Simple SummaryAcorus tatarinowiiSchott (ATS) is a plant-based medicine that has been used historically to manage epilepsy, but its exact mechanisms are still not fully understood. This lack of clarity limits its use in clinical treatments. To explore how ATS might help prevent epilepsy, we used a rat model with chronic epilepsy induced by pentylenetetrazole (PTZ). We analyzed the brain’s chemical makeup using a technique called UPLC/MS and identified key differences with statistical methods like PCA and OPLS-DA. We also looked at the gut bacteria using 16S rRNA sequencing. Our results showed that giving ATS orally (50 mg/kg) significantly improved seizure latency and pathology in epileptic rats. Important factors included changes in ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and gut flora. These findings provide a foundation for further research into ATS’s potential as an epilepsy treatment.As a phytotherapeutic agent with historical applications in epilepsy management,Acorus tatarinowiiSchott (ATS) remains pharmacologically enigmatic, particularly regarding its pathophysiological mechanisms. This knowledge gap significantly hinders the clinical application of ATS-based treatments. To explore the potential of ATS in combating epileptogenesis, we utilized a pentylenetetrazole (PTZ)-induced chronic epilepsy rat model. Brain metabolomic analysis was performed by ultra-performance liquid chromatography coupled with mass spectrometry (UPLC/MS). Principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA) were performed for screening differential metabolites. Gut microbiota composition was analyzed through 16S rRNA gene sequencing and examined using Spearman correlation analysis. The results show that oral ATS (50 mg/kg) significantly improved the seizure latency and pathology of rats with epilepsy. Ascorbate and aldarate metabolism, glycerophospholipid metabolism, arachidonic acid metabolism, and intestinal flora were crucial for ATS’s ability to counteract epilepsy. The therapeutic effects of ATS against epilepsy were investigated with brain metabolomics and gut microbiota analysis, providing the basis for further comprehensive research.
Min Li,Jia-Yao Si,Peng-Fei Xie,Zhen-Jie Feng,Sheng-Jie Li,Feng Zhou,Jian-Mei Li
The global aging crisis has increased the risk of atherosclerosis (AS), positioning vascular senescence as a critical therapeutic target. Procyanidin C1 (PCC1), a bioactive polyphenol from hawthorn, demonstrates dual senolytic and longevity-enhancing effects. This study explored the regulatory role and mechanisms of PCC1 in AS using an ApoE −/− mouse model fed a high-fat diet (HFD) and a D-galactose (D-Gal)-induced cellular senescence model. Hawthorn oligomeric proanthocyanidins (HOPCs), as well as PCC1, showed potent anti-atherosclerotic and anti-aging effects by improving serum lipid metabolism and reducing aortic root plaque, vascular senescence markers and inflammatory adhesion molecules. Metabolomic analysis demonstrated that PCC1 significantly suppresses key enzymes in arachidonic acid (AA) metabolism, thereby decreasing downstream pro-inflammatory mediators. Target identification studies, including drug affinity responsive target stability (DARTS) assay, liquid chromatography-tandem mass spectrometry (LC-MS/MS), cellular thermal shift assay (CETSA), and molecular docking, identified heat shock protein 90 (HSP90) as a direct target of PCC1, leading to inhibition of its downstream signaling. In vitro, PCC1 selectively cleared senescent cells, suppressed the senescence-associated secretory phenotype (SASP), enhanced endothelial nitric oxide synthase (eNOS) phosphorylation, and inhibited the toll-like receptor 2 (TLR2)/nuclear factor kappa-B (NF-κB) pathway, demonstrating multimodal anti-aging and anti-inflammatory effects. Together, these findings indicate that PCC1 mitigates atherosclerosis by targeting both metabolic and inflammatory pathways through senescent cell clearance and HSP90-mediated blockade of the TLR2/NF-κB signaling axis. This dual mechanism highlights PCC1 as a promising vasoprotective agent and supports the potential application of hawthorn extracts in functional foods aimed at preventing aging-related cardiovascular diseases.
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