AJPS  Vol.12 No.11 , November 2021
Exploring the Anti-Hypertensive Properties of Medicinal Plants and Their Bioactive Metabolites: An Extensive Review
Abstract: Medicinal plants are extensively used in traditional folk medicine. High blood pressure is associated with the risk of cardiovascular diseases (CVDs) and many other serious health complications resulting from it as a major concern of morbidity and mortality in health sector. Use of diuretics, angiotensin converting enzyme (ACE) inhibitors, beta adrenergic receptor antagonists (beta blockers), alpha adrenergic receptor antagonists (alpha blockers), calcium channel blockers (CCBs) etc. are not efficient enough to cure hypertension. Side effects regarding these medications lead to intolerance, impaired control of the disease, and also mismanagement of therapy. So, approach regarding quenching new potent therapeutic compounds from medicinal plants draws attention nowadays. For example, as a first-line therapeutic agent, an alkaloid is highly effective in lowering systolic blood pressure which is isolated from root extract of the plant of Rauwolfia serpentina species, namely reserpine. This article comes up with a list of 63 plant species from 37 families, compiling information related to plant parts used for making extracts, types of extract and animals used in these studies, antihypertensive effect of the extracts etc. It also refers to 74 chemically defined molecules, with in vitro and in vivo anti-hypertensive potential, isolated from these extracts along with their dosage and mechanism of action by using electronic searches of published articles from various databases and reference books. Our present work would be beneficial for researchers to investigate and invent novel antihypertensive therapy to treat hypertension.

1. Introduction

The definition of hypertension (HTN) is when office systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) is equal or greater than 140 mmHg, and 90 mmHg respectively [1]. HTN is often called “the silent killer”. If HTN is left untreated, end organ damage may occur [2]. People with elevated blood pressure (BP) may face some major risk of being affected by coronary artery disease with the following complications e.g., blindness in diabetic patients, heart failure, renal diseases, and stroke [3]. 972 million people had HTN in 2000 and this number was predicted to be about 1.56 billion in 2025 [4]. Obesity, unhealthy diet, tobacco use, physical inactivity, and HTN are some factors that increase the risk of CVDs [5]. Reducing SBP by 5 mmHg is shown to lower mortality rate by 9%, 14%, and 7% respectively for coronary heart disease, stroke, and in total [6].

Until now, there are different antihypertensive therapies available, such as: ACE (classified as EC3.4.15.1) inhibitors, angiotensin receptor blocker (ARB), beta blockers, diuretics, and also CCBs [7] [8]. They show their antihypertensive effect by controlling cardiac output (CO) (affecting stroke volume and heart rate), and peripheral or systemic vascular resistance.

Impairment in production of nitric oxide (NO) is a very common reason behind endothelial dysfunction, which leads to HTN [9] [10]. Figure 1 shows that, endothelial NO synthase (eNOS) produces NO from L-arginine in the blood vessels to control cardiovascular function [11]. High BP was induced due to chronic blocking of NO after administrating Nω-Nitro-l-arginine methyl ester (l-NAME) depending upon dose and time [12]. l-NAME contributes to endothelial dysfunction in resistant vessels by decreasing metabolites of NO present in plasma and downregulating expression of eNOS protein [13].

Oxidative stress also promotes HTN pathogenesis [15]. In a rat model of NO depletion-induced hypertension, excess reactive oxygen species (ROS) and declined amount of endogenous antioxidant enzymes have been found [16]. High amount of vascular superoxide ( O 2 ), malondialdehyde (MDA), and plasma protein carbonyl were found in NO deficient hypertensive rats [17] [18]. O 2 quenches NO to produce peroxynitrite (ONOO) directly and decreases NO bioavailability [19].

Again, l-NAME causes overproduction of ROS and activates the renin-angiotensin system (RAS) [20] [21]. Angiotensin II (Ang-II) is a potential vasoconstrictor and for that as shown in Figure 2, RAS is a compulsory factor in pathogenesis of HTN [22]. Renin is released by renal artery constriction and Ang-II

Figure 1. The mechanism of action of Nitrates, and nitrites that increase NO in vascular smooth muscle cells (VSMC). Steps producing vascular contraction are presented with red arrows, and those causing vascular relaxation are displayed with blue arrows [14]. MLCK* = activated myosin light-chain kinase; GC* = activated guanylyl cyclase or guanylate cyclase; PDE = phosphodiesterase.

production is increased by activating RAS in NO deficient hypertensive rats [23] [24]. In l-NAME treated rats, Ang-II stimulates the Ang-II type 1 receptor (AT1R) which produces O 2 activated by nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase [13]. Elevated ACE, cardiac and plasma Ang-II, and AT1R expression also confirmed RAS stimulation in those above-mentioned rats [25].

RAS is also a vital factor because chronic NO inhibition results in arterial remodeling and AT1R blockers prevent that [26]. Vascular remodeling occurs by Ang-II binding to AT1R and activating serine/threonine kinase (Akt), one of its own intracellular downstream signaling protein responsible for Ang-II driven proliferation in VSMC [27]. Signal transducers and activators of transcription protein get phosphorylated by Janus kinases induced by AT1R activation that causes vascular proliferation and remodeling [28].

Figure 2. Sites of action of drugs that interfere with the RAS, also known as the renin-angiotensin-aldosterone system (RAAS) [14].

Despite using these agents, many patients cannot control their high BP [29]. HTN cannot be effectively managed in about 30% of the patients who comply with prescription therapies [30]. The available antihypertensive agents are not successful in all the cases along with disease severity [31]. These agents are categorized as combination therapy, costly and their ambiguous regimen of cure decreases drug adherence and may also surge adverse effects as well as drug interactions [32]. Among these, ACE inhibitors cause bronchospasm and cough [33]; ACE inhibitors and CCBs can cause angioedema with upper respiratory tract obstruction [34]; CCBs also increase the risk of cancer by inhibiting the growth of vascular cells and angiogenic growth factors due to increasing apoptosis [35]; beta blockers induce side effects related to central nervous system [36]. Dyspnea, headache, edema, cough, hair loss, and flushes are also reported as side effects of antihypertensive drugs [37]. So, the acceptance of alternative therapy is increasing day by day, as natural herbal products using medicinal plants show fewer side effects [38]. Numerous of them have the potential for therapy of CVDs including, HTN, arrhythmia, and venous insufficiency [39].

The goal of our work is to accumulate various phytoconstituents that exhibit in vitro and in vivo antihypertensive effects so that they can be used to make safe, patient-adhered, low-cost antihypertensive therapy with preferable minimum side effects. Combination of these natural compounds can also be therapeutic as more than one compound, responsible for antihypertensive effect, are often found in extracts. Our review includes 63 species of plants from 37 family, plant parts used for making extracts, types of extract and animals used for these experiment, antihypertensive effect of the extracts as well as 74 confirmed antihypertensive compounds isolated from these extracts with their dosage and mechanism of action.

2. Discussion about Promising Anti-Hypertensive Plants

Herbal medicine is a tremendous source for seeking out novel therapeutic compounds for numerous diseases. The idea of generating medicine from scratch had originally come out from the traditional uses of herbs and plants by our fellow ancestor to cure many of their ailments. Herbal medicines are quite preferable among people for its significantly low side effects and also the belief regarding nature made.

Traditional use of some plants like Cocos nucifera Linn (Arecaceae), Curcuma domestica (Zingiberaceae), Terminalia bellerica Roxb. (Combretaceae) etc. are well known for treating HTN. Aim of this article is highlighting and compiling the data regarding chemo-profiles, pharmacology of various plant species used to treat HTN. Information regarding plant species is collected from online resources and journals such as PubMed, Google Scholar, SciFinder, ScienceDirect and so on. Table 1 illustrates a comprehensive overview of phytoconstituents, dosage, use, extracts of potential medicinal plants with prominent anti-hypertensive activity.

Among the described compounds, we think four of the compounds were therapeutically efficient. The first one, tilianin which is derived from Agastache mexicana, demonstrated dose-dependent anti-hypertensive effects, with an ED50 of 53.51 mg/kg which was lower than the LD50 of 6624 mg/kg, offers a wide spectrum of pharmacology responses. In addition, this study provides evidence about safety and efficacy of tilianin as antihypertensive agent, as well as, claims of no damage at physiologic, functional and cellular levels in rodent models [41]. The next one is naringenin, isolated from Cochlospermum vitifolium, exhibit a statistically significant dose-dependent decay on SBP (control: 184.00 mmHg vs. sample: 154.93 mmHg) after 24 h post-administration at 50 mg/kg, and also, a significant decrease of SBP (control: 184.00 mmHg vs. sample: 142.64 mmHg) and DBP (control: 159.62 mmHg vs. sample: 122.05 mmHg) at 160 mg/kg [55]. Curcumin nanoemulsion is our favorite choice, prepared from Curcuma domestica and having a 71.166% inhibition (after corrections) on HMGCR (a liver enzyme that contributes to cholesterol synthesis) to assess antihypercholesterolemic activity when compared to pravastatin. Curcumin:

1) Inhibits hepatic HMG-CoA activity and lowers HMGR gene expression (that produces the HMG-CoA enzyme).

2) Suppresses triglyceride and cholesterol accumulation in the liver due to its antihyperlipidemic properties.

3) Enhances PPARα gene expression that regulates fatty acid oxidation.

Table 1. Anti-hypertensive plant species with isolated phytochemicals and their mechanism of action.

4) Elevates the transcription of the LXRα gene, which controls the CYP7A1 enzyme (encoding cholesterol-7a-hydroxlylase, an enzyme that participates in converting cholesterol to bile acids before excretion).

5) Prevents atherosclerotic lesion formation in the atherogenic diet-fed mice, as evidenced by a decrease in the atherogenic indicator and an increase in the % ratio of HDL and total cholesterol [60].

In comparison to pure curcumin, curcumin nanoemulsion demonstrated a higher rate of ACE inhibition, which suggests that higher inhibition activity of curcumin exerted by the nanoemulsion carrier system was caused by improving its solubility [61]. The last one 2,7-dihydroxy-3,4,9-trimethoxyphenanthrene, obtained from Laelia anceps, caused relaxant activity on norepinephrine precontracted aortic rings with Emax of 90% ± 1.35% (with endothelium) and 96.45% ± 1.2% (without endothelium) [74].

3. Observed Compounds Having BP Lowering Properties

The discussed antihypertensive compounds, structure demonstrated in Figures 3-7, are 31 types of compounds, such as 1) anthocyanidin (cyanidin-3-O-rutinoside), 2) anthocyanin (anthocyanin fraction), 3) biogenic amine (acetylcholine), 4) catecholamines (L-3,4-dihydroxyphenylalanine), 5) chalcones (marein, coreopsis chalcones), 6) chromenes (methylripariochromene A, acetovanillochromene, orthochromene A), 7) cinnamates (cynarin, caffeic acid, cinnamic acid), 8) coumarins (6,7,8-trimethoxycoumarin, 6,7-dimethoxycoumarin), 9) cyclic acid glucoside (edulilic acid), 10) diarylheptanoid (curcumin), 11) dihydrophenanthrene (2,7-dihydroxy-3,4,9-trimethoxyphenanthrene), 12) flavones (apigenin, vicenin-2, orientin, isoorientin, isovitexin, luteolin), 13) flavonols (quercetin, taxifolin, 3-O-methylquercetine, rutin, quercetine glycosides, 5-hydroxy-3,4',7-tri- methoxyflavone, verbenacoside, isoquercitrin), 14) flavonoid glucosides (tilianin,

Figure 3. Reported compounds from medicinal plants manifest anti-hypertensive activity.

Figure 4. Reported compounds from medicinal plants manifest anti-hypertensive activity.

Figure 5. Reported compounds from medicinal plants manifest anti-hypertensive activity.

Figure 6. Reported compounds from medicinal plants manifest anti-hypertensive activity.

Figure 7. Reported compounds from medicinal plants manifest anti-hypertensive activity.

quercetagetin-7-O-glucoside, flavanomarein, isosinensin), 15) flavan 3-ols (catechin, epicatechin), 16) flavanones (naringenin, isoaromadendrin), 17) hydroxybenzoate ether (vanillic acid), 18) isoflavone (genistein), 19) isoquinoline alkaloid (berberine), 20) lignan glucoside (secoisolariciresinol diglucoside), 21) phenolic acid, 22) phenylpropanoids (3,4 Dicaffeoylquinic acid, 3,5-Dicaffeoyl- quinic acid, 4,5-Dicaffeoylquinic acid, chlorogenic acid, ferulic acid, rosmarinic acid), 23) polyphenolic flavonoid (theaflavin-3,3'-digallate), 24) proanthocyanidins (procyanidin B5, procyanidin B3, procyanidin B2, procyanidin C1), 25) sesquiterpenes (spathulenol), 26) steroidal trisaccharide (Nuatigenin-3-O-β- chacotriose), 27) tannins and galloyl derivatives (glucogallin, gallic acid, galloylshikimic acid, methyl gallate, digalloylquinic acid, digallic acid, trigalloylglucose, tetragalloylquinic acid, 6-O-galloyl-D-glucose), 28) thiocyanate (erucin), 29) triterpene (momordin Іb), 30) triterpenoids (22α-hydroxychiisanogenin, chiisanogenin, ursolic acid), and 31) triterpenoid saponins (22α-hydroxychiisanoside, chiisanoside). Highest number of compounds are tannins and galloyl derivatives, flavonols, flavones, phenylpropanoids, proanthocyanidins and flavonoid glucosides.

Structure of the compounds reveals that most of the compounds possess heterocyclic oxygen atom which is thought to exert the desired antihypertensive or antioxidative activities. The possible way would be chelating with the zinc atom present in the center of the ACE I.

4. Conclusion

The goal of our research is to let everyone know that there are an ample number of natural compounds that can be made into antihypertensive therapies. We noticed that the majority of the researches focused on the effect of the extracts on antihypertensive therapy along with the mechanism of action and more than half of them elucidated structures of compounds responsible for the activity. As a result, expanding studies into mechanisms and structure elucidation can contribute to the development of new drugs. 63 plant species from 37 families and 74 isolated compounds are reviewed here. Among them, tilianin, naringenin, curcumin nanoemulsion, 2,7-dihydroxy-3,4,9-trimethoxyphenanthrene are the topmost candidate for producing antihypertensive therapy from natural products in a safe, efficient, and patient adhering way. On the other hand, relaxation of blood vessels, formation of NO, blockage of calcium channels, increase in potassium, suppression of the renin-angiotensin pathway, activation of intracellular cGMP, and inactivation of the sympathetic system are mostly the mechanisms discovered in these medicinal plants for antihypertensive activity. Depending upon the side effects of the ongoing therapies, we think it is high time that the pharmaceuticals took the appropriate steps to synthesize effective drug candidate from these phytochemicals that can reach every human being’s doorway. Further studies of the rest of the compounds could also lead to promising antihypertensive therapies.


*Co-first authors.

#Corresponding author.

Cite this paper: Asif, M. , Lisa, S. and Qais, N. (2021) Exploring the Anti-Hypertensive Properties of Medicinal Plants and Their Bioactive Metabolites: An Extensive Review. American Journal of Plant Sciences, 12, 1705-1740. doi: 10.4236/ajps.2021.1211119.

[1]   Williams, B., Mancia, G., Spiering, W., Agabiti Rosei, E., Azizi, M., Burnier, M., Clement, D.L., Coca, A., de Simone, G., Dominiczak, A., Kahan, T., Mahfoud, F., Redon, J., Ruilope, L., Zanchetti, A., Kerins, M., Kjeldsen, S.E., Kreutz, R., Laurent, S., Lip, G.Y.H., McManus, R., Narkiewicz, K., Ruschitzka, F., Schmieder, R.E., Shlyakhto, E., Tsioufis, C., Aboyans, V., Desormais, I. and ESC Scientific Document Group (2018) 2018 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). European Heart Journal, 39, 3021-3104.

[2]   Aggarwal, M. and Khan, I.A. (2006) Hypertensive Crisis: Hypertensive Emergencies and Urgencies. Cardiology Clinics, 24, 135-146.

[3]   Abegaz, T.M., Shehab, A., Gebreyohannes, E.A., Bhagavathula, A.S. and Elnour, A.A. (2017) Nonadherence to Antihypertensive Drugs. Medicine, 96, e5641.

[4]   Kearney, P.M., Whelton, M., Reynolds, K., Muntner, P., Whelton, P.K. and He, J. (2005) Global Burden of Hypertension: Analysis of Worldwide Data. The Lancet, 365, 217-223.

[5]   Pierdomenico, S.D., Di Nicola, M., Esposito, A.L., Di Mascio, R., Ballone, E., Lapenna, D. and Cuccurullo, F. (2009) Prognostic Value of Different Indices of Blood Pressure Variability in Hypertensive Patients. American Journal of Hypertension, 22, 842-847.

[6]   Whelton, P.K., He, J., Appel, L.J., Cutler, J.A., Havas, S., Kotchen, T.A., Roccella, E.J., Stout, R., Vallbona, C., Winston, M.C., Karimbakas, J. and for the National High Blood Pressure Education Program Coordinating Committee (2002) Primary Prevention of Hypertension Clinical and Public Health Advisory from the National High Blood Pressure Education Program. JAMA, 288, 1882-1888.

[7]   Staffileno, B.A. (2005) Treating Hypertension with Cardioprotective Therapies: The Role of ACE Inhibitors, ARBs, and β-Blockers. Journal of Cardiovascular Nursing, 20, 354-364.

[8]   Niaz, T., Hafeez, Z. and Imran, M. (2017) Prospectives of Antihypertensive Nano-ceuticals as Alternative Therapeutics. Current Drug Targets, 18, 1269-1280.

[9]   Hermann, M., Flammer, A. and Lscher, T.F. (2006) Nitric Oxide in Hypertension. The Journal of Clinical Hypertension, 8, 17-29.

[10]   Landmesser, U. and Drexler, H. (2007) Endothelial Function and Hypertension. Current Opinion in Cardiology, 22, 316-320.

[11]   Farah, C., Michel, L.Y.M. and Balligand, J.-L. (2018) Nitric Oxide Signalling in Cardiovascular Health and Disease. Nature Reviews Cardiology, 15, 292-316.

[12]   Alp Yildirim, F.I., Eker Kizilay, D., Ergin, B., Balci Ekmekçi, Ö., Topal, G., Kucur, M., Demirci Tansel, C. and Uydeş Doğan, B.S. (2015) Barnidipine Ameliorates the Vascular and Renal Injury in l-NAME-Induced Hypertensive Rats. European Journal of Pharmacology, 764, 433-442.

[13]   Maneesai, P., Prasarttong, P., Bunbupha, S., Kukongviriyapan, U., Kukongviriyapan, V., Tangsucharit, P., Prachaney, P. and Pakdeechote, P. (2016) Synergistic Antihypertensive Effect of Carthamus tinctorius L. Extract and Captopril in l-NAME-Induced Hypertensive Rats via Restoration of ENOS and AT1R Expression. Nutrients, 8, 122.

[14]   Katzung, B.G., Masters, S.B. and Trevor, A.J., Eds. (2012) Basic and Clinical Pharmacology. 12th Edition, McGraw-Hill Medical, New York.

[15]   Rodríguez-Rodríguez, P., Ramiro-Cortijo, D., Reyes-Hernández, C.G., López de Pablo, A.L., González, M.C. and Arribas, S.M. (2018) Implication of Oxidative Stress in Fetal Programming of Cardiovascular Disease. Frontiers in Physiology, 9, 602.

[16]   Saravanakumar, M. and Raja, B. (2011) Veratric Acid, a Phenolic Acid Attenuates Blood Pressure and Oxidative Stress in l-NAME Induced Hypertensive Rats. European Journal of Pharmacology, 671, 87-94.

[17]   Poasakate, A., Tong-un, T., Ishida, W., Prachaney, P., Maneesai, P., Potue, P. and Pakdeechote, P. (2019) Effect of Cratoxylum formosum Dyer Extract on Sperm Motility and Concentration in L-NAME Hypertensive Rats. Srinagarind Medical Journal, 34, 312-317.

[18]   Wunpathe, C., Maneesai, P., Rattanakanokchai, S., Bunbupha, S., Kukongviriyapan, U., Tong-un, T. and Pakdeechote, P. (2020) Tangeretin Mitigates L-NAME-Induced Ventricular Dysfunction and Remodeling through the AT1R/PERK1/2/PJNK Signaling Pathway in Rats. Food & Function, 11, 1322-1333.

[19]   Pacher, P., Beckman, J.S. and Liaudet, L. (2007) Nitric Oxide and Peroxynitrite in Health and Disease. Physiological Reviews, 87, 315-424.

[20]   Rincón, J., Correia, D., Arcaya, J.L., Finol, E., Fernández, A., Pérez, M., Yaguas, K., Talavera, E., Chávez, M., Summer, R. and Romero, F. (2015) Role of Angiotensin II Type 1 Receptor on Renal NAD(P)H Oxidase, Oxidative Stress and Inflammation in Nitric Oxide Inhibition Induced-Hypertension. Life Sciences, 124, 81-90.

[21]   Sonoda, K., Ohtake, K., Uchida, H., Ito, J., Uchida, M., Natsume, H., Tamada, H. and Kobayashi, J. (2017) Dietary Nitrite Supplementation Attenuates Cardiac Remodeling in l-NAME-Induced Hypertensive Rats. Nitric Oxide, 67, 1-9.

[22]   Genest, J. (1961) Angiotensin, Aldosterone and Human Arterial Hypertension. Canadian Medical Association Journal, 84, 403-419.

[23]   Johnson, R.A. and Freeman, R.H. (1994) Renin Release in Rats during Blockade of Nitric Oxide Synthesis. American Journal of Physiology—Regulatory, Integrative and Comparative Physiology, 266, R1723-R1729.

[24]   Pollock, D.M., Polakowski, J.S., Divish, B.J. and Opgenorth, T.J. (1993) Angiotensin Blockade Reverses Hypertension during Long-Term Nitric Oxide Synthase Inhibition. Hypertension, 21, 660-666.

[25]   Gao, Y., Wang, Z., Zhang, Y., Liu, Y., Wang, S., Sun, W., Guo, J., Yu, C., Wang, Y., Kong, W. and Zheng, J. (2018) Naringenin Inhibits NG-Nitro-L-Arginine Methyl Ester-Induced Hypertensive Left Ventricular Hypertrophy by Decreasing Angiotensin-Converting Enzyme 1 Expression. Experimental and Therapeutic Medicine, 16, 867-873.

[26]   Okazaki, H., Minamino, T., Tsukamoto, O., Kim, J., Okada, K., Myoishi, M., Wakeno, M., Takashima, S., Mochizuki, N. and Kitakaze, M. (2006) Angiotensin II Type 1 Receptor Blocker Prevents Atrial Structural Remodeling in Rats with Hypertension Induced by Chronic Nitric Oxide Inhibition. Hypertension Research, 29, 277-284.

[27]   Dugourd, C., Gervais, M., Corvol, P. and Monnot, C. (2003) Akt Is a Major Downstream Target of PI3-Kinase Involved in Angiotensin II-Induced Proliferation. Hypertension, 41, 882-890.

[28]   Touyz, R.M. and Berry, C. (2002) Recent Advances in Angiotensin II Signaling. Brazilian Journal of Medical and Biological Research, 35, 1001-1015.

[29]   de Kloet, A.D., Krause, E.G., Shi, P.D., Zubcevic, J., Raizada, M.K. and Sumners, C. (2013) Neuroimmune Communication in Hypertension and Obesity: A New Therapeutic Angle? Pharmacology & Therapeutics, 138, 428-440.

[30]   Taylor, D.A. and Abdel-Rahman, A.A. (2009) Novel Strategies and Targets for the Management of Hypertension. In: Enna, S.J. and Williams, M., Eds., Advances in Pharmacology, Vol. 57, Elsevier Inc., Amsterdam, 291-345.

[31]   Lonn, E. (2004) The Clinical Relevance of Pharmacological Blood Pressure Lowering Mechanisms. The Canadian Journal of Cardiology, 20, 83B-88B.

[32]   Kagathara, V.G., Ambikar, D.B. and Vyawahare, N.S. (2009) Hypertension—Animal Models and Phytomedicines: A Review. Pharmacologyonline, 2, 436-461.

[33]   Wood, R. (1995) Bronchospasm and Cough as Adverse Reactions to the ACE Inhibitors Captopril, Enalapril and Lisinopril. A Controlled Retrospective Cohort Study. British Journal of Clinical Pharmacology, 39, 265-270.

[34]   Hom, K.A., Hirsch, R. and Elluru, R.G. (2012) Antihypertensive Drug-Induced Angioedema Causing Upper Airway Obstruction in Children. International Journal of Pediatric Otorhinolaryngology, 76, 14-19.

[35]   Shapovalov, G., Skryma, R. and Prevarskaya, N. (2013) Calcium Channels and Prostate Cancer. Recent Patents on Anti-Cancer Drug Discovery, 8, 18-26.

[36]   McAinsh, J. and Cruickshank, J.M. (1990) Beta-Blockers and Central Nervous System Side Effects. Pharmacology & Therapeutics, 46, 163-197.

[37]   Özkaya, E. and Yazganoğlu, K.D. (2014) Adverse Cutaneous Drug Reactions to Cardiovascular Drugs. Springer London, London.

[38]   Pal, S.K. and Shukla, Y. (2003) Herbal Medicine: Current Status and the Future. Asian Pacific Journal of Cancer Prevention, 4, 281-288.

[39]   Valli, G. and Giardina, E.-G.V. (2002) Benefits, Adverse Effects and Drug Interactions of Herbal Therapies with Cardiovascular Effects. Journal of the American College of Cardiology, 39, 1083-1095.

[40]   Jung, I.H., Kim, S.E., Lee, Y.-G., Kim, D.H., Kim, H., Kim, G.-S., Baek, N.-I. and Lee, D.Y. (2018) Antihypertensive Effect of Ethanolic Extract from Acanthopanax sessiliflorus Fruits and Quality Control of Active Compounds. Oxidative Medicine and Cellular Longevity, 2018, Article: ID 5158243.

[41]   Hernández-Abreu, O., Torres-Piedra, M., García-Jiménez, S., Ibarra-Barajas, M., Villalobos-Molina, R., Montes, S., Rembao, D. and Estrada-Soto, S. (2013) Dose-Dependent Antihypertensive Determination and Toxicological Studies of Tilianin Isolated from Agastache mexicana. Journal of Ethnopharmacology, 146, 187-191.

[42]   Bilanda, D.C., Dimo, T., Dzeufiet Djomeni, P.D., Bella, N.M.T., Aboubakar, O.B.F., Nguelefack, T.B., Tan, P.V. and Kamtchouing, P. (2010) Antihypertensive and Antioxidant Effects of Allanblackia floribunda Oliv. (Clusiaceae) Aqueous Extract in Alcohol- and Sucrose-Induced Hypertensive Rats. Journal of Ethnopharmacology, 128, 634-640.

[43]   Bello, I., Usman, N.S., Mahmud, R. and Asmawi, Mohd.Z. (2015) Mechanisms Underlying the Antihypertensive Effect of Alstonia scholaris. Journal of Ethnopharmacology, 175, 422-431.

[44]   Jorge, V.-G., Ángel, J.-R.L., Adrián, T.-S., Francisco, A.-C., Anuar, S.-G., Samuel, E.-S., Ángel, S.-O. and Emmanuel, H.-N. (2013) Vasorelaxant Activity of Extracts Obtained from Apium graveolens: Possible Source for Vasorelaxant Molecules Isolation with Potential Antihypertensive Effect. Asian Pacific Journal of Tropical Biomedicine, 3, 776-779.

[45]   Inokuchi, J., Okabe, H., Yamauchi, T., Nonaka, G. and Nishioka, I. (1986) Antihypertensive Substance in Seeds of Areca catechu L. Life Sciences, 38, 1375-1382.

[46]   Dib, I., Tits, M., Angenot, L., Wauters, J.N., Assaidi, A., Mekhfi, H., Aziz, M., Bnouham, M., Legssyer, A., Frederich, M. and Ziyyat, A. (2017) Antihypertensive and Vasorelaxant Effects of Aqueous Extract of Artemisia campestris L. from Eastern Morocco. Journal of Ethnopharmacology, 206, 224-235.

[47]   Abd El-Wahab, A.E., Ghareeb, D.A., Sarhan, E.E., Abu-Serie, M.M. and El Demellawy, M.A. (2013) In Vitro Biological Assessment of Berberis vulgaris and Its Active Constituent, Berberine: Antioxidants, Anti-Acetylcholinesterase, Anti-Diabetic and Anticancer Effects. BMC Complementary and Alternative Medicine, 13, Article No. 218.

[48]   Getiye, Y., Tolessa, T. and Engidawork, E. (2016) Antihypertensive Activity of 80% Methanol Seed Extract of Calpurnia aurea (Ait.) Benth. subsp. aurea (Fabaceae) Is Mediated through Calcium Antagonism Induced Vasodilation. Journal of Ethnopharmacology, 189, 99-106.

[49]   Cheang, W.S., Ngai, C.Y., Tam, Y.Y., Tian, X.Y., Wong, W.T., Zhang, Y., Lau, C.W., Chen, Z.Y., Bian, Z.-X., Huang, Y. and Leung, F.P. (2015) Black Tea Protects against Hypertension-Associated Endothelial Dysfunction through Alleviation of Endoplasmic Reticulum Stress. Scientific Reports, 5, Article No. 10340.

[50]   Lima-Landman, M.T.R., Borges, A.C.R., Cysneiros, R.M., De Lima, T.C.M., Souccar, C. and Lapa, A.J. (2007) Antihypertensive Effect of a Standardized Aqueous Extract of Cecropia glaziovii Sneth in Rats: An in Vivo Approach to the Hypotensive Mechanism. Phytomedicine, 14, 314-320.

[51]   Belmokhtar, M., Bouanani, N.E., Ziyyat, A., Mekhfi, H., Bnouham, M., Aziz, M., Matéo, P., Fischmeister, R. and Legssyer, A. (2009) Antihypertensive and Endothelium-Dependent Vasodilator Effects of Aqueous Extract of Cistus ladaniferus. Biochemical and Biophysical Research Communications, 389, 145-149.

[52]   Guerrero, L., Castillo, J., Quiñones, M., Garcia-Vallvé, S., Arola, L., Pujadas, G. and Muguerza, B. (2012) Inhibition of Angiotensin-Converting Enzyme Activity by Flavonoids: Structure-Activity Relationship Studies. PLoS ONE, 7, e49493.

[53]   Loizzo, M.R., Said, A., Tundis, R., Rashed, K., Statti, G.A., Hufner, A. and Menichini, F. (2007) Inhibition of Angiotensin Converting Enzyme (ACE) by Flavonoids Isolated from Ailanthus excelsa (Roxb) (Simaroubaceae). Phytotherapy Research, 21, 32-36.

[54]   Escher, G.B., Marques, M.B., do Carmo, M.A.V., Azevedo, L., Furtado, M.M., Sant’Ana, A.S., da Silva, M.C., Genovese, M.I., Wen, M., Zhang, L., Oh, W.Y., Shahidi, F., Rosso, N.D. and Granato, D. (2020) Clitoria ternatea L. Petal Bioactive Compounds Display Antioxidant, Antihemolytic and Antihypertensive Effects, Inhibit α-Amylase and α-Glucosidase Activities and Reduce Human LDL Cholesterol and DNA Induced Oxidation. Food Research International, 128, Article ID: 108763.

[55]   Sánchez-Salgado, J.C., Castillo-España, P., Ibarra-Barajas, M., Villalobos-Molina, R. and Estrada-Soto, S. (2010) Cochlospermum vitifolium Induces Vasorelaxant and Antihypertensive Effects Mainly by Activation of NO/CGMP Signaling Pathway. Journal of Ethnopharmacology, 130, 477-484.

[56]   Bankar, G.R., Nayak, P.G., Bansal, P., Paul, P., Pai, K.S.R., Singla, R.K. and Bhat, V.G. (2011) Vasorelaxant and Antihypertensive Effect of Cocos nucifera Linn. Endocarp on Isolated Rat Thoracic Aorta and DOCA Salt-Induced Hypertensive Rats. Journal of Ethnopharmacology, 134, 50-54.

[57]   Yang, Q., Sun, Y., Zhang, L., Xu, L., Hu, M., Liu, X., Shi, F. and Gu, Z. (2014) Antihypertensive Effects of Extract from Flower Buds of Coreopsis tinctoria on Spontaneously Hypertensive Rats. Chinese Herbal Medicines, 6, 103-109.

[58]   Potue, P., Maneesai, P., Kukongviriyapan, U., Prachaney, P. and Pakdeechote, P. (2020) Cratoxylum formosum Extract Exhibits Antihypertensive Effects via Suppressing the Renin-Angiotensin Cascade in Hypertensive Rats. Journal of Functional Foods, 73, Article ID: 104137.

[59]   Guerrero, M.F., Carrón, R., Martin, M.L., San Román, L. and Reguero, M.T. (2001) Antihypertensive and Vasorelaxant Effects of Aqueous Extract from Croton schiedeanus Schlecht in Rats. Journal of Ethnopharmacology, 75, 33-36.

[60]   Shin, S.-K., Ha, T.-Y., McGregor, R.A. and Choi, M.-S. (2011) Long-Term Curcumin Administration Protects against Atherosclerosis via Hepatic Regulation of Lipoprotein Cholesterol Metabolism. Molecular Nutrition & Food Research, 55, 1829-1840.

[61]   Rachmawati, H. (2016) In Vitro Study on Antihypertensive and Antihypercholesterolemic Effects of Curcumin Nanoemulsion. Scientia Pharmaceutica, 84, 131-140.

[62]   Prando, T.B.L., Barboza, L.N., de OliveiraAraújo, V., Gasparotto, F.M., de Souza, L.M., Lourenço, E.L.B. and Gasparotto Junior, A. (2016) Involvement of Bradykinin B2 and Muscarinic Receptors in the Prolonged Diuretic and Antihypertensive Properties of Echinodorus grandiflorus (Cham. & Schltdl.) Micheli. Phytomedicine, 23, 1249-1258.

[63]   Salma, U., Khan, T. and Shah, A.J. (2018) Antihypertensive Effect of the Methanolic Extract from Eruca sativa Mill., (Brassicaceae) in Rats: Muscarinic Receptor-Linked Vasorelaxant and Cardiotonic Effects. Journal of Ethnopharmacology, 224, 409-420.

[64]   Eka, M.E.B., Itam, E.H., Eyonng, E.U., Anam, E.M. and Nsa, E.E. (2011) Effect of Erythrina senegalensis Extract on Serum Glucose Concentration in Alloxan Induced Diabetic Rats after a Treatment Period of 14 Days. Multidisciplinary Journal of Research Development, 17, 110-113.

[65]   Jiang, C., Liang, L. and Guo, Y. (2012) Natural Products Possessing Protein Tyrosine Phosphatase 1B (PTP1B) Inhibitory Activity Found in the Last Decades. Acta Pharmacologica Sinica, 33, 1217-1245.

[66]   Bilanda, D.C., Bidingha, R. à G., Djomeni Dzeufiet, P.D., Fouda, Y.B., Ngapout, R.F., Tcheutchoua, Y., Owona, P.E., Njonte Wouamba, S.C., Tanfack Tatchou, L., Dimo, T. and Kamtchouing, P. (2020) Antihypertensive and Antidiabetic Activities of Erythrina senegalensis DC (Fabaceae) Stem Bark Aqueous Extract on Diabetic Hypertensive Rats. Journal of Ethnopharmacology, 246, Article ID: 112200.

[67]   Luo, L., Wu, W., Zhou, Y., Yan, J., Yang, G. and Ouyang, D. (2010) Antihypertensive Effect of Eucommia ulmoides Oliv. Extracts in Spontaneously Hypertensive Rats. Journal of Ethnopharmacology, 129, 238-243.

[68]   Consolini, A.E., Baldini, O.A.N. and Amat, A.G. (1999) Pharmacological Basis for the Empirical Use of Eugenia uniflora L. (Myrtaceae) as Antihypertensive. Journal of Ethnopharmacology, 66, 33-39.

[69]   Ahmed, B., Al-Howiriny, T.A., Mossa, J.S. and El Tahir, K.E.H. (2005) Isolation, Antihypertensive Activity and Structure Activity Relationship of Flavonoids from Three Medicinal Plants. Indian Journal of Chemistry—Section B, 44B, 400-404.

[70]   Hakkou, Z., Maciuk, A., Leblais, V., Bouanani, N.E., Mekhfi, H., Bnouham, M., Aziz, M., Ziyyat, A., Rauf, A., Hadda, T.B., Shaheen, U., Patel, S., Fischmeister, R. and Legssyer, A. (2017) Antihypertensive and Vasodilator Effects of Methanolic Extract of Inula viscosa: Biological Evaluation and POM Analysis of Cynarin, Chlorogenic Acid as Potential Hypertensive. Biomedicine & Pharmacotherapy, 93, 62-69.

[71]   Chaudhry, M.A., Alamgeer, Mushtaq, M.N., Bukhari, I.A. and Assiri, A.M. (2021) Ipomoea hederacea Jacq.: A Plant with Promising Antihypertensive and Cardio-Protective Effects. Journal of Ethnopharmacology, 268, Article ID: 113584.

[72]   Wilcox, C.S. (2005) Oxidative Stress and Nitric Oxide Deficiency in the Kidney: A Critical Link to Hypertension? American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 289, R913-R935.

[73]   Bopda, O.S.M., Longo, F., Bella, T.N., Edzah, P.M.O., Taïwe, G.S., Bilanda, D.C., Tom, E.N.L., Kamtchouing, P. and Dimo, T. (2014) Antihypertensive Activities of the Aqueous Extract of Kalanchoe pinnata (Crassulaceae) in High Salt-Loaded Rats. Journal of Ethnopharmacology, 153, 400-407.

[74]   Vergara-Galicia, J., Ortiz-Andrade, R., Rivera-Leyva, J., Castillo-España, P., Villalobos-Molina, R., Ibarra-Barajas, M., Gallardo-Ortiz, I. and Estrada-Soto, S. (2010) Vasorelaxant and Antihypertensive Effects of Methanolic Extract from Roots of Laelia anceps Are Mediated by Calcium-Channel Antagonism. Fitoterapia, 81, 350-357.

[75]   Vergara-Galicia, J., Ortiz-Andrade, R., Castillo-España, P., Ibarra-Barajas, M., Gallardo-Ortiz, I., Villalobos-Molina, R. and Estrada-Soto, S. (2008) Antihypertensive and Vasorelaxant Activities of Laelia autumnalis Are Mainly through Calcium Channel Blockade. Vascular Pharmacology, 49, 26-31.

[76]   Maghrani, M., Zeggwagh, N.-A., Michel, J.-B. and Eddouks, M. (2005) Antihypertensive Effect of Lepidium sativum L. in Spontaneously Hypertensive Rats. Journal of Ethnopharmacology, 100, 193-197.

[77]   Prasad, K. (2004) Antihypertensive Activity of Secoisolariciresinol Diglucoside (SDG) Isolated from Flaxseed: Role of Guanylate Cyclase. International Journal of Angiology, 13, 7-14.

[78]   Suzuki, A., Kagawa, D., Fujii, A., Ochiai, R., Tokimitsu, I. and Saito, I. (2002) Short- and Long-Term Effects of Ferulic Acid on Blood Pressure in Spontaneously Hypertensive Rats. American Journal of Hypertension, 15, 351-357.

[79]   Veeramani, C., Al-Numair, K.S., Chandramohan, G., Alsaif, M.A., Alhamdan, A.A. and Pugalendi, K.V. (2012) Antihypertensive Effect of Melothria maderaspatana Leaf Fractions on DOCA-Salt-Induced Hypertensive Rats and Identification of Compounds by GC-MS Analysis. Journal of Natural Medicines, 66, 302-310.

[80]   Yeh, C.-T., Huang, W.-H. and Yen, G.-C. (2009) Antihypertensive Effects of Hsian-Tsao and Its Active Compound in Spontaneously Hypertensive Rats. The Journal of Nutritional Biochemistry, 20, 866-875.

[81]   Dangi, S.Y., Jolly, C.I. and Narayanan, S. (2002) Antihypertensive Activity of the Total Alkaloids from the Leaves of Moringa oleifera. Pharmaceutical Biology, 40, 144-148.

[82]   Khan, M.Y. and Kumar, V. (2017) Mechanism of Antihypertensive Effect of Mucuna pruriens L. Seed Extract and Its Isolated Compounds. Journal of Complementary and Integrative Medicine, 14, Article ID: 20170014.

[83]   Alu’datt, M.H., Rababah, T., Alhamad, M.N., Gammoh, S., Ereifej, K., Alodat, M., Hussein, N.M., Kubow, S. and Torley, P.J. (2016) Antioxidant and Antihypertensive Properties of Phenolic-Protein Complexes in Extracted Protein Fractions from Nigella damascena and Nigella arvensis. Food Hydrocolloids, 56, 84-92.

[84]   Shaw, H.-M., Wu, J.-L. and Wang, M.-S. (2017) Antihypertensive Effects of Ocimum gratissimum Extract: Angiotensin-Converting Enzyme Inhibitor in Vitro and in Vivo Investigation. Journal of Functional Foods, 35, 68-73.

[85]   Alcaide-Hidalgo, J.M., Margalef, M., Bravo, F.I., Muguerza, B. and López-Huertas, E. (2020) Virgin Olive Oil (Unfiltered) Extract Contains Peptides and Possesses ACE Inhibitory and Antihypertensive Activity. Clinical Nutrition, 39, 1242-1249.

[86]   Matsubara, T., Bohgaki, T., Watarai, M., Suzuki, H., Ohashi, K. and Shibuya, H. (1999) Antihypertensive Actions of Methylripariochromene A from Orthosiphon aristatus, an Indonesian Traditional Medicinal Plant. Biological and Pharmaceutical Bulletin, 22, 1083-1088.

[87]   Siow, H.-L. and Gan, C.-Y. (2013) Extraction of Antioxidative and Antihypertensive Bioactive Peptides from Parkia speciosa Seeds. Food Chemistry, 141, 3435-3442.

[88]   Lewis, B.J., Herrlinger, K.A., Craig, T.A., Mehring-Franklin, C.E., DeFreitas, Z. and Hinojosa-Laborde, C. (2013) Antihypertensive Effect of Passion Fruit Peel Extract and its Major Bioactive Components Following Acute Supplementation in Spontaneously Hypertensive Rats. The Journal of Nutritional Biochemistry, 24, 1359-1366.

[89]   Ajebli, M. and Eddouks, M. (2019) Antihypertensive Activity of Petroselinum crispum through Inhibition of Vascular Calcium Channels in Rats. Journal of Ethnopharmacology, 242, Article ID: 112039.

[90]   de Jesús Ariza-Ortega, T., Zenón-Briones, E.Y., Castrejón-Flores, J.L., Yáñez-Fernández, J., de las Mercedes Gómez-Gómez, Y. and del Carmen, Oliver-Salvador M. (2014) Angiotensin-I-Converting Enzyme Inhibitory, Antimicrobial, and Antioxidant Effect of Bioactive Peptides Obtained from Different Varieties of Common Beans (Phaseolus vulgaris L.) with In Vivo Antihypertensive Activity in Spontaneously Hypertensive Rats. European Food Research and Technology, 239, 785-794.

[91]   Adedapo, A.D.A., Ajayi, A.M., Ekwunife, N.L., Falayi, O.O., Oyagbemi, A., Omobowale, T.O. and Adedapo, A.A. (2020) Antihypertensive Effect of Phragmanthera incana (Schum) Balle on NG-Nitro-L-Arginine Methyl Ester (L-NAME) Induced Hypertensive Rats. Journal of Ethnopharmacology, 257, Article ID: 112888.

[92]   Zhao, W., Yu, J., Su, Q., Liang, J., Zhao, L., Zhang, Y. and Sun, W. (2013) Antihypertensive Effects of Extract from Picrasma quassiodes (D. Don) Benn. in Spontaneously Hypertensive Rats. Journal of Ethnopharmacology, 145, 187-192.

[93]   Ahmed, Z.B., Yousfi, M., Viaene, J., Dejaegher, B., Demeyer, K., Mangelings, D. and Vander Heyden, Y. (2018) Potentially Antidiabetic and Antihypertensive Compounds Identified from Pistacia atlantica Leaf Extracts by LC Fingerprinting. Journal of Pharmaceutical and Biomedical Analysis, 149, 547-556.

[94]   Chen, Z.-Y., Peng, C., Jiao, R., Wong, Y.M., Yang, N. and Huang, Y. (2009) Anti-hypertensive Nutraceuticals and Functional Foods. Journal of Agricultural and Food Chemistry, 57, 4485-4499.

[95]   Luna-Vázquez, F., Ibarra-Alvarado, C., Rojas-Molina, A., Rojas-Molina, J., Yahia, E., Rivera-Pastrana, D., Rojas-Molina, A. and Zavala-Sánchez, Á.M. (2013) Nutraceutical Value of Black Cherry Prunus serotina Ehrh. Fruits: Antioxidant and Antihypertensive Properties. Molecules, 18, 14597-14612.

[96]   do Nascimento, K.F., Moreira, F.M.F., Alencar Santos, J., Kassuya, C.A.L., Croda, J.H.R., Cardoso, C.A.L., do Carmo Vieira, M., Góis Ruiz, A.L.T., Ann Foglio, M., de Carvalho, J.E. and Formagio, A.S.N. (2018) Antioxidant, Anti-Inflammatory, Antiproliferative and Antimycobacterial Activities of the Essential Oil of Psidium guineense Sw. and Spathulenol. Journal of Ethnopharmacology, 210, 351-358.

[97]   Jiménez-Ferrer, E., Hernández Badillo, F., González-Cortazar, M., Tortoriello, J. and Herrera-Ruiz, M. (2010) Antihypertensive Activity of Salvia elegans Vahl. (Lamiaceae): ACE Inhibition and Angiotensin II Antagonism. Journal of Ethnopharmacology, 130, 340-346.

[98]   Hsu, F.-L., Lee, Y.-Y. and Cheng, J.-T. (1994) Antihypertensive Activity of 6-O-Galloyl-D-Glucose, a Phenolic Glycoside from Sapium sebiferum. Journal of Natural Products, 57, 308-312.

[99]   Lombardo-Earl, G., Roman-Ramos, R., Zamilpa, A., Herrera-Ruiz, M., Rosas-Salgado, G., Tortoriello, J. and Jiménez-Ferrer, E. (2014) Extracts and Fractions from Edible Roots of Sechium edule (Jacq.) Sw. with Antihypertensive Activity. Evidence-Based Complementary and Alternative Medicine, 2014, Article ID: 594326.

[100]   Simões, L.O., Conceição-Filho, G., Ribeiro, T.S., Jesus, A.M., Fregoneze, J.B., Silva, A.Q.G., Petreanu, M., Cechinel-Filho, V., Niero, R., Niero, H., Tamanaha, M.S. and Silva, D.F. (2016) Evidences of Antihypertensive Potential of Extract from Solanum capsicoides All. in Spontaneously Hypertensive Rats. Phytomedicine, 23, 498-508.

[101]   Yamaguchi, S., Matsumoto, K., Koyama, M., Tian, S., Watanabe, M., Takahashi, A., Miyatake, K. and Nakamura, K. (2019) Antihypertensive Effects of Orally Administered Eggplant (Solanum melongena) Rich in Acetylcholine on Spontaneously Hypertensive Rats. Food Chemistry, 276, 376-382.

[102]   Mimaki, Y. (1995) Steroidal Saponins from the Bulbs of Triteleia lactea and Their Inhibitory Activity on Cyclic AMP Phosphodiesterase. Phytochemistry, 38, 1279-1286.

[103]   Ibarrola, D.A., Hellión-Ibarrola, M.C., Montalbetti, Y., Heinichen, O., Campuzano, M.A., Kennedy, M.L., Alvarenga, N., Ferro, E.A., Dölz-Vargas, J.H. and Momose, Y. (2011) Antihypertensive Effect of Nuatigenin-3-O-β-Chacotriose from Solanum sisymbriifolium Lam. (Solanaceae) (Ñuatî Pytâ) in Experimentally Hypertensive (ARH + DOCA) Rats under Chronic Administration. Phytomedicine, 18, 634-640.

[104]   Estrada-Soto, S., González-Trujano, Ma.E., Rendón-Vallejo, P., Arias-Durán, L., Ávila-Villarreal, G. and Villalobos-Molina, R. (2021) Antihypertensive and Vasorelaxant Mode of Action of the Ethanol-Soluble Extract from Tagetes lucida Cav. Aerial Parts and Its Main Bioactive Metabolites. Journal of Ethnopharmacology, 266, Article ID: 113399.

[105]   Khan, A.-U. and Gilani, A.H. (2008) Pharmacodynamic Evaluation of Terminalia bellerica for Its Antihypertensive Effect. Journal of Food and Drug Analysis, 16, 6-14.

[106]   Ahmadvand, H., Khosrobeig, A., Nemati, L., Boshtam, M., Jafari, N., Hosseini, R.H., Pournia, Y., Ahmadvand, H., Khosrobeig, A., Nemati, L., Boshtam, M., Jafari, N., Hosseini, R.H. and Pournia, Y. (2012) Rosmarinic Acid Prevents the Oxidation of Low Density Lipoprotein (LDL) in Vitro. Journal of Biological Sciences, 12, 301-307.

[107]   Mihailovic-Stanojevic, N., Belščak-Cvitanović, A., Grujić-Milanović, J., Ivanov, M., Jovović, Dj., Bugarski, D. and Miloradović, Z. (2013) Antioxidant and Antihypertensive Activity of Extract from Thymus serpyllum L. in Experimental Hypertension. Plant Foods for Human Nutrition, 68, 235-240.

[108]   Gasparotto Junior, A., Gasparotto, F.M., Lourenço, E.L.B., Crestani, S., Stefanello, M.E.A., Salvador, M.J., da Silva-Santos, J.E., Marques, M.C.A. and Kassuya, C.A.L. (2011) Antihypertensive Effects of Isoquercitrin and Extracts from Tropaeolum majus L.: Evidence for the Inhibition of Angiotensin Converting Enzyme. Journal of Ethnopharmacology, 134, 363-372.

[109]   Perez-Hernandez, N., Ponce-Monter, H., Medina, J.A. and Joseph-Nathan, P. (2008) Spasmolytic Effect of Constituents from Lepechinia caulescens on Rat Uterus. Journal of Ethnopharmacology, 115, 30-35.

[110]   Al-Akwaa, A.A., Asmawi, M.Z., Dewa, A. and Mahmud, R. (2020) Antihypertensive Activity and Vascular Reactivity Mechanisms of Vitex pubescens Leaf Extracts in Spontaneously Hypertensive Rats. Heliyon, 6, e04588.