; 17(7):1839-49. DOI: 10.1158/1078-0432.CCR-10-0720. View

11.

Sadik G, Tanaka T, Kato K, Yamamori H, Nessa B, Morihara T . Phosphorylation of tau at Ser214 mediates its interaction with 14-3-3 protein: implications for the mechanism of tau aggregation. J Neurochem. 2008; 108(1):33-43. DOI: 10.1111/j.1471-4159.2008.05716.x. View

12.

Wu X, Duan L, Gao X, Guo M, Wang D . [Study on preventive and therapeutic effects of Erzhi Pills on mice with Parkinson's disease induced by MPTP]. Zhongguo Zhong Yao Za Zhi. 2019; 44(19):4219-4224. DOI: 10.19540/j.cnki.cjcmm.20190603.405. View

13.

Hao D, Xiao P . Network pharmacology: a Rosetta Stone for traditional Chinese medicine. Drug Dev Res. 2014; 75(5):299-312. DOI: 10.1002/ddr.21214. View

14.

Li H, Kang T, Qi B, Kong L, Jiao Y, Cao Y . Neuroprotective effects of ginseng protein on PI3K/Akt signaling pathway in the hippocampus of D-galactose/AlCl3 inducing rats model of Alzheimer's disease. J Ethnopharmacol. 2016; 179:162-9. DOI: 10.1016/j.jep.2015.12.020. View

15.

Long H, Cheng Y, Zhou Z, Luo H, Wen D, Gao L . PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer's Disease and Parkinson's Disease. Front Pharmacol. 2021; 12:648636. PMC: 8082498. DOI: 10.3389/fphar.2021.648636. View

16.

Irvine K, Laws K, Gale T, Kondel T . Greater cognitive deterioration in women than men with Alzheimer's disease: a meta analysis. J Clin Exp Neuropsychol. 2012; 34(9):989-98. DOI: 10.1080/13803395.2012.712676. View

17.

Souza L, Filho C, Goes A, Del Fabbro L, de Gomes M, Savegnago L . Neuroprotective effect of physical exercise in a mouse model of Alzheimer's disease induced by β-amyloid₁₋₄₀ peptide. Neurotox Res. 2013; 24(2):148-63. DOI: 10.1007/s12640-012-9373-0. View

18.

Bean L, Ianov L, Foster T . Estrogen receptors, the hippocampus, and memory. Neuroscientist. 2014; 20(5):534-45. PMC: 4317255. DOI: 10.1177/1073858413519865. View

19.

Pirskanen M, Hiltunen M, Mannermaa A, Helisalmi S, Lehtovirta M, Hanninen T . Estrogen receptor beta gene variants are associated with increased risk of Alzheimer's disease in women. Eur J Hum Genet. 2005; 13(9):1000-6. DOI: 10.1038/sj.ejhg.5201447. View

20.

Vorhees C, Williams M . Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc. 2007; 1(2):848-58. PMC: 2895266. DOI: 10.1038/nprot.2006.116. View