Andrographolide enhances hippocampal BDNF signaling and suppresses neuronal apoptosis, astroglial activation, neuroinflammation, and spatial memory deficits in a rat model of chronic cerebral hypoperfusion

  • Da-Peng WangEmail author
  • Hang Yin
  • Qi Lin
  • Shu-Ping Fang
  • Jian-Hua Shen
  • Yi-Fang Wu
  • Shao-Hua Su
  • Jian HaiEmail author
Original Article


Andrographolide is a medical herbal compound with documented anti-inflammatory activity and therapeutic efficacy in animal models of Alzheimer’s disease, traumatic brain injury, and ischemic stroke. The present study examined the potential therapeutic effects of andrographolide on chronic cerebral hypoperfusion (CCH)–induced hippocampal neuronal damage and cognitive dysfunction. A CCH model was established in male Sprague Dawley (SD) rats using 2-vessel occlusion (2VO). After 4 weeks of CCH, spatial learning and memory were assessed in the Morris water maze and structural damage to the hippocampus by hematoxylin and eosin (HE) staining. Astrocyte activation was examined by immunohistochemical staining and Western blotting for glial fibrillary acid protein (GFAP), while expression levels of the pro-inflammatory cytokine-tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), the apoptosis effector cysteinyl aspartate specific proteinase-3 (caspase-3), and the neuroprotectant brain-derived neurotrophic factor (BDNF) and the TrkB receptor were estimated by Western blotting. After 4 weeks of CCH, the hippocampus of 2VO rats exhibited marked neurodegeneration as well as elevated GFAP, TNF-α, IL-1β, and caspase-3 compared to Sham controls. In addition, spatial learning was impaired compared to Sham controls. Andrographolide treatment during CCH suppressed astrocyte activation as evidenced by reduced GFAP expression, enhanced expression of BDNF and TrkB, improved impaired spatial learning and memory, and reversed upregulated TNF-α, IL-1β, and caspase-3 expression. These results reveal a potential neuroprotective effect of andrographolide on hippocampal neuronal damage and cognitive impairment from CCH due to suppression of astrocyte activation and enhancement of BDNF-TrkB signaling.


Andrographolide Chronic cerebral hypoperfusion Astrocyte Cognitive impairment BDNF signaling 


Author contributions

DP. W. wrote the manuscript. H.Y., Q.L., SP. F., and JH. S. prepared the experiments and collected the data. YF. W. and SH. S. analyzed and interpreted the data. DP. W. and J.H. designed the study. All authors read and approved the manuscript.

Funding information

This work received funding from the National Nature Science Foundation of China (81771410) and Priority of Shanghai key discipline of medicine (2017ZZ02020).

Compliance with ethical standards

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurosurgery, Tong Ji HospitalTong Ji University School of MedicineShanghaiChina
  2. 2.Department of NeurosurgeryZao Zhuang Municipal HospitalZaozhuangChina
  3. 3.Department of Pharmacy, Institutes of Medical SciencesShanghai Jiao Tong University School of MedicineShanghaiChina
  4. 4.Department of NeurosurgeryFeng Cheng HospitalShanghaiChina
  5. 5.Department of NeurosurgeryAffiliated Dongtai Hospital of Nantong UniversityNantongChina

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