1. Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats.
- Author
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Li, Xiang, Huang, Liangliang, Liu, Ge, Fan, Wenxiang, Li, Binbin, Liu, Rui, Wang, Ziyu, Fan, Qiru, Xiao, Wei, Li, Yunman, and Fang, Weirong
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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 - 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]
- Published
- 2020
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