Qiliqiangxin capsule improves the cognitive disorders in heart failure rats through regulating blood brain barrier function

This study aimed to investigate the protective effects of Qiliqiangxin capsule (QLQX) against cognitive impairment in rats with heart failure (HF), as well as the underlying mechanisms. Heart failure was induced in rats by LAD ligation. The animals were randomized into four groups (sham, model, QLQX [0.6 g/kg/d], and valsartan [13.3 mg/kg/d]) and received treatment for 60 days. Cardiac function was evaluated by echocardiography, while cognitive function was assessed using the Morris water maze. Myocardial and hippocampal morphology were examined by HE and Nissl staining, respectively. Hippocampal levels of Ang II, Aβ 42 , and ROS were quantified via ELISA and DHE staining. Finally, Western blot analysis was performed to measure the expression of AT1R, NF-κB, P-gP, RAGE, and the tight junction proteins (Claudin-5, Occludin). Echocardiographic assessments revealed that QLQX significantly improved cardiac function in rats with HF-induced cognitive impairment. The Morris water maze test demonstrated that, compared with the model group, QLQX treatment enhanced the targeting of swimming path and increased the number of platform crossings—consistently indicating alleviation of cognitive dysfunction. Histological analysis using HE staining confirmed that QLQX preserved myocardial structural integrity. Nissl staining further demonstrated that QLQX mitigated neuronal damage in the hippocampus. Additionally, QLQX reduced the levels of Ang II, AT1R, ROS, and Aβ 42. It also downregulated the expression of NF-κB and P-gP while upregulating that of Claudin-5 and Occludin. QLQX improves cardiac function and mitigates cognitive decline in rats with heart failure. These protective effects likely involve the reduction of Ang II, AT1R, and ROS levels, alongside inhibition of the NF-κB pathway. Furthermore, QLQX upregulates the tight junction proteins Claudin-5 and Occludin, which helps preserve blood-brain barrier (BBB) integrity. This cascade of events ultimately reduces cerebral Aβ deposition. • Qiliqiangxin capsule alleviates heart failure-induced cognitive deficits. • Qiliqiangxin reduces hippocampal Aβ 42 and improves blood-brain barrier integrity. • The mechanism involves suppression of the Ang II/ROS/NF-κB pathway. • Qiliqiangxin upregulates tight junction proteins Claudin-5 and Occludin. • First demonstration of Qiliqiangxin's role in HF-related cognitive impairment.