In Vitro and In Vivo Studies of Crategus and Inula helenium extracts: Their Effects on Rat Blood Pressure
DOI:
https://doi.org/10.48048/tis.2025.9158Keywords:
Vasorelaxation, Ca2 L-type channels, Ca2 R-type channels, Phenylephrine, Verapamil, Phentolamine, Tail cuff, Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Adrenaline-hydrochlorideAbstract
The contraction of aortic tissues induced by 50 mM KCl is primarily mediated through the activation of voltage-dependent L-type Ca2+ channels in smooth muscle cells. In this study, the effects of Crategus Rosaceae and Inula helenium extracts on KCl-induced contraction were investigated. Extracts of Crataegus attenuated the KCl-induced contraction by 15.0 ± 2.6 and 70.0 ± 2.8 % at concentrations ranging from 20 - 70 μg/mL, while Inula helenium extract reduced the contraction by 5.0 ± 3.1 and 80.0 ± 2.8 % at concentrations of 10 - 50 μg/mL. These findings suggest that the extracts inhibit KCl-induced contraction by modulating L-type Ca2+ channels. Further experiments were conducted in Ca2+-free Krebs solution and in the presence of the L-type Ca2+ channel blocker, verapamil. Crategus Rosaceae and Inula helenium extracts significantly reduced aortic contractions in the presence of KCl and Ca2+, with reductions of 45.0 ± 2.2 and 38.0 ± 2.4 %, respectively, suggesting that the relaxant effects are mediated by reduced Ca2+ influx through L-type Ca2+ channels. Additionally, Crataegus and Inula helenium extracts inhibited phenylephrine (1 μM)-induced contraction, with reductions of 75.0 ± 2.4 and 88.0 ± 2.2 %, respectively, further suggesting an effect on both receptor-controlled and L-type Ca2+ channels. When combined with the α-adrenoceptor blocker phentolamine, the extracts reduced phenylephrine-induced contraction by 20.0 ± 2.1 and 10.0 ± 2.3 %, respectively. Endothelium-dependent relaxant effects of the extracts were confirmed in experiments with L-NAME (100 μM), where the relaxant effects of Crataegus and Inula helenium were significantly reduced to 15.0 ± 2.9 and 24.3 ± 2.4 %, respectively, in the absence of the endothelial layer. These findings suggest that the relaxant effects are mediated through the nitric oxide (NO)-cGMP-PKG signaling pathway. In vivo experiments using the tail cuff method demonstrated a dose-dependent decrease in systolic blood pressure (SBP) in hypertensive rats treated with Crataegus extract at doses of 50, 100 and 200 µg/mL, further supporting the extract’s potential antihypertensive effects.
HIGHLIGHTS
- Modulation of L-type Ca2+ channels: Crataegus Rosaceae and Inula helenium extracts significantly reduced KCl-induced aortic contractions, suggesting modulation of voltage-dependent L-type Ca2+
- Dual mechanism of relaxation: Both extracts inhibited contractions induced by phenylephrine, indicating effects on receptor-controlled and L-type Ca2+
- Endothelium-dependent relaxation: Relaxant effects were mediated via the NO-cGMP-PKG pathway, confirmed through reduced efficacy in the presence of L-NAME.
- In vivo antihypertensive activity: Crataegus extract produced a dose-dependent reduction in systolic blood pressure in hypertensive rats, demonstrating its antihypertensive potential.
- Concentration-dependent effects: Crataegus and Inula helenium extracts showed a graded response, with contractions reduced by up to 80 % at varying concentrations.
GRAPHICAL ABSTRACT
Downloads
References
D Ghosh, AU Syed, MP Prada, MA Nystoriak, LF Santana, M Nieves-Cintrón and MF Navedo. Calcium channels in vascular smooth muscle. Advances in Pharmacology 2017; 78, 49-87.
] LL Cribbs. T-type Ca2+ channels in vascular smooth muscle: Multiple functions. Cell Calcium 2006; 40(2), 221-230.
MK Pozilov, UG Gayibov, MI Asrarov, HS Ruziboev and TF Aripov. Physiological alterations of mitochondria under diabetes condition and its correction by polyphenol Gossitan. Journal of Microbiology, Biotechnology and Food Sciences 2022; 12(2), e2224.
TM Lincoln, N Dey and H Sellak. Invited review: cGMP-dependent protein kinase signaling mechanisms in smooth muscle: from the regulation of tone to gene expression. Journal of Applied Physiology 2001; 91(3), 1421-1430.
OS Zoirovich, AIZ Ugli, ID Raxmatillayevich, ML Umarjonovich, ZM Ravshanovna, GS Narimanovna, GU Gapparjanovich and AT Fatikhovich. The effect of Ájuga Turkestánica on the rat aortic smooth muscle ion channels. Biomedical and Pharmacology Journal 2024; 17(2), 1213-1222.
SS Khushmatov, SZ Omonturdiev, KA Eshbakova, PB Usmanov and ZO Toshmatov. Relaxant effect of the flavonoid pulicarin. Medicinal Plant Research 2012, 2(5), 21-25.
MR Zaripova, SN Gayibova, RR Makhmudov, AA Mamadrahimov, NL Vypova, UG Gayibov, SM Miralimova and TF Aripov. Characterization of Rhodiola heterodonta (Crassulaceae): phytocomposition, antioxidant and antihyperglycemic activities. Preventive Nutrition and Food Science 2024, 29(2), 135-145.
AA Abdullaev, DR Inamjanov, DS Abduazimova, SZ Omonturdiyev, UG Gayibov, SN Gayibova and TF Aripov. Silybum marianum’s impact on physiological alterations and oxidative stress in diabetic rats. Biomedical and Pharmacology Journal 2024; 17(2), 1291-1300.
M Fritz and G Rinaldi. Blood pressure measurement with the tail-cuff method in Wistar and spontaneously hypertensive rats: Influence of adrenergic- and nitric oxide-mediated vasomotion. Journal of Pharmacological and Toxicological Methods 2008; 58(3), 215-221.
J Duarte, R Pérez‐Palencia, F Vargas, MA Ocete, F Pérez-Vizcaino, A Zarzuelo and J Tamargo. Antihypertensive effects of the flavonoid quercetin in spontaneously hypertensive rats. British Journal of Pharmacology 2001; 133(1), 117-124.
SZ Omonturdiev, DR Inomjonov, A Abdullaev, BJ Komilov, UG Gayibov, KA Eshbakova, PB Usmanov and TF Aripov. Studying the influence of quercetin flavonoid on contractility of rat aortic smooth muscle cells. Norwegian Journal of Development of the International Science 2023; 112, 8-13.
C Sobey. Potassium channel function in vascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology 2001; 21(1), 28-38.
YT Mirzayeva, AA Zaripov, IZ Zhumaev, PB Usmanov, SY Rustamov, SN Boboev, SB Qurbonova, EB Ibragimov, MK Musaeva, SB Sobirov and SM Adizov. The protective effect of indole alkaloid vincanine against hypoxia-induced vasorelaxation in a rat aorta model. Biomedical and Pharmacology Journal 2024; 17(1), 483-491.
Z Shakiryanova, R Khegay, U Gayibov, A Latif and O Smirnova. Isolation and study of a bioactive extract enriched with anthocyanin from red grape pomace (Cabernet Sauvignon). Agronomy Research 2023; 21(3), 1293-1303.
C Vandier, JL Guennec and G Bedfer. Signaling pathways used by norepinephrine to contract the artery: A demonstration using guinea pig aortic ring segments. Advances in Physiology Education 2002; 26(1-4), 195-203.
IP Hall. Second messengers, ion channels, and pharmacology of airway smooth muscle. European Respiratory Journal 2000; 5(6), 1120-1127.
AV Mahmudov, OS Abduraimov, SB Erdonov, UG Gayibov and LY Izotova. Bioecological features of Nigella sativa L. in different conditions of Uzbekistan. Plant Science Today 2022; 9(2), 421-426.
LL Cribbs. Vascular smooth muscle calcium channels: Could “T” be a target? Circulation Research 2001; 89(7), 560-562.
S Wra and T Burdyga. Sarcoplasmic reticulum function in smooth muscle. Physiological Reviews 2010; 90(1), 113-178.
N Halidi. 2011, Calcium dynamics and intercellular communication in arterial smooth muscle cells in vitro. Ph. D. Dissertation. École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
IZ Zhumaev, SN Boboev, PB Usmanov, SB Qurbonova, SY Rustamov, AT Esimbetov, GS Begdullaeva1, AA Zaripov and SM Adizov. Mechanism of positive inotropic effect of vincanine on cardiac muscle contraction activity. Biomedical and Pharmacology Journal 2022; 15(4), 2309-2316.
C Vandier, JY Le Guennec and G Bedfer. Signaling pathways used by norepinephrine to contract the artery: A demonstration using guinea pig aortic ring segments. Advances in Physiology Education 2002; 26(3), 195-203.
AQQ Azimova, AX Islomov, SA Maulyanov, DG Abdugafurova, LU Mahmudov, IZO Abdullaev, AS Ishmuratova, SQQ Siddikova and IR Askarov. Determination of vitamins and pharmacological properties of vitis vinifera L. plant fruit part (Mixed Varieties) syrup-honey. Biomedical and Pharmacology Journal 2024; 17(4), 2779-2786.
K Chitaley, DS Weber and RC Webb. RhoA/Rho-kinase, vascular changes, and hypertension. Current Hypertension Reports 2001; 3(2), 139-144.
T Stevens. Is there a role for store-operated calcium entry in vasoconstriction? American Journal of Physiology-Lung Cellular and Molecular Physiology 2001; 280(5), 866-869.
O Gaibullayeva, A Islomov, D Abdugafurova, B Elmurodov, B Mirsalixov, L Mahmudov, I Adullaev, K Baratov, S Omonturdiev and S Sa'dullayeva. Inula helenium l. root extract in sunflower oil: Determination of its content of water-soluble vitamins and immunity-promoting effect. Biomedical and Pharmacology Journal 2024; 17(4), 2729-2737.
B Fisslthaler, N Hinsch, T Chataigneau, R Popp, L Kiss, R Busse and I Fleming. Nifedipine increases cytochrome P4502C expression and endothelium-derived hyperpolarizing factor-mediated responses in coronary arteries. Hypertension 2000; 36(2), 270-275.
WF Jackson. Ion channels and vascular tone. Hypertension 2000; 35(1), 173-194.
M Fritz and G Rinaldi. Influence of nitric oxide-mediated vasodilation on blood pressure measured with the tail-cuff method in rats. Journal of Biomedical Science 2007; 14(6), 757-765.
YA Bin Jardan, A Ahad, M Raish, MA Alam, AM Al-Mohizea and FI Al-Jenoobi. Effects of garden cress, fenugreek, and black seed on the pharmacodynamics of metoprolol: An herb-drug interaction study in hypertensive rats. Pharmaceutical Biology 2021; 59(1), 1086-1095.
J Ibrahim, BC Berk and AD Hughes. Comparison of blood pressure measurements by tail-cuff and carotid arterial methods in conscious spontaneously hypertensive and Wistar-Kyoto rats. Clinical and Experimental Hypertension 2006; 28(1), 57-72.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Walailak University
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
