This study investigated the cardioprotective effects of Isoliensinine, a bisbenzylisoquinoline alkaloid from Nelumbo nucifera Gaertn, and its underlying mechanisms. Spontaneous hypertensive rats (SHR) received Isoliensinine (2.5, 5, 10 mg/kg/day) or valsartan (10 mg/kg/day) for 10 weeks, with Wistar-Kyoto rats as controls. Cardiac function, histopathology, apoptosis, and transcriptomic changes were evaluated in vivo and in Angtension II (AngII)-stimulated H9c2 cardiomyocytes in vitro. Isoliensinine significantly improved left ventricular function, and ameliorated pathological cardiac damage in SHR. Transcriptomic analysis revealed that Isoliensinine reversed 111 up-regulated and 127 down-regulated transcripts in cardiac tissues of SHR, with enrichment of pathways related to apoptosis and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Both in vivo and in vitro experiments confirmed that Isoliensinine reduced cardiomyocyte apoptosis and restored PI3K/AKT phosphorylation. Cellular thermal shift assay (CETSA) and molecular docking supported potential binding of Isoliensinine to PI3K and AKT. Co-treatment with PI3K/AKT activator 740Y-P did not negate the effects of Isoliensinine, suggesting pathway specificity. These findings indicated that Isoliensinine alleviates hypertensive cardiac dysfunction by inhibiting cardiomyocyte apoptosis primarily through modulation of the PI3K/AKT pathway and may serve as a promising therapeutic agent for hypertension.

Ulcerative colitis (UC), a chronic relapsing-remitting-inflammatory disorder affecting the colonic and rectal mucosa, poses significant challenges in the management of inflammatory bowel disease (IBD). This study investigated the therapeutic potential of carvone, a monoterpene abundant in cilantro and spearmint essential oils. Using an integrated network pharmacology approach combined with experimental validation, we identified 62 potential therapeutic targets. Our findings suggest that carvone may treat UC by regulating key genes (ESR1, SRC, PIK3R1, TNF) and multiple pathways, including TNF-α/NF-κB signaling, inflammation response, and cell proliferation. In a dextran sulfate sodium (DSS)-induced colitis model, carvone significantly ameliorated disease progression, as evidenced by reduced disease activity index scores, preserved body weight, maintained colon length, and improved histopathological parameters. Molecular analyses demonstrated that carvone substantially downregulated key pro-inflammatory mediators, including IL-6, IL-1β, and TNF-α, both in vivo and in vitro. Mechanistically, carvone effectively suppressed of NF-κB p65 phosphorylation and nuclear translocation, indicating its role in regulating the NF-κB signaling pathway. Additionally, high-throughput 16S-rDNA sequencing analysis revealed that while carvone treatment did not significantly alter overall gut microbiota diversity or community structure, it selectively normalized the abundance of pathogenic Bacteroides species, including B. eggerthii, B. vulgatus, and B. clarus, to levels comparable to healthy controls. These findings suggest that carvone exerts therapeutic efficacy in UC through associations with alterations in the NF-κB inflammatory signaling pathway and shifts in disease-associated gut microbiota composition. However, we acknowledge the need for further causal validation studies, such as gene-deficient cell or mouse models and fecal microbiota transplantation experiments, to fully elucidate the mechanisms underlying these effects. This highlights carvone’s potential as a novel therapeutic strategy for UC management.