Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Complementary Medicine and Therapies
Published in: BMC Complementary Medicine and Therapies 1/2021

Open Access 01-12-2021 | Hypertension | Research article

Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance

Authors: Abel Degu, Abiy Abebe, Ephrem Engidawork

Published in: BMC Complementary Medicine and Therapies | Issue 1/2021

Login to get access

Abstract

Background

Otostegia integrifolia Benth. (Lamiaceae) leaves are used to treat hypertension in Ethiopian folk medicine. However, the claim has so far not been investigated scientifically. Thus, the objective of this study was to evaluate the antihypertensive activity of 80% methanol leaf extract of O. integrifolia in animal model of hypertension and possible underlying mechanisms in isolated rat aorta.

Methods

Antihypertensive effect of various oral doses of the extract (250, 500 and 1000 mg/kg) was determined in fructose-induced hypertensive rats using the non-invasive tail-cuff method. Thoracic aortic strips of rats were isolated and suspended in organ bath, and the vasodepressor effect as well as the possible mechanism (s) of action were studied by means of isometric tension recording experiments ex vivo. Phytochemical analysis was also performed to suggest possible constituents related to the activity.

Results

Blood pressure was significantly lowered in a dose-dependent manner following extract administration, suggesting that the extract possesses antihypertensive activity. The extract also caused a dose-dependent relaxation of aortic strip precontracted with KCl at a concentration of 6.25–125 μg/L, with a maximum relaxation (100%) achieved at a cumulative concentration of 318.75 μg/ml. The relaxation mechanism was found to be independent of muscarinic receptors, prostanoids, histamine receptors, ATP dependent K+ channels, sarcoplasmic reticulum stored Ca2+ and the endothelium system. The extract shifted the Ca2+ concentration-response curve to the right similar to that caused by nifedipine, suggesting that vasorelaxation could possibly be mediated via calcium channel blockade. The extract was found to contain phenolic compounds (164.3 mg/g, expressed as gallic acid equivalents) and flavonoids (125.7 mg/g, expressed as quercetin equivalents).

Conclusion

The findings revealed that the plant is endowed with antihypertensive activity, providing evidence for its traditional use. The effect maybe, at least in part, due to dilation of blood vessels through blockade of Ca+ 2 channels mediated by phenolic and flavonoid constituents.
Appendix
Available only for authorised users
Literature
1.
Mills KT, Bundy JD, Kelly TN, Reed JE, Kearney PM, Reynolds K, et al. Global disparities of hypertension prevalence and control: a systematic analysis of population-based studies from 90 countries. Circulation. 2016;134:441–50.PubMedPubMedCentralCrossRef
2.
Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. ESC/ESH guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Cardiology (ESC) and the European Society of Hypertension (ESH). Eur Heart J. 2018;39:3021–104.PubMedCrossRef
3.
Unger T, Borghi C, Charchar F, Khan NA, Poulter NR, Prabhakaran D, et al. International Society of Hypertension global hypertension practice guidelines. Hypertension. 2020;75:1334–57.PubMedCrossRef
4.
Zeng Z, Chen J, Xiao C, Chen W. A global view on prevalence of hypertension and human develop index. Ann of Glob Health. 2020;86(1):67.
5.
Jalal DI, Smits G, Johnson RJ, Chonchol M. Increased fructose associates with elevated blood pressure. Clin J Am Soc Nephrol. 2010;21:1543–9.CrossRef
6.
Tran LT, Yuen VG, McNeill JH. The fructose-fed rat: a review on the mechanisms of fructose-induced insulin resistance and hypertension. Mol Cell Biochem. 2009;332:145–59.PubMedCrossRef
7.
8.
Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Boehm M, et al. ESH/ESC guidelines for the management of arterial hypertension: the task force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Blood Press. 2013;22:193–278.CrossRef
9.
10.
Campese V, Schneider EL. Reevaluating the use of antihypertensive medications, a first step toward reducing polypharmacy in very old patients. J Clin Hypertens. 2010;12:621–4.CrossRef
11.
Bahramnezhad F, Chalik R, Bastani F, Taherpour M, Navab E. The social network among the elderly and its relationship with quality of life. Electron Physician. 2017;9:4306.PubMedPubMedCentralCrossRef
12.
13.
Araya S, Abera B, Giday M. Study of plants traditionally used in public and animal health management in Seharti Samre District, southern Tigray, Ethiopia. J Ethnobiol Ethnomed. 2015;11:22.PubMedPubMedCentralCrossRef
14.
Aboutabl EA, Sokkar NM, Megid RM, De Pooter HL, Masoud H. Composition and antimicrobial activity of Otostegia fruticosa Forssk. Oil. J Essent Oil Res. 1995;7:299–303.CrossRef
15.
Al-Musayeib NM, Abbas FA, Ahmad MS, Mossa JS, El-Feraly FS. Labdane diterpenes from Otostegia fruticosa. Phytochemistry. 2000;54:771–5.PubMedCrossRef
16.
Endale A, Bisrat D, Animut A, Bucar F, Asres K. In vivo antimalarial activity of a labdane diterpenoid from the leaves of Otostegia integrifolia benth. Phytother Res. 2013;27:1805–9.PubMedCrossRef
17.
Kidane D, Tomass Z, Dejene T. Community knowledge of traditional mosquito repellent plants in Kolla Temben District, Tigray, Northern Ethiopia. Sci Res Essays. 2013;8:1139–44.
18.
Chekol YA, Desta ZY. Determination of antioxidant and antimicrobial activities of leaf extracts of Otostegia integrifolia. Chem Cent J. 2018;12:1–5.CrossRef
19.
Kemal J, Alemu S, Tsegaye B, Tamerat N. Study on ruminant tick infestation, phytochemical analysis and in vitro acaricidal effect of Calpurnia aurea and Otostegia integrifolia extracts on Amblyomma variegatum. Ethiop Vet J. 2020;24(1):34–51.
20.
Andemariam SW. Legislative regulation of traditional medicinal knowledge in Eritrea via-a-Vis Eritrea's commitments under the convention on biological diversity: issues and alternatives. Law Env’t & Dev J. 2010;6:130.
21.
National Research Council. Guide for the care and use of laboratory animals. National Academies Press; 2010.
22.
Altemimi A, Lakhssassi N, Baharlouei A, Watson D, Lightfoot D. Phytochemicals: extraction, isolation, and identification of bioactive compounds from plant extracts. Plants. 2017;6:42.PubMedCentralCrossRef
23.
Shi P, Du W, Wang Y, Teng X, Chen X, Ye L. Total phenolic, flavonoid content, and antioxidant activity of bulbs, leaves, and flowers made from Eleutherine bulbosa (mill.) Urb. Int J Food Sci Nutr. 2018;7:148–54.
24.
Hwang IS, Ho HE, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats. J Hypertens. 1987;10:512–6.CrossRef
25.
26.
Hock FJ, editor. Cardiovascular activity. Drug discovery and evaluation: Pharmacological assays; 2016. p. 49–51.
27.
Ayele Y, Urga K, Engidawork E. Evaluation of in vivo antihypertensive and in vitro vasodepressor activities of the leaf extract of syzygium guineense (willd) DC. Phytother Res. 2010;24:1457–62.PubMedCrossRef
28.
Gilani AH, Aftab K, Suria A, Siddiqui S, Salem R, Siddiqui BS, et al. Pharmacological studies on hypotensive and spasmolytic activities of pure compounds from Moringa oleifera. Phytother Res. 1994;8:87–91.CrossRef
29.
Getiye Y, Tolessa T, Engidawork E. Antihypertensive activity of 80% methanol seed extract of Calpurnia aurea (Ait.) Benth. Subsp. aurea (Fabaceae) is mediated through calcium antagonism induced vasodilation. J Ethnopharmacol. 2016;189:99–106.PubMedCrossRef
30.
Khan AU, Mustafa MR, Khan AU, Murugan DD. Hypotensive effect of Gentiana floribunda is mediated through Ca++ antagonism pathway. BMC Complement Altern Med. 2012;12:121.PubMedPubMedCentralCrossRef
31.
Ashina K, Tsubosaka Y, Nakamura T, Omori K, Kobayashi K, Hori M, Ozaki H, Murata T. Histamine induces vascular hyperpermeability by increasing blood flow and endothelial barrier disruption in vivo. PLoS One. 2015;10:e0132367.PubMedPubMedCentralCrossRef
32.
Siddiqi HS, Mehmood MH, Rehman NU, Gilani AH. Studies on the antihypertensive and antidyslipidemic activities of Viola odorata leaves extract. Lipids Health Dis. 2012;11:6.PubMedPubMedCentralCrossRef
33.
Villanueva C, Giulivi C. Subcellular and cellular locations of nitric oxide synthase isoforms as determinants of health and disease. Free Radic Biol Med. 2010;49:307–16.PubMedPubMedCentralCrossRef
34.
Charlton M, Thompson J. Drugs acting on the heart: antihypertensive drugs. Anaesth Intensive Care. 2018;19:365–9.CrossRef
35.
36.
Fransen P, Van Hove CE, Leloup AJ, Martinet W, De Meyer GR, Lemmens K, et al. Dissecting out the complex Ca2+−mediated phenylephrine-induced contractions of mouse aortic segments. PLoS One. 2015;10:e0121634.PubMedPubMedCentralCrossRef
37.
Madero M, Perez-Pozo SE, Jalal D, Johnson RJ, Sánchez-Lozada LG. Dietary fructose and hypertension. Curr Hypertens Rep. 2011;13:29–35.PubMedCrossRef
38.
Shewamene Z, Abdelwuhab M, Birhanu Z. Methanolic leaf exctract of Otostegia integrifolia Benth reduces blood glucose levels in diabetic, glucose loaded and normal rodents. BMC Complement Altern Med. 2015;15:19.PubMedPubMedCentralCrossRef
39.
Macheboeuf D, Morgavi DP, Papon Y, Mousset JL, Arturo-Schaan M. Dose–response effects of essential oils on in vitro fermentation activity of the rumen microbial population. Anim Feed Sci Tech. 2008;145:335–50.CrossRef
40.
Blacher J, Levy BI, Mourad JJ, Safar ME, Bakris G. Hypertension control and cardiovascular disease–Authors' reply. Lancet. 2017;389:154–5.PubMedCrossRef
41.
Gilani AH, Jabeen Q, Ghayur MN, Janbaz KH, Akhtar MS. Studies on the antihypertensive, antispasmodic, bronchodilator and hepatoprotective activities of the Carum copticum seed extract. J Ethnopharmacol. 2005;98:127–35.PubMedCrossRef
42.
Su XH, Duan R, Sun YY, Wen JF, Kang DG, Lee HS, et al. Cardiovascular effects of ethanol extract of Rubus chingii Hu (Rosaceae) in rats: an in vivo and in vitro approach. J Physiol Pharmacol. 2014;65:417–24.PubMed
43.
Schmitt CA, Dirsch VM. Modulation of endothelial nitric oxide by plant-derived products. Nitric Oxide. 2009;21:77–91.PubMedCrossRef
44.
McNeill JR, Jurgens TM. A systematic review of mechanisms by which natural products of plant origin evoke vasodilatation. Can J Physiol Pharmacol. 2006;84:803–21.PubMedCrossRef
45.
Wen JF, Cui X, Jin JY, Kim SM, Kim SZ, Kim SH, et al. High and low gain switches for regulation of cAMP efflux concentration: distinct roles for particulate GC-and soluble GC-cGMP-PDE3 signaling in rabbit atria. Circ Res. 2004;94:936–43.PubMedCrossRef
46.
Janbaz KH, Qayyum A, Saqib F, Imran I, Zia-Ul-Haq M, De Feo V. Bronchodilator, vasodilator and spasmolytic activities of Cymbopogon Martinii. J Physiol Pharmacol. 2014;65:859–66.PubMed
47.
Safaeian L, Hajhashemi V, Javanmard SH, Naderi HS. The effect of protocatechuic acid on blood pressure and oxidative stress in glucocorticoid-induced hypertension in rat. Iran J Pharm Res. 2016;15:83.PubMedPubMedCentral
48.
Ciumărnean L, Milaciu MV, Runcan O, Vesa ȘC, Răchișan AL, Negrean V, et al. The effects of flavonoids in cardiovascular diseases. Molecules. 2020;25:4320.PubMedCentralCrossRef
49.
Serban MC, Sahebkar A, Zanchetti A, Mikhailidis DP, Howard G, Antal D, et al. Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. 2016;5:e002713.PubMedPubMedCentralCrossRef
50.
51.
Hiwatashi K, Shirakawa H, Hori K, Yoshiki Y, Suzuki N, Hokari M, et al. Reduction of blood pressure by soybean saponins, renin inhibitors from soybean, in spontaneously hypertensive rats. Biosci Biotechnol Biochem. 2010;74:2310–2.PubMedCrossRef
52.
Santos MR, Moreira FV, Fraga BP, Souza DP, Bonjardim LR, Quintans-Junior LJ. Cardiovascular effects of monoterpenes: a review. Rev Bras Farmacogn. 2011;21:764–71.CrossRef
Metadata
Title
Methanol (80%) leaf extract of Otostegia integrifolia Benth (Lamiaceae) lowers blood pressure in rats through interference with calcium conductance
Authors
Abel Degu
Abiy Abebe
Ephrem Engidawork
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Complementary Medicine and Therapies / Issue 1/2021
Electronic ISSN: 2662-7671
DOI
https://doi.org/10.1186/s12906-021-03222-4

Other articles of this Issue 1/2021

BMC Complementary Medicine and Therapies 1/2021 Go to the issue

Research article

Extracts of endophytic fungi from leaves of selected Nigerian ethnomedicinal plants exhibited antioxidant activity

Research

Protective effect of Glechoma hederacea extract against gallstone formation in rodent models

Research article

Evaluation of expression and serum concentration of anti-Mullerian hormone as a follicle growth marker following consumption of fennel and flaxseed extract in first-generation mice pups

Research article

Clinical safety of total glucosides of paeony adjuvant therapy for rheumatoid arthritis treatment: a systematic review and meta-analysis

Research article

Germacrone alleviates neurological deficits following traumatic brain injury by modulating neuroinflammation and oxidative stress

Research

The benefit of combining curcumin, bromelain and harpagophytum to reduce inflammation in osteoarthritic synovial cells