Metabolic Brain Disease

, Volume 34, Issue 1, pp 245–255 | Cite as

Berberine ameliorates lipopolysaccharide-induced learning and memory deficit in the rat: insights into underlying molecular mechanisms

  • Sepideh Sadraie
  • Zahra Kiasalari
  • Mohadeseh Razavian
  • Shekoofe Azimi
  • Ladan Sedighnejad
  • Siamak Afshin-Majd
  • Tourandokht Baluchnejadmojarad
  • Mehrdad RoghaniEmail author
Original Article


Systemic lipopolysaccharide (LPS) triggers neuroinflammation with consequent development of behavioral and cognitive deficits. Neuroinflammation plays a crucial role in the pathogenesis of neurodegenerative disorders including Alzheimer’s disease (AD). Berberine is an isoquinoline alkaloid in Berberis genus with antioxidant and anti-inflammatory property and protective effects in neurodegenerative disorders. In this research, beneficial effect of this alkaloid against LPS-induced cognitive decline was assessed in the adult male rats. LPS was intraperitoneally administered at a dose of 1 mg/kg to induce neuroinflammation and berberine was given via gavage at doses of 10 or 50 mg/kg, one h after LPS, for 7 days. Treatment of LPS group with berberine at a dose of 50 mg/kg (but not at a dose of 10 mg/kg) improved spatial recognition memory in Y maze, performance in novel object recognition task (NORT), and prevented learning and memory dysfunction in passive avoidance tasks. Furthermore, berberine lowered hippocampal activity of acetylcholinesterase (AChE), malondialdehyde (MDA), protein carbonyl, activity of caspase 3, and DNA fragmentation and improved antioxidant capacity through enhancing glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase, and glutathione (GSH). Besides, berberine attenuated inflammation-related indices, as was evident by lower levels of nuclear factor-kappa B (NF-κB), toll-like receptor 4 (TLR4), tumor necrosis factor α (TNFα), and interleukin 6 (IL-6). Berberine also appropriately restored hippocampal 3-nitrotyrosine (3-NT), cyclooxygenase 2 (Cox 2), glial fibrillary acidic protein (GFAP), sirtuin 1, and mitogen-activated protein kinase (p38 MAPK) with no significant alteration of brain-derived neurotrophic factor (BDNF). In summary, berberine could partially ameliorate LPS-induced cognitive deficits via partial suppression of apoptotic cascade, neuroinflammation, oxido-nitrosative stress, AChE, MAPK, and restoration of sirtuin 1.


Berberine Lipopolysaccharide Learning and memory Apoptosis Oxidative stress Neuroinflammation 







Alzheimer’s disease


brain-derived neurotrophic factor

Cox 2

cyclooxygenase 2


glial fibrillary acidic protein




glutathione peroxidase


interleukin 6






mitogen-activated protein kinase


nuclear factor-kappa B


novel object recognition task


reactive nitrogen species


reactive oxygen species

Sirt 1

sirtuin 1


superoxide dismutase


toll-like receptor 4


tumor necrosis factor α



This research project was the result of MD thesis project (Sepideh Sadraie), approved and financially supported in part by Shahed University in 2016.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.


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Authors and Affiliations

  • Sepideh Sadraie
    • 1
  • Zahra Kiasalari
    • 2
  • Mohadeseh Razavian
    • 1
  • Shekoofe Azimi
    • 3
  • Ladan Sedighnejad
    • 3
  • Siamak Afshin-Majd
    • 2
    • 4
  • Tourandokht Baluchnejadmojarad
    • 5
  • Mehrdad Roghani
    • 2
    Email author
  1. 1.School of MedicineShahed UniversityTehranIran
  2. 2.Neurophysiology Research CenterShahed UniversityTehranIran
  3. 3.Department of Physiology, School of MedicineShahed UniversityTehranIran
  4. 4.Department of Neurology, School of MedicineShahed UniversityTehranIran
  5. 5.Department of Physiology, School of MedicineIran University of Medical SciencesTehranIran

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