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Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats.
- Source :
-
Journal of Ethnopharmacology . Mar2020, Vol. 249, pN.PAG-N.PAG. 1p. - Publication Year :
- 2020
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Abstract
- Ginkgo biloba L. (Ginkgoaceae) is a traditional Chinese medicine known to treating stroke and other cardio-cerebrovascular diseases for thousands of years in China. Ginkgo diterpene lactones (GDL) attracted much attention because of their neuroprotective properties. To uncover the effects of GDL, which consist of ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), on ischemic stroke, as well as the underlying molecular mechanisms. We used middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models mimicking the process of ischemia/reperfusion in vivo and in vitro, respectively. Anticoagulant effects of GDL were investigated on platelet activating factor (PAF), arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation both in vivo and in vitro. We also evaluated the effects of GDL on lipopolysaccharide (LPS)-induced inflammatory response in primary cultured rats′ astrocytes. Infarct size, neurological deficit score, and brain edema were measured at 72 h after MCAO. Immunohistochemistry was utilized to analyze neurons necrosis and astrocytes activation. Expression of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α) and interleukin-1β (IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) and real time PCR. The levels of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) were assessed by real time PCR or Western blot. Compared with MCAO/R rats, GDL significantly reduced infarct size and brain edema, improved neurological deficit score. Meanwhile, GDL suppressed platelet aggregation, astrocytes activation, pro-inflammatory cytokines releasing, TLR4 mRNA expression and transfer of NF-κB from cytoplasm to nucleus. Furthermore, GDL alleviated OGD/R injury and LPS-induced inflammatory response in primary astrocytes, characterized by promoting cell viability, decreasing lactate dehydrogenase (LDH) activity, and inhibiting IL-1β and TNF-α releasing. In summary, GDL attenuate cerebral ischemic injury, inhibit platelet aggregation and astrocytes activation. The anti-inflammatory activity might be associated with the downregulation of TLR4/NF-κB signal pathway. Our present findings provide an innovative insight into the novel treatment of GDL in ischemic stroke therapy. Image 1 [ABSTRACT FROM AUTHOR]
- Subjects :
- *IN vitro studies
*LIPOPOLYSACCHARIDES
*CYTOKINES
*INTERLEUKINS
*TERPENES
*HERBAL medicine
*IN vivo studies
*ADENOSINE diphosphate
*NEURONS
*INFLAMMATION
*ANTI-inflammatory agents
*ANIMAL experimentation
*IMMUNOHISTOCHEMISTRY
*WESTERN immunoblotting
*GINKGO
*CELL receptors
*SIGNAL peptides
*ANTICOAGULANTS
*NF-kappa B
*RATS
*CELLULAR signal transduction
*LACTONES
*MOLECULAR biology
*BLOOD platelet activation
*GENE expression
*COMPARATIVE studies
*CELL survival
*NEUROPROTECTIVE agents
*ENZYME-linked immunosorbent assay
*TUMOR necrosis factors
*MESSENGER RNA
*NEUROGLIA
*ARACHIDONIC acid
*POLYMERASE chain reaction
*CEREBRAL ischemia
*REPERFUSION injury
*CHINESE medicine
*CYTOPLASM
*PHARMACODYNAMICS
*DISEASE complications
Subjects
Details
- Language :
- English
- ISSN :
- 03788741
- Volume :
- 249
- Database :
- Academic Search Index
- Journal :
- Journal of Ethnopharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 140848612
- Full Text :
- https://doi.org/10.1016/j.jep.2019.112365