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Effect of Danggui Shaoyaosan on Improvement of Cognitive Ability of SAMP8 Mice and Its Mechanism via Regulating Ubiquitin Proteasome PathwayChinese Full TextEnglish Full Text (MT)

CHEN Yunhui;XIA Jun;HUAI Wenying;LIU Dan;ZHANG Tiane;LI Yan;Xie Yongmei;TANG Songqi;YOU Yu;PENG Wei;Chengdu University of Traditional Chinese Medicine;Sichuan University;University of Louisville;Hainan Medical University;

Abstract: Objective: To investigate the mechanism of Danggui Shaoyaosan(DSS) in the improvement of the cognitive ability of SAMP8 mice with Alzheimer’s disease(AD)via regulating the ubiquitinproteasome pathway(UPP). Method:Fifteen SAMR1 mice were used as a normal group,and 60 SAMP8 mice were randomly divided into a model group and DSS high,medium,and low-dose groups(57.6,28.8,and14.4 g·kg-1·d-1),with 15 mice in each group. Intragastric administration was conducted for eight continuous weeks. Place navigation and spatial capacity were evaluated by Morris water maze. Pathological structure changes in neurons in the hippocampal CA1 area was detected by hematoxylin-eosin(HE)staining. The protein expression levels of hippocampal β-amyloid protein(Aβ) and phosphorylation(p)-Tau were determined by immunohistochemical staining(IHC)and enzyme-linked immunosorbent assay(ELISA),and the mRNA and protein expression levels of hippocampal ubiquitin(Ub),ubiquitin ligase E3(E3),26S proteasome,ubiquitin carboxyl terminal hydrolase-1(UCHL1),and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction(Real-time PCR)and Western blot,respectively. Result: As compared with the normal group,the escape latency was prolonged in the model group(P<0.05)with the reduced number of crossing platform quadrants and time ratio in the platform quadrant(P<0.05). The model group decreased neurons and condensed cell bodies in the CA1 area,and increased β-amyloid precursor protein(β-APP)and p-Tau positive cells(P<0.05). In the model group,the protein expression levels of Aβ and p-Tau were increased(P<0.05),the mRNA and protein expression levels of Ub were increased(P<0.05),and the mRNA and protein expression levels of E3,26S proteasome,UCHL1,and UCHL3 were decreased(P<0.05). As compared with the model group,the escape latency was shortened in the DSS high and medium-dose groups(P<0.05)with an increased number of crossing platform quadrants and residence time ratio(P<0.05). The pathological changes in CA1 of each DSS group were significantly improved,and the number of β-APP positive staining cells decreased(P<0.05). The number of p-Tau positive staining cells decreased in the DDS medium and low-dose groups(P<0.05). The protein expression levels of Aβ and p-Tau in each DDS group decreased(P<0.05),and the mRNA expression level of Ub in each group decreased(P <0.05). The mRNA expression levels of 26S,E3,and UCHL3 in the DDS high and medium-dose groups increased(P<0.05),and the mRNA expression level of UCHL1 in the DDS medium-dose group increased(P<0.05). The protein expression level of Ub in each DDS group decreased,and the protein expression levels of 26S,E3,UCHL1+3 in the DDS high and medium-dose groups increased(P<0.05). Conclusion: DSS can improve the cognitive ability of SAMP8 mice,and its mechanism may be related to the reduction of the abnormal deposition of Aβ and p-Tau via decreasing the expression of Ub and increasing that of E3,26S,UCHL1,and UCHL3 in the UPP.
  • DOI:

    10.13422/j.cnki.syfjx.20211107

  • Series:

    (E) Medicine & Public Health

  • Subject:

    Traditional Chinese Medicinal Herbs

  • Classification Code:

    R285.5

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