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The journal of nutrition, health & aging

, Volume 22, Issue 6, pp 710–717 | Cite as

Berberine Improves Cognitive Deficiency and Muscular Dysfunction via Activation of the AMPK/SIRT1/PGC-1a Pathway in Skeletal Muscle from Naturally Aging Rats

  • Y. Yu
  • Y. Zhao
  • F. Teng
  • J. Li
  • Y. Guan
  • J. Xu
  • X. Lv
  • F. Guan
  • Ming ZhangEmail author
  • L. Chen
Article

Abstract

Objective

The manifestations of aging include cognitive deficits and muscular dysfunction, which are closely linked to impairment of mitochondrial biogenesis. Berberine, an isoquinoline alkaloid, presents multiple anti-diabetic pharmacological effects. Evidence has indicated that insulin resistance and cognitive impairment share the same pathogenesis, and berberine could reverse glucose metabolism abnormalities and muscle mitochondrial dysfunction induced by a high-fat diet. This study was used to investigate whether berberine could be used as an anti-aging drug to prevent cognitive deficits and muscular dysfunction in natural aging.

Methods

Biochemical indicators and an intraperitoneal glucose tolerance test were tested in 5-monthold rats (5 mo group), 24-month-old rats (24 mo group) and 24-month-old rats that had undergone 6 months of berberine treatment (BBR group). A Morris water maze test was conducted to assess the cognitive ability of the rats. Insulin resistance in whole-body was evaluated by intraperitoneal glucose tolerance test (IPGTT). The morphology of the skeletal muscle tissue was observed by hematoxylin-eosin (HE) staining. The levels of total cholesterol, triglyceride, ATP and reactive oxygen species (ROS) were assessed with corresponding reagent kits. The protein expressions of GLUT4, AMPK, SIRT1 and PGC-1α in skeletal muscle were examined by Western blot.

Results

The results showed that administration of berberine for 6 months significantly improved cognitive deficits and insulin resistance in naturally aging rats (p<0.01). Furthermore, berberine treatment helped normalize the disordered alignment and the decreased number of muscle fibers (p<0.01) in the skeletal muscle of 24 mo rats. Berberine decreased the levels of ROS in both the serum and the skeletal muscle of 24 mo rats (p<0.01). Berberine increased the protein expression of p-AMPK, SIRT1 and PGC-1α and increased the production of ATP in the skeletal muscle of aging rats (p<0.01).

Conclusions

Berberine markedly ameliorates aging-related reductions in cognitive ability and muscular function, and the activation of the AMPK/SIRT1/PGC-1α pathway in skeletal muscle may be the underlying protective mechanism of berberine on muscular function.

Key words

Berberine aging cognitive deficits skeletal muscle insulin resistance mitochondrial biogenesis 

List of abbreviations

PGC-1α

proliferator-activated receptor γ coactivator 1-α

AMPK

adenosine monophosphate-activated protein kinase

SIRT1

sirtuin type 1

FBG

fasting blood glucose

T-CHO

total cholesterol

TG

triglyceride

BCA

bicinchoninic acid

RIPA

Radiommunoprecipitation Assay

PMSF

phenylmethanesulfonyl fluoride

mo

month-old

IPGTT

intraperitoneal glucose tolerance test

MWM

Morris water maze

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Copyright information

© Serdi and Springer-Verlag France SAS, part of Springer Nature 2018

Authors and Affiliations

  • Y. Yu
    • 1
  • Y. Zhao
    • 1
  • F. Teng
    • 1
  • J. Li
    • 1
  • Y. Guan
    • 1
  • J. Xu
    • 1
  • X. Lv
    • 2
  • F. Guan
    • 1
  • Ming Zhang
    • 1
    Email author
  • L. Chen
    • 1
  1. 1.Department of Pharmacology, College of Basic Medical Sciences, School of NursingJilin UniversityChangchun, JilinChina
  2. 2.The Second HospitalJilin UniversityChangchunChina

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