|Year : 2018 | Volume
| Issue : 1 | Page : 92
Preventive effect of hydroalcoholic extract of Rosa damascena on cardiovascular parameters in acute hypertensive rats induced by angiotensin II
Maryam Rahimi1, Mina Ghoreshi1, Bahman Emami2, Mohammad Naser Shafei3, Mahmoud Hosseini4, Abolfazl Khajavirad5
1 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Science, Mashhad, Iran
2 Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
3 Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
4 Division of Neurocognitive Sciences, Psychiatry and Behavioral Sciences Research Center, Mashhad, University of Medical Sciences, Mashhad, Iran
5 Department of Physiology, Faculty of Medicine; Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
|Date of Submission||19-Jun-2017|
|Date of Acceptance||25-Jan-2018|
|Date of Web Publication||12-Oct-2018|
Mohammad Naser Shafei
Neurogenic Inflammation Research Center, Mashhad University of Medical Sciences, Mashhad
Source of Support: None, Conflict of Interest: None
Background: Rosa damascena (R.D) is an aromatic plant with numerous therapeutic effects including cardiovascular effect. The mechanism cardiovascular effect of R.D is unclear and suggested mediated through renin–angiotensin system (RAS). Therefore, in this study, the role of hydroalcoholic extract of R.D on acute hypertension induced by AngII was evaluated. Methods: After anesthesia, femoral artery and vein of rats were cannulated for recording cardiovascular responses and drug injection, respectively. Systolic blood pressure (SBP), mean arterial blood pressure (MAP), and heart rate (HR) were recorded continuously by power lab software. Rats were divided into saline, AngII (50 ng/kg), AngII + Losartan (10 mg/kg), and three groups of R.D extract (250, 500, and 1000 mg/kg). Losartan and AngII were administered intravenously and the other ones intraperitoneal. In the R.D groups, 30 min after injection of the extract, AngII was injected and the maximum changes in SBP, MAP, and HR were calculated and compared to that in control and AngII groups. Results: Results show that AngII significantly increased SBP, MAP, and decreased HR than the control group which was blocked by losartan. SBP and MAP in R.D + AngII groups were significantly lower than AngII alone (P < 0.05 –P < 0.001). Only MAP in higher dose (1000 mg/kg) was significantly lower than low dose (250 mg/kg; P < 0.05). Two higher doses also significantly decreased bradycardia induced by AngII (P < 0. 01). Conclusions: The preventive effect of hydroalcoholic extract of R.D on cardiovascular parameters maybe is mediated by suppression of AngII activity.
Keywords: Angiotensin II, blood pressure, heart rate, rennin–angiotensin system, Rosa damascena
|How to cite this article:|
Rahimi M, Ghoreshi M, Emami B, Shafei MN, Hosseini M, Khajavirad A. Preventive effect of hydroalcoholic extract of Rosa damascena on cardiovascular parameters in acute hypertensive rats induced by angiotensin II. Int J Prev Med 2018;9:92
|How to cite this URL:|
Rahimi M, Ghoreshi M, Emami B, Shafei MN, Hosseini M, Khajavirad A. Preventive effect of hydroalcoholic extract of Rosa damascena on cardiovascular parameters in acute hypertensive rats induced by angiotensin II. Int J Prev Med [serial online] 2018 [cited 2019 Mar 18];9:92. Available from: http://www.ijpvmjournal.net/text.asp?2018/9/1/92/243213
| Introduction|| |
Rosa damascena mill L (R.D) is one of the important species rose families (Rosacea) that cultivated in several areas of the world including Iran, for perfume and therapeutic purposes.,,, The presence several compounds such as citronellol, geraniol, kaempferol, phenylethyl alcohol, and flavonoids have been shown in this plant.,,
In traditional medicine, R.D is used in abdominal and chest pain, digestive disorder, depression, grief, nervous stress and tension, and headaches and migraine.
The R.D also has several pharmacological effects such as relaxation of tracheal, hypotensive, antioxidant, hypnotic, ileum contraction, and antidiabetic effects.
In the present time, there are a few studies about cardiovascular of R.D. In a previous study, we show that hydroalcoholic extract of R.D decreased blood pressure and heart rate (HR) in normotensive rats. Another studies also indicated that rose oil of R.D could decrease systolic blood pressure (SBP)., The fragrance inhalation of rose oil in humans also decreased 40% sympathetic activity and 30% adrenaline concentration. It was also indicated that R.D contains cyanidin-3-O-beta-glucoside a compound of flavonoids that decreased angiotensin converting enzyme (ACE) activity. Based on above evidence, we suggested that R.D has a beneficial effect on cardiovascular parameters through an inhibitory effect on renin–angiotensin system (RAS). Therefore, the effects of hydroalcoholic extract of R.D on blood pressure and HR in acute hypertensive rats induced by angiotensin II (AngII), the main production of RAS were evaluated.
| Methods|| |
Preparation of extract
The R.D was collected from Khorasan Province, Mashhad, Iran, and identified by botanists in the Herbarium (No: 254-1804-01). We used maceration method in this study. The 100 g of dried flowers, powdered then macerated in 600 cc ethanol 70% for 72 h. After that, the mixture was filtered. The solvent was evaporated by a rotary evaporator under reduced pressure at 40°C. Concentrations of the extract were prepared by adding distilled water.
Animals and surgery
Experiments were performed on 42 male Wistar rats (200–250 g). The animals were anesthetized with urethane (1.4 g/kg, intraperitoneally [i.p]). The left femoral artery was cannulated with a polyethylene catheter (PE-50) filled with heparinized saline that connected to a blood pressure transducer and SBP, mean arterial blood pressure (MAP), and HR continuously recorded by a power Lab system (ID instrument, Australia). The left femoral vein also cannulated for drug injection. Measurement, a time of 20 min, was held before the injection of any drug for stabilization of the blood pressure. The surgery and all the related procedures were approved by the Animal Research Ethics Committee of Mashhad University of Medical Sciences (approval number: 931,725).
The drugs are included urethane, AngII, and losartan (Los; Sigma, Co; USA). All drugs dissolved in saline.
Rats were divided into six groups as follows (n = 7 in each group)
- Control group; received saline through intravenous (i.v)
- AngII group; received AngII (50 ng/kg, i.v)
- Los group; received losartan (10 mg/kg, i.v) 30 min before injection of AngII
- R.D 250 group; received 250 mg/kg of R.D extract (i.p) 30 min before injection of AngII
- R.D 500 group; received 500 mg/kg of R.D extract (i.p) 30 min before injection of AngII
- R.D 1000 group; received 1000 mg/kg of R.D extract (i.p) 30 min before injection of AngII.
Volume injection in all groups was 0.4 ml.
The AngII group received AngII (50 ng/kg) i.v, in AngII + losartan group first animal treat with Los (10 mg/kg, i.v) after 30 min AngII (50 ng/kg) injected and blood pressure was recorded. In the R.D groups, three doses of extract (250, 500, and 1000 mg/kg) administrated then after 30 min AngII (50 ng/kg, i.v) injected and changes of SBP, MAP, and HR were evaluated.
The changes (Δ) of SBP, MAP, and HR values were calculated and expressed as a mean ± standard error of the mean. Statistical comparisons done by one-way ANOVA followed by the Tukey's post hoc test. P < 0.05 was used to indicate statistical significance.
| Results|| |
Effects of saline on cardiovascular responses
Injection of saline (i.v) had no significant effects on SBP (before: 95 ± 3.4 mm Hg and after: 103.5 ± 2.17 mm Hg), MAP (before: 92 ± 3.4 mm Hg and after: 98.4 ± 2.17 mm Hg), or HR (before: 340 ± 8.22 beats/min and after: 335.18 ± 7.1 beats/min).
Effect of intravenous injection of angiotensin II alone and after pretreatment with losartan on cardiovascular responses
As shown in [Figure 1]a and [Figure 1]b, injections of AngII (50 ng/kg; i.v) significantly increased maximal changes of SBP and MAP compared to control group (P < 0.001, n = 7). The maximal changes of HR also decreased than control group [P < 0.05; [Figure 1]c.
|Figure 1: Effects of angiotensin II (50 ng/kg; intravenous) and angiotensin II + losartan (10mg/kg) on SBP (a) MAP (b), and HR (c) in anesthetized rats. Data were expressed as a mean ± standard error of the mean. One-way ANOVA used for statistical analysis. (n = 7) ***P < 0.001 compare to control +++P < 0.001; compare to angiotensin II group #: P < 0.05 Los + angiotensin II compare to control SBP = systolic blood pressure, MAP: mean arterial blood pressure, HR = heart rate|
Click here to view
In Los + AngII group, injection of Los (10 mg/kg, i.v) 30 min before AngII (50 ng/kg; i.v) significantly attenuates increased ΔSBP (P < 0. 01) and ΔMAP (P < 0.001; n = 7) induced by AngII. The change of HR in Los + AngII group was lower than AngII alone group, but it was not significant [Figure 1]c.
Effect of pretreatment with hydroalcoholic extract of Rosa damascena on cardiovascular parameters in acute hypertension induced by angiotensin II
In these group rats pretreated with three doses of R.D (250, 500, and 1000 mg/kg, i.p), separately. After 30 min, AngII (50 ng/kg; i.v) slowly injected and cardiovascular parameters recorded.
In dose 250 + AngII, changes of SBP and MAP were not more significant than AngII but were significant compare to Los + AngII [P < 0.01; [Figure 2] and [Figure 3]. The changes of HR also were not more significant than AngII alone but were more significant than Los + AngII [P < 0.05; [Figure 4].
|Figure 2: Effects of hydroalcoholic extract of Rosa damascena on changes of systolic blood pressure in anesthetized rats. Three doses of extract (250, 500, and 1000 mg/kg) injected (intraperitoneally) after 30 min angiotensin II injected and changes of systolic blood pressure determined. Data were expressed as a mean ± standard error of the mean. One-way ANOVA used for statistical analysis (n = 7). *: P < 0.01, **: P < 0.01, and ***: P < 0.001 compared to angiotensin II +: P < 0.01 dose 250 compared to angiotensin II + Los|
Click here to view
|Figure 3: Effects of hydroalcoholic extract of Rosa damascena on changes of mean arterial blood pressure in anesthetized rats. Three doses of extract (250, 500, and 1000 mg/kg) injected (intraperitoneally) after 30 min angiotensin II injected and cardiovascular responses determined. Data were expressed as a mean ± standard error of the mean. One-way ANOVA used for statistical analysis (n = 7). **: P < 0.01 and ***: P < 0.001 compare to angiotensin II + P < 0.05, ++; P < 0.01 compared to angiotensin II + Los|
Click here to view
|Figure 4: Effects of hydroalcoholic extract of Rosa damascena on changes of heart rate in anesthetized rats. Three doses of extract (250, 500, and 1000 mg/kg) injected (intraperitoneally) after 30 min angiotensin II injected and cardiovascular responses determined. Data were expressed as a mean ± standard error of the mean. One-way ANOVA used for statistical analysis. (n = 7) *; P < 0.01 compare to angiotensin II + P < 0.05 compare to angiotensin II + Los|
Click here to view
In dose R.D 500, ΔSBP and ΔMAP significantly reduced compared to AngII group [P < 0.01, [Figure 2] and [Figure 3] and were not significant than Los + AngII. The changes of HR in this dose also decreased but did not significant than AngII alone and Los + AngII groups [Figure 4].
In dose R.D 1000 + AngII, ΔSBP, and ΔMAP significantly reduced compared to AngII group [P < 0.05, [Figure 2] and [Figure 3]. However, these effects were not more significant than the Los + age group. The changes of HR did not significant than AngII alone and Los + AngII groups [Figure 4].
| Discussion|| |
In the present study, AngII significantly increased ΔSBP, ΔMAP, and ΔHR and two higher doses of hydroalcoholic extract of R.D significantly attenuate these effects of AngII (50 ng/kg). Therefore, hypotensive effects of R.D are partly mediated by inhibition of RAS.
The RAS is one of the important systems involved in cardiovascular regulation., The most important product of RAS is AngII that has a complicated effect on the cardiovascular system by several mechanisms such as vasoconstriction, activation of sympathetic nervous, and increased secretion of aldosterone. The cardiovascular effect of AngII mostly mediated by its Ang II type 1 (AT1) receptor. In this study, we used losartan as an AT1 antagonist. Our results showed that the effect of AngII significantly attenuates by losartan that confirmed the role of AT1 in the cardiovascular effect of AngII. The cardiovascular effect of AT1 receptor mediated by complex intracellular signaling pathways such as activation of phospholipase C (PLC), protein kinase C, Src family kinases, tyrosine kinases, and mitogen-activated protein kinase pathways., Effect of this receptor on these signaling pathways is time dependent.
For example, AngII within seconds activates of PLC and increased cytosolic Ca++ and vascular contraction. Because in this study, acute effect of AngII decreased by R.D and AT1 also expressed in vascular smooth muscle cells; it is suggested that the ameliorating effect of R.D on AngII is mediated by inhibition short effects of AngII such as PLC pathway in smooth muscle of vessels.
The R.D has several compounds, especially flavonoids. This compound has several beneficial effects on the cardiovascular system, for example, the inhibitory effect of flavonoids on ACE has been shown in a previous study. The ACE by hydrolysis AngI to AngII plays a vital role in the regulation of blood pressure and electrolyte balance., The R.D contains flavonoids and its compound cyanidin-3-O-beta-glucoside has an ACE inhibitory effect. Therefore, it is possible that the R.D by inhibition of ACE decreased the production of AngII caused a hypotensive effect. Terpenes and kaempferol are other compounds of R.D that those inhibitory effects of ACE have been indicated., It is conceivable that the effect of R.D on AngII is mediated by these compounds. However, in this study, the AngII was used, therefore, ACE inhibitory effect R.D was not evaluated.
The AngII by increased vascular superoxide production and decreased nitric oxide (NO) bioavailability also play an important role in AngII-induced hypertension. Hence, the NO-AngII imbalance may be an important component in the vascular pathophysiology of hypertension. It is well known that R.D has strong antioxidant properties. Therefore, extract of R.D maybe decreases the effect of AngII by antioxidant effect.
Another mechanism hypertensive effect of AngII is activation of the sympathetic system. There are evidences that the release of norepinephrine and epinephrine in presynaptic of the sympathetic system and adrenal medulla increased by AT1 receptor of AngII., The inhibitory effect of R.D on sympathetic system and decreased secretion of epinephrine and norepinephrine in human has been shown. Based on this evidence, it is conceivable that the cardiovascular effect of R.D mediated by attenuating effect of AngII on sympathetic system.
The depressant effect of R.D on the central nervous system and hypnotic, antianxiety, and anticonvulsant effects also has been reported., It is conceivable that R.D by an effect on the brain cardiovascular areas or by effect on local AngII in brain modulate the effect of AngII on the cardiovascular system. However, future studies should be performed to assess beneficial cardiovascular effects of this plant.
| Conclusions|| |
In summary, hydroalcoholic extract of R.D attenuate cardiovascular responses induced by AngII and this effect is comparable with losartan. Therefore, the effect of R.D on the cardiovascular system partly is mediated by suppression activity of RAS especially AngII.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
| References|| |
Boskabady MH, Shafei MN, Saberi Z, Amini S. Pharmacological effects of Rosa damascena
. Iran J Basic Med Sci 2011;14:295-307.
Hongratanaworakit T. Relaxing effect of rose oil on humans. Nat Prod Commun 2009;4:291-6.
Hummer KE, Janick J. Rosaceae: taxonomy, economic importance, genomics. Genetics and Genomics of Rosaceae. New York: Springer; 2009. p. 1-17.
Yassa N, Masoomi F, Rankouhi SR, Hadjiakhoondi A. Chemical composition and antioxidant activity of the extract and essential oil of Rosa damascena
from Iran, population of Guilan. DARU 2015;17:175-80.
Babu KG, Singh B, Joshi VP, Singh V. Essential oil composition of Damask rose (Rosa damascena
Mill.) distilled under different pressures and temperatures. Flavour Fragrance J 2002;17:136-40.
Yassa N, Masoomi F, Rankouhi SR, Hadjiakhoondi A. Chemical composition and antioxidant activity of the extract and essential oil of Rosa damascena
from Iran, population of Guilan. DARU 2009;17:175-80.
Kwon EK, Lee DY, Lee H, Kim DO, Baek NI, Kim YE, et al
. Flavonoids from the buds of Rosa damascena
inhibit the activity of 3-hydroxy-3-methylglutaryl-coenzyme a reductase and angiotensin I-converting enzyme. J Agric Food Chem 2010;58:882-6.
Wood G, Bache F, Remington J, Sadtler S. The Dispensatory of the United States of America. Philadelphia: Griggand Elliot; 2004. p. 4.
Zargari A. Medicinal Plants. Vol. 2. Tehran: Tehran University Press; 1992.
Baniasad A, Khajavirad A, Hosseini M, Shafei MN, Aminzadah S, Ghavi M, et al
. Effect of hydro-alcoholic extract of Rosa damascena
on cardiovascular responses in normotensive rat. Avicenna J Phytomed 2015;5:319-24.
Kumar N, Bhandari P, Singh B, Bari SS. Antioxidant activity and ultra-performance LC-electrospray ionization-quadrupole time-of-flight mass spectrometry for phenolics-based fingerprinting of rose species: Rosa damascena
, Rosa bourboniana
and Rosa brunonii
. Food Chem Toxicol 2009;47:361-7.
Rakhshandah H, Hosseini M, Dolati K. Hypnotic effect of Rosa damascena
in mice. Iran J Pharm Res 2010;20:181-5.
Dolati K, Rakhshandeh H, Shafei MN. Effect of aqueous fraction of Rosa damascena
on ileum contractile response of guinea pigs. Avicenna J Phytomed 2013;3:248-53.
Gholamhoseinian A, Fallah H, Sharifi-Far F, Mirtajaddini M. The inhibitory effect of some Iranian plants extracts on the alpha glucosidase. Iran J Basic Med Sci 2008;11:1-9.
Haze S, Sakai K, Gozu Y. Effects of fragrance inhalation on sympathetic activity in normal adults. Jpn J Pharmacol 2002;90:247-53.
Mohebbati R, Shafei MN, Soukhtanloo M, Mohammadian Roshan N, Khajavi Rad A, Anaeigoudari A, et al
. Adriamycin-induced oxidative stress is prevented by mixed hydro-alcoholic extract of Nigella sativa
and curcuma longa in rat kidney. Avicenna J Phytomed 2016;6:86-94.
Shafei MN, Niazmand S, Enayatfard L, Hosseini M, Daloee MH. Pharmacological study of cholinergic system on cardiovascular regulation in the cuneiform nucleus of rat. Neurosci Lett 2013;549:12-7.
Mahmoudabady M, Shafei MN, Niazmand S, Khodaee E. The effects of hydroalchoholic extract of Teucrium polium
L. On hypertension induced by angiotensin II in rats. Int J Prev Med 2014;5:1255-60.
Veerasingham SJ, Raizada MK. Brain renin-angiotensin system dysfunction in hypertension: Recent advances and perspectives. Br J Pharmacol 2003;139:191-202.
Mehta PK, Griendling KK. Angiotensin II cell signaling: Physiological and pathological effects in the cardiovascular system. Am J Physiol Cell Physiol 2007;292:C82-97.
Touyz RM, Schiffrin EL. Signal transduction mechanisms mediating the physiological and pathophysiological actions of angiotensin II in vascular smooth muscle cells. Pharmacol Rev 2000;52:639-72.
Touyz RM. Recent advances in intracellular signalling in hypertension. Curr Opin Nephrol Hypertens 2003;12:165-74.
Ottaviani JI, Actis-Goretta L, Villordo JJ, Fraga CG. Procyanidin structure defines the extent and specificity of angiotensin I converting enzyme inhibition. Biochimie 2006;88:359-65.
Neal B, MacMahon S, Chapman N; Blood Pressure Lowering Treatment Trialists' Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: Results of prospectively designed overviews of randomised trials. Blood pressure lowering treatment trialists' collaboration. Lancet 2000;356:1955-64.
Olszanecki R, Bujak-Gizycka B, Madej J, Suski M, Wołkow PP, Jawień J, et al
. Kaempferol, but not resveratrol inhibits angiotensin converting enzyme. J Physiol Pharmacol 2008;59:387-92.
Al Shukor N, Van Camp J, Gonzales GB, Staljanssens D, Struijs K, Zotti MJ, et al
. Angiotensin-converting enzyme inhibitory effects by plant phenolic compounds: A study of structure activity relationships. J Agric Food Chem 2013;61:11832-9.
De Ciuceis C, Amiri F, Brassard P, Endemann DH, Touyz RM, Schiffrin EL, et al
. Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of angiotensin II-infused macrophage colony-stimulating factor-deficient mice: Evidence for a role in inflammation in angiotensin-induced vascular injury. Arterioscler Thromb Vasc Biol 2005;25:2106-13.
Rajagopalan S, Kurz S, Münzel T, Tarpey M, Freeman BA, Griendling KK, et al
. Angiotensin II-mediated hypertension in the rat increases vascular superoxide production via membrane NADH/NADPH oxidase activation. Contribution to alterations of vasomotor tone. J Clin Invest 1996;97:1916-23.
Reid IA. Interactions between ANG II, sympathetic nervous system, and baroreceptor reflexes in regulation of blood pressure. Am J Physiol 1992;262:E763-78.
Cavadas C, Grand D, Mosimann F, Cotrim MD, Fontes Ribeiro CA, Brunner HR, et al
. Angiotensin II mediates catecholamine and neuropeptide Y secretion in human adrenal chromaffin cells through the AT1 receptor. Regul Pept 2003;111:61-5.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]