Naoxintong capsule attenuates heart damage after ischemic stroke via Nuclear factor-κB / Pyrin domain-containing protein 3 / Caspase-1 signaling

Ethnopharmacological relevance: Ischemic stroke (IS) is a major cause of mortality. Inflammation exerts an essential part of brain-heart communication after IS. Naoxintong capsule (NXT), derived from the classical Traditional Chinese Medicine (TCM) formulation Bu-Yang-Huan-Wu-Tang, are extensively employed in China to manage IS, myocardial infarction (MI), and atherosclerosis. Previous clinical studies have demonstrated the protective effects of NXT in anti-atherosclerosis, cerebral infarction, angina, and acute coronary syndrome. However, the potential therapeutic mechanism of NXT for IS remains unknown. Aim of the study: This study aims to investigate a potential mechanism for enhancing brain-heart interaction following an ischemic stroke. Materials and methods: C57BL/6J mice underwent permanent middle cerebral artery occlusion (MCAO) for durations of 6, 12, and 24 h. The effects of NXT on the brain were observed via TTC, Nissl and TUNEL staining, immunofluorescence staining, and Zea-Longa scores. Simultaneously, the effects of NXT on the heart were evaluated via H&E staining and echocardiography. Inflammatory factors in heart and serum were determined via ELISA orluminex liquid suspension chip detection. Network pharmacology predicted the targets and signaling pathways of NXT. The binding affinity between potential targets and active compounds of NXT was assessed through molecular docking. The expression levels of I kappa B alpha, IKK(3, NF-kappa B, NLRP3, and caspase-1 were evaluated via Western blotting. Results: The Zea-Longa scores, infarct rate, and the rate of apoptosis in the brain at 6, 12, and 24 h of MCAO mice were markedly decreased by NXT. Additionally, they clearly enhanced the NeuN positive rate and prevented microglia from activating at 24 h. NXT significantly reduced the level of myocardial injury biomarkers (Lactate