Isoliquiritigenin attenuates diabetic cardiomyopathy via inhibition of hyperglycemia-induced inflammatory response and oxidative stress

• Published in: Phytomedicine (Stuttgart) Vol. 78; p. 153319
• Main Authors: Gu, Xuemei, Shi, Yujuan, Chen, Xiaojun, Sun, Zijia, Luo, Wu, Hu, Xiang, Jin, Ge, You, Shengban, Qian, Yuanyuan, Wu, Wenjun, Liang, Guang, Wu, Gaojun, Chen, Zimiao, Chen, Xiong
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01-11-2020
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Antioxidants - pharmacology; Apoptosis - drug effects; Cardiomyopathy; Cardiotonic Agents - pharmacology; Chalcones - pharmacology; Diabetes; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetic Cardiomyopathies - drug therapy; Glucose - metabolism; Glucose - pharmacology; Hyperglycemia - drug therapy; Hyperglycemia - physiopathology; Inflammation; Isoliquiritigenin; Male; Mice, Inbred C57BL; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Myocytes, Cardiac - pathology; NF-E2-Related Factor 2 - metabolism; Oxidative stress; Oxidative Stress - drug effects; Rats; Reactive Oxygen Species - metabolism; Streptozocin; DHE; Oxidative stress; Ef; ANP; Cardiomyopathy; DMSO; Ck; CK-MB; GaaAPDH; Er; FS; BSA; DCFH-Da; DMEM; FBS; Isoliquiritigenin; DAPI; Inflammation; DCM; 3-nt; CMC-Na; Bax; Bcl2; Diabetes; ERK
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2020.153319

•ISL reduced the high glucose-mediated inflammation and ROS in H9c2 cells.•ISL attenuated the inflammation and ROS -mediated cardiac injury.•ISL exhibited anti-inflammatory effects via inactivation of MAPKs.•ISL inhibited the overproduction of ROS via induction of Nrf2.•MAPKs/Nrf2 may be novel targets in diabetic cardiomyopathy treatment.
Inflammation and oxidative stress play essential roles in the occurrence and progression of diabetic cardiomyopathy (DCM). Isoliquiritigenin (ISL), a natural chalcone, exhibits strong anti-inflammatory and antioxidant activities.
In this study, we aimed to investigate the protective effects of ISL on DCM using high glucose (HG)-challenged cultured cardiomyocytes and streptozotocin (STZ)-induced diabetic mice.
Embryonic rat heart-derived H9c2 cells challenged with a high concentration of glucose were used to evaluate the anti-inflammatory and antioxidant effects of ISL. STZ-induced diabetic mice were used to study the effects of ISL in DCM in vivo. Furthermore, cardiac fibrosis, hypertrophy, and apoptosis were explored both in vitro and in vivo.
ISL effectively inhibited HG-induced hypertrophy, fibrosis, and apoptosis probably by alleviating the inflammatory response and oxidative stress in H9c2 cells. Results from in vivo experiments showed that ISL exhibited anti-inflammatory and antioxidant stress activities that were characterized by the attenuation of cardiac hypertrophy, fibrosis, and apoptosis, which resulted in the maintenance of cardiac function. The protective effects of ISL against inflammation and oxidative stress were mediated by the inhibition of mitogen-activated protein kinases (MAPKs) and induction of nuclear factor-erythroid 2 related factor 2 (Nrf2) signaling pathway, respectively.
Our results provided compelling evidence that ISL, by virtue of neutralizing excessive inflammatory response and oxidative stress, could be a promising agent in the treatment of DCM. Targeting the MAPKs and Nrf2 signaling pathway might be an effective therapeutic strategy for the prevention and treatment of DCM.
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