Generic placeholder image

The Natural Products Journal

Editor-in-Chief

ISSN (Print): 2210-3155
ISSN (Online): 2210-3163

Research Article

Measurement of Hemodynamic Parameters and Antidepressant Activity in Hypertensive Rats Following Two Weeks Consumption of Acacia Tortilis Leaves Extract

Author(s): Abdulhalim Serafi*, Aisha Azmat, Muhammad Ahmed, Mohammed Bafail and Zahir Hussain

Volume 12, Issue 5, 2022

Published on: 08 February, 2022

Article ID: e141221198866 Pages: 8

DOI: 10.2174/2210315511666211214094034

Price: $65

Abstract

Background: Depression is common in hypertensive patients, and monotherapy may contribute to controlling depression in hypertensive patients and improving socioeconomic outcomes. Previous studies have shown that Acacia tortilis possesses hypotensive activity.

Objectives: The present study was planned to evaluate the hemodynamic activity and antidepressant effects of an ethanolic extract of Acacia tortilis leaves (ATEL) in salt-induced hypertensive rats.

Methods: Sprague-Dawley rats were divided into 5 groups for experiments. The rats received respective treatment for 15 days: G1: Control (C); G2: hypertensive control (HC: high dietary salt, 4% 10ml/kg); G3-5: HC+ ATEL (50, 100, 150mg/kg respectively). Cardiac hemodynamics (mean arterial blood pressure: MAP and heart rate: HR) were measured in the anaesthetized rats by an invasive method. For this method, one carotid artery was catheterized, a pressure catheter (pressure- volume Millar microtip catheter connected to the Mikro-Tip Pressure-Volume System from Ultra Foundation Systems, PowerLab) was inserted, and the blood pressure (MAP in mm Hg) and HR (beats/min) were monitored continuously during the experiment. For the neuropharmacological studies, antidepressant activity was assessed by a forced swim test on the 15th day.

Results: A dose-dependent significant increase in mobility time was observed in rats (G3-5) treated with HC + different doses of ATEL (p < 0.05). However, the mobility time was significantly reduced by HC (G2) treatment compared to the control (p< 0.05). The hypertensive control (high dietary salt: HC) group showed a significant increase in systolic blood pressure (SP), diastolic blood pressure (DP), MAP and HR (p<0.05) compared to the control (G1) group. At all doses (50, 100, and 150 mg/kg), MAP and HR were found to decrease significantly (p<0.05) compared to the values in the HC (G2) group. Further analysis revealed an improvement in heart rate variability (HRV) in ATEL-treated hypertensive rats.

Conclusion: The present research suggests that increased dietary salt intake not only increases blood pressure significantly but also increases depression. ATEL contains some efficacious constituents, such as N, N-dimethyltryptamine (DMT: a 5-HT1A agonist), with predominant antidepressant and antihypertensive activity. Hence, ATEL appears to be a valuable plant extract that can be useful, at least as an adjunct, for therapy in patients who suffer from both depression and hypertension. Keywords: Ethanolic extract of Acacia.

Keywords: Ethanolic extract of Acacia tortilis leaves (ATEL), mean arterial pressure (MAP), heart rate variability (HRV), antidepressant activity, forced swim test, DMT, 5-HT1A receptor.

Graphical Abstract

[1]
Li, Z.; Li, Y.; Chen, L.; Chen, P.; Hu, Y. Prevalence of depression in patients with hypertension: A systematic review and meta-analysis. Medicine (Baltimore), 2015, 94(31), e1317.
[http://dx.doi.org/10.1097/MD.0000000000001317] [PMID: 26252317]
[2]
Kretchy, I.A.; Owusu-Daaku, F.T.; Danquah, S.A. Mental health in hypertension: Assessing symptoms of anxiety, depression and stress on anti-hypertensive medication adherence. Int. J. Ment. Health Syst., 2014, 8(1), 25.
[http://dx.doi.org/10.1186/1752-4458-8-25] [PMID: 24987456]
[3]
de Jonge, P.; Rosmalen, J.G.M.; Kema, I.P.; Doornbos, B.; van Melle, J.P.; Pouwer, F.; Kupper, N. Psychophysiological biomarkers explaining the association between depression and prognosis in coronary artery patients: A critical review of the literature. Neurosci. Biobehav. Rev., 2010, 35(1), 84-90.
[http://dx.doi.org/10.1016/j.neubiorev.2009.11.025] [PMID: 19962401]
[4]
Young, A.S.; Klap, R.; Sherbourne, C.D.; Wells, K.B. The quality of care for depressive and anxiety disorders in the United States. Arch. Gen. Psychiatry, 2001, 58(1), 55-61.
[http://dx.doi.org/10.1001/archpsyc.58.1.55] [PMID: 11146758]
[5]
Wing, R.R.; Phelan, S.; Tate, D. The role of adherence in mediating the relationship between depression and health outcomes. J. Psychosom. Res., 2002, 53(4), 877-881.
[http://dx.doi.org/10.1016/S0022-3999(02)00315-X] [PMID: 12377297]
[6]
Beers, M.H.; Passman, L.J. Antihypertensive medications and depression. Drugs, 1990, 40(6), 792-799.
[http://dx.doi.org/10.2165/00003495-199040060-00003] [PMID: 2078996]
[7]
Neamati, N.; Barchi, J.J., Jr. New paradigms in drug design and discovery. Curr. Top. Med. Chem., 2002, 2(3), 211-227.
[http://dx.doi.org/10.2174/1568026023394227] [PMID: 11944817]
[8]
Tanae, M.M.; Lima-Landman, M.T.R.; De Lima, T.C.M.; Souccar, C.; Lapa, A.J. Chemical standardization of the aqueous extract of Cecropia glaziovii Sneth endowed with antihypertensive, bronchodilator, antiacid secretion and antidepressant-like activities. Phytomedicine, 2007, 14(5), 309-313.
[http://dx.doi.org/10.1016/j.phymed.2007.03.002] [PMID: 17434301]
[9]
Lim, T.K. Edible Medicinal and Non-Medicinal Plants: Modified Stems, Roots, Bulbs; Springer International Publishing: Cham, Switzerland, 2018.
[10]
Azmat, A.; Ahmed, M. Pharmacological evidence of hypotensive activity of Somina (Herbal Drug) in normotensive rats. Trop. J. Pharm. Res., 2014, 13(11), 1863.
[http://dx.doi.org/10.4314/tjpr.v13i11.13]
[11]
Serafi, S.A.; Azmat, A.; Ahmed, M.; Bafail, M.; Hussain, Z. In vivo pharmacodynamics studies of acacia tortilis found in Kingdom of Saudi Arabia on cardiovascular system of rats. Int. J. Pharmacol., 2018, 14(8), 1066-1071.
[http://dx.doi.org/10.3923/ijp.2018.1066.1071]
[12]
Mukhtar, M.H.; Almalki, W.H.; Azmat, A.; Abdalla, M.R.; Ahmed, M. Evaluation of anti-diabetic activity of Acacia tortilis (Forssk.) hayne leaf extract in streptozotocin-induced diabetic rats. Int. J. Pharmacol., 2017, 13(5), 438-447.
[http://dx.doi.org/10.3923/ijp.2017.438.447]
[13]
Alharbi, W.D.M.; Azmat, A. Pharmacological evidence of neuro-pharmacological activity of Acacia tortilis leaves in mice. Metab. Brain Dis., 2016, 31(4), 881-885.
[http://dx.doi.org/10.1007/s11011-016-9821-2] [PMID: 27025511]
[14]
Grillo, A.; Salvi, L.; Coruzzi, P.; Salvi, P.; Parati, G. Sodium intake and hypertension. Nutrients, 2019, 11(9), 1970.
[http://dx.doi.org/10.3390/nu11091970] [PMID: 31438636]
[15]
Luqman, S.; Srivastava, S.; Kumar, R.; Maurya, A.K.; Chanda, D. Experimental assessment of Moringa oleifera leaf and fruit for its antistress, antioxidant, and scavenging potential using in vitro and in vivo assays. Evid. Based Complement Alternat. Med., 2012, 2012, 519084.
[16]
Adam, O.A.O.; Abadi, R.S.M.; Ayoub, S.M.H. The effect of extraction method and solvents on yield and antioxidant activity of certain sudanese medicinal plant extracts. J. Phytopharmacol., 2019, 8(5), 248-252.
[http://dx.doi.org/10.31254/phyto.2019.8507]
[17]
Komaki, A.; Hoseini, F.; Shahidi, S.; Baharlouei, N. Study of the effect of extract of Thymus vulgaris on anxiety in male rats. J. Tradit. Complement. Med., 2015, 6(3), 257-261.
[http://dx.doi.org/10.1016/j.jtcme.2015.01.001] [PMID: 27419090]
[18]
Animals Act 1986. Code of Practice for the Housing and Care of Animals Used in Scientific Procedures. 1986. Available from: http://www.official-documents.gov.uk/document/hc8889/hc01/0107/0107.pdf (accessed Feb 25, 2021).
[19]
Percie du Sert, N.; Hurst, V.; Ahluwalia, A.; Alam, S.; Avey, M.T.; Baker, M.; Browne, W.J.; Clark, A.; Cuthill, I.C.; Dirnagl, U.; Emerson, M.; Garner, P.; Holgate, S.T.; Howells, D.W.; Karp, N.A.; Lazic, S.E.; Lidster, K.; MacCallum, C.J.; Macleod, M.; Pearl, E.J.; Petersen, O.H.; Rawle, F.; Reynolds, P.; Rooney, K.; Sena, E.S.; Silberberg, S.D.; Steckler, T.; Würbel, H. The ARRIVE guidelines 2.0: Updated guidelines for reporting animal research. PLoS Biol., 2020, 18(7), e3000410.
[http://dx.doi.org/10.1371/journal.pbio.3000410] [PMID: 32663219]
[20]
National Research Council. Nutrient requirements of laboratory animals, 4th ed.; National Academies Press: Washington, D.C., 1995.
[21]
Charan, J.; Kantharia, N.D. How to calculate sample size in animal studies? J. Pharmacol. Pharmacother., 2013, 4(4), 303-306.
[http://dx.doi.org/10.4103/0976-500X.119726] [PMID: 24250214]
[22]
Walkowska, A.; Kuczeriszka, M.; Sadowski, J.; Olszyñski, K.H.; Dobrowolski, L.; Červenka, L.; Hammock, B.D.; Kompanowska- Jezierska, E. High salt intake increases blood pressure in normal rats: putative role of 20-HETE and no evidence on changes in renal vascular reactivity. Kidney Blood Press. Res., 2015, 40(3), 323-334.
[http://dx.doi.org/10.1159/000368508] [PMID: 26067851]
[23]
Walum, E. Acute oral toxicity. Environ. Health Perspect., 1998, 106(Suppl. 2), 497-503.
[PMID: 9599698]
[24]
Roux, S.; Sablé, E.; Porsolt, R.D. Primary observation (Irwin) test in rodents for assessing acute toxicity of a test agent and its effects on behavior and physiological function. Curr. Protoc. Pharmacol., 2005, 10, 10.10.
[25]
Redfors, B.; Shao, Y.; Omerovic, E. Influence of anesthetic agent, depth of anesthesia and body temperature on cardiovascular functional parameters in the rat. Lab. Anim., 2014, 48(1), 6-14.
[http://dx.doi.org/10.1177/0023677213502015] [PMID: 23985835]
[26]
Radespiel-Tröger, M.; Rauh, R.; Mahlke, C.; Gottschalk, T.; Mück-Weymann, M. Agreement of two different methods for measurement of heart rate variability. Clin. Auton. Res., 2003, 13(2), 99-102.
[http://dx.doi.org/10.1007/s10286-003-0085-7] [PMID: 12720094]
[27]
Faul, F.; Erdfelder, E.; Lang, A.G.; Buchner, A.-G. Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences. Behav. Res. Methods, 2007, 39(2), 175-191.
[http://dx.doi.org/10.3758/BF03193146] [PMID: 17695343]
[28]
Cruz, A.; Rodríguez-Gómez, I.; Pérez-Abud, R.; Vargas, M.Á.; Wangensteen, R.; Quesada, A.; Osuna, A.; Moreno, J.M. Effects of clofibrate on salt loading-induced hypertension in rats. J. Biomed. Biotechnol., 2011, 2011, 469481.
[http://dx.doi.org/10.1155/2011/469481] [PMID: 20981147]
[29]
Chugh, G.; Asghar, M.; Patki, G.; Bohat, R.; Jafri, F.; Allam, F.; Dao, A.T.; Mowrey, C.; Alkadhi, K.; Salim, S. A high-salt diet further impairs age-associated declines in cognitive, behavioral, and cardiovascular functions in male Fischer brown Norway rats. J. Nutr., 2013, 143(9), 1406-1413.
[http://dx.doi.org/10.3945/jn.113.177980] [PMID: 23864508]
[30]
Ernsberger, P.; Azar, S.; Iwai, J. Open-field behavior in two models of genetic hypertension and the behavioral effects of salt excess. Behav. Neural Biol., 1983, 37(1), 46-60.
[http://dx.doi.org/10.1016/S0163-1047(83)91061-0] [PMID: 6882342]
[31]
Gilman, T.L.; George, C.M.; Andrade, M.A.; Mitchell, N.C.; Toney, G.M.; Daws, L.C. High salt intake lowers behavioral inhibition. Front. Behav. Neurosci., 2019, 13, 271.
[http://dx.doi.org/10.3389/fnbeh.2019.00271] [PMID: 31920580]
[32]
Gu, J-W.; Bailey, A.P.; Tan, W.; Shparago, M.; Young, E. Long-term high salt diet causes hypertension and decreases renal expression of vascular endothelial growth factor in Sprague-Dawley rats. J. Am. Soc. Hypertens., 2008, 2(4), 275-285.
[http://dx.doi.org/10.1016/j.jash.2008.03.001] [PMID: 19122855]
[33]
Dobrian, A.D.; Schriver, S.D.; Lynch, T.; Prewitt, R.L. Effect of salt on hypertension and oxidative stress in a rat model of diet-induced obesity. Am. J. Physiol. Renal Physiol., 2003, 285(4), F619-F628.
[http://dx.doi.org/10.1152/ajprenal.00388.2002] [PMID: 12799306]
[34]
Zhu, Z.; Zhu, S.; Wu, Z.; Liu, D.; Yang, Y.; Wang, X.; Zhu, J.; Tepel, M. Effect of sodium on blood pressure, cardiac hypertrophy, and angiotensin receptor expression in rats. Am. J. Hypertens., 2004, 17(1), 21-24.
[http://dx.doi.org/10.1016/j.amjhyper.2003.08.004] [PMID: 14700507]
[35]
Wu, H.; Liang, Y.; Zheng, Y.; Bai, Q.; Zhuang, Z.; Zheng, D.; Wang, Y. Up-regulation of intrarenal renin-agiotensin system contributes to renal damage in high-salt induced hypertension rats. Kidney Blood Press. Res., 2014, 39(6), 526-535.
[http://dx.doi.org/10.1159/000368463] [PMID: 25531334]
[36]
Dahl, L.K.; Knudsen, K.D.; Heine, M.A.; Leitl, G.J. Effects of chronic excess salt ingestion. Modification of experimental hypertension in the rat by variations in the diet. Circ. Res., 1968, 22(1), 11-18.
[http://dx.doi.org/10.1161/01.RES.22.1.11] [PMID: 5635607]
[37]
Del Bigio, M.R.; Yan, H.J.; Kozlowski, P.; Sutherland, G.R.; Peeling, J. Serial magnetic resonance imaging of rat brain after induction of renal hypertension. Stroke, 1999, 30(11), 2440-2447.
[http://dx.doi.org/10.1161/01.STR.30.11.2440] [PMID: 10548682]
[38]
Reule, S.; Drawz, P.E. Heart rate and blood pressure: Any possible implications for management of hypertension? Curr. Hypertens. Rep., 2012, 14(6), 478-484.
[http://dx.doi.org/10.1007/s11906-012-0306-3] [PMID: 22972532]
[39]
McNeely, J.D.; Windham, B.G.; Anderson, D.E. Dietary sodium effects on heart rate variability in salt sensitivity of blood pressure. Psychophysiology, 2008, 45(3), 405-411.
[http://dx.doi.org/10.1111/j.1469-8986.2007.00629.x] [PMID: 18047481]
[40]
Dell’Acqua, C.; Dal Bò, E.; Messerotti Benvenuti, S.; Palomba, D. Reduced heart rate variability is associated with vulnerability to depression. J. Affective Disord. Reports, 2020, 1(100006), 100006.
[http://dx.doi.org/10.1016/j.jadr.2020.100006]
[41]
Billman, G.E. The effect of heart rate on the heart rate variability response to autonomic interventions. Front. Physiol., 2013, 4, 222.
[http://dx.doi.org/10.3389/fphys.2013.00222] [PMID: 23986716]
[42]
Maurel, J.L.; Autin, J.-M.; Funes, P.; Newman-Tancredi, A.; Colpaert, F.; Vacher, B. High-efficacy 5-HT1A agonists for antidepressant treatment: A renewed opportunity. J. Med. Chem., 2007, 50(20), 5024-5033.
[http://dx.doi.org/10.1021/jm070714l] [PMID: 17803293]
[43]
Cameron, L.P.; Benson, C.J.; Dunlap, L.E.; Olson, D.E. Effects of n, n-dimethyltryptamine on rat behaviors relevant to anxiety and depression. ACS Chem. Neurosci., 2018, 9(7), 1582-1590.
[http://dx.doi.org/10.1021/acschemneuro.8b00134] [PMID: 29664276]
[44]
Dabire, H.; Cherqui, C.; Fournier, B.; Schmitt, H. Comparison of effects of some 5-HT1 agonists on blood pressure and heart rate of normotensive anaesthetized rats. Eur. J. Pharmacol., 1987, 140(3), 259-266.
[http://dx.doi.org/10.1016/0014-2999(87)90282-2] [PMID: 2958302]
[45]
Ramage, A.G. Influence of 5-HT1A receptor agonists on sympathetic and parasympathetic nerve activity. J. Cardiovasc. Pharmacol., 1990, 15(Suppl. 7), S75-S85.
[http://dx.doi.org/10.1097/00005344-199001001-00010] [PMID: 1702490]
[46]
Ramage, A.G.; Villalón, C.M. 5-hydroxytryptamine and cardiovascular regulation. Trends Pharmacol. Sci., 2008, 29(9), 472-481.
[http://dx.doi.org/10.1016/j.tips.2008.06.009] [PMID: 19086344]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy