Daming capsule protects against myocardial infarction by promoting mitophagy via the SIRT1/AMPK signaling pathway.

Myocardial infarction (MI) is a myocardial injury caused by coronary thrombosis or persistent ischemia and hypoxia. Due to its high morbidity and mortality, a safer and more effective treatment strategy is urgently needed. Daming capsule (DMC), a hypolipidemic drug, reportedly exerts cardioprotective effects in clinical and basic research, although its protective mechanism remains unknown. To investigate the mechanism underlying DMC-mediated improvement of cardiac function post-MI, C57/BL6 mice subjected to coronary artery ligation were administered DMC for 4 weeks. Our data demonstrated that DMC significantly improved cardiac structure and function compared to the saline group. Moreover, DMC inhibited inflammatory response and oxidative stress and improved mitochondrial structure and function in MI mice and hypoxia-stressed cardiomyocytes. Next, our research proved that DMC increased the expression of mitophagy receptor NLRX1. Interestingly, with the administration of DMC and siNLRX1, NLRX1 expression, mitochondria and lysosome colocalization, and mitochondrial membrane potential decreased, while mitochondrial ROS accumulation increased, suggesting that DMC promoted mitophagy to improve mitochondrial function via NLRX1 regulation. Further analysis showed that DMC activated the SIRT1/AMPK signaling pathway in vivo and in vitro. Our data showed that SIRT1 knockdown downregulated NLRX1 expression, leading to structural damage and functional impairment in mitochondria, as well as increased oxidative stress, inflammatory response, and decreased cardiac function in MI mice. Collectively, our findings reveal that DMC improves cardiac function post-MI by increasing mitophagy and inhibiting oxidative stress and inflammotory response in cardiomyocytes through the SIRT1/AMPK signaling pathway.

Anthocyanin is involved in the activation of pyroptosis in oral squamous cell carcinoma.

BACKGROUND: The anti-carcinogenic effects of anthocyanin are well documented. Oral squamous cell carcinoma is one of the most common and lethal cancer types due to its high degree of malignancy and poor prognosis. The main purpose of the current study was to investigate the potential inhibitory effects of anthocyanin on oral squamous cell carcinoma and identify effective targets for therapy. METHODS: Cell viability was measured using cell counting kit-8 (CCK8). Cell migration and invasion abilities were determined using scratch-wound and Transwell invasion assays, respectively. mRNA and protein expression patterns of nucleotide-binding oligomerization domain-like receptor pyrin domain containing 3 (NLRP3), caspase-1 and IL-1ß were detected using qRT-PCR, immunofluorescence and western blot. The gasdermin D (GSDMD) level was determined via confocal microscopy and western blot. RESULTS: Anthocyanin reduced the viability of oral squamous cell carcinoma cells and inhibited migration and invasion abilities. Simultaneously, activation of pyroptosis was associated with enhanced expression of NLRP3, caspase-1, and IL-1ß. Upon administration of caspase-1 inhibitors, anthocyanin-activated pyroptosis was suppressed and cell viability, migration, and invasion rates concomitantly enhanced. CONCLUSION: Anthocyanin promotes the death of oral squamous cell carcinoma cells through activation of pyroptosis and inhibits tumor progression.