Ginkgolide B Alleviates Learning and Memory Impairment in Rats With Vascular Dementia by Reducing Neuroinflammation via Regulating NF-κB Pathway

Ginkgobalide B (GB) as the main active ingredient of traditional Chinese medicine Ginkgo biloba extract is reported to reduce neuroinflammation, protect neurons and promote cognitive learning ability. To explore that GB can reduce neuroinflammation through regulating nuclear factor-kappaB (NF-κB) signaling pathway and overcome cognitive dysfunction in rats with vascular dementia (VD), we aim at investigating the potential effect of GB on enhancing cognitive function in rats with VD. It was found that GB improved survival of oxygen-glucose deprivation (OGD) treated SH-SY5Y cells by attenuating inflammatory response via Toll-like Receptor 4 (TLR4)/NF-κB pathway. When rats were treated with bilateral common carotid artery occlusion (BCCAO) for 24 h, saline and GB were administered in Sprague-Dawley (SD) rats via a single intraperitoneal injection for consecutive 14 days. The behavioral changes of VD like rats treated with GB were observed through open field test, Morris water maze (MWM) and Y-maze electric maze. Nissl staining and immunofluorescence were used to observe changes of neurons in the hippocampus of rats. Western blot analysis was performed by detecting NF-κB pathway related inflammatory factors. The results found that GB can significantly improve the learning and memory ability of VD rats by reducing TLR4/NF-κB mediated neuroinflammation. In conclusion, GB seemed to be a potential drug for amelioration of learning and memory impairment in rats with VD.

[1]  M. Fisher,et al.  Acupuncture Attenuates Inflammation in Microglia of Vascular Dementia Rats by Inhibiting miR-93-Mediated TLR4/MyD88/NF-κB Signaling Pathway , 2020, Oxidative medicine and cellular longevity.

[2]  Yongzhao Fan,et al.  Neuroprotective effect of different physical exercises on cognition and behavior function by dopamine and 5-HT level in rats of vascular dementia , 2020, Behavioural Brain Research.

[3]  Yue Hou,et al.  Kellerin alleviates cognitive impairment in mice after ischemic stroke by multiple mechanisms , 2020, Phytotherapy research : PTR.

[4]  W. Xiao,et al.  Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats. , 2020, Journal of ethnopharmacology.

[5]  Jun Xiang,et al.  Ginkgolide B protects human pulmonary alveolar epithelial A549 cells from lipopolysaccharide‐induced inflammatory responses by reducing TRIM37‐mediated NF‐κB activation , 2020, Biotechnology and applied biochemistry.

[6]  Zhiwei Feng,et al.  Insight into Ginkgo biloba L. Extract on the Improved Spatial Learning and Memory by Chemogenomics Knowledgebase, Molecular Docking, Molecular Dynamics Simulation, and Bioassay Validations , 2020, ACS omega.

[7]  J. Hai,et al.  URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion , 2019, Journal of Neuroinflammation.

[8]  Miao‐kun Sun,et al.  Rehmannioside A attenuates cognitive deficits in rats with vascular dementia (VD) through suppressing oxidative stress, inflammation and apoptosis. , 2019, Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie.

[9]  X. Niu,et al.  Anti-inflammatory effect of Yam Glycoprotein on lipopolysaccharide-induced acute lung injury via the NLRP3 and NF-κB/TLR4 signaling pathway. , 2019, International immunopharmacology.

[10]  Jianmin Huang,et al.  Panax notoginseng Saponins Attenuate Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Human SH-SY5Y Cells by Regulating the Expression of Inflammatory Factors through miR-155. , 2019, Biological & pharmaceutical bulletin.

[11]  Zhenzhong Wang,et al.  Antioxidant effects of ginkgolides and bilobalide against cerebral ischemia injury by activating the Akt/Nrf2 pathway in vitro and in vivo , 2019, Cell Stress and Chaperones.

[12]  Zhenguang Liu,et al.  Mechanism of Lycium barbarum polysaccharides liposomes on activating murine dendritic cells. , 2019, Carbohydrate polymers.

[13]  Peiyuan Lv,et al.  FoxO1-mediated autophagy plays an important role in the neuroprotective effects of hydrogen in a rat model of vascular dementia , 2019, Behavioural Brain Research.

[14]  Soo-Jin Jeong,et al.  Hwangryunhaedok-Tang Exerts Neuropreventive Effect on Memory Impairment by Reducing Cholinergic System Dysfunction and Inflammatory Response in a Vascular Dementia Rat Model , 2019, Molecules.

[15]  Rui Zhang,et al.  Cardioprotection of Ginkgolide B on Myocardial Ischemia/Reperfusion-Induced Inflammatory Injury via Regulation of A20-NF-κB Pathway , 2018, Front. Immunol..

[16]  S. Khoshnam,et al.  Memory deficits and hippocampal inflammation in cerebral hypoperfusion and reperfusion in male rats: Neuroprotective role of vanillic acid , 2018, Life sciences.

[17]  M. Akhtar,et al.  Betulinic acid, a natural PDE inhibitor restores hippocampal cAMP/cGMP and BDNF, improve cerebral blood flow and recover memory deficits in permanent BCCAO induced vascular dementia in rats , 2018, European journal of pharmacology.

[18]  Xuezhong Zhou,et al.  Neuroprotective effects of Ginkgo biloba extract and Ginkgolide B against oxygen–glucose deprivation/reoxygenation and glucose injury in a new in vitro multicellular network model , 2018, Frontiers of Medicine.

[19]  Lijia Xu,et al.  In Silico Investigation of the Pharmacological Mechanisms of Beneficial Effects of Ginkgo biloba L. on Alzheimer’s Disease , 2018, Nutrients.

[20]  Se Jin Park,et al.  Blockade of platelet-activating factor receptor attenuates abnormal behaviors induced by phencyclidine in mice through down-regulation of NF-κB , 2018, Brain Research Bulletin.

[21]  Shuntaro Ikeda,et al.  Predicting outcome of Morris water maze test in vascular dementia mouse model with deep learning , 2018, PloS one.

[22]  T. Kohlmann,et al.  Similar treatment outcomes with Ginkgo biloba extract EGb 761 and donepezil in Alzheimer’s dementia in very old age: A retrospective observational study , 2018, International journal of clinical pharmacology and therapeutics.

[23]  R. Kalaria,et al.  The pathology and pathophysiology of vascular dementia , 2017, Neuropharmacology.

[24]  P. Gorelick,et al.  Pharmacotherapy for Vascular Cognitive Impairment , 2017, CNS Drugs.

[25]  Eric E. Smith,et al.  Clinical presentations and epidemiology of vascular dementia. , 2017, Clinical science.

[26]  F. Guimarães,et al.  Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia , 2017, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[27]  Florian J. Gerich,et al.  Astroglial NF-kB contributes to white matter damage and cognitive impairment in a mouse model of vascular dementia , 2016, Acta neuropathologica communications.

[28]  Ming Lu,et al.  Ginkgolide B Protects Against Ischemic Stroke Via Modulating Microglia Polarization in Mice , 2016, CNS neuroscience & therapeutics.

[29]  Chenyun He,et al.  TLR4-MyD88-TRAF6-TAK1 Complex-Mediated NF-κB Activation Contribute to the Anti-Inflammatory Effect of V8 in LPS-Induced Human Cervical Cancer SiHa Cells , 2016, Inflammation.

[30]  John T O'Brien,et al.  Vascular dementia , 2015, The Lancet.

[31]  C. Iadecola,et al.  The Pathobiology of Vascular Dementia , 2013, Neuron.

[32]  Z. Qin,et al.  Inhibition of NF-κB activation is associated with anti-inflammatory and anti-apoptotic effects of Ginkgolide B in a mouse model of cerebral ischemia/reperfusion injury. , 2012, European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences.

[33]  Nirmal Singh,et al.  Defensive effect of natrium diethyldithiocarbamate trihydrate (NDDCT) and lisinopril in DOCA–salt hypertension-induced vascular dementia in rats , 2012, Psychopharmacology.

[34]  Hao Wang,et al.  Effect of ginkgolide B on striatal extracellular amino acids in middle cerebral artery occluded rats. , 2011, Journal of ethnopharmacology.

[35]  S. Pendlebury,et al.  Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis , 2009, The Lancet Neurology.

[36]  L. Pantoni Treatment of vascular dementia: evidence from trials with non-cholinergic drugs , 2004, Journal of the Neurological Sciences.