ACE Inhibitory and Antihypertensive Activities of Wine Lees and Relationship among Bioactivity and Phenolic Profile

Abstract

Wine lees (WL) are by-products generated in the winemaking process. The aim of this study was to investigate the angiotensin-converting enzyme inhibitory (ACEi) activity, and the blood pressure (BP) lowering effect of WL from individual grape varieties. The relationship among their activities and phenolic profiles was also studied. Three WL, from Cabernet, Mazuela, and Garnacha grape varieties, were firstly selected based on their ACEi properties. Their phenolic profiles were fully characterized by UHPLC-ESI-Q-TOF-MS. Then, their potential antihypertensive effects were evaluated in spontaneously hypertensive rats (SHR). BP was recorded before and after their oral administrations (2, 4, 6, 8, 24, and 48 h) at a dose of 5 mL/kg bw. Cabernet WL (CWL) exhibited a potent antihypertensive activity, similar to that obtained with the drug Captopril. This BP-lowering effect was related to the high amount of anthocyanins and flavanols present in these lees. In addition, a potential hypotensive effect of CWL was discarded in normotensive Wistar-Kyoto rats. Finally, the ACEi and antihypertensive activities of CWL coming from a different harvest were confirmed. Our results suggest the potential of CWL for controlling arterial BP, opening the door to commercial use within the wine industry.

Keywords: Cabernet grape variety; SHR; blood pressure; hypertension; polyphenols; winery by-product.

Figure 1

Graphical representation of the three in vivo studies carried out to investigate (A) the effect of three wine lees (WL) on blood pressure (BP) in spontaneously hypertensive rats (SHR), (B) the effect of Cabernet WL (CWL) on BP in normotensive Wistar–Kyoto rats (WKY) and (C) the effect of CWL from a different harvest (CWL2) at 6 h post-administration in SHR.

Figure 2

Dose–response curves (effect as a function of the dose in µL) for Cabernet, Garnacha, Merlot, and Macabeo wine lees (WL). Values are the average of three replicates ± SD.

Figure 3

Overlapped extract ion chromatograms (EIC) of (A) non-anthocyanin wine lees (WL)-phenolic compounds analyzed by UHPLC-(ESI-)-Q-TOF-MS and (B) anthocyanin WL-phenolic compounds analyzed by UHPLC-(ESI + )-Q-TOF-MS. Chromatographic peaks are numbered according to Table 3 and Table 4.

Figure 4

Decrease of systolic blood pressure (SBP, A) and diastolic blood pressure (DBP, B) in spontaneous hypertensive rats after the administration of water, Captopril (50 mg/kg bw), and the three selected wine lees (WL; 5 mL/kg bw): Garnacha WL, Cabernet WL, and Mazuela WL. Data are expressed as mean (n = 6) ± SEM. Significant differences (p < 0.05) between treatments are represented by different letters in the legend. p value was estimated by two-way ANOVA and Tukey test was used as post hoc.

Figure 5

Decrease in systolic blood pressure (SBP, A) and diastolic blood pressure (DBP, B) caused in Wistar–Kyoto rats after the acute administration of water or Cabernet WL (5 mL/g bw). Data are expressed as mean (n = 6) ± SEM. No significant differences (p < 0.05) were found. p was estimated by two-way ANOVA.

Figure 6

Variability between Cabernet wine lees (CWL) from two different harvests (CWL and CWL2). ACEi activity for both harvests is represented as dose–response curve (%, A) and IC₅₀ (B). Data are shown as mean ± SD (n = 3). No significant differences (p < 0.05) were found between IC₅₀ values (Student’s T-test). Decrease in systolic blood pressure (SBP, C) and diastolic blood pressure (DBP, D) caused in spontaneous hypertensive rats by the acute administration of water, CWL, or CWL2 (both 5 mL/kg bw). Data are shown as mean ± SEM (n = 6). No significant differences (p < 0.05) were found between CWL and CWL2 (Student’s T-test). * represents significant differences (p < 0.05) between CWL and CWL2 and their respective water control groups estimated by Student’s T-test.