Medicinal Plants in the Treatment of Hypertension: A Review

Traditional medicine is a comprehensive term for ancient, culture-bound health care practices that existed before the use of science in health matters and has been used for centuries. Medicinal plants are used to treat patients with cardiovascular diseases, which may occur due to ailments of the heart and blood vessels and comprise heart attacks, cerebrovascular diseases, hypertension, and heart failure. Hypertension causes difficulty in the functioning of the heart and is involved in atherosclerosis, raising the risk of heart attack and stroke. Many drugs are available for managing these diseases, though common antihypertensive drugs are generally accompanied by many side effects. Medicinal herbs have several active substances with pharmacological and prophylactic properties that can be used in the treatment of hypertension. This review presents an overview of some medicinal plants that have been shown to have hypotensive or antihypertensive properties.


Introduction
Cardiovascular diseases (CVDs) are a major cause of weakness and early death and, therefore, constitute a main communal health problem. 1 High blood pressure (BP), mentioned as a silent killer, is triggered by a range of factors, including the interaction of genetic and environmental components causing disorderliness in BP regulation. 2 Hypertension (HTN) is the most common risk factor in acute myocardial infarction and is accountable for about 16.5% deaths annually across the world. It is also the most important reason for the morbidity and mortality accompanying CVDs. 3 It has been predicted that by the year 2025, 29% of the world's adults, or almost 1.56 billion people, will suffer from HTN. 4 HTN is described as systolic blood pressure (SBP) ≥ 140 mm Hg and diastolic blood pressure (DBP) ≥ 90 mm Hg, according to the mean of 2 or more appropriate measurements of seated BP. 5 Many antihypertensive mediators are used for the treatment of HTN, such as diuretics, sympatholytic agents, renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, calcium channel blockers, β-adrenergic and α 1 /β-adrenergic antagonists, and vasodilators. 6 These drugs have various side effects, including muscle cramps, abnormal heart rate, blurred vision, skin rash, vomiting, kidney failure, extreme tiredness, headache, and edema. 7 Current growth in the acceptance of alternative medicines and natural products has drawn attention to traditional medicines for the treatment of CVDs. 8 Approximately 75% to 80% of the world's population, predominantly in developing countries, uses herbal medicines for primary healthcare because of their better compatibility with the human body, lower costs than novel pharmaceuticals, and fewer side effects. 9 Persian medicine, an ancient and well-known traditional system of medicine, is based on the theory of humors for the prevention and treatment of diseases. 10 Persian medical scholars like Avicenna and Rhazes have described various types of diseases and recommended lifestyle modifications and herbal treatments for the alleviation of problems.
Medicinal plants have also been examined for their therapeutic properties. Some of them play an essential role in the production of over 50% of the currently available

Bindii (Tribulus terrestris)
Tribulus terrestris is a medicinal plant used for treating HTN. Bindii causes a decrease in BP in spontaneously hypertensive (SHR) rats. Its methanolic and aqueous extracts (0.3-15 mg/mL) have been shown to have vasodilatory properties. 22 This plant is used for its diuretic effects. Furthermore, all of the saponins (furostanol and spirostanol saponins and sulphated saponins of tigogenin and diosgenin) of this plant prevent the production of H 2 O 2 along with the proliferation of VSMCs. 23

Black Cumin (Nigella sativa)
The Nigella sativa plant, well recognized as the seed of blessing, has been used in the Middle East, Europe, and Africa for years. This plant and its components cause a decrease in BP. 24 Oral administration of N. sativa seed oil extract (100 or 200 mg) to mild hypertensive male patients for eight weeks results in a decline of 10.6 and 9.6 mm Hg in SBP and DBP, respectively. 25 Black cumin also lowers BP through vasorelaxation by means of its ability to block Ca 2+ channels. Other mechanisms that may elucidate the hypotensive effect of N. sativa relate to its diuretic function, antioxidant activities, and anti-inflammatory properties. 26 Black-Jack (Bidens pilosa L.) Black Jack, from the Asteraceae family, is an annual plant that grows in South America and is also found in tropical and subtropical regions around the world. Black Jack leaf extract was able to inhibit and reduce HTN in different rat models. 27 In fructose-fed rats, six hours after treatment with 75 and 150 mg/kg of methanolic leaf extract, SBP was decreased by 17% and 21%, respectively. 27 Additionally, B. pilosa has anti-cancer and anti-obesity effects as well as radical scavenging ability. 27

Black plum (Vitex doniana)
After oral administration of the fresh black plum fruit, both SBP and DBP were considerably diminished in 45 minutes. BP began returning to standard after 2 hours. 28

Greater burdock (Arctium Lappa)
Burdock is also used for the treatment of HTN. This plant has reactive oxygen species (ROS) scavenging action, is able to inhibit vascular inflammation, and can stimulate vasorelaxation. 29 Arctigenin (a dietary phytoestrogen) is one bioactive component in the dry seeds of burdock that causes an increase in NO production and a decrease in the levels of superoxide anion. 30

Burhead (Echinodorus grandiflorus)
Echinodorus grandiflorus is used in Brazilian folk medicine as a diuretic drug. The aqueous extracts of this plant can cause a decline in the mean arterial pressure (MAP) in addition to cardiac output and vascular resistance in SHRs. Burhead also induces persistent diuresis and decreased BP by activating muscarinic and bradykinin receptors with effects on prostaglandins and nitric oxide pathways. 31

Cardamom (Elettaria cardamomum)
Elettaria cardamomum fruit powder has been assessed for its antihypertensive capability. In powder form (3 g), it has been shown to reduce mean MAP as well as SBP and DBP by 19

Chinese Sage (Salvia miltiorrhiza)
A traditional Chinese herb, Salvia miltiorrhiza, has been revealed to have cardioprotective effects on animals and humans. In addition to its vasodilatory capability, Chinese sage possesses anti-hypertensive properties including antioxidative effects through decreased ROS production, increased antioxidative enzymes, and anti-proliferative activities by preventing platelet-derived growth factor (PDGF)-induced proliferation of VSMCs, and antiinflammatory capacity by inhibiting TNF-α and NF-κB production. 36,37 Cinnamon (Cinnamomum zeylanicum) Another plant used for the treatment of HTN is Cinnamomum zeylanicum. Cinnamon has reduced BP in numerous rat models and in people with prediabetes and type2 diabetes (T2D). The aqueous extract of its stem bark causes a reduction in SBP and prevents contractions prompted by potassium chloride (also known as KCl), related to the endothelium, NO, and ATP-sensitive K+ channel (K ATP channel

Coriander (Coriandrum sativum)
Coriander is used as a traditional medicine for the treatment of cardiovascular and gastrointestinal diseases. It has been shown to display antioxidant effects. 41 Intravenous use of the aqueous methanolic extract of the seeds (1-30 mg/mL) causes a reduction in SBP, DBP, and MABP, possibly through the Ca 2+ antagonist. Additionally, this extract exhibits diuretic affects. 42

Dogbane (Apocynum venetum)
The leaves of the dogbane plant seem to be rich in flavonoids and quercetin variants, which have been found to help fight HTN. Extracts of dogbane leaves (10 μg/ mL) induce vasorelaxation by enhancing NO, causing the scavenging of ROS. This plant's extracts improve renal function as an antihypertensive effect. 43

Dog-strangling Vine (Cynanchum wilfordii)
Cynanchum wilfordii is used in traditional Chinese medicine, and nearly all parts of this plant are considered advantageous for different vascular diseases. Ethanolic extracts (100 and 200 mg/kg/d) of C. wilfordii reduced BP in high fat/cholesterol-fed rats, by motivating Akt, triggering increased eNOS activity as well as increased NO and cyclic guanosine monophosphate (cGMP) production in addition to a decline in the expression of VCAM-1 and endothelin-1 (ET-1). 44

Harmel (Peganum harmala)
Wild Syrian rue (family Zygophyllaceae) is called "Espand" in Persian, and different parts of this plant including its seeds, bark, and root have been used in folk medicine. 45 Espand is used for the treatment of HTN. Peganum harmala prompts relaxation through both endothelial cells and VSMCs. Three harmala alkaloids, i.e. Harmine, harmaline, and harmalol, are espand's active constituents which have shown vasodilatory properties by increasing NO production. 46

Fang Ji (Stephania tetrandra)
Stephania tetrandra is able to regulate high BP by reducing inducible nitric oxide synthase (iNOS) expression and blocking Ca 2+ channels. An alkaloid tetrandrine, the bioactive constituent of this plant, has anti-inflammatory and anti-oxidant effects, both of which are probably involved in the plant's antihypertensive effects. 47

Garden Cress (Lepidium sativum L.)
The hypotensive effect of garden cress is associated with the augmented urinary removal of sodium, potassium, and chlorides. Lepidium sativum has been revealed to have anti-inflammatory effects. Lepidium sativum induces diuresis and effective antioxidant capability, to which its antihypertensive effects may be ascribed. 48

Garden Nasturtium (Tropaeolum majus L.)
Garden nasturtium belongs to the family Tropaeolaceae. Studies have confirmed that Tropaeolum majus has a positive influence on the circulatory system. Hydroethanolic extracts of garden nasturtium have been revealed to decrease MAP in SHR rats. The ethanolic extract of T. majus (300 mg/kg), cure element (100 mg/ kg), or isoquercitrin (10 mg/kg), have diuretic activities.
All the above-mentioned constituents are able to reduce plasma ACE levels. Isoquercitrin (an active flavonoid) causes the growth of NO production. 49

Garlic (Allium sativum)
Garlic supplements have revealed their effectiveness in the treatment of HTN, decreasing BP by about 10 mm Hg systolic and 8 mm Hg diastolic, like standard BP medication. This herb is recognized for its antibacterial, antioxidant, anti-inflammatory, anti-cancer, and hypocholesteremic effects. 50 One study displayed that garlic had an approximately 80% effectiveness in the treatment of HTN. Aged garlic extract (AGE) induces a constant drop in BP compared to with other forms of garlic. Furthermore, garlic supplements prompt a major decrease in both SBP and DBP by 3.75 and 3.39 mm Hg, respectively. 51 In another study, patients with HTN who ingested garlic tablets (300-1500 mg/d) for 24 weeks described a considerable reduction in SBP by 9.2 mm Hg and DBP by 6.27 mm Hg. 52 Moreover, AGE has superoxide scavenging abilities in human neutrophils, and daily use of 150 or 400 mg/kg of garlic extract prompted an increase in eNOS activity and a decline in nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase in the aortas of fructose-fed rats. 53 The components of garlic inhibit ACE activity, diminish Ang II-induced vasoconstrictor responses, prevent VSMCs proliferation in smooth muscles, antagonize endothelin-1 prompted vasoconstriction, and inhibit the stimulation of NF-κB. 54

Giant dodder (Cuscuta reflexa)
Cuscuta, commonly known as dodder, is a genus of the family convolvolaceace. The ethanolic extract of C. reflexa led to a decline in SBP and DBP in anesthetized rats. In a dose-dependent manner, antihypertensive activity and bradycardia occurred. 55

Ginger (Zingiber officinale)
Zingiber Officinale, generally recognized as ginger, has been broadly used in the daily diet and for different therapeutic purposes. Ginger contains a large amount of potassium, which plays a role in the regulation of BP and heartbeat. Administration of two bioactive components of ginger, (6)-gingerol and (6)-shogaol, orally (70-140 mg/ kg) or intravenously (1.75-3.5 mg/kg) creates tri-phasic BP profiles: first a rapid drop, then an intermediate increase, and lastly, a delayed decline in BP. Currently, (6)-gingerol is considered to be a new Ang II type 1 receptor antagonist. 56 Recently, it has been found that ginger decreases levels of total cholesterol, triglycerides, low-density lipoprotein (LDL), and very low-density lipoproteins (VLDL). It also inhibits ACE-1 activity. 57

Ginseng (Panax spp.)
Ginseng is used in different forms, either as capsules, tablets, extracts, dried roots, oil, or as tea, and has hypotensive effects. 58 Small doses of ginseng increase BP, whereas higher doses are hypotensive. Thus, ginseng regulates BP levels in hypotensive patients probably through vascular function change, controlling the autonomic nervous system, or adjusting the arterial baroreflex. 58 The panax ginseng extract in mild hypertensive patients induces a considerable decline of 3.1 mm Hg in SBP and mm Hg in 2.3 DBP. 59 Ginsenoside Rg3(red ginseng) stimulates eNOS, enhances NO and cGMP levels, and stimulates Ca 2+ -gated K + channels. Moreover, ginseng has an anti-proliferative influence on VSMCs, and it has antihypertensive and anti-atherosclerotic abilities. 60 Red ginseng also reduces Ang II-induced VSMC growth. Another hypotensive mechanism of ginseng is its antioxidant ability, perhaps by increasing antioxidant enzymes and scavenging free radicals. Furthermore, ginseng displays anti-inflammatory properties by protecting the release of TNF-α and decreasing NF-κB and p38 MAPK pathways. 60

King of Bitters (Andrographis paniculata)
King of bitter has been used in Asian traditional medicine for the treatment of CVDs. 71 The extracts of A. paniculata has been shown to lower ACE and ROS activities in SHR rats and cause a reduction in BP. The crude extract of A. paniculate, a compound of 14-deoxy-11,12-didehydroandrographolide, prompts considerable hypotensive properties by increasing NO release and inhibiting the rise in intracellular Ca 2+ . 72 It has been revealed to have anti-inflammatory, anti-bacterial, and antioxidant effects. 72

Kudzu (Pueraria lobata)
Pueraria lobata reduced BP in dogs and hypertensive patients through its vasodilatory effect, with its ability to stimulate Ca 2+ -activated K + (KCa)channels. 73 This plant has anti-inflammatory and anti-oxidant activities, which can relatively explain its anti-hypertensive effects.
Puerarin is the major bioactive compound in this plant which has antihypertensive and other cardioprotective properties. 74

Large-fruited elm (Ulmus macrocarpa)
Oral administration of 100 mg/kg root bark of Ulmus macrocarpa (RBUM) reduced SBP in SHR rats by 20 mm Hg. The anti-hypertensive influence of RBUM could be due to its ability to improve structural and functional modifications of vascular endothelium. 75

Lemongrass (Cymbopogon citratus)
Lemongrass is a plant whose leaves and oil are used to make medicine. Lemongrass is widely used in Southern Asia, China, and Brazil. Its antihypertensive effects have been ascribed to Citral, its active phytochemical compound. 76

Melon-Gubat (Melothria maderaspatana)
Melothria maderaspatana causes a reduction in BP in hypertensive humans. The use of melon-gubat tea for 45 days in subjects with mild HTN resulted in a substantial reduction by 23.8 mm Hg and 15.5 mm Hg in systolic and diastolic BP, respectively. 82

Murungai (Moringa oleifera)
The crude extract of the leaves of the Murungai plant triggers a decrease in SBP, DBP, and MBP in a dosedependent manner by lessening vascular dysfunction and oxidative stress and stimulating endothelium-dependent vasorelaxation. The antihypertensive activity has been attributed to the thiocarbamate and isothiocyanate elements of the purified extract. 83

Onion (Allium cepa)
Onion was shown to decrease BP in fructose-fed and anesthetized normotensive rats. 84 Organo-sulfur compounds have been correlated with reducing BP by sustaining the elasticity of the major arteries accompanied by lowering the blood viscosity, thereby preventing blood clotting. 85 Quercetin, the composite most usually related to onions, can decrease BP an average of 5 mm Hg by decreasing oxidative stress through its reaction with free radicals and progressing vascular function. 85 Aqueous extracts of onion (400 mg/kg/d) increased eNOS expression but decreased that of VCAM-1. The antioxidant effects of onion seem to be the result of the inhibition of NADPH oxidase activity together with a simultaneous rise in antioxidant kinetics of glutathione peroxidase (GPX) enzymes and SOD. 86

Pointed Phoenix Tail (Gynura procumbens)
In Thai, Gynura procumbens is called "longevity spinach, " and in Chinese, it is called "Pointed Phoenix Tail. " The aqueous extract of pointed phoenix tail decreases BP in SHRs. In rat aortic rings, it inhibited contractions induced by Ang I and Ang II through a NO-dependent mechanism and inhibited ACE activity. 87 Furthermore, the crude extract of this plant (0.003 and 0.009 g/mL) suppressed both KCl-and phenylephrine-induced contractions, associated with the opening of K channels, preventing the Ca 2+ channels and discharge of prostacyclin, so it displayed a vasodilatory effect. 88

Pomegranate (Punica granatum)
The pomegranate is a fruit-bearing deciduous shrub in the family Lythraceae that grows in the region extending from Iran to northern India. Pomegranate decreases the activity of ACE by nearly 36%. One study displayed a modest decrease in SBP after drinking 50 ml/day of its juice for a year. 89

Prickly Custard apple (Annona muricata).
Annona muricata is a species of the custard apple tree family. Annonaceae, which has edible fruit. A. muricata is native to Central America and the Caribbean. The methanolic extract of the A. muricata leaf has been described to decrease a raised BP by reducing peripheral vascular resistance. 90

Qingxue Dan (Chunghyul-dan)
Chunghyul-dan is an herbal complex that has antihypertensive effects on stroke patients with stage 1 HTN. In stroke patients, after the administration of 1200 mg Chunghvul-dan, SBP and DBP were considerably reduced in comparison with baseline. 91

Radish (Raphanus sativus)
Radish is an edible root vegetable of the family Brassicaceae, grown and used throughout the world. The leaf ethyl acetate extract (30 and 90 mg/kg) reduced SBP in SHRs, whereas the seeds (0.1-3 mg/kg) reduced BP along with HR. Radish extracts increase NO production and raise antioxidant levels. The anti-proliferative and antiinflammatory capabilities of the radish may be partially involved in its antihypertensive effect. 92

Roselle (Hibiscus sabdariffa)
Hibiscus sabdariffa L. (HS) tea is used as a beverage and a treatment for HTN and hyperlipidemia. In patients with HTN, treatment with the dried extract of the calyx (250 mg) for 4 weeks has displayed remarkable antihypertensive effects. 93

Saffron (Crocus sativus)
Crocus sativus L., generally known as saffron, is a fragrant plant belonging to the Iridaceae family. This plant is native to Spain, Morocco, Greece, Iran, India, and Pakistan. 97 Administration of 400 mg of saffron tablets to healthy humans for seven days led to a decrease of 11 and 5 mm Hg in SBP and MAP, respectively. In male Wistar rats, crocin treatment (200 mg/kg for 7 days) caused a major drop in oxidative stress and an increase in antioxidant enzymes. 98 Additionally, saffron and its components blocked the inflammatory pathways comprising NF-κB and TNF-α. 99

Sesame (Sesamum indicum)
Sesame is a flowering plant in the genus Sesamum. Sesame oil is a suitable prophylactic treatment for HTN. The alcoholic extract of the seeds (1-30 mg/kg) was shown to trigger a reduction in BP in anesthetized rats. 100

Shell Ginger (Alpinia zerumbet)
Shell Ginger, also known as bright ginger, is a perennial species of ginger from the family of Zingiberaceae. Alpinia zerumbet, a west Asian plant, has modest hypotensive properties. The vasorelaxant responses of methanolic fraction of the essential oil of shell ginger are induced through its effects on endothelial cells or VSMCs. 101 In DOCA-salt-treated rats, the methanolic extract of this plant's leaves (100 and 300 μg/mL) prompted vasodilation by raising NO or cGMP production. 1-20 mg/kg of Alpinia zerumbet essential oil blocks Ca 2+ channels, and 0.1 mg/L of this oil causes a decrease in the levels of oxidized LDL in plasma. 102

Stone breaker (Phyllanthus niruri)
Phyllanthus niruri is a plant that causes a reduction in BP in rabbits and humans. The aqueous extract of stone breaker (200 mg/kg) raises plasma antioxidants (GSH, GPx, SOD, and catalase CAT). Additionally, diverse solvent extracts of stone breaker have been reported to prevent NF-κB, TNF-α, and COX-2. 103

Sumac (Rhus coriaria)
Sumac is a medicinal plant traditionally used for the treatment of CVDs. Rhus coriaria is known for its antioxidant activity. Hydrolysable tannins obtained from the leaves of sumac have been reported to display a vasorelaxant effect in an endothelium-dependent and NO-mediated manner. Importantly, this extract also has effective anti-inflammatory capabilities and can cause a decrease in TNF-α. 104

Sweet basil (Ocimum basilicum)
Ocimum basilicum L. is an herb used in traditional Chinese medicine to treat CVDs. In one study, the aqueous extract reduced BP levels in rats in a dose-dependent manner (100-400 mg/kg). It also induced a vasorelaxant effect and had ROS scavenging ability. 105

Sweet flag (Acorus calamus)
Sweet flag is a commonly known drug in the traditional system of medicine. The solvent extracts of sweet flag caused a reduction in MAP in normotensive rats. Acorus calamus has vasoconstrictive or vasodilatory properties in rabbit aorta as well, possibly due to a Ca 2+ dependent mechanism. 106

Sweet violet (Viola odorata)
Viola odorata, commonly known as sweet violet, is native to Europe and Asia. The leaf extract of sweet violet (0.1, 0.3, and 1 mg/kg) lowered the MAP of rats. The extract induces relaxation and NO production, and Ca 2+ influx control causes this vasodilatory effect. The extract also improves CVDs risk factors by stimulating a substantial decline in total cholesterol and LDL-C. 107

Tea (Camellia sinensis)
Tea is a beverage of cured leaves or leaf buds of the tea plant Camellia sinensis. 108 It has pleiotropic effects comprising antibacterial, anti-inflammatory, anti-cancer, and antidiabetic properties, accompanied by antihypertensive actions. Green tea decreases both SBP and DBP by 1.98 and 1.92, respectively. 109 Remarkably, it has been stated that green tea induces a more potent hypotensive effect than black tea. 110 One study established that hypertensive patients who used up to 4479 mg of black tea for 24 weeks showed a substantial decrease by 2 and 2.1 mm Hg in SBP and DBP, respectively. 111 The bioactive constituents of tea have been shown to exert anti-oxidant and anti-inflammatory effects. The mechanisms of oxidative stress reduction by tea which include increasing CAT antioxidant enzyme, inhibition of eNOS uncoupling, superoxides scavenging capacity, and reducing NAPDH oxidase production, cause a reduction in BP besides TNF-α levels. 108 Epigallocatechin gallate (EGCG), derived from tea, caused a decrease in VCAM-1 levels, prevented NF-κB activation, and stimulated prevention of proliferation in human aortic VSMCs through the upregulation of HO-1 enzyme expression. 112

Tianma (Gastrodia elata Blume)
Gastrodia elata is a saprophytic perennial herb of the family Orchidaceae and is used in traditional Chinese medicine. Gastrodia rhizome has antihypertensive properties. The acidic polysaccharides extracted from the rhizome trigger a significant reduction in BP levels. 113 The methanolic extracts (0.02 ml/g) of Tianma exhibited anti-inflammatory properties by decreasing iNOS expression and NO levels. In old patients with refractory HTN, gastrodin, a main bioactive constituent of Tianma, triggered a decline in SBP and pulse pressures, raised NO levels, and decreased endothelin levels. Gastrodin (a phenolic glycoside) decreased SBP by interfering with the RAAS and diminished serum levels of Ang II along with the expression of both ACE and AT1R. 114

Tomato (Lycopersicon esculentum)
The tomato is the edible part of the plant Solanum lycopersicum. Tomato extract contains carotenoids which are recognized as operative antioxidants. The extract of tomato (Lyc-O-Mato) moderately decreased BP in patients with HTN. 115 Tomato extract has a clinically substantial capacity to decrease SBP by more than 10 mm Hg and DBP by more than 5 mm Hg. 115 The root extract of tomato reduced BP levels in hypertensive rats. The antioxidantrich extract of tomato has been revealed to decrease both SBP and DBP in hypertensive patients. 116

Turmeric (Curcuma longa)
Curcuma longa or turmeric, originates from Southeast India and is widely cultivated in the tropical areas of South Asia. Turmeric, also called curcumin, has antiinflammatory and anti-cancer properties. 117 Curcumin exerts advantageous effects on CVDs, such as HTN. Curcumin decreases AT 1 R expression in arteries by disturbing SP1/AT 1 R DNA binding, thereby decreasing AT 1 R-mediated vasoconstriction and then inhibiting the progress of HTN. 118

Umbrella tree (Musanga cecropioides)
Musanga cecropioides, the African corkwood or umbrella tree, is found throughout the tropical rain forests, mostly in West Africa. The latex and the leaf extract of this plant are used as a vasorelaxant and a hypotensive mediator. The water extract of the stem bark produces a dose-dependent decrease in MABP at the dose of 10 mg/kg (4.51 ± 0.5 mm Hg) and at the 40 mg/kg dose (65.23 ± 6.28 mm Hg). 119

Vidanga (Embelia ribes)
Embelia ribes, commonly known as false black pepper, is a species in the family Primulaceae. It is widely dispersed throughout India. Embelia ribes has hypotensive effects. The aqueous extract of E. ribes (100 mg/kg) is able to reduce both SBP and HR and enhance endogenous antioxidants, including SOD, CAT, and GSH. 120

White Horehound (Marrubium vulgare)
Marrubium vulgare (common horehound) is a flowering plant native to Europe, northern Africa, and southwestern and central Asia. White horehound causes a significant decrease in SBP. This hypotensive effect may be due to its anti-hypertrophic and vasorelaxant properties. The diterpene marrubenol isolated from this plant can strongly block L-type Ca 2+ channels and subsequently prevent the contraction of VSMCs. Also, phenylpropanoids extracted from white horehound can prevent the lipoproteininduced secretion of endothelin-1. 121 Some medicinal plants which are commonly acknowledged to be beneficial in the treatment of HTN are discussed in Table 1.

Medicinal plants used for the treatment of HTN in Iran
The Sassanid Empire in Iran had an efficient and advanced official system of medicine that prominently influenced the advancement of medical sciences. 122 For the duration of the golden age of the Islamic era, from the 9th to the 12th centuries A.D., medical information from numerous fields concerning cardiology thrived because of outstanding Persian physicians and scholars. 123 Avicenna assumed and demonstrated that some natural medicaments have the capacity to help other treatments by directing them towards specific body organs. 124,125 In view of that, Avicenna suggested the combination therapy of a cardiac medicine with Lemon balm (Melissa officinalis L.) or Behmen (Centaurea behen L.). 122 The com parison of herbal medicines used in studying HTN in different regions of Iran has indicated that different parts of Iran use diverse plants to treat this disorder. 126 In Mobarakeh of Isfahan, curly dock (Rumex crispus L.), jujube (Ziziphus jujuba L.), and olive (Olea europaea L.) are used conventionally. 127 In Sistan and Baluchestan prov ince, nigella (Nigella sativa L.) is used to treat HTN. 128 Milk thistle (Silybum marianum L.), yarrow (Achillea tenuifolia), chicory (Cichorium intybus), barberry (Berberis vulgaris), shepherd's purse (Capsella bursa-pastoris), field horsetail (Equisetum arvense), Persian walnut (Juglans regia), and annual yellow sweetclover (Melilotus indicus) are used in Kazerun to treat HTN. 129 In the Arasbaran region, barberry, yarrow (Achillea millefolium L.), ecballium (Ecballium elaterium), common hawthorn (Cra taegus monogyna), and English yew (Taxus baccata L.) are considered to have BP lowering potential. 130 Falcaria vulgaris (Falcaria vulgaris), saffron (Crocus haussknechtii), berberidaceae (Ber beris integerrima), Christ's thorn jujube, ramsons (Allium ursinum), salsify (Tragopogon porrifolius), and dill (Anethum graveolens) are used to treat high BP in Lorestan Province. 131 Warty-leaved rhubarb (Rheum ribes L.) and Christ's thorn (Paliurus spina-christi) are used to decrease BP in Ilam province. 132 The bioactive substances of dill could be a source for anti-HTN and anti-diabetes properties. 133 Barberry has a lowering effect on BP. Valerian has BP diminishing effects in animals. 134 Medicinal plants that have been recognized as being effective in controlling and treating HTN are listed in Table 2. 128,134,135 Study limitations A small number of traditionally used plants have been confirmed precisely through animal studies and clinical trials, but the detailed mechanisms of action of these plants are still unknown. Medicinal plants are unsuccessful in attaining the anticipated scale due to a shortage of scientific data on their safety and efficiency. Thus, systematic validation studies are required.

Conclusion
Avicenna had a remarkable influence on the field of cardiology, and his role had the most prominent effects on the progress of cardiological science. In the third volume of the Canon of Medicine, Avicenna defined numerous cardiovascular conditions and disorders. HTN is among the most prevalent diseases in the world, though it can be regulated and prohibited, and causes many difficulties for affected patients. Many simple approaches can be adopted to regulate high BP, such as lifestyle changes, pharmacotherapy, or both.

Future view
Traditional botanical research on medicinal plants suggests novel areas of study on the antihyper tensive effects of medicinal plants. With regard to their safety and efficacy, medicinal plants can be processed to produce natural medications; however, their effect should be confirmed by pharmacological research and clinical trials. Studies in the future, which will focus on elongated randomized trials, may be of assistance in clarifying the durable effects of medicinal plants. In addition, studies on different herbs with antihyper tensive effects have been promising so far and will lead to the discovery of new antihyper tensive herbal medicines in the near future.

Ethical Issues
Not applicable.

Conflict of Interest
Authors declare no conflict of interest.