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. 2017 Nov 14;18(11):2412.
doi: 10.3390/ijms18112412.

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

Raúl Enrique Cuevas-Durán  1 , Juan Carlos Medrano-Rodríguez  2 , María Sánchez-Aguilar  3 , Elizabeth Soria-Castro  4 , María Esther Rubio-Ruíz  5 , Leonardo Del Valle-Mondragón  6 , Alicia Sánchez-Mendoza  7 , Juan Carlos Torres-Narvaéz  8 , Gustavo Pastelín-Hernández  9 , Luz Ibarra-Lara  10
Affiliations

Extracts of Crataegus oxyacantha and Rosmarinus officinalis Attenuate Ischemic Myocardial Damage by Decreasing Oxidative Stress and Regulating the Production of Cardiac Vasoactive Agents

Raúl Enrique Cuevas-Durán et al. Int J Mol Sci. .

Abstract

Numerous studies have supported a role for oxidative stress in the development of ischemic damage and endothelial dysfunction. Crataegus oxyacantha (Co) and Rosmarinus officinalis (Ro) extracts are polyphenolic-rich compounds that have proven to be efficient in the treatment of cardiovascular diseases. We studied the effect of extracts from Co and Ro on the myocardial damage associated with the oxidative status and to the production of different vasoactive agents. Rats were assigned to the following groups: (a) sham; (b) vehicle-treated myocardial infarction (MI) (MI-V); (c) Ro extract-treated myocardial infarction (MI-Ro); (d) Co extract-treated myocardial infarction (MI-Co); or (e) Ro+Co-treated myocardial infarction (MI-Ro+Co). Ro and Co treatments increased total antioxidant capacity, the expression of superoxide dismutase (SOD)-Cu2+/Zn2+, SOD-Mn2+, and catalase, with the subsequent decline of malondialdehyde and 8-hydroxy-2'-deoxyguanosine levels. The extracts diminished vasoconstrictor peptide levels (angiotensin II and endothelin-1), increased vasodilators agents (angiotensin 1-7 and bradikinin) and improved nitric oxide metabolism. Polyphenol treatment restored the left intraventricular pressure and cardiac mechanical work. We conclude that Ro and Co treatment attenuate morphological and functional ischemic-related changes by both an oxidant load reduction and improvement of the balance between vasoconstrictors and vasodilators.

Keywords: Crataegus oxyacantha; Rosmarinus officinalis; antioxidant status; myocardial function; vasoconstrictor; vasodilators.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Chromatography of the foliar extract of Rosmarinus officinalis (a) compared to the chromatogram at 280 nm of the standards rosmarinic acid and carnosol (c); Crataegus oxyacantha (b) compared to the chromatogram at 360 nm of the rutin and quercetin standards (d).
Figure 2
Figure 2
The effect of extracts from Rosmarinus officinalis, Crataegus oxyacantha, and their combination on oxidative stress markers. Total antioxidant capacity (TAC) (a); malondialdehyde (MDA) (b); and 8-hydroxy-2′-deoxyguanosine (8-OH-2dG) (c); The concentrations were evaluated in the ischemic left ventricle areas from rats subjected to sham—or myocardial infarction (MI) and treated seven days with either vehicle (V), Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co) or their combination (Ro+Co). The values show the mean ± SEM from 6 different experiments. p < 0.05 ANOVA one way post Tukey, * Sham vs. MI-V, # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, Φ MI-V vs. MI-Ro+Co, + MI-Ro vs. MI-Ro+Co.
Figure 3
Figure 3
The effect of extracts from Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co), and their combination (Ro+Co) on superoxide dismutase (SOD)-Cu2+/Zn2+ (a); SOD-Mn2+ (b); and catalase (c) protein expression in ischemic left ventricle area from sham, myocardial infarction (MI)-vehicle treated, MI-Ro, MI-Co, and MI-Ro+Co experimental groups. The values show the mean ± SEM (n = 6 per group). p < 0.05 ANOVA one way post Tukey * Sham vs. MI-V, # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, Φ MI-V vs. MI-Ro+Co, + MI-Ro vs. MI-Ro+Co, & MI-Co vs. MI-Ro+Co. ND (Not detected).
Figure 4
Figure 4
The effect of extracts from Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co) and their combination (Ro+Co) on vasoconstrictor agent levels. Endothelin-1 (a) and angiotensin II (b) concentration were determined in myocardial ischemic area homogenate from sham, myocardial infarction (MI)-vehicle treated, MI-Ro, MI-Co, and MI-Ro+Co experimental group. The values show the mean ± SEM from six different experiments. p < 0.05 ANOVA one way post Tukey, * Sham vs. MI-V, # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, Φ MI-V vs. MI-Ro+Co, α MI-Ro vs. MI-Co, & MI-Co vs. MI-Ro+Co.
Figure 5
Figure 5
The effect of extracts from Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co), and their combination (Ro+Co) on NADPH oxidase (NOX4) (a) and p22phox (b) protein expression in ischemic area of the left ventricles from sham, myocardial infarction (MI)-vehicle treated, MI-Ro, MI-Co, and MI-Ro+Co experimental groups. The values show the mean ± SEM of six different experiments. p < 0.05 ANOVA one way post Tukey, * Sham vs. MI-V, # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, Φ MI-V vs. MI-Ro+Co.
Figure 6
Figure 6
The effect of extarcts from Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co), and their combination (Ro+Co) on vasorelaxing components concentration. Angiotensin-(1–7) (a) and bradykinin (b) were quantified in the myocardial ischemic areas from sham, myocardial infarction (MI)-vehicle treated (MI-V), MI-Ro, MI-Co, and MI-Ro+Co. The values correspond to the mean ± SEM of six different experiments. p < 0.05 ANOVA one way post Tukey # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, + MI-Ro vs. MI-Ro+Co, α MI-Ro vs. MI-Co, & MI-Co vs. MI-Ro+Co.
Figure 7
Figure 7
Extracts of Rosmarinus officinalis (Ro), Crataegus oxyacantha (Co), and their combination (Ro+Co) increases endothelial nitric oxide synthase (eNOS) expression and BH4:BH2 ratio. (a) Representative immunoblot and eNOS expression; (b) biopterin concentrations; and (c) BH4:BH2 ratio in ischemic areas from sham, myocardial infarction (MI)-vehicle (MI-V)-treated, MI-Ro, MI-Co, and MI-Ro+Co. The values correspond to the mean ± SEM of six rats/group. p < 0.05 ANOVA one way post Tukey, * Sham vs. MI-V, # MI-V vs. MI-Ro, Δ MI-V vs. MI-Co, Φ MI-V vs. MI-Ro+Co.
Figure 8
Figure 8
Extracts prevent ultrastructural damage in myocardium of infarcted rats. Sham (a,f,k); myocardial infarction (MI)-vehicle treated (MI-V, (b,g,l)); MI-Ro (c,h,m); MI-Co (d,i,n); and MI-Ro+Co (e,j,o) were analyzed by electron microscopy. The figure depicts the sarcomere showing mitochondria arranged in rows (formula image); band I (→) and * showed swealling mitochondria. Magnification 12,000× for sarcomere (a–e), and the scale bar represents 500 nm; 20,000× for mitochondria and nuclei, and the scale bar represents 2 µm (f–o).
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