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256 Zahra Taghipour and Mamak Hashemi Habib Abadi
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Plant Treatment group Control group Study design
Cinnamomum
camphora (L.) J .
Presl.
Punica granatum L.
Crocus sativus L. C. sativus L. Placebo Randomized, double-
C. camphora forest – Randomized clinical trial 31 – Anti-inflammator y; ↓ DBP,
Seed/oil Placebo Double-blind, placebo-
controlled trial
Pomegranate juice – Before-and-after
single-arm study
Pomegranate juice Water Single-blind clinical trial 21 2 weeks Hypotensiv e; ↓ VC AM-1;
Peel of pomegranate
in combination
with other herbs
Whole pomegranate
capsule
Pomegranate juice – Randomized clinical trial 100 5 days Cardioprotectiv e; ↓ intensity,
Crocin tablets Placebo Randomized, double-
Crocin tablets Placebo tablet Randomized, double-
Placebo Randomized, double-
blind, placebocontrolled study
Placebo
capsules
Double-blind, placebo-
controlled,
randomized controlled
trial
blind, placebocontrolled trial
blind, placebocontrolled trial
blind, placebocontrolled trial
No. of
patients
Treatment
duration Result Reference
Wu etal. (2020)
51 4 weeks Antihyperlipidemia Mirmiran etal.
13 SD Hypotensive Asgary etal.
24 22 days Antio xidant; ↑ physical
55 8 weeks Cardiopreventiv e;
44 12 weeks ↓ TC, LDL, TG, FBS, and
48 6 weeks ↓ Chol; no effect on
44 8 weeks No effect on lipid profile Javandoost etal.
hs-CRP
↑ E-selectin
fitness and stamina
hypotensive (↓ DBP)
occurrence, and duration
of angina pector is; ↓
troponin and MDA
VEGF; anti-inflammatory
metabolic syndrome (BP,
TG, HDL, LDL, FBS, and
anthropometric measures)
(2010)
(2013)
Asgary etal.
(2014)
Gopi etal. (2017)
Stockton etal.
(2017)
Razani etal.
(2017)
Kermani etal.
(2017a)
Kermani etal.
(2017b)
(2017)
Melissa off icinalis
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L.
chebula W illd. ex
Flem.
Saffron capsule Placebo
capsule
Saffron tablets Placebo tablet Randomized, double-
Saffron stigma in
combination with
training
Saffron capsule Placebo
Crocin Placebo Randomized, double-
Lyophilized aqueous
extract of M.
officinalis leaves
Hydroalcoholic
extract
Dried aerial parts
capsules
Hydroalcoholic
extract
Aqueous extract of T.
chebula
Placebo in
combination
with training
capsule
Placebo Randomized, double-
Placebo Randomized, double-
Placebo
capsule
Placebo Randomized, double-
Placebo Randomized double-
Randomized, double-
blind, placebocontrolled trial
blind, placebocontrolled trial
Randomized, double-
blind, placebocontrolled trial
Randomized, double-
blind, placebocontrolled trial
blind, placebocontrolled trial
blind, placebocontrolled trial
blind, placebocontrolled trial
Randomized, double-
blind, placebocontrolled trial
blind, placebocontrolled trial
blind, placebocontrolled
63 6 weeks ↓ miR-21; no effect on
anthropometric indices
and biochemical
parameters
80 12 weeks ↓ Waist circumference and
MDA
23 5 days/
week for
2 weeks
12 SD Improvement in WAnT Abassi etal.
84 8 weeks Improvement in CAD by ↑
55 14 days Improvement of palpitation Alijaniha etal.
70 12 weeks Improvement of ApoA-I,
80 2 months ↑ EF, maximum workload,
62 12 weeks Improvement in lipid profile
60 12 weeks Improved endothelial
↓ LDH; no effect on CK Ghanbari-Niaki
expression of SIRT1 and
AMPK and ↓ expression
of LOX1 and NF-κB
ApoB/ApoA-I and lipid
ratios; cardioprotective
and glycemic contr ol;
anti-inflammatory
inflammator y; ↓ MDA;
↓ risk of CVD and
hypergly cemia;
modulation of blood lipid
and HbA1c levels
Khatir etal.
(2018)
Ebrahimi etal.
(2019)
etal. (2019)
(2020)
Abedimanesh
etal. (2020)
(2015)
Asadi etal.
(2018)
Javid etal.
(2018)
Asadi etal.
(2019)
Pingali etal.
(2020)
Continued
Herbal Medicine for Cardiovascular Disease 257
No. of Treatment
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Plant Treatment group Control group Study design patients duration Result Reference
Aqueous extract of T.
chebula in
combination with
Guggulu
Syzygium
aromaticum (L.)
Merr. & L.M.
Perry
Lam.
vulgare L.
Salix sp. Salicis cortex extract Placebo Randomized double-
Polyphenolic clove
extract
Malunggay (M.
oleifera) leaves
capsule
supplements
Natural sports
supplement
β-Glucan-enriched
barley
Diets with brown rice/
whole wheat,
barley
Consumption of
barley
Diets containing
barley
Higher consumption
of barley
Placebo
capsules
– Open-label pilot study 13 30 days Maintained healthy glucose
– Prospective cohort
Placebo Randomized double-
– Randomized controlled
– Controlled clinical trial 21 5 weeks ↓ Cardiovascular risk Hallfrisch etal.
– Controlled clinical trial 25 5 weeks ↓ LDL Behall etal.
– Controlled clinical trial 18 5 weeks ↓ Cardiovascular risk Behall etal.
– Case–control study 95 10 years Preventionn of metabolic
Placebo-controlled,
double-blind,
randomized trial
study
blind, placebocontrolled
crossover study
blind, placebocontrolled
90 3 months No effect on LDL level, BMI,
and waist
metabolism; inhibition
α-amylase and
α-glucosidase activities
56 12 weeks Anti-inflammator y;
hypoglycemic
24 24 h ↑ NO Jacob etal.
18 4 weeks No clinically significant
improvement in CVD risk
factors
syndrome, diabetes,
and CVD
51 4 weeks Platelet deaggregation Krivoy etal.
Donato etal.
(2021)
Mohan etal.
(2019)
Mozo and
Caole-Ang
(2015)
(2018)
Keogh etal.
(2003)
(2003)
(2004a)
(2004b)
Valachovicová
etal. (2006)
(2001)
258 Zahra Taghipour and Mamak Hashemi Habib Abadi
Lemon detox diet Placebo Before-and-after clinical
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Burm.f.
CitraVes™ – Pilot open-label study 20 12 weeks ↓ Waist circumference and
Cichorium
intybus L.
oleracea L.
Atr opa belladonna
L.
mukul (Hook. ex
Stocks) Engl.
Cicer arietinum L. Diet including
Cucumis sativus L. Diet containing
jatamansi
(D. Don) DC.
Chicory coffee – Clinical study 27 1 week Antithrombotic; anti-
P. oleracea seeds
capsule
Purslane extract
capsule
A. belladonna
tincture
Organic extract of
Guggulu
Policol® – Observational
canned drained
chickpeas
cucumber
– – Open-label, prospective
N. jatamansi capsule Placebo Single-blind,
84 7 days ↓ Body fat and insulin
intervention trial
Placebo
capsules
Placebo
capsules
Placebo Single-blind placebo-
Placebo Clinical trial 406 6 months Cardioprotective; regulation
Wheat diet Randomized, crossover
– Clinical study 12 2 weeks Anti-inflammator y;
Triple-blinded,
randomized,
placebo-controlled
clinical trial
Randomized, placebo-
controlled clinical trial
controlled study
prospective study
interventions
study
randomized,
placebo-controlled
study
94 1 month ↓ LDL, TG Sabzghabaee
63 12 weeks ↓ SBP, HbA1c Wainstein etal.
8 SD Parasympathetic Bettermann etal.
– 3 months ↓ TC, LDL; ↑ HDL Llabrés etal.
27 5 weeks ↓ TC, LDL Pittaway etal.
– – Anti-inflammator y;
40 4 weeks Hypotensiv e; ↓ SBP and
resistance through caloric
restr iction; ↓ hs-CRP
without hematologic
changes
LDL
inflammatory
of abnormal lipid
metabolism; modifying BP
antio xidant; ↓ F2 isoprostanes, PGE
MCP-1
antioxidant
DBP
, and
2
Kim etal. (2015)
Raimondo etal.
(2021)
Schumacher
etal. (2011)
etal. (2014)
(2016)
(2001)
Agrawal etal.
(2000)
(2017)
(2007)
Sánchez-
Moreno etal.
(2006)
Rajyalakshmi
etal. (2018)
Bhat and Malik
(2020)
Continued
Herbal Medicine for Cardiovascular Disease 259
No. of Treatment
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Plant Treatment group Control group Study design patients duration Result Reference
entiscus L.
Chios mastic powder Placebo Clinical study 133 12–18
months
Mastic gum Placebo Prospective,
randomiz
ed,
156 8 weeks Hypocholester olemic;
Cardioprotectiv e; ↓ TC, LDL,
TC/HDL
hypoglycemic
Triantafyllou
etal. (2007)
Kartalis etal.
(2016)
placebo-controlled,
pilot study
Olive leaf extract
tablet
Olive leaf extract
capsules
Olive leaf extract
capsule
blinded study
No medication Open, controlled,
parallel-group, co-twin
study
Placebo Randomized, placebo-
controlled, crossover
trial
Matched
control
Randomized, double-
blind, placebocontrolled, crossover
11 7 days Inhibition of platelet
activation
20 8 weeks Antihypertensiv e;
hypocholesterolemic
46 12 weeks Improvement of insulin
sensitivity and pancreatic
β-cell secretory capacity
18 SD Cardioprotective; modulates
vascular function and IL-8
production
Singh etal.
(2008)
Perrinjaquet-
Moccetti etal.
(2008)
de Bock etal.
(2013)
Lockyer etal.
(2015)
trial
Tablet olive oil
by-product called
pâté
95% ethanolic
extract from leaves
Placebo tablet Crossover trial with two
intervention periods
Captopril Phase-II, randomized,
double-blind,
19 2 months Improvement of lipid profile,
oxidative stress, and
Dinu etal.
(2021)
MCP-1 levels
134 8 weeks Antihypertensive Elkafrawy etal.
(2020)
captopril-controlled
clinical trial
260 Zahra Taghipour and Mamak Hashemi Habib Abadi
AMPK, AMP-activated protein kinase; ApoA-I, apolipoprotein A-I, ApoB; apolipoprotein B; BMI, body mass index; BP, blood pressure; CAD, coronary artery disease; Chol, cholesterol;
CK, creatine kinase; DBP, diastolic blood pressure; EF, ejection fraction; FBS, fasting blood sugar; HbA1c, glycated hemoglobin; HDL, high-density lipoprotein cholesterol; hs-CRP,
high-sensitivity C-reactive protein; IL-8, interleukin-8; LDH, lactate dehydrogenase; LDL, low-density lipoprotein cholesterol; LOX1, lectin-like oxidized LDL receptor 1; MCP-1, monocyte
chemoattractant protein-1; MDA, malondialdehyde; miR, microRNA; NF-κB, nuclear factor-κB; NO, nitric oxide; SD, single dose; SIRT1, Sirtuin 1; TC, total cholesterol; TG, triglycerides;
VCAM-1, vascular endothelial adhesion molecule 1; VEGF, vascular endothelial growth factor; WAnT, Wingate anaerobic test.
Herbal Medicine for Cardiovascular Disease 261
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Crocus sativus L.
The aqueous extract of the stigmas of Crocus
sativus L. (i.e., saffron) has shown antioxi-
dant and cardioprotective effects in various
animal studies, such as hypotensive, antiarrhythmic, hypolipidemic, and anti-atherosclerotic. Crocin, one of its valuable constituents,
has demonstrated cardioprotective effect via
increasing heart angiogenesis through a mechanism involved in elevating protein kinase B
(Akt) and extracellular signal-regulated protein
kinase 1/2 (ERK1/2), microRNA (miR)-126,
miR-210 expression and CD31. In addition,
it has shown antagonistic effects on calcium
(Ca) channels and aortic relaxation via the
nitric oxide synthase pathway (Ghorbanzadeh etal., 2017).
Melissa officinalis L.
Various extraction methods of leaves and
aerial parts of Melissa officinalis L. (lemon
balm) have demonstrated cardioprotective
effects such as anti-ventricular arrhythmia, antihyperglycemic, antihyperlipidemic, and antioxidant. It also has improved
post-ischemic dysfunction by elevating
mitochondrial permeability transition pore
(mPTP) and Ca2+. Patients receiving lemon
balm in clinical trials have significantly improved palpitation and ejection fraction as
well as lipid and glycemic profiles (Ragone
etal., 2019).
Punica granatum L.
Parts of Punica granatum L. (pomegranate)
plants have been studied in CVD, showing
improvement in cardiac fibrosis and cardiotonic as well as antiarrhythmic effects
(Huang etal., 2005; Rao and Krishnamurthy, 2019). Fifty patients with unstable angina were shown to have significant reduction in the intensity, occurrence, and
duration of angina pectoris by receiving
pomegranate juice (Razani etal., 2017).
Cydonia oblonga Mill.
Cydonia oblonga Mill. (quince) improved
hemostasis and thrombosis in addition to
exhibiting other cardioprotective effects such
as hypotensive and improvement of metabolic
parameters (Zhou etal., 2014a). Furthermore,
inhibition of myocardial hypertrophy and
the renin–angiotensin–aldosterone system
(RAAS) has been shown in animal studies
(Zhou etal., 2015).
Moringa oleifera Lam.
The cardiprotective effects of Moringa oleifera Lam. have been demonstrated in many
studies, and hypolipidemic, anti-inflammatory, antioxidant, anticoagulant, and platelet antiaggregatory effects have been obtained (Rajanandh etal., 2012).
Abassi, W., Ouerghi, N., Jebabli, N., Feki, M. and Bouassida, A. (2020) Effect of a single dose of saffron
(Crocus sativus) on anaerobic power in young active males. Science & Sports 35(3), 176–179. DOI:
10.1016/j.scispo.2019.06.008.
Abd El-Hady, F.K. and El-Shahid, Z.A. (2014) Influence of some culinary plants on the suppression of human
low density lipoprotein (LDL) peroxidation (in-vitro). International Journal of Pharmaceutical Sciences
Review and Research 26(1), 209–215.Available at: https://www.scopus.com/inward/record.uri?eid=2-s2.
0-84900471183&partnerID=40&md5=cc34fb1696cf55452514694b15cb67ca (accessed 20 January 2023).
Abdel-Rahman, R.F., Hessin, A.F., Abdelbaset, M., Ogaly, H.A., Abd-Elsalam, R.M. etal. (2017) Antihyper-
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and Cellular Longevity 2017, 9460653. DOI: 10.1155/2017/9460653.
Abedimanesh, N., Motlagh, B., Abedimanesh, S., Bathaie, S.Z., Separham, A. etal. (2020) Effects of crocin
and saffron aqueous extract on gene expression of SIRT1, AMPK, LOX 1, NF-κB, and MCP-1 in patients
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