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Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion.
J Neuroinflammation. 2010 Sep 14; 7:55.JN

Abstract

BACKGROUND

Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of Lamiophlomis rotata (Benth.) Kudo. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo.

METHODS

For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h.

RESULTS

ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation.

CONCLUSION

These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway.

Authors+Show Affiliations

Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

20836895

Citation

Jiang, Wanglin, et al. "Inhibition of Nuclear factor-κB By 6-O-acetyl Shanzhiside Methyl Ester Protects Brain Against Injury in a Rat Model of Ischemia and Reperfusion." Journal of Neuroinflammation, vol. 7, 2010, p. 55.
Jiang W, Zhang S, Fu F, et al. Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion. J Neuroinflammation. 2010;7:55.
Jiang, W., Zhang, S., Fu, F., Zhu, H., & Hou, J. (2010). Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion. Journal of Neuroinflammation, 7, 55. https://doi.org/10.1186/1742-2094-7-55
Jiang W, et al. Inhibition of Nuclear factor-κB By 6-O-acetyl Shanzhiside Methyl Ester Protects Brain Against Injury in a Rat Model of Ischemia and Reperfusion. J Neuroinflammation. 2010 Sep 14;7:55. PubMed PMID: 20836895.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inhibition of nuclear factor-κB by 6-O-acetyl shanzhiside methyl ester protects brain against injury in a rat model of ischemia and reperfusion. AU - Jiang,Wanglin, AU - Zhang,Shuping, AU - Fu,Fenghua, AU - Zhu,Haibo, AU - Hou,Jian, Y1 - 2010/09/14/ PY - 2010/06/02/received PY - 2010/09/14/accepted PY - 2010/9/15/entrez PY - 2010/9/15/pubmed PY - 2010/12/14/medline SP - 55 EP - 55 JF - Journal of neuroinflammation JO - J Neuroinflammation VL - 7 N2 - BACKGROUND: Recent studies have demonstrated an inflammatory response associated with the pathophysiology of cerebral ischemia. The beneficial effects of anti-inflammatory drugs in cerebral ischemia have been documented. When screening natural compounds for drug candidates in this category, we isolated 6-O-acetyl shanzhiside methyl ester (ND02), an iridoid glucoside compound, from the leaves of Lamiophlomis rotata (Benth.) Kudo. The objectives of this study were to determine the effects of ND02 on a cultured neuronal cell line, SH-SY5Y, in vitro, and on experimental ischemic stroke in vivo. METHODS: For TNF-α-stimulated SH-SY5Y cell line experiments in vitro, SH-SY5Y cells were pre-incubated with ND02 (20 μM or 40 μM) for 30 min and then incubated with TNF-α (20 ng/ml) for 15 min. For in vivo experiments, rats were subjected to middle cerebral artery occlusion (MCAO) for 1 h followed by reperfusion for 23 h. RESULTS: ND02 treatment of SH-SY5Y cell lines blocked TNF-α-induced nuclear factor-κB (NF-κB) and IκB-α phosphorylation and increased Akt phosphorylation. LY294002 blocked TNF-α-induced phosphorylation of Akt and reduced the phosphorylation of both IκB-α and NF-κB. At doses higher than 10 mg/kg, ND02 had a significant neuroprotective effect in rats with cerebral ischemia and reperfusion (I/R). ND02 (25 mg/kg) demonstrated significant neuroprotective activity even after delayed administration 1 h, 3 h and 5 h after I/R. ND02, 25 mg/kg, attenuated histopathological damage, decreased cerebral Evans blue extravasation, inhibited NF-κB activation, and enhanced Akt phosphorylation. CONCLUSION: These data show that ND02 protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and that these protective effects may be due to blocking of neuronal inflammatory cascades through an Akt-dependent NF-κB signaling pathway. SN - 1742-2094 UR - https://www.unboundmedicine.com/medline/citation/20836895/Inhibition_of_nuclear_factor_κB_by_6_O_acetyl_shanzhiside_methyl_ester_protects_brain_against_injury_in_a_rat_model_of_ischemia_and_reperfusion_ L2 - https://jneuroinflammation.biomedcentral.com/articles/10.1186/1742-2094-7-55 DB - PRIME DP - Unbound Medicine ER -