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Berberine Improves Diabetic Encephalopathy Through the SIRT1/ER Stress Pathway in db/db Mice.

Abstract
The association between diabetes and dementia has been well demonstrated by epidemiologic studies. Berberine (BBR) has been reported to ameliorate diabetes and diabetic encephalopathy (DE). However, the mechanism is still unknown. In this study, we employ a diabetic model, db/db mice, to explore whether BBR could protect DE through the SIRT1/endoplasmic reticulum (ER) stress pathway. Behavioral results (Morris water maze, Y-maze spontaneous alternation test, and fear conditioning test) showed that oral administration of BBR (50 mg/kg) improved the learning and memory ability. Furthermore, BBR promoted lipid metabolism and decreased fasting glucose in db/db mice. Moreover, western blot analysis revealed that BBR increased the synapse- and nerve-related protein expression (PSD95, SYN, and NGF) and decreased the protein expression of inflammatory factors (TNF-α and NF-κB) in the hippocampus of db/db mice. BBR also increased the protein expression of SIRT1 and downregulated ER stress-associated proteins (PERK, IRE-1α, eIF-2α, PDI, and CHOP) in the hippocampus of db/db mice. Taken together, the present results suggest that the SIRT1/ER stress pathway might be a crucial mechanism in the neuroprotective effect of BBR against DE.
AuthorsHong-Ying Li, Xin-Chen Wang, Yu-Min Xu, Na-Chuan Luo, Si Luo, Xu-Yi Hao, Shu-Yi Cheng, Jian-Song Fang, Qi Wang, Shi-Jie Zhang, Yun-Bo Chen
JournalRejuvenation research (Rejuvenation Res) Vol. 21 Issue 3 Pg. 200-209 (Jun 2018) ISSN: 1557-8577 [Electronic] United States
PMID28782427 (Publication Type: Journal Article)
Chemical References
  • Biomarkers
  • Blood Glucose
  • Insulin
  • Berberine
  • Sirt1 protein, mouse
  • Sirtuin 1
Topics
  • Animals
  • Berberine (pharmacology)
  • Biomarkers (blood)
  • Blood Glucose (metabolism)
  • Brain Diseases (complications, drug therapy)
  • Cognition Disorders (blood)
  • Conditioning, Psychological
  • Diabetes Mellitus, Experimental (complications)
  • Endoplasmic Reticulum Stress
  • Fear
  • Female
  • Glucose Tolerance Test
  • Hippocampus (metabolism)
  • Inflammation
  • Insulin (blood)
  • Lipid Metabolism
  • Maze Learning
  • Memory
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction (drug effects)
  • Sirtuin 1 (metabolism)

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