Protective Effect of Vitis labrusca Leaves Extract on Cardiovascular Dysfunction through HMGB1-TLR4-NFκB Signaling in Spontaneously Hypertensive Rats

Abstract

The Vitis labrusca is a grapevine that has antioxidant, neuroprotective, hepatoprotective, and anticarcinogenic activity. However, the effect of Vitis labrusca leaves on the cardiovascular system is yet to be ascertained. The present study was designed to investigate the effects of Vitis labrusca leaves extract (HP1) on cardiovascular remodeling in spontaneously hypertensive rats. Experiments were performed in rats and were randomly divided into the following groups: Wistar Kyoto rat (WKY), normal control group; spontaneously hypertensive rats (SHR), negative control group; SHR + Losa, positive control group (losartan, 10 mg/kg/daily, AT1 receptor blocker) and SHR + HP1 (100 mg/kg/daily). HP1 was orally administered daily for 4 weeks. The HP1 treatment significantly improved blood pressure, electrocardiographic parameters, and echocardiogram parameters compared to hypertensive rats. Additionally, the left ventricular (LV) remodeling and LV dysfunction were significantly improved in HP1-treated hypertensive rats. Furthermore, an increase in fibrotic area has been observed in hypertensive rats compared with WKY. However, administration of HP1 significantly attenuated cardiac fibrosis in hypertensive rats. Moreover, HP1 suppressed the expression of high mobility group box 1 (HMGB1), toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), receptor for advanced glycation end products (RAGE), and extracellular signal-regulated kinases (ERK1/2) induced by hypertensive rats, resulting in improved vascular remodeling. Therefore, these results suggest that HP1 can improve the cardiovascular remodeling in hypertensive rats, and the mechanisms may be related to the suppressive effect of HP1 on HMGB1-TLR4-NFκB signaling in the cardiovascular system. Thus, the protective role of the traditional herbal medicine HP1 may provide new insights into the development of therapeutic drugs on the development of hypertensive cardiovascular dysfunction.