Liquiritin Protects Against Cardiac Fibrosis After Myocardial Infarction by Inhibiting CCL5 Expression and the NF-κB Signaling Pathway

Abstract

Xue Han,1,* Yakun Yang,1,* Muqing Zhang,2,3 Li Li,4 Yucong Xue,2 Qingzhong Jia,4 Xiangting Wang,2,5 Shengjiang Guan3,6 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 2College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 3Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China; 4School of Pharmacy, Hebei Medical University, Shijiazhuang, People’s Republic of China; 5Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, People’s Republic of China; 6School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiangting Wang, College of Integrative Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China, Email [email protected] Shengjiang Guan, Affiliated Hospital, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, People’s Republic of China, Email [email protected]: Despite significant advances in interventional treatment, myocardial infarction (MI) and subsequent cardiac fibrosis remain major causes of high mortality worldwide. Liquiritin (LQ) is a flavonoid extract from licorice that possesses a variety of pharmacological properties. However, to our knowledge, the effects of LQ on myocardial fibrosis after MI have not been reported in detail. The aim of our research was to explore the potential role and mechanism of LQ in MI-induced myocardial damage.Methods: The MI models were established by ligating the left anterior descending branch of the coronary artery. Next, rats were orally administered LQ once a day for 14 days. Biochemical assays, histopathological observations, ELISA, and Western blotting analyses were then conducted.Results: LQ improved the heart appearance and ECG, decreased cardiac weight index and reduced levels of cardiac-specific markers such as CK, CK-MB, LDH, cTnI and BNP. Meanwhile, LQ reduced myocardial infarct size and improved hemodynamic parameters such as LVEDP, LVSP and ±dp/dtmax. Moreover, H&E staining showed that LQ attenuated the pathological damage caused by MI. Masson staining showed that LQ alleviated myocardial cell disorder and fibrosis while reducing collagen deposition. LQ also decreased the levels of oxidative stress and inflammation. Western blotting demonstrated that LQ significantly down-regulated the expressions of Collagen I, Collagen III, TGF-β 1, MMP-9, α-SMA, CCL5, and p-NF-κB.Conclusion: LQ protected against myocardial fibrosis following MI by improving cardiac function, and attenuating oxidative damage and inflammatory response, which may be associated with inhibition of CCL5 expression and the NF-κB pathway.Keywords: liquiritin, cardiac fibrosis, myocardial infarction, CCL5 expression, NF-κB signaling pathway

Keywords

• liquiritin
• cardiac fibrosis
• myocardial infarction
• ccl5 expression
• nf-κb signaling pathway