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  • Importantly we observed significantly the reduced myocardial


    Importantly, we observed significantly the reduced myocardial infarct size, the improved left ventricular function and the inhibited fibrosis after I/R with oral GA-BH4 supplementation before ischemia (Fig. 1, Fig. 2, Fig. 3). Usually, there is a view that the antioxidation induced by reducing agents might be one of the most likely mechanisms contributing to the protective effect against I/R injury. Considering the antioxidant effect of GA [41] and 6S-BH4 [29] on scavenging of ROS generated, the vehicle (GA) and GA-6S-BH4 treatments were performed simultaneously in this study. As the results shown, GA, as well as GA-6S-BH4, administration has no or slight effects against myocardial I/R injury. Therefore, it is concluded that the protective effects on acute and chronic myocardial I/R injury might be associated with preserved eNOS enzyme function secondary to significantly higher myocardial BH4 levels. Thus, the results demonstrated that BH4 depletion is a critical factor in acute and chronic I/R injury and that its oral supplementation with GA-coated can confer protection. In summary, our data indicate that the encapsulation of BH4 in GA results in better exogenous BH4 stability. Oral administration of GA-BH4 provides protection against myocardial I/R injury, possibly by maintaining myocardial BH4 levels, preserving eNOS function and inhibiting ROS generation. The increased N-Benzylacetamidine hydrobromide and the high activity of the encapsulated BH4 could make this approach an attractive choice for clinical applications.
    Introduction Ventricular hypertrophy is mainly caused by mechanical stimulation, that is, long-term hemodynamic overload, resulting in increased ventricular wall tension and hypertrophy of cardiac myocytes [1]. At the same time, angiotensin II, catecholamine, and endothelin-1 can stimulate cardiac myocyte hypertrophy [2,3]. Myocardial ischemia, hypoxia, or stimulation of various inflammatory factors can also result in ventricular hypertrophy. Studies have shown that patients with left ventricular hypertrophy 6-fold higher risk of death than other individuals [4]. Therefore, the prevention and treatment of ventricular hypertrophy have become the focus of attention and research. Endothelial nitric oxide synthase (eNOS), a gene on the seventh human chromosome, is closely related to the pathogenesis of cardiovascular diseases [5]. The protein has two structures with monomers and two polymers; however, only two polymers have biological activity [6]. eNOS can catalyze the production of NO, which has protective effects on the cardiovascular system and is beneficial to the maintenance of blood vessel tension and the relaxation and contraction of the myocardium [7]. eNOS plays a vital role in the development of the heart, and the lack of eNOS causes congenital atrial/ventricular septal defect, which causes ventricular hypertrophy and heart failure and leads to double aortic stenosis, reflux, endocarditis, aortic aneurysm, and aortic dissection [8]. Millettia pulchra (Benth.) Kurz var. Laxior (Dunn) Z. Wei (Papilionaceae) (MKL) (Yulangsan) is a traditional herb of the Guangxi Zhuang Autonomous Region of China. The extracts from the MKL roots have extensive pharmacological activities, such as anti-hepatic impairment and anti-inflammatory and anti-hypertensive effects [[9], [10], [11], [12]]. MHBFC is a flavonoid monomer that was isolated from the ethyl acetate fraction of MKL roots; it was extracted with 60% ethanol in our previous studies [12] and has been demonstrated to inhibit myocardial ischemia-reperfusion injury [13], scavenge hydroxyl radicals and oxyradicals [14], and reverse cardiac hypertrophy [15]. In the process of reversing cardiac hypertrophy, MHBFC may activate the eNOS-NO pathway by augmenting the expression of eNOS; however, it is not clear whether the effect of reversing cardiac hypertrophy depends on the eNOS gene. Therefore, in the present study, the model of cardiac hypertrophy after abdominal aortic banding in eNOS knockout mice was used to answer this question.