Objective: To investigate anti-gastric cancer effects of gingerenone A (GA) and explore its association with the PI3K/Akt/FOXO1 signaling pathway, autophagy, and apoptosis.
Methods: Cell viabilities were detected via CCK-8 assay. Proliferation, migration, invasion, and apoptosis were assessed by colony formation, EdU, Transwell assays, and flow cytometry. Autophagy, mitochondrial dysfunction, and apoptosis were detected via Western blot, immunofluorescence, and staining assays. Inhibitors and siFOXO1 were used for molecular mechanism studies. An MKN-45 xenograft model was used to evaluate in vivo efficacy and safety.
Results: GA reduced gastric cancer cell proliferation, migration, and invasion, and promoted apoptosis, with MKN-45 cells being most sensitive. GA induced autophagy-related changes, mitochondrial dysfunction, and apoptosis-related changes, with suppression of PI3K/Akt signaling and reduced inhibitory phosphorylation of FOXO1; these effects were attenuated by the pharmacological and genetic interventions. In vivo, GA inhibited tumor growth without notable histopathological damage to major organs at the tested doses.
Conclusions: GA may exert anti-gastric cancer effects via PI3K/Akt/FOXO1 signaling pathway, with autophagy-related changes and apoptosis-related responses. It could be a candidate compound for gastric cancer therapy.

Objective: To evaluate the cardioprotective potential of Caesalpinia digyna root extract (CDRE) and its major bioactive constituent, bergenin, against isoproterenol (ISO)-induced myocardial infarction (MI) in rats. Methods: CDRE was prepared via methanolic extraction and standardized using RP-HPLC. MI was induced in Sprague-Dawley rats by ISO administration. Animals were pretreated with the extract and bergenin prior to the ISO challenge. Cardioprotective effects were assessed by measuring serum cardiac biomarkers, evaluating myocardial hypertrophy, inflammation, and fibrosis, and determining the expression of Nrf2, FGF21, NF-κB p65, and brain natriuretic peptide. Results: Pretreatment with the CDRE and bergenin significantly attenuated ISO-induced MI, as evidenced by reduced creatine kinase-MB and lactate dehydrogenase levels and improved histopathological architecture. CDRE and bergenin markedly alleviated myocardial hypertrophy, inflammatory infiltration, and fibrotic changes. They also upregulated Nrf2 and FGF21 expression, and downregulated NF-κB p65 and brain natriuretic peptide expression. Conclusions: The findings demonstrate significant cardioprotective effects of CDRE and bergenin, by modulating oxidative stress, inflammation, and fibrotic pathways, validating its traditional use for the management of MI.

Objective: To explore whether curcumin alleviates transverse aortic constriction (TAC)-induced heart failure by modulating the DNMT-Sfrp1-Wnt/β-catenin signaling. Methods: Male C57BL/6J mice underwent TAC or sham surgery and then received vehicle or curcumin at 50, 100, or 200 mg/kg/day for 4 weeks. Cardiac structure and performance were evaluated by echocardiography together with invasive hemodynamics, while apoptosis, DNMT activity, Sfrp1 promoter methylation, and Wnt/β-catenin signaling were examined using TUNEL staining, bisulfite sequencing, quantitative RT-PCR, and Western blotting. Results: Compared with untreated TAC mice, curcumin preserved left ventricular systolic function, lowered NT-proBNP, and mitigated ventricular enlargement. It also reduced cardiomyocyte apoptosis, decreased Bax and cleaved caspase-3, and increased Bcl-2. Furthermore, curcumin downregulated Dnmt1, Dnmt3a, and Dnmt3b, reduced total DNMT activity, alleviated methylation of the Sfrp1 promoter, restored Sfrp1 expression, and diminished nuclear β-catenin as well as c-Myc and cyclin D1. Conclusions: Curcumin mitigates TAC-induced cardiac dysfunction and adverse remodeling by modulating the DNMT-Sfrp1-Wnt/β-catenin pathway. These data indicate that curcumin may act as an epigenetic regulator in pathological cardiac remodeling.