In vitro angiotensin-converting enzyme inhibition by phenolic compounds isolated from the root bark of Morus nigra

Hypertension is a major health issue across the world, with a high prevalence and progressive chronical effects. The root bark of Morus nigra has been traditionally utilized to treat hypertension^[1], yet not many studies explained the antihypertensive effect of this plant. This study was conducted to test the potential antihypertensive activity of isolated phenolic compounds of Morus nigra root bark as inhibitors of the angiotensin converting enzyme (ACE) in vitro.

The methanolic extract of Morus nigra was processed by various chromatographic techniques leading to the isolation of seven compounds. Their chemical structures were elucidated by 1- and 2D-NMR spectroscopy and HRMS, identifying them as morusin, kuwanon U, kuwanon E, albanol A and B, and moracin P and R (1-7, respectively). All c ompounds were tested for their ACE inhibitory activity. Compound 4 exerted a complete ACE inhibition at 65µM, whereas 3, 1 and 2 showed 90%, 60% and 50% inhibition at 85, 86, and 83µM, respectively. IC₅₀values for 1, 3, and 4 were determined as 34, 43 and 45µM, respectively, revealing 3 as an over two-times more potent ACE inhibitor as compared to 2.

Fig. 1

Our results showed that presence of a 4′-OH group on the B ring is important for a significant ACE inhibition by the geranylflavanone kuwanons (2 and 3). This finding is in good agreement with previous reports on related SAR of other types of flavonoids^[2].

This work was supported by the NKFIH, Hungary (K119770), the EU-funded Hungarian grant EFOP-3.6.1 – 16 – 2016 – 00008, and GINOP-2.3.2 – 15 – 2016 – 00012. A.H. acknowledges the János Bolyai fellowship of the Hungarian Academy of Sciences and the Kálmán Szász Prize.

[1] Ziaei SA et al. Journal of Kerman University of Medical Sciences, 2009; 16: 134 – 142.

[2] Guerrero L et al. PloS One, 2012; 7: e49493.