Plant

(Family)

Plant Parts, Type of extract

Animal used

Isolated Antihypertensive Phytochemicals

Use and Dosage

Mechanism of action

Citation

Acanthopanax sessiliflorus

(Araliaceae)

Fruits,

Ethanolic extract

Male Wistar rats

3(a) 22α- hydroxychiisanoside

3(b) 22α- hydroxychiisanogenin

3(c) chiisanoside

3(d) chiisanogenin

3(e) momordin Іb (Figure 3)

In vivo antithrombotic and antiplatelet activities.

125, 250, 500 and 1000 mg/kg/day.

Ethanolic extracts from A. sessiliflorus showed effects by

1) scavenging free radical

2) NO production facilitation

3) inhibition of ACE

[40]

Agastache mexicana

(Lamiaceae)

Aerial parts,

Methanolic extracts and

EtOH: H₂O (7:3) extracts

Male Wistar rats

3(f) tilianin

(Figure 3)

Vasorelaxant activity.

12.5, 25, 75, 100 mg/kg.

6624 mg/kg is the lethal dose.

Tilianin isolated from methanolic extract of A. mexicana exhibited endothelium-dependent vasorelaxant effect by

1) NO production and

2) opening K⁺ channel

[41]

Allanblackia floribunda Oliv.

(Clusiaceae)

Bark,

Aqueous extract.

Sucrose- induced hypertensive rats (SuHR), Alcohol- induced hypertensive rats (AHR)

Not reported

Prevention of HTN in rats induced by alcohol, sugar, and also oxidative stress.

Aqueous extract of 200 and 400 mg/kg/day.

Extract of A. floribunda Oliv. significantly impeded

1) the upsurge of MDA, superoxide dismutase (SOD), catalase

2) the decrease of glutathione in kidney, liver, aorta, and heart of SuHR and AHR.

[42]

Alstonia scholaris

(Apocynaceae)

Bark and leaves,

Methanol extract, dichloromethane fraction, ethyl acetate fraction and n-butanol fraction,

Sprague Dawley rats

Not reported

Vasorelaxant activity.

0.5, 1 and 2

mg/mL.

Prepared extracts from A. scholaris possess vasodilation by

1) blocking Ca²⁺ channels

2) soluble guanylate cyclase (sGC) direct activation

3) inhibition of inositol 1,4,5-triphosphate formation

[43]

Apium graveolens (Apiaceae)

Plant materials,

Hexane, dichloromethane, ethyl acetate and methanol extracts

Male Wistar rats

3(g) apigenin

(Figure 3)

Vasorelaxant activity.

62, 110 and 200 μg/mL (ethyl acetate extract).

Extracts of A. graveolens exerts vasodilation by interfering with

1) voltage-dependent Ca²⁺ channels (VDCC)

2) receptor-operated Ca²⁺ channels (ROCC).

[44]

Areca Catechu L.

(Arecaceae)

Seed,

Areca II-5-C

Male

Spontaneous Hypertensive Rats (SHR)

Not reported

Antihypertensive effects, 100 and 200 mg/kg comparable with 30 and 100 mg/kg of captopril.

10 and 15 mg/kg (IV).

Inhibitory hypertensive effect of A. catechu specially Areca II-5-C is mediated by the

1) inhibition of pressor responses to both Angiotensin I and Ang-II.

[45]

Artemisia campestris L

(Asteraceae)

Aerial part,

Aqueous extract (AcAE)

Wistar rats and Albino mice

3(h) chlorogenic acid

3(i) 3,4‑ dicaffeoylquinic acid

3(j) 3,5- dicaffeoylquinic acid

3(k) 4,5- dicaffeoylquinic acid

3(l) vicenin-2

(Figure 3)

Antihypertensive, hypotensive and vasorelaxant effect.

40, 150 mg/kg/day.

Aqueous extract (AcAE) of A. campestris exerts hypotensive, antihypertensive, and

vasorelaxant effect by

1) calmodulin-NO-cGC- PKG pathway

2) Ca²⁺ influx inhibition through volage-operated calcium channels (VOCC)

3) intracellular Ca²⁺ mobilization activation into sarcoplasmic reticulum

[46]

Berberis vulgaris

(Berberaceae)

Roots,

Ethanolic extract

Not reported

3(m) berberine (Figure 3)

In vitro antioxidant effect.

0.2 - 1 mg/ml extract decreased production of thiobarbituric acid reactive substances (TBARS) from 9 ± 0.3 to 4 ± 1.1 nmol/g. 0.2 - 1 mg/ml extract and berberine lowered NO, 2,2-diphenyl-1- picrylhydrazyl (DPPH) oxidation in the range of 16% - 25% and 13% - 46% than control respectively (p < 0.05); increased liver glutathione peroxidase and SOD activity in the range of 10% - 70% and 55% - 270% respectively.

Not reported

[47]

Calpurnia aurea (Ait.)

(Fabaceae)

Seed,

80% methanol extract

Sprague- Dawley rats, Guinea pigs

Not reported

Hypotensive and antihypertensive effects, 5 - 250 mg/L of 80% methanol extract, maximum 92.1% relaxation achieved for 250 mg/L.

Pre-treatment with 80% methanol extract resulted rightward non-parallel shift in Ca²⁺ dose-response curves by

1) blocking Ca²⁺ influx via VDCC which relaxes VSMC.

[48]

Camellia sinensis O. Ktze

(Theaceae)

Black tea extract

Male Sprague Dawley rats

4(a) theaflavin-3,3’-digallate (TF3) (Figure 4)

1.5 μg/ml extract and 0.1, 0.5 μg/ml TF3 significantly improved (p < 0.05) endothelium- dependent relaxations in homocysteine- treated rat aorta.

Black tea extract exerts effects by

1) promoting Homocysteine metabolism

2) inhibition of phosphorylated ATF3, eIF2α, and cleaved ATF6 expression which reduces endoplasmic reticulum stress

3) reducing oxidative stress

[49]

Cecropia glaziovii Sneth

(Cecropiaceae)

Leaves,

Aqueous extract and n-butanol fraction

Rats and mice of three-month- old

4(b) procyanidin B5

4(c) procyanidin B3

4(d) catechin

4(e) procyanidin B2

4(f) epicatechin

4(g) procyanidin C1

4(h) orientin

4(i) isoorientin and

4(j) isovitexin

(Figure 4)

Pronounced hypotension.

0.5 g/kg/bid.

Not reported

[50]

Cistus ladaniferus

(Cistaceae)

Aerial parts,

Aqueous extract

Adult Wistar rats

4(k) quercetin

(Figure 4)

Antihypertensive properties.

Aqueous extract of 500 mg/kg/day.

The antihypertensive effects of C. ladaniferus are mostly

1) due to an endothelium-dependent vasodilatory activity.

[51]

Clitoria ternatea

(Fabaceae)

Petals,

Aqueous extract, crude lyophilized extracts (CLE)

Not reported

Not reported

6.7 mg/mL CLE induced 61% ACE I inhibitory activity.

1) Reference [52] found flavonoid compounds like quercetin, kaempferol, quercetin-3-rutinoside, and (-) epicatechin presenting more than 42% ACE I inhibition. Flavonoids’ number and position of -OH groups in the rings, as well as the existence of double bonds, which form stable chelating complexes with zinc in active site of ACE I [53] .

[54]

Cochlospermum vitifolium

(Cochlospermaceae)

Bark,

Methanolic extract

Wistar rats and Spontaneously hypertensive rats

4(l) naringenin (NG)

(Figure 4)

120 mg/kg extract, 50 and 160 mg/kg NG exerted acute antihypertensive effects

The NO-cGMP pathway has been identified as the most important signaling mechanism of plant extracts and Naringenin’s vasorelaxant activities. Other mechanisms involved also-

1) synthesis of NO

2) PGI₂ production

3) Activation of K⁺ channel on endothelial dysfunction.

[55]

Cocos nucifera Linn.

(Arecaceae)

Endocarp.

Ethanolic extract

Male Wistar rats

5(a) ferulic acid

5(b) vanillic acid (Figure 5)

3(h) chlorogenic acid

(Figure 3)

Vasorelaxant and antihypertensive effects.

300 mg/kg.

The vasorelaxant and antihypertensive effects of C. nucifera ethanolic extract is linked to

1) activating NO/GC pathway directly

2) muscarinic receptors stimulation

3) cyclooxygenase pathway

[56]

Coreopsis tinctoria

(Asteraceae)

Dried and powdered flower buds,

Ethanol extract

Spontaneously hypertensive rats (SHR),

Wistar-Kyoto rats

4(k) quercetin

(Figure 4)

5(c) quercetagetin-7- O-glucoside

5(d) flavanomarein

5(e) marein

5(f) luteolin

5(g) coreopsis chalcones

(Figure 5)

Antihypertensive activity.

100 mg/kg ethanol extract.

Flavonoids from C. tinctoria ethanolic extracts produce decent effect by

1) downregulating plasma Ang-II and ACE, AT₁R, transforming grown factor-β (TGF-β) expression in left ventricle, but upregulating ACE II

[57]

Cratoxylum formosum

(Hypericaceae)

Leaves,

Aqueous extract

Sprague- Dawley rats

5(h) phenolic acid

(Figure 5)

Aqueous extract of 100, 300, and 500 mg/kg lowered SBP (158.2 ± 1.5 mmHg, 137.4 ± 2.1 mmHg, and 139.3 ± 2.5 mmHg) significantly (p < 0.05, n = 8) in hypertensive rats against control.

C. formosum aqueous extract exhibits therapeutic effects by

1) rising plasma NO levels, and decreasing oxidative stress

2) reducing serum ACE, plasma Ang-II and AT₁R upregulating in l-NAME induced hypertensive rats

3) suppressing RAS

[58]

Croton schiedeanus Schlecht

(Euphorbiaceae)

Leaves,

Aqueous extract

Spontaneously hypertensive rats

Not been elucidated

Antihypertensive, bradycardic, and vasorelaxant effects.

Aqueous extract of 5 - 100 mg/kg.

C. schiedeanus Aqueous extract exerts antihypertensive, bradycardic, vasorelaxant effects by

1) Ca²⁺ influx blocking through VDCC

[59]

Curcuma domestica

(Zingiberaceae)

Curcumin nanoemulsion

Not reported

5(i) curcumin

(Figure 5)

Antihyperlipidemic,

71.166% inhibition of HMG-CoA reductase (HMGCR) compared to pravastatin after correction, ACE inhibitory activity of curcumin nanoemulsion at 2 mg/mL.

Curcumin inhibits HMGCR production which synthesizes cholesterol in liver [60] .

[61]

Echinodorus grandiflorus (Cham. & Schltdl.) Micheli.

(Alismataceae)

Leaves,

Ethanol soluble fraction (ESEG)

Male Wistar rats

Not reported

Diuretic activity like hydrochlorothiazide of ESEG (30 - 300 mg/kg, p.o.), sparing ${\text{HCO}}_3^{-}$ and serum nitrite increased. Furthermore, intraduodenal ESEG administration induces antihypertension and hypotension in 2K1C rats significantly.

The hypotensive and antihypertensive action of ethanol soluble fraction of E. grandiflorus are mediated by

1) muscarinic and bradykinin B2 receptor activation, with directly involving NO and prostaglandin pathways.

[62]

Eruca sativa Mill.,

(Brassicaceae)

Aerial parts,

Crude extract of E. sativa, n-hexane, chloroform, ethyl acetate, and aqueous extract.

Balb^C mice and Sprague- Dawley rats

4(k) quercetin

(Figure 4)

5(j) erucin

(Figure 5)

Antihypertensive activity,

vasodilatory and partly cardiac effects at

1, 3, 10, 30 and 100 mg/kg

E. sativa aqueous and crude extract mediated antihypertensive effect through

1) NO release linked by muscarinic receptors

2) Ca⁺² influx and release inhibitory effect

[63]

Erythrina senegalensis DC

(Fabaceae)

Stem barks,

Aqueous extract

Male albinos Wistar rats,

Hypertensive

diabetic rats (HDR)

Alkaloids, flavonoids, phenols in extract whose antidiabetic and antihypertensive activity have been showed [64] .

Antihypertensive, cardiomodulator, antioxidant, hypolipidemic, and hypoglycemic properties.

100 and 200 mg/kg of aqueous extract were tested on two groups of HDR, for 28 days.

Aqueous extract of E. senegalensis mainly act by

1) activating AMP-activated protein kinase, expressing Glucose transporter 4 and Glucose transporter 1, and inhibiting protein tyrosine phosphatase 1B by are involved in stimulating basal and insulin responsive glucose uptake [65] .

[66]

Eucommia ulmoides Oliv

(Eucommiaceae)

Barks,

50% ethanol extract (Lignans)

(EuL)

Male Sprague- Dawley rats and male spontaneously hypertensive rats.

Not reported

EuL of 150 and 300 mg/kg bid lowered SBP significantly (p < 0.05, n = 8) than control.

1) EuL increased plasma NO in vivo. This effect is linked with endothelium, that did not follow the result of in vitro. In vivo EuL metabolizes into compounds which release NO from endothelium. EuL in vitro cannot do it.

[67]

Eugenia uniflora L.

(Myrtaceae)

Leaves,

Aqueous Crude Extracts

Normotensive male Wistar rats

Not reported

For hypotension, ED₅₀ was found to be 3 mg dried leaves (d.l.)/kg.

For diuresis, 120 mg d.l./kg extract exhibited most potently compared to amiloride.

1) Hypotensive effect of the leave extract of E. uniflora is moderated by direct vasodilation

2) Weak diuresis is related to renal blood flow increase.

[68]

Euphorbia cuneata Vahl.

(Euphorbiaceae)

Aerial parts,

Alcoholic extract

Normotensive albino rats

4(l) naringenin

(Figure 4)

5(k) isoaromadendrin

5(l) taxifolin

5(m) isosinensin

(Figure 5)

Naringenin (3.3 mg/kg) decreased BP by 20 mmHg; isoaromadendrin (3.3 mg/kg) decreased BP and heart rate (HR) by 36.5 mmHg and 4% respectfully; taxifolin (3.3 mg/kg) decreased BP by 20 mmHg; isosinensin (3.3 mg/kg) decreased BP and HR by 15 mmHg and 6.2% respectfully; isosinensin (6.6 mg/kg) decreased BP and HR by 16.6 mmHg and 16.6% respectfully

1) Isosinensin found in alcoholic extracts of E. cuneata lowers blood pressure due to decrease in HR produced by

vasodilatation

2) Isoaromadendrin was most potent having four hydroxyl groups.

[69]

Inula viscosa L.

(Asteraceae)

Leaves,

Petroleum ether extract, dichloromethane extract, ethyl acetate extract and methanol extract.

Hypertensive l-NAME Wistar rats

5(n) 3-O-methylquercetine

5(o) cynarin

5(f) luteolin

(Figure 5)

3(h) chlorogenic acid

(Figure 3)

Antihypertensive effect.

Methanol extract of 40 mg/kg.

1) Methanol extract exhibited antihypertensive effect predominantly by endothelium-dependent vasodilation.

2) Chlorogenic acid and cynarin isolated from I. viscosa Methanol extract, possess strong vasorelaxant activity.

[70]

Ipomoea hederacea Jacq.

(Convolvulaceae)

Dried seeds,

Aqueous- ethanolic extracts, butanol fraction (Ih.Bn)

Albino rats

Not specified

Antihypertensive activity. Ih.Bn of 0.01 - 100 mg/kg body weight (BW) dose dependently decreased DBP, SBP, HR, mean arterial pressure (MAP), pulse pressure.

1) Potent hypotensive effect was presented by butanol fractions of I. hederacea by β blocking, α₁ blocking, and stimulating inducible NO synthase/cyclic guanosine monophosphate (cGMP).

[71]

Kalanchoe pinnata

(Crassulaceae)

Leaves,

Aqueous extract

Male albinos Wistar rats

Not elucidated

Antihypertensive activity. In salt hypertensive rats, concurrent administration of 25, 50 and 100 mg/kg/day extract prevented SBP increase significantly by 32%, 24%, 47% and also reduced DBP increase by 35%, 33%, 56%.

Antihypertensive extracts of K. pinnata act by cardiode-pression, increasing diuresis or through vasorelaxant activity.

1) Conversion from ${\text{O}}_2^{-}$ to H₂O and H₂O₂ is catalyzed by SOD, thus SOD metabolizes ${\text{O}}_2^{-}$ and prevents HTN [72] .

[73]

Laelia anceps

(Orchidaceae)

Roots,

crude methanolic

extract

Wistar rats

5(p) 2,7-dihydroxy- 3,4,9- trimethoxyphenanthrene

(Figure 5)

Vasorelaxant and antihypertensive effects.

L-type (voltage-gated) Ca²⁺ channel (L-VGCC) agonist FPL 64176 (3.16 μM)- induced contraction was significantly diminished by 11.2, 65 μg/mL methanolic extract

1) Root extract of L. anceps causes vasorelaxation by blockade of L-VGCC.

[74]

Laelia autumnalis

(Orchidaceae)

Plant material, crude methanolic extract (MELa)

Wistar rats

Not reported

Vasorelaxant and antihypertensive activity.

MELa (0.15 - 50 μg/mL),

100 mg/kg (orally).

Methanolic extract of L. autumnalis produced antihypertensive effect by

1) inhibiting VGCC, receptor-controlled Ca²⁺ channel, cGMP pathway involving blocking of Ca²⁺ channels through endothelium-independent pathway

2) inhibiting Ca²⁺ mobilization from intracellular stores

3) increasing cGMP levels

[75]

Lepidium sativum L

(Brassicaceae)

Seeds,

Aqueous extract

WKY and spontaneously hypertensive male rats

Not determined

Decreasing BP and increasing water and electrolytes excretion.

20 mg/kg for 3 weeks.

L. Sativum aqueous extract demonstrated antihypertensive effects-

1) by mediated diuretic and natriuretic action.

[76]

Linum usitatissimum

(Liliaceae)

Seed

Sprague Dawley normotensive male rats

5(q) secoisolariciresinol diglucoside (SDG) (Figure 5)

In vivo antihypertensive activity.

Decrease in SBP, DBP, and MAP were dose dependent for SDG of 3, 5 mg/kg, 5 - 150 mins after administration.

Pretreatment with methylene blue (1 mg/kg) prevented SDG (10 mg/kg) induced reduction in arterial pressures.

SDG exhibited antihypertensive effect by

1) directly stimulating GC (like nitrovasodilator) and not due to NO synthase

2) due to SDG’s metabolites (secoisolariciresinol, enterolactone and enterodiol)

[77]

Melothria maderaspatana

(Cucurbitaceae)

Leaf,

Ethyl acetate extract

Male albino Wistar rats

5(a) ferulic acid (Figure 5)

In vivo antihypertensive activity.

30, 60, 120 mg/kg BW extract reduced SBP and DBP significantly (p < 0.05) after 6 weeks of administration in DOCA-salt hypertensive rats than control.

Ferulic acid found in the extract was reported having antihypertensive effect on spontaneously hypertensive rats [78] by

1) NO-mediated vasodilation

2) improving bioavailability of NO

[79]

Mesona procumbens Hemsl.

(Lamiaceae)

Dried full plant,

Water extract (WEHT)

Male 6-week-old spontaneously hypertensive rats and Wistar-Kyoto rats

5(r) caffeic acid (CA) (Figure 5)

In vivo antihypertensive activity.

WEHT (1 g/kg of BW) significantly reduced SBP, DBP, HR by 17.7%, 11%, and 7.3%.

CA (0.1 g/kg of BW) significantly reduced SBP, DBP, HR by 23.4%, 15%, 11.2%.

1) Water extract of M. procumbens had scavenging activity on free radicals and ROS (e.g., hydroxyl or peroxyl/hydroperoxy radicals)

2) plasma metabolites of CA act as antioxidants

3) Both reduced oxidative stresses, or increased antioxidant capacity in cell.

[80]

Moringa oleifera

(Moringaceae)

Leaves,

Hot water extract

Frog heart, Taenia coli of guinea pig

Not reported

Alkaloidal salts (3 - 48 ng/ml) collected from the extract showed negative inotropic effect on isolated frog heart dose-dependently; inhibited calcium response on frog heart and guinea pig taenia coli.

Alkaloidal salts from M. oleifera hot water extract induced

1) negative inotropic effect because of the presence of CCB, or Ca²⁺ antagonist.

[81]

Mucuna pruriens L.

(Fabaceae)

Seeds,

Ethyl acetate extract (MPEA)

Wistar rats

6(a) genistein

6(b) ursolic acid (UA)

6(c) L-3,4- dihydroxyphenylalanine (L-DOPA)

(Figure 6)

In vitro antihypertensive activity.

IC₅₀ of MPEA, Genistein, UA, L-DOPA are 156.45 ± 3.90 μg/mL, 68.59 ± 2.47 μg/mL, 465.83 ± 51.2 μg/mL, and 119.58 ± 4.53 μg/mL (n = 3).

Ethyl acetate extract of M. pruriens, Genistein, UA, L-DOPA showed

1) inhibition by non-competitive mode

2) ACE inhibition by protein precipitating (L-DOPA showed very little precipitation).

[82]

Nigella damascene

(Ranunculaceae)

Flour of Seeds,

Methanol extract

Not reported

Not reported

Highest 43.24% ACE inhibition was shown for bound phenolic-acid extract of seed flour. Highest 84.385% antioxidant activity was shown for glutelin-1 fraction of free phenolic-25˚C extract.

Not reported

[83]

Nigella arvensis

(Ranunculaceae)

Flour of Seeds,

Methanol extract

Not reported

Not reported

Highest 55.55% ACE inhibition was shown for free phenolic-25˚C extract of seed flour. Highest 69.76% antioxidant activity was shown for albumin fraction of free phenolic-25˚C extract.

Not reported

[83]

Ocimum gratissimum

(Lamiaceae)

Fresh whole plant with leaves, stems, and flowers,

Water extract

Wistar Kyoto rats, spontaneously hypertensive rats

6(d) rutin

(Figure 6)

In vitro and in vivo antihypertensive activity.

IC₅₀ of the water extract, and Rutin are 56.3 ± 3.12 μg/mL, and 43.08 μg/mL (n = 3).

Rutin found in water extract of O. gratissimum

1) inhibited ACE

2) inhibited endothelin-1 (ET-1)

[84]

Olea europea L. variety Picual

(Oleaceae)

Fruits,

Water-soluble extract of olive oil

Male Spontaneously hypertensive rats

Not reported

In vitro and in vivo antihypertensive effect.

Peptides (0.425 mg/kg of BW) in the extract reduced maximum 20 mmHg BP at 6 h (IC₅₀ = 2.5 ± 0 μg

protein/mL, n = 3).

Olive oil water-soluble extract from O. europea showed antihypertensive effect by

1) inhibiting ACE

2) increasing NO bioavailability

3) acting on ET-1 expression

[85]

Orthosiphon aristatus

(Lamiaceae)

Leaves,

Chloroform- soluble portion from the water decoction of the leaves

Stroke prone spontaneously hypertensive rats (SHRSP), Male Wistar rats, male Hartley guinea pigs

6(e) methylripariochromene A (MRC)

6(f) acetovanillochromene (AVC)

6(g) orthochromene A (OC)

(Figure 6)

100 mg/kg MRC decreased 15 to 30 mmHg mean BP of SHRSP at 3.5 h to 24 h (p < 0.05 or p < 0.01, n = 8); 3.8 × 10⁻⁵ M and 1.1 × 10⁻⁴ M MRC suppressed contractile force of isolated guinea pig atria by 18.8% ± 2.6% (p < 0.05, n = 4) and 54.74% ± 2.8% (p < 0.01, n = 4). IC₅₀ of AVC, OC are 1.01 × 10⁻⁴ M, 1.32 × 10⁻⁴ M.

Methylripariochromene A isolated from the leaves of O. aristatus

1) decreased the slow Ca²⁺ inward current

2) decreased CO

3) increased urinary volume and electrolyte excretions

4) have Ca²⁺ antagonism

[86]

Osyris abyssinica var. speciosa

(Santalaceae)

Aerial parts,

Alcoholic extract

Normotensive Wistar albino rats

4(f) epicatechin

(Figure 4)

Epicatechin of 3.3 mg/kg decreased BP, and HR by 8.3 mmHg, and 6% respectfully; and 6.6 mg/kg decreased BP, and HR by 8.3 mmHg, and 7.1% respectfully.

Epicatechin found from O. abyssinica

1) Lower HR by vasodilatation

[69]

Parkia speciosa

(Fabaceae)

Seeds,

Hydrolyzed with and without Alcalase

Not reported

Not found

Hydrolyzed samples showed slightly more DPPH scavenging activity of 2.1 - 2.9 mg gallic acid equivalent (GAE)/g seed than non-hydrolyzed ones (1.6 - 2.2 mg GAE/g seed).

Hydrolyzed samples inhibited 50.6% - 80.2% of ACE activity.

Hydrolyzed seeds of P. speciosa

1) Inhibit ACE

[87]

Passiflora edulis

(Passifloraceae)

Fruit Peel,

Ethanol extract

Male Spontaneously hypertensive rats

6(h) edulilic acid (EA)

6(i) anthocyanin fraction (AF) (Figure 6)

For 2.5, and 50 mg ethanol extract/kg BW, maximum MAP reduced were 8.9 ± 3, and 13 ± 2.5 mmHg; maximum SBP reduced were 10 ± 2.9, and 13.8 ± 2.8 mmHg; maximum DBP reduced were 7.6 ± 2.9, and 10.2 ± 2.2 mmHg. EA and AF significantly decreased (p < 0.001) mean variation in HR from baseline over 5 days.

Ethanol extract of P. edulis peel extract

1) diminishes sympathetic nervous system activation

[88]

Petroselinum crispum (Mill.) Fuss.

(Apiaceae)

Aerial parts,

Aqueous extract

Albino adult male Wistar rats

Not reported

In vivo and in vitro antihypertensive effect.

Significant reduction of SBP, MAP and DBP

(p < 0.01) was

observed after 6 h of treating with 160 mg/kg extract.

Significant vasorelaxation (p < 0.0001) of aortic rings pre-contracted by epinephrine was seen for 0.02 - 2.5 μg/ml extract (IC₅₀ = 0.38 ± 0.07 μg/ml).

Aqueous extract of P. crispum

1) decreases tension in endothelium-denuded and endothelium-intact aortic rings

2) blocks the entry of extracellular Ca²⁺ via blocking VOCC and ROCC.

3) increases synthesis of NO.

[89]

Phaseolus vulgaris L. varieties plus black (PB), azufrado higuera (AH) and pinto Saltillo (PS)

(Fabaceae)

Seeds,

Protein extraction by isoelectric

precipitation

Male Wistar spontaneously hypertensive rats

Not reported

Total hydrolysates from each variety showed ACE inhibition of IC₅₀ = 4.34 ± 0.29, 4.82 ± 1.59, 25.96 ± 0.86 μg/mL respectively.

Peptide fraction < 1 kDa showed highest % antioxidant activity among each variety (99.2% ± 0.9%, 87.6% ± 0.7%, and 82.7% ± 2.0% respectively).

Peptide fraction 3 - 10 kDa of AH

variety lowered SBP up to 27.13 ± 11.17 mmHg at 2 h and up to 23.55 ± 12.44 mmHg at 4 h (p ≤ 0.01, n = 3).

Not reported

[90]

Phragmanthera incana (Schum) Balle

(Loranthaceae)

Leaves,

Ethanol extract

Wistar male rats

Not found

50, 100, 200 mg ethanol extract/kg p.o. significantly decreased (p < 0.05 and p < 0.001, n = 6) SBP compared to the l-NAME rat group after four weeks’ treatment.

100, 200 mg ethanol extract/kg p.o.

significantly (p < 0.05, p < 0.01 respectively, n = 6) increased serum nitrite levels compared to the l-NAME rat group.

P. incana ethanol extract holds antihypertensive and antioxidant activity by

1) reducing peroxidation of lipid

2) restoring plasma nitrite levels counterbalance the effect of ROS

[91]

Picrasma quassiodes (D. Don) Benn.

(Simaroubaceae)

Dried branches,

Dichloromethane extract

Male spontaneously hypertensive rats (SHR), Wistar Kyoto rats

Not found

50, 100, and 200 mg extract/kg significantly lowered (p < 0.01, n = 8) SBP compared to control group. 100, and 200 mg extract/kg significantly increased NO and SOD than SHR control group (p < 0.01, p < 0.05 respectively, n = 6).

Extract of P. quassiodes exerts effects by

1) vascular oxidative stress minimization by increasing SOD activity

2) endothelial function preservation and increase eNOS expression to promote synthesis and release of NO that result in direct vasorelaxation.

[92]

Pistacia atlantica Desf

(Anacardiaceae)

Leaves,

Dried residue of organic phase redissolved in absolute methanol

Not reported

6(j) glucogallin,

6(k) gallic acid,

6(l) galloylshikimic acid,

6(m) methyl gallate,

6(n) digalloylquinic acid,

6(o) digallic acid,

6(p) trigalloylglucose

6(q) tetragalloylquinic acid (Figure 6)

In vitro antidiabetic and antihypertension activity.

Extracts of 35 - 140 μg/ml produced a dose-dependent ACE I inhibition

ranging from 15.1% - 74% (average IC₅₀ = 102 ± 10.2 μg/ml).

Phenolic compounds retrieved from leaves of P. atlantica show ACE inhibitory activity by

1) forming chelate complex with zinc within the active site of ACE I

2) interactions through hydrogen bonds that is established between -OH groups of compounds close to active site which blocks activity of ACE.

[93]

Prunus serotina Ehrh.

(Rosaceae)

Fruits,

Lyophilized aqueous and methanolic extracts

Adult male Wistar rats

3(h) chlorogenic acid (CGA) (Figure 3)

7(a) cyanidin-3-O- rutinoside

7(b) proanthocyanidins

7(c) quercetine glycosides (Figure 7)

The flesh extract showed E_max of 27.9% ± 3.6%, EC₅₀ of 120 ± 5.7 μg/mL, peel extract showed E_max of 54.5% ± 4%, EC₅₀ of 34.9 ± 3.4 μg/mL, and whole fruit extract showed E_max of 59% ± 5.9%, EC₅₀ of 101.8 ± 7.5 μg/mL vasorelaxant response.

1) synergistic effect of the compounds

2) CGA inhibit ROS generating enzymes (NADPH, xanthine oxidase), reduce the formation of ONOO⁻ and increase bioavailability of NO. It also has protective role in eNOS [94] .

[95]

Psidium guineense Sw.

(Myrtaceae)

Leaves,

Essential oil

Female and male Swiss mice, female Wistar rats

7(d) spathulenol

(Figure 7)

Antioxidant activity.

P. guineense essential oil and spathulenol exhibited DPPH free radical activity of IC₅₀ = 60.7 - 65.92 and 82.43 - 89.38 μg/mL (n = 3), respectively; and MDA lipoperoxidation with IC₅₀ = 35.23 - 40.50 and 24.30 - 28.68 μg/mL (n = 3), respectively.

Not reported

[96]

Salvia elegans Vahl.

(Lamiaceae)

Aerial parts (flowers, leaves, and stems),

hydroalcoholic extract (SeHA) and n-butanol extract (SeBuOH)

ICR albino mice

Not found

In vitro inhibitory effect on ACE.

SeHA significantly lowered (p < 0.05) SBP from dose as low as 0.75 μg/kg, DBP at 10 mg/kg.

SeHA inhibited 50.27% ± 5.09% ACE

(n = 5) while SeBuOH inhibited 78.40% ± 2.24% ACE (n = 5).

SeHA inhibited antihypertensive effect by

1) inhibiting the secretion of ET-1

2) increasing NO production and release

3) activating Ca²⁺-dependent K⁺ conductance that allows hyperpolarization after entry of Ca²⁺.

[97]

Salvia verbenaca L.

(Lamiaceae)

Aerial parts,

Alcoholic extract

Normotensive albino rats

7(e) 5-hydroxy-3, 4', 7-trimethoxyflavone (HMF),

7(f) verbenacoside (VBC) (Figure 7)

HMF (3.3 mg/kg) decreased BP and HR by 30 mmHg and 28.5% respectfully; VBC (3.3 mg/kg) decreased BP and HR by 13.2 mmHg and 15.4% respectfully;

Alcoholic extract 0.5 gm/kg decreased BP and HR by 36.2 mmHg and 18.18%.

1) 5-hydroxy-3, 4', 7-trimethoxyflavone and verbenacoside isolated from alcoholic extract of S. verbenaca decreased HR by vasodilatation

2) 5-hydroxy-3, 4', 7-trimethoxyflavone showed potent activity having four -OH groups

3) alcoholic extract lowered BP by synergistic effect of flavonoids present

[69]

Sapium sebiferum (L.) Roxb.

(Euphorbiaceae)

Leaves,

Aqueous extract

Spontaneously hypertensive rats

7(g) 6-O-galloyl-D-glucose (GDG) (Figure 7)

GDG of 1, and 5 mg/kg lowered

MAP by 17.3 ± 7.1 and 29.6 ± 10.4 mmHg (n = 6) in SHR, and decrease in plasma noradrenaline was parallel to the antihypertensive action.

GDG lowers blood pressure by

1) blocking of noradrenaline release and/or

2) direct vasorelaxation

[98]

Sechium edule (Jacq.) Sw.

(Cucurbitaceae)

Roots,

Hydroalcoholic extract (SeRHA)

Male Sprague- Dawley albino rats,

male ICR albino mice

7(h) cinnamic acid (Figure 7)

SeRHA of 200 mg/kg decreases DBP, SBP significantly after Ang-II treatment (p < 0.05).

SeRHA of 150, 300, 600 μg/ml lowered aorta contraction by 14%, 44%, and 66% of E_max after Ang-II treatment (average EC₅₀ = 1.5 × 10⁻⁸ M).

The hydroalcoholic root extracts of S. edule may

1) antagonize AT₁R or by interfering Ca²⁺ fluxes activated by Ang-II

2) obstruct the second messenger system initiated by Ang-II

3) alter Ca²⁺ fluxes in the VSMC and on the RAAS.

[99]

Solanum capsicoides All.

(Solanaceae)

Aerial parts,

Methanol extract

Normotensive Wistar-Kyoto (WKY) rats, Spontaneously hypertensive rats (SHR)

Not reported

In vitro, in vivo antihypertensive activity.

Significant increase in the vasorelaxation of endothelium denuded mesenteric rings from SHR (E_max = 102.1% ± 5.7%, EC₅₀ = 29.6 - 55.8 μg/ml, p < 0.05). 40 mg/kg methanol extract significantly (p < 0.05) reduced MAP greater in SHR (25.4% ± 1.4%) when compared WKY rats (17.7% ± 2.6%).

Methanol extract induced antihypertensive effect by

1) reducing peripheral vascular resistance

2) reducing sensitivity to the adrenergic agonist

3) increasing NO sensitivity

[100]

Solanum melongena

(Solanaceae)

Fruits,

Lyophilized powders

Male 14-week-old spontaneously hypertensive rats

7(i) acetylcholine (ACh) (Figure 7)

10⁻³ - 10^−0.5 μM ACh which is identified from eggplant powder, exerted concentration- dependent vasorelaxation (EC₅₀ = 0.0372 ± 0.008 μM).

And SBP decreased significantly (p < 0.05) after 3 h and 9 h by 4.81 and 10 mmHg.

ACh showed antihypertensive activity by

1) activating the M3 muscarinic ACh receptor on blood vessels

2) suppressing the secretion of hypertensive

catecholamines

3) suppressing sympathetic nervous activity

[101]

Solanum sisymbriifolium Lam.

(Solanaceae)

Root,

Hydro ethanolic crude root extract (CRE), Butanol fraction (F_BtOH), B3 subfraction

Swiss adult albino male mice

7(j) nuatigenin- 3-O-β-chacotriose (B_3-1) (Figure 7)

CRE of 50 mg/kg, F_BtOH of 5 mg/kg, and B3 subfraction of 1 mg/kg significantly decreased DBP and SBP (p < 0.001 and p < 0.01, n = 6). 1, 2.5, 5 mg/kg B_3-1 significantly decreased (p < 0.001; n = 6) DBP and SBP.

B_3-1 induced vasorelaxation by

1) inhibiting cyclic adenosine monophosphate (cAMP) phosphodiesterase, cAMP increases indirectly in VSMC [102] .

[103]

Tagetes lucida Cav.

(Asteraceae)

Aerial parts,

Ethanolic extract

Normotensive male Wistar rats, male spontaneously hypertensive rats

7(k) 6,7,8- trimethoxycoumarin,

7(l) 6,7-dimethoxycoumarin (Figure 7)

Ethanolic extract of 3.03 - 1000 μg/ml showed E_max of 99%, EC₅₀ of 40.5 μg/ml (endothelium intact) and E_max of 100%, EC₅₀ of 148.2 μg/ml (endothelium denuded). The extract relaxed KCl-induced contraction with EC₅₀ of 100 μg/ml and E_max of 100%. Both compounds displayed significant activity (p < 0.05) in concentration and partly endothelium dependent manner.

Ethanol extract showed endothelium derived relaxant effect by

1) Producing NO that outspreads to VSMC to activate sGC which produces cGMP, and induces relaxes smooth muscle as the main second messenger.

2) Blocking the L-VGCC

[104]

Terminalia bellerica Roxb.

(Combretaceae)

Fruits,

Aqueous- methanolic extract, crude extract (Tb.Cr)

Sprague- Dawley rats, guinea-pigs, rabbits

Not reported

Tb.Cr of 100, 30, and 10 mg/kg showed a dose-dependent decrease of 44.7% ± 3.1%, 25.1% ± 2.3%, and 15.6% ± 2.0% in MAP of rats; 0.1 - 10 mg/ml inhibited guinea-pig atrial force and contraction rate (EC₅₀ = 4.5 ± 1.2 and 5.9 ± 1.3 mg/mL respectively, n = 4) and also relaxed K⁺ and phenylephrine (PE) induced contraction in isolated rabbit aorta (EC₅₀ = 6.4 ± 1.3, 7.5 ± 1.3 mg/mL respectively, n = 4 - 5).

Crude extract of T. bellerica fruit induced antihypertension by

1) negative inotropic and chronotropic effect due to the Ca²⁺ antagonism effect decreasing CO and so reducing BP

2) equipotently blocking Ca²⁺ influx through VDCC and ROCC

3) suppressing the PE agonist, and thus inhibiting internal store release of Ca²⁺

4) endothelium-independent vasodilation

[105]

Thymus serpyllum L.

(Lamiaceae)

Whole plant,

Aqueous and freeze-dried extract

Normotensive Wistar rats, Male spontaneously hypertensive rats (SHR)

7(m) rosmarinic acid (Figure 7)

Freeze dried extract (100 mg/kg BW dissolved into saline of 0.2 ml) decreased SBP, DBP, and total peripheral vascular resistance significantly (p < 0.001, n = 7) in SHR.

In vitro NO-scavenging ability of 1 mg/ml extract led to 63.43% reduced nitrite production (IC₅₀ = 122.36 μg/ml).

Rosmarinic acid found in this extract had in vitro antioxidant effect against low density lipoprotein (LDL) oxidation [106] by

1) inhibiting conjugated diene and TBARS formation.

[107]

Tropaeolum majus L.

(Tropaeolaceae)

Leaves,

semi-purified fraction (TMLR) and hydroethanolic extract (HETM)

Wistar-Kyoto rats, Spontaneously hypertensive rats

7(n) isoquercitrin (ISQ) (Figure 7)

50, 100 mg/kg TMLR, 100, 300 mg/kg HETM, and 2, 4 mg/kg ISQ significantly (p < 0.001, n = 6) decreased MAP in a dose-dependent manner in normotensive rats; 300 mg/kg HETM, 50, 100 mg/kg TMLR (p < 0.01) and 10 mg/kg ISQ (p < 0.001) significantly inhibited ACE activity in conscious rats compared to control.

Isoquercitrin inhibited ACE activity but single administration of hydroethanolic extract, semi-purified fraction, Isoquercitrin did not change HR because results of ACE inhibition take several months to bring to light.

ACE inhibition by Isoquercitrin may also be occurring in central nervous system.

[108]

Vitex pubescens

(Lamiaceae)

Leaves,

Petroleum ether extract (VPPE)

Spontaneously hypertensive rats

7(d) Spathulenol (Figure 7)

VPPE of 500 mg/kg significantly decreased (p < 0.001, n = 6) SBP, DBP from 3 days, and 0.25 - 4 mg/ml significantly relaxed (p < 0.001, n = 6) pre-contracted endothelium intact aortic ring.

Fraction F2-VPPE of 0.5, 1, 2 mg/mL significantly (p < 0.001) attenuated CaCl₂-induced of endothelium-denuded aortic ring vasoconstriction.

Fraction F2-VPPE of V. pubescens induced relaxation by

1) Activating K_ATP channel which causes hyperpolarization and Ca²⁺ inflow inhibition through VDCC

2) intracellular Ca²⁺ release inhibition from Ca²⁺ storage

3) extracellular Ca²⁺ inflow inhibition through ROCC.

Spathulenol show vasorelaxant activity [109] by Ca²⁺ inflow inhibition through VDCC.

[110]