Liquiritin Attenuates Lipopolysaccharides-Induced Cardiomyocyte Injury via an AMP-Activated Protein Kinase-Dependent Signaling Pathway

Abstract

Background: Liquiritin (LIQ) is a traditional Chinese medicine that has been reported to regulate inflammation, oxidative stress and cell apoptosis. However, the beneficial effects of LIQ in lipopolysaccharides (LPS)-induced septic cardiomyopathy (SCM) has not been reported. The primary goal of this study was to investigate the effects of LIQ in LPS-induced SCM model.Methods: Mice were pre-treated with LIQ for 7 days before they were injected with LPS (10 mg/kg) for inducing SCM model. Echocardiographic analysis was used to evaluate cardiac function after 12 h of LPS injection. Thereafter, mice were sacrificed to collect hearts for molecular and histopathologic assays by RT-PCR, western-blots, immunohistochemical and terminal deoxynucleotidyl transferase nick-end labeling (TUNEL) staining analysis respectively. AMPKα2 knockout (AMPKα2−/−) mice were used to elucidate the mechanism of LIQ Neonatal rat cardiomyocytes (NRCMs) treated with or without LPS were used to further investigate the roles and mechanisms of LIQ in vitro experiments.Results: LIQ administration attenuated LPS-induced mouse cardiac dysfunction and reduced mortality, based upon the restoration of EF, FS, LVEDs, heart rate, dp/dt max and dp/dt min deteriorated by LPS treatment. LIQ treatment also reduced mRNA expression of TNFα, IL-6 and IL-1β, inhibited inflammatory cell migration, suppressed cardiac oxidative stress and apoptosis, and improved metabolism. Mechanistically, LIQ enhanced the phosphorylation of AMP-activated protein kinase α2 (AMPKα2) and decreased the phosphorylation of mTORC1, IκBα and NFκB/p65. Importantly, the beneficial roles of LIQ were not observed in AMPKα2 knockout model, nor were they observed in vitro model after inhibiting AMPK activity with an AMPK inhibitor.Conclusion: We have demonstrated that LIQ exerts its protective effects in an SCM model induced by LPS administration. LIQ reduced inflammation, oxidative stress, apoptosis and metabolic alterations via regulating AMPKα2 dependent signaling pathway. Thus, LIQ might be a potential treatment or adjuvant for SCM treatment.

The Material Basis and Mechanism of Xuefu Zhuyu Decoction in Treating Stable Angina Pectoris and Unstable Angina Pectoris

“…Also, Kanzonol B (MOL004815) could regulate the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in microglia [ 65 ]. Among the particularly excellent compounds for unstable angina, liquiritin (MOL004903) reduces mRNA expression of TNF α , IL-6, and IL-1 β , inhibits inflammatory cell migration, suppresses oxidative stress and apoptosis in the heart, and improves metabolism [ 66 ]. Sigmoidin-B (MOL004935), which has anti-inflammatory effects, is also present here in unstable angina.…”

Liquiritin Attenuates Angiotensin II-Induced Cardiomyocyte Hypertrophy via ATE1/TAK1-JNK1/2 Pathway

“…Yi et al [ 31 ] demonstrated that the protective effects of LIQ on myocardial tissue in aconitine induced cardiotoxicity occurred by synergistically inhibiting CaM expression and Cx43 dephosphorylation. Another study indicated that LIQ exerts cardioprotective effects by reducing oxidative stress, inflammation, apoptosis, and metabolic alteration by regulating the AMPK α 2-dependent signaling pathway in LPS induced cardiomyocyte injury [ 17 ]. In addition, Vu et al [ 32 ] confirmed that LIQ could inhibit hypoxia/reoxygenation- (HR-) induced H9c2 cell death by preserving mitochondria and elevating the mitochondrial Ca 2+ level.…”

“…Another study indicated that LIQ exerts cardioprotective effects by reducing oxidative stress, inflammation, apoptosis, and metabolic alteration by regulating the AMPKα2-dependent signaling pathway in LPS induced cardiomyocyte injury [17]. In addition, Vu et al [32] confirmed that LIQ could inhibit hypoxia/reoxygenation-(HR-) induced H9c2 cell death by preserving mitochondria and elevating the mitochondrial Ca 2+ level.…”

“…LIQ, the main flavone compound derived from licorice, exhibits anti-inflammatory, antioxidant, antiapoptotic, and cardioprotective activities [13][14][15][16]. Previous studies indicated that LIQ could alleviate myocardial fibrosis and attenuate myocardial damage [17,18]. Although licorice exhibits antihypertrophic activity, the antihypertrophic effect of its main component LIQ and the mechanism underlying the same remain unclear.…”

Plant-Derived Compounds as Promising Therapeutics for Vitiligo

“…ex DC. ( Du et al, 2021 ; Mou et al, 2021 ). They have many biological activities, such as antiviral, anti-inflammatory, anti-oxidation, anti-tumor and so on ( Pastorino et al, 2018 ).…”