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• Two new compounds were isolated from the stem barks of Syringa pinnatifolia. • Alashinols I and J (1a and 1b) features an unusual carbon skeleton. • The absolute configurations were determined by ECD calculations. • Compounds 1a and 1b showed protection of anti-oxidative stress in H9c2 cells. Two novel phenols, alashinols I and J (1a and 1b), which are enantiomers, were isolated from the stem bark of Syringa pinnatifolia and possess unusual carbon skeletons. The structures were elucidated based on NMR and MS data analyses, and their absolute configurations were assigned by ECD calculations. Additionally, 1a and 1b were moderately effective at inhibiting oxidative stress-induced injury to H9c2 cardiomyocytes at concentrations of 40 and 80 μM, respectively, and 1a also shown protective effect against hypoxia-induced injury to H9c2 cells at a concentration of 40 μM. [ABSTRACT FROM AUTHOR]

Background: Zerumbone (ZER) is a humulane sesquiterpene isolated from Syringa pinnatifolia Hemsl., a representative Mongolian herbal medicine that is used to treat cardiovascular diseases. Cardiac fibrosis is a common pathological process in cardiovascular disease that results from the excessive accumulation of extracellular matrix (ECM), and the transforming growth factor (TGF)-β/Smad pathway is a canonical signaling pathway that directly induces expressions of ECM-related genes. Currently, the cardioprotective effect and underlying mechanisms of ZER on the inhibition of cardiac fibrosis are not well known.Purpose: To explore the cardioprotective properties and pharmacological mechanism of ZER against cardiac fibrosis via the TGF-β1/Smad signaling pathway.Methods: Myocardial infarction (MI) model was induced by ligation of the left anterior descending coronary artery in ICR mice. The mice were randomly divided into six groups: sham, model, low-dose ZER (ZER-L), medium-dose ZER (ZER-M), high-dose ZER (ZER-H) and fosinopril. Mice in each group were intragastrically administered treatments for 21 days, and cardiac function was evaluated by 2D echocardiography. The pathological structure of the heart was examined by hematoxylin and eosin (HE) and Masson staining. Content of collagen I and collagen III were assessed by immunofluorescence methods. The inhibitory effect of ZER on TGF-β1 protein expression was predicted by molecular docking technology. Reverse transcriptase polymerase chain reaction (RT-PCR) and western blotting were used to measure the levels of genes and proteins expressed in the TGF-β1/Smad signaling pathway and MMPs. TGF-β1-treated cardiac fibroblasts (CFs) of neonatal SD rats were adopted for in vitro studies.Results: Cardiac ejection fraction (EF) and fractional shortening (FS) in the model group were markedly decreased compared with those in the sham group, indicating that the MI model was successfully established. ZER and fosinopril elevated EF and FS values, suggesting cardioprotective effects. Pathological staining and immunofluorescence analysis showed that the content of collagen I and collagen III increased in the cardiac tissue of mice in model group, while ZER treatment obviously reduced collagen levels. The molecular docking simulations predicted the hydrophobic interactions between ZER and TGF-β1. In addition, the expression of TGF-β1, p-Smad2/3 and MMPs in the ZER treatment group was significantly decreased compared with the model group. In vitro studies further confirmed that α-smooth muscle actin (α-SMA) and p-Smad2/3 increased markedly in cardiac fibroblasts after incubation with TGF-β1, and treatment with ZER suppressed the expression of α-SMA and TGF-β1 downstream proteins in cardiac fibroblasts.Conclusion: ZER rescues cardiac function by attenuating cardiac fibrosis, and the antifibrotic effect may be mediated by blocking the TGF-β1/Smad pathway. [ABSTRACT FROM AUTHOR]