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Blockage of ROS and NF-κB-mediated inflammation by a new chalcone L6H9 protects cardiomyocytes from hyperglycemia-induced injuries.
Biochim Biophys Acta. 2015 Jul; 1852(7):1230-41.BB

Abstract

Increased oxidative stress and cardiac inflammation have been implicated in the pathogenesis of diabetic cardiomyopathy (DCM). We previously found that a novel chalcone derivative, L6H9, was able to reduce LPS-induced inflammatory response in macrophages. This study was designed to investigate its protective effects on DCM and the underlying mechanisms. H9C2 cells were cultured with DMEM containing 33 mmol/L of glucose in the presence or absence of L6H9. Pretreatment with L6H9 significantly reduced high glucose-induced inflammatory cytokine expression, ROS level increase, mitochondrial dysfunction, cell apoptosis, fibrosis, and hypertrophy in H9c2 cells, which may be mediated by NF-κB inhibition and Nrf2 activation. In mice with STZ-induced diabetes, oral administration of L6H9 at 20 mg/kg/day for 8 weeks significantly decreased the cardiac cytokine and ROS level, accompanied by decreasing cardiac apoptosis and hypertrophy, and, finally, improved histological abnormalities and fibrosis, without affecting the hyperglycemia. L6H9 also attenuated the diabetes-induced NF-κB activation and Nrf2 decrease in diabetic hearts. These results strongly suggest that L6H9 may have great therapeutic potential in the treatment of DCM via blockage of inflammation and oxidative stress. This study also provides a deeper understanding of the regulatory role of Nrf2 and NF-κB in DCM, indicating that they may be important therapeutic targets for diabetic complications.

Authors+Show Affiliations

Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China; Department of Cardiology, the 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.Department of Cardiology, the 2nd Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.Department of Cardiology, the 5th Affiliated Hospital of Wenzhou Medical University, Lishui, Zhejiang, China.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: yi_wang1122@163.com.Chemical Biology Research Center, School of Pharmaceutical Science, Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: wzmcliangguang@163.com.

Pub Type(s)

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

Language

eng

PubMed ID

25736300

Citation

Zhong, Peng, et al. "Blockage of ROS and NF-κB-mediated Inflammation By a New Chalcone L6H9 Protects Cardiomyocytes From Hyperglycemia-induced Injuries." Biochimica Et Biophysica Acta, vol. 1852, no. 7, 2015, pp. 1230-41.
Zhong P, Wu L, Qian Y, et al. Blockage of ROS and NF-κB-mediated inflammation by a new chalcone L6H9 protects cardiomyocytes from hyperglycemia-induced injuries. Biochim Biophys Acta. 2015;1852(7):1230-41.
Zhong, P., Wu, L., Qian, Y., Fang, Q., Liang, D., Wang, J., Zeng, C., Wang, Y., & Liang, G. (2015). Blockage of ROS and NF-κB-mediated inflammation by a new chalcone L6H9 protects cardiomyocytes from hyperglycemia-induced injuries. Biochimica Et Biophysica Acta, 1852(7), 1230-41. https://doi.org/10.1016/j.bbadis.2015.02.011
Zhong P, et al. Blockage of ROS and NF-κB-mediated Inflammation By a New Chalcone L6H9 Protects Cardiomyocytes From Hyperglycemia-induced Injuries. Biochim Biophys Acta. 2015;1852(7):1230-41. PubMed PMID: 25736300.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Blockage of ROS and NF-κB-mediated inflammation by a new chalcone L6H9 protects cardiomyocytes from hyperglycemia-induced injuries. AU - Zhong,Peng, AU - Wu,Lianpin, AU - Qian,Yuanyuan, AU - Fang,Qilu, AU - Liang,Dandan, AU - Wang,Jingying, AU - Zeng,Chunlai, AU - Wang,Yi, AU - Liang,Guang, Y1 - 2015/02/28/ PY - 2014/12/04/received PY - 2015/02/20/revised PY - 2015/02/23/accepted PY - 2015/3/5/entrez PY - 2015/3/5/pubmed PY - 2015/8/28/medline KW - Chalcone derivative KW - Diabetic cardiomyopathy KW - Inflammation KW - NF-κB KW - Nrf2 KW - Oxidative stress SP - 1230 EP - 41 JF - Biochimica et biophysica acta JO - Biochim Biophys Acta VL - 1852 IS - 7 N2 - Increased oxidative stress and cardiac inflammation have been implicated in the pathogenesis of diabetic cardiomyopathy (DCM). We previously found that a novel chalcone derivative, L6H9, was able to reduce LPS-induced inflammatory response in macrophages. This study was designed to investigate its protective effects on DCM and the underlying mechanisms. H9C2 cells were cultured with DMEM containing 33 mmol/L of glucose in the presence or absence of L6H9. Pretreatment with L6H9 significantly reduced high glucose-induced inflammatory cytokine expression, ROS level increase, mitochondrial dysfunction, cell apoptosis, fibrosis, and hypertrophy in H9c2 cells, which may be mediated by NF-κB inhibition and Nrf2 activation. In mice with STZ-induced diabetes, oral administration of L6H9 at 20 mg/kg/day for 8 weeks significantly decreased the cardiac cytokine and ROS level, accompanied by decreasing cardiac apoptosis and hypertrophy, and, finally, improved histological abnormalities and fibrosis, without affecting the hyperglycemia. L6H9 also attenuated the diabetes-induced NF-κB activation and Nrf2 decrease in diabetic hearts. These results strongly suggest that L6H9 may have great therapeutic potential in the treatment of DCM via blockage of inflammation and oxidative stress. This study also provides a deeper understanding of the regulatory role of Nrf2 and NF-κB in DCM, indicating that they may be important therapeutic targets for diabetic complications. SN - 0006-3002 UR - https://www.unboundmedicine.com/medline/citation/25736300/Blockage_of_ROS_and_NF_κB_mediated_inflammation_by_a_new_chalcone_L6H9_protects_cardiomyocytes_from_hyperglycemia_induced_injuries_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0925-4439(15)00062-9 DB - PRIME DP - Unbound Medicine ER -