MHY1485

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in clinic, and type 2 diabetes mellitus (T2DM) is an independent risk factor for AF. Salidroside (Sal), the active ingredient of the Rhodiola rosea, has hypoglycemic, anti-inflammatory, anti-fibrotic and anti-arrhythmic effects. The aim of this study is to investigate the effects and underlying molecular mechanisms of Sal on T2DM associated atrial inflammation and the pathogenesis of AF. In the in vivo study, T2DM mice model was established by high-fat diet and intraperitoneal injection of streptozotocin (STZ). Sal (25 mg/kg/d, 50 mg/kg/d, and 100 mg/kg/d) was administered orally for 4 weeks. T2DM caused atrial electrical and structural remodeling and significantly increased the susceptibility of AF. Meanwhile, mTOR-STAT3-MCP-1 signaling and inflammatory markers were also significantly enhanced in diabetic atria. However, Sal dose-dependently ameliorated cardiac dysfunction, mitigated atrial structural and electrical remodeling, and reduced atrial inflammation. Moreover, Sal-treated group exhibited remarkably down-regulated activity of mTOR-STAT3-MCP-1 pathway, and decreased atrial monocyte/macrophage infiltration. In palmitic acid (PA)-challenged HL-1 cells, Sal attenuated cytotoxicity, downregulated the expressions of TNF-α, IL-6, MCP-1, and inhibited the activation of mTOR-STAT3 signaling. However, co-treatment with MHY1485 (a mTOR agonist) reversed these effects. Taken together, the present study demonstrates that Sal treatment decreases the susceptibility of AF in diabetic mice by reducing mTOR-STAT3-MCP-1 signaling and atrial monocyte/macrophage infiltration. Sal treatment may represent a novel preventive therapy for cardiac arrhythmia and atrial fibrillation in diabetic patients.

Non-Small Cell Lung Cancer (NSCLC), a prevalent type of lung cancer, has a poor prognosis and contributes to a high mortality rate. Agrimonolide, which belongs to the Rosaceae family, possesses various biomedical activities. This study aimed to explore the efficacy and mechanism of agrimonolide in NSCLC.

The viability, proliferation, and tumor-forming ability of A549 cells were detected using the Cell Counting Kit-8 assay (CCK-8) assay, EdU staining, and colony formation assay. The cell cycle was detected using flow cytometry. Cell migration and invasion were detected using wound healing and transwell assays. Western blot was used to detect Epithelial-Mesenchymal Transition (EMT)-, ferroptosis-, and mechanistic targets of rapamycin (mTOR) signaling pathway-related proteins. Lipid peroxidation was detected using the thiobarbituric acid reactive substances (TBARS) assay kit, while lipid Reactive Oxygen Species (ROS) was detected using a BODIPY 581/591 C11 kit. The level of Fe2+ was detected using corresponding assay kits.

In this study, agrimonolide with varying concentrations (10, 20, and 40 μM) could inhibit the proliferation, induce cycle arrest, suppress metastasis, induce ferroptosis, and block the mTOR signaling pathway in NSCLC cells. To further reveal the mechanism of agrimonolide associated with the mTOR signaling pathway in NSCLC, mTOR agonist MHY1485 (10 μM) was used to pre-treat A549 cells, and functional experiments were conducted again. It was found that the protective effects of AM on NSCLC cells were all partially abolished by MHY1485 pre-treatment.

Agrimonolide inhibited the malignant progression of NSCLC and induced ferroptosis by blocking the mTOR signaling pathway, thus indicating the potential of agrimonolide as a prospective candidate for treating NSCLC.