Glycyrrhetinic acid alleviates atrial fibrillation by inhibiting the expression of PIM1

Abstract

AbstractGlycyrrhetinic acid (GA) is known to exert a cardioprotective effect, while its mechanism in atrial fibrillation (AF) remains poorly defined. Accordingly, isoprenaline (ISO) was applied to establish the rat AF model, and then GA (5, 10, and 20 mg/kg/day) was administrated to these rats for a total of 21 days. The fibrosis and pathological conditions of rat atrial tissues were observed. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was adopted to calculate the levels of proto‐oncogene serine/threonine‐protein kinase Pim1 (PIM1) and Interleukin (IL)‐4/6/13/17. For in‐vitro experiments, isolated cardiac fibroblasts received the transfection with PIM1‐specific overexpression plasmid or siPIM1 and the treatment with ISO. Subsequently, cell viability was gauged by cell counting kit‐8 assay. The protein levels of alpha‐smooth muscle actin (α‐SMA), collagen I and III, transforming growth factor‐beta1 (TGF‐β1) and mothers against decapentaplegic homolog 7 (Smad7) were measured by western blot. GA led to the shortened duration of AF and alleviated myocardial fibrosis and atrial tissue lesions in ISO‐treated AF rats in vivo. Meanwhile, GA inhibited the expressions of PIM1 and IL‐4/6/13/17 in the atrial tissue of AF model rats. In the meantime, enhanced cell viability, inhibited expressions of PIM1, IL‐4/6/13/17, α‐SMA, collagen‐I, collagen‐III and TGF‐β1, and promoted Smad7 expression were observable in ISO‐treated cardiac fibroblasts in vitro. Oppositely, the effects of GA were reversed following PIM1 overexpression, while knockdown of PIM1 enhanced the effects of GA on cardiac fibroblasts. Collectively speaking, GA alleviates AF through suppressing the expression of PIM1.