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Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation.
Free Radic Biol Med. 2009 Aug 01; 47(3):229-40.FR

Abstract

Many natural polyphenolic compounds have been shown to attenuate reactive oxygen/nitrogen species (ROS/RNS) formation and protect against ischemia/reperfusion injury both in vitro and in vivo. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum, exhibits antioxidative and anti-inflammatory effects. Here, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD-R) and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of TSG on ischemia/reperfusion brain injury and the related mechanisms. We demonstrated that OGD-R-induced neuronal injury, intracellular ROS generation, and mitochondrial membrane potential dissipation were reversed by TSG. The elevation of H2O2-induced [Ca2+]i was also attenuated by TSG. Inhibition of the c-Jun N-terminal kinase (JNK) and Bcl-2 family-related apoptotic signaling pathway was involved in the neuroprotection afforded by TSG. Meanwhile, TSG inhibited iNOS mRNA expression induced by OGD-R, which may be mediated by the activation of SIRT1 and inhibition of NF-kappaB activation. In vivo studies further demonstrated that TSG significantly reduced the brain infarct volume and the number of positive cells by TUNEL staining in the cerebral cortex compared to the MCAO group. Our study indicates that TSG protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways.

Authors+Show Affiliations

Department of Pharmacology, Tongji Medical College, Wuhan, Hubei 430030, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19272442

Citation

Wang, Ting, et al. "Protection By Tetrahydroxystilbene Glucoside Against Cerebral Ischemia: Involvement of JNK, SIRT1, and NF-kappaB Pathways and Inhibition of Intracellular ROS/RNS Generation." Free Radical Biology & Medicine, vol. 47, no. 3, 2009, pp. 229-40.
Wang T, Gu J, Wu PF, et al. Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. Free Radic Biol Med. 2009;47(3):229-40.
Wang, T., Gu, J., Wu, P. F., Wang, F., Xiong, Z., Yang, Y. J., Wu, W. N., Dong, L. D., & Chen, J. G. (2009). Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. Free Radical Biology & Medicine, 47(3), 229-40. https://doi.org/10.1016/j.freeradbiomed.2009.02.027
Wang T, et al. Protection By Tetrahydroxystilbene Glucoside Against Cerebral Ischemia: Involvement of JNK, SIRT1, and NF-kappaB Pathways and Inhibition of Intracellular ROS/RNS Generation. Free Radic Biol Med. 2009 Aug 1;47(3):229-40. PubMed PMID: 19272442.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protection by tetrahydroxystilbene glucoside against cerebral ischemia: involvement of JNK, SIRT1, and NF-kappaB pathways and inhibition of intracellular ROS/RNS generation. AU - Wang,Ting, AU - Gu,Jun, AU - Wu,Peng-Fei, AU - Wang,Fang, AU - Xiong,Zhe, AU - Yang,Yuan-Jian, AU - Wu,Wen-Ning, AU - Dong,Ling-Dan, AU - Chen,Jian-Guo, Y1 - 2009/03/09/ PY - 2008/11/19/received PY - 2008/12/21/revised PY - 2009/02/11/accepted PY - 2009/3/11/entrez PY - 2009/3/11/pubmed PY - 2009/12/16/medline SP - 229 EP - 40 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 47 IS - 3 N2 - Many natural polyphenolic compounds have been shown to attenuate reactive oxygen/nitrogen species (ROS/RNS) formation and protect against ischemia/reperfusion injury both in vitro and in vivo. 2,3,5,4'-tetrahydroxystilbene-2-O-beta-D-glucoside (TSG), an active component of the rhizome extract from Polygonum multiflorum, exhibits antioxidative and anti-inflammatory effects. Here, we used an in vitro ischemic model of oxygen-glucose deprivation followed by reperfusion (OGD-R) and an in vivo ischemic model of middle cerebral artery occlusion (MCAO) to investigate the neuroprotective effects of TSG on ischemia/reperfusion brain injury and the related mechanisms. We demonstrated that OGD-R-induced neuronal injury, intracellular ROS generation, and mitochondrial membrane potential dissipation were reversed by TSG. The elevation of H2O2-induced [Ca2+]i was also attenuated by TSG. Inhibition of the c-Jun N-terminal kinase (JNK) and Bcl-2 family-related apoptotic signaling pathway was involved in the neuroprotection afforded by TSG. Meanwhile, TSG inhibited iNOS mRNA expression induced by OGD-R, which may be mediated by the activation of SIRT1 and inhibition of NF-kappaB activation. In vivo studies further demonstrated that TSG significantly reduced the brain infarct volume and the number of positive cells by TUNEL staining in the cerebral cortex compared to the MCAO group. Our study indicates that TSG protects against cerebral ischemia/reperfusion injury through multifunctional cytoprotective pathways. SN - 1873-4596 UR - https://www.unboundmedicine.com/medline/citation/19272442/Protection_by_tetrahydroxystilbene_glucoside_against_cerebral_ischemia:_involvement_of_JNK_SIRT1_and_NF_kappaB_pathways_and_inhibition_of_intracellular_ROS/RNS_generation_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(09)00088-4 DB - PRIME DP - Unbound Medicine ER -