nutrients

Review
Effects of Vegetables on Cardiovascular Diseases and
Related Mechanisms
Guo-Yi Tang 1 , Xiao Meng 1 , Ya Li 1 , Cai-Ning Zhao 1 , Qing Liu 1 and Hua-Bin Li 1,2, * ID

1 Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition,
School of Public Health, Sun Yat-Sen University, Guangzhou 510080, China;
[email protected] (G.-Y.T.); [email protected] (X.M.); [email protected] (Y.L.);
[email protected] (C.-N.Z.); [email protected] (Q.L.)
2 South China Sea Bioresource Exploitation and Utilization Collaborative Innovation Center,
Sun Yat-Sen University, Guangzhou 510006, China
* Correspondence: [email protected]; Tel.: +86-20-873-323-91

Received: 10 July 2017; Accepted: 6 August 2017; Published: 10 August 2017

Abstract: Epidemiological studies have shown that vegetable consumption is inversely related to the
risk of cardiovascular diseases. Moreover, research has indicated that many vegetables like potatoes,
soybeans, sesame, tomatoes, dioscorea, onions, celery, broccoli, lettuce and asparagus showed great
potential in preventing and treating cardiovascular diseases, and vitamins, essential elements, dietary
fibers, botanic proteins and phytochemicals were bioactive components. The cardioprotective effects
of vegetables might involve antioxidation; anti-inflammation; anti-platelet; regulating blood pressure,
blood glucose, and lipid profile; attenuating myocardial damage; and modulating relevant enzyme
activities, gene expression, and signaling pathways as well as some other biomarkers associated to
cardiovascular diseases. In addition, several vegetables and their bioactive components have been
proven to protect against cardiovascular diseases in clinical trials. In this review, we analyze and
summarize the effects of vegetables on cardiovascular diseases based on epidemiological studies,
experimental research, and clinical trials, which are significant to the application of vegetables in
prevention and treatment of cardiovascular diseases.

Keywords: cardiovascular disease; vegetable; bioactive component; effect; mechanism

1. Introduction
Cardiovascular diseases (CVDs) have spread worldwide, and their prevalence is increasing
dramatically [1,2]. CVDs have become one of the biggest threats to people’s health, as reported by
the World Health Organization (WHO), and CVDs caused 17.7 million deaths (coronary heart disease
(CHD): 7.4 million, stroke: 6.7 million) in 2015, accounting for 31% of all global deaths [3]. Besides
high morbidity and mortality, CVDs also lead to serious disabilities and decrease the living standards
of patients, creating a huge burden for individuals, families, and countries [4–6]. Therefore, it is urgent
and worthwhile to investigate prevention and treatment strategies of CVDs [7].
CVDs are a class of chronic non-infectious diseases related to substantial complicated risk
factors such as high blood pressure, hyperlipidemia, diabetes, overweight and obesity, metabolic
syndrome, smoking, excessive alcohol consumption, imbalanced diet, and a lack of physical
activity [6,8–13]. Efficient strategies can be applied to preventing and treating CVDs by targeting these
risk factors, e.g., reducing blood pressure, regulating the blood lipid profile, reducing oxidative stress,
modulating inflammatory status, inhibiting thrombosis, and attenuating myocardial damage as well
as ameliorating metabolism syndrome [13–19]. Meanwhile, a healthy lifestyle, including a balanced
diet, reasonable physical activity, moderate alcohol consumption, and stopping smoking, is beneficial
to persons at high risk of CVDs [13,20–23]. Among these methods, establishing and insisting on a

Nutrients 2017, 9, 857; doi:10.3390/nu9080857 www.mdpi.com/journal/nutrients

Nutrients 2017, 9, 857 2 of 25

healthy eating pattern would be a substantial, sustainable, and economical choice. As recommended
in the 2015–2020 Dietary Guidelines for Americans, people should follow a rational eating pattern
with the aim of achieving and maintaining good health and lowering the risk of chronic diseases like
CVDs, diabetes, overweight, and obesity throughout all stages of life [24].
It has been proven by epidemiological studies that vegetable consumption is negatively associated
with the risks of CVDs [25–30]. Furthermore, evidence from experimental research suggested that
many vegetables were effective in preventing CVDs, such as potatoes, soybeans, sesame, tomatoes,
dioscorea, onions, celery, broccoli, lettuce, and asparagus [31–35]. Some bioactive components might
account for the cardioprotective effects of vegetables, like vitamins, essential elements, dietary fibers,
botanic proteins, and phytochemicals [36–41]. The potential mechanisms of action could involve
antioxidation; anti-inflammation; anti-platelet; regulating blood glucose, lipid profile, and blood
pressure; and attenuating myocardial damage [42–45]. In addition, clinical trials indicated that the
consumption of several vegetables was beneficial to cardiovascular health [46–49]. The present review
summarizes the effects of vegetables on CVD prevention and treatment, with special attention paid to
the mechanisms of action.

2. Epidemiological Studies
Numerous epidemiological studies have indicated that vegetables were inversely associated
with CVD incidence and many kinds of vegetables possessed cardioprotective effects, such as
tomatoes, potatoes, onions, cereals, and cruciferous vegetables [26–30]. Moreover, a variety of bioactive
components in vegetables have been proven to convey health benefits in preventing and treating
CVDs, like botanical protein, dietary fiber, vitamins, essential elements, and phytochemicals [27,28,50].

2.1. Cross-Sectional Studies

Several cross-sectional studies evaluated the relationship between vegetable intake and CVD
risks [26,51,52]. It was found that total cholesterol (TC), the TC/high density lipoprotein cholesterol
(HDL-C) ratio, and hemoglobin A1c were significantly improved in women who consumed
more than 10 servings/week of tomato-based food products compared to those consuming fewer
than 1.5 servings/week [51]. Specifically, a significant improvement was observed in women
with higher consumption compared to those with lower consumption, i.e., TC (5.38 mmol/L vs.
5.51 mmol/L, p = 0.029), the TC/HDL-C ratio (4.08 vs. 4.22, p = 0.046), and hemoglobin A1c (5.02% vs.
5.13%, p < 0.001), and consumers with higher intake were 31% (95% confidence intervals (CI): 6–50%),
40% (95% CI: 13–59%), and 66% (95% CI: 20–86%) less likely to have increased TC (≥6.21 mmol/L),
low-density lipoprotein cholesterol (LDL-C) (≥4.14 mmol/L), and hemoglobin A1c (≥6%), respectively.
In another study of 4774 Iranian subjects, significant correlations between potato intake and diabetes,
high fasting blood sugar level as well as low serum HDL level were observed (odds ratio (OR): 1.38,
95% CI: 1.14–1.67, p < 0.001; OR: 1.40, 95% CI: 1.17–1.68, p < 0.001; OR: 1.10, 95% CI: 1.01–1.20, p = 0.02;
respectively) [26]. These results suggested a potential effect of potato consumption on CVDs, as high
fasting blood glucose, low serum HDL, and diabetes are recognized as CVD risk factors. Furthermore,
it was indicated in a cross-sectional study with 3995 Mediterranean participants at high CVD risk that
gazpacho (a Mediterranean vegetable-based cold soup that contains plenty of phytochemicals) intake
was negatively correlated with hypertension [52]. It was found that both the systolic and diastolic
blood pressure of the participants reduced with means of −1.9 mm Hg (95% CI: −3.4 to −0.6) and
−2.6 mm Hg (95%CI: −4.2 to −1.0) and of −1.5 mm Hg (CI: −2.3 to −0.6) and −1.9 mm Hg (95% CI:
−2.8 to −1.1), respectively, in moderate (1 to 19 g/day) and high (more than 20 g/day) gazpacho
intake categories, compared with the control group. Moreover, the incidence of hypertension was
decreased after gazpacho intake of 250 g/week and for high gazpacho intake groups compared with
the control group, with OR = 0.85 (95% CI: 0.73–0.99) and OR = 0.73 (95% CI: 0.55–0.98), respectively.
Nutrients 2017, 9, 857 3 of 25

2.2. Case-Control Studies

Similar results were illustrated in case-control studies investigating the association between
vegetable intake and CVD risks [27,53–55]. In one study, the relationship between onion intake and
acute myocardial infarction (MI) in Italy was analyzed [53]. Compared to the control group, the risks
of acute MI for the group consuming less than one portion of onion per week and more than one
portion per week significantly decreased (OR = 0.90, 95% CI: 0.69–1.21 and OR = 0.78, 95% CI: 0.56–0.99,
respectively). Another case-control study in Korea suggested that consuming vegetables was inversely
correlated with stroke risk [27]. It was shown that participants who consumed four to six servings of
vegetables per day and more than six servings per day were 32% and 69% less likely, respectively, to
suffer from stroke. Researchers also found that intake of vitamin B1, vitamin B2, vitamin B6, niacin,
folate, calcium, and potassium was significantly inversely correlated with stroke risk. In addition, the
effects of vegetable consumption on the connection between hypertension and the relative telomere
length of peripheral leukocytes were measured in a study [54]. On one hand, it was reported that
longer age-adjusted relative telomere length was related to higher vegetable consumption (p = 0.01).
On the other hand, subjects with longer age-adjusted relative telomere length were 30% less likely
to suffer from hypertension (OR = 0.70, 95% CI: 0.52–0.96, p = 0.03). The significant and negative
connection between hypertension-relative telomere length and hypertension was only observed in
those with greater (more than 150 g/day) vegetable intake (OR = 0.28, 95% CI: 0.14–0.57, p < 0.001),
but not in those with lower (less than 50 g/day) vegetable intake (p = 0.008). Interestingly, in a study
conducted in central Iran, evidence indicated that there was a marginally significant independent
association between potato consumption and risk of stroke [55]. If compared with those with the
lowest (5.3 ± 0.4 g/day) consumption, subjects with the highest (60.0 ± 6.1 g/day) potato consumption
were more likely to have strokes (OR: 1.9, 95% CI: 1.0–3.6).

2.3. Cohort Studies

It has been confirmed by cohort studies that vegetable consumption was inversely relative to
CVDs including hypertension, stroke, CHD, and even death [28,30,50]. Vegetables exerted a protective
effect on CVD patients. A cohort study in Spain reported that cereal protein and fiber were negatively
correlated with hypertension risk [28]. Cereal protein and fiber significantly lowered hypertension
risk in participants in the highest quintile of intake compared with those in the lowest (hazard ratio
(HR) = 0.5, 95% CI: 0.2–0.9, p = 0.06 and HR = 0.6, 95% CI 0.3–1.0, p = 0.05, respectively). Researchers
also found that the risk reduction was more significant in older individuals compared to the young,
in men compared to women, and in obese patients compared to those with a normal body weight.
In another study, lycopene consumption was negatively correlated to CVD risks after a nine-year
follow-up (HR = 0.83, 95% CI: 0.70–0.98), and to CHD risk after an 11-year follow-up (HR = 0.74,
95% CI: 0.58–0.94) [50]. Moreover, researchers found that vegetable intake could help decrease the
risk of total mortality, with HRs (95% CIs) for total mortality across increasing quintiles of intake at 1
(reference), 0.88 (0.79–0.97), 0.88 (0.79–0.98), 0.76 (0.62–0.92), and 0.84 (0.69–1.00) for total vegetables
(p = 0.03), and 1 (reference), 0.91 (0.84–0.98), 0.88 (0.77–1.00), 0.85 (0.76–0.96), and 0.78 (0.71–0.85) for
cruciferous vegetables (p < 0.0001) [30]. Therefore, their findings supported the notion that increasing
intake of vegetables, especially cruciferous vegetables, might help reduce CVD risk.
However, some studies found no significant inverse connection between vegetable consumption
and CVD risks [56,57]. On the one hand, researchers focused on the connection between vegetable
flavonoid intake and CVD risk in women in a cohort study, only to find that for both CVDs and
important cardiovascular events, there was no significant linear trend across quintiles of vegetable
flavonoid consumption (p = 0.63 and 0.80, respectively), and neither for the individual flavonol or
flavone [56]. According to prospective data from another cohort study, broccoli consumption was not
significantly associated with a reduction of CVD risk, and no significant association between broccoli
flavonol or flavone consumption and nonfatal MI or fatal CHD risk was observed in U.S. women [57].
On the other hand, harmful components were found in a few kinds of vegetables or badly cooked
Nutrients 2017, 9, 857 4 of 25

ones [58,59]. The findings of a study indicated that habitually high consumption of soybean isoflavones
might modestly but significantly increase the risks of ischemic stroke in women [58]. The HRs from the
lowest (median intake: 6.0 mg/day) to the highest (median intake: 53.6 mg/day) quintiles were 1.00,
1.05, 1.10, 1.11, and 1.24, respectively (95% CI: 1.08–1.42, p = 0.002). In another study, researchers found
that the HRs for subjects consuming four or more servings per week were 1.11 (95% CI: 0.96–1.28,
p = 0.05) for baked, boiled, or mashed potatoes, 1.17 (95% CI: 1.07–1.27, p = 0.001) for French fries,
and 0.97 (95% CI: 0.87–1.08, p = 0.98) for potato chips, compared with those consuming less than one
serving per month [59]. These results indicated that a higher intake of badly cooked potato might
increase the risks of developing hypertension independently and prospectively.

2.4. Other Epidemiological Studies

Besides the studies mentioned above, there are some epidemiological studies aiming to find an
association between vegetable consumption and CVDs. Results from these epidemiological studies are
also promising, as presented in Table 1.

Table 1. Other vegetables associated with CVDs.

Vegetables Subjects Effects References

Vegetables with U.S. male physicians aged
Lowered the risks of CHD [60]
carotenoids 40–84 years (n = 15,220)
Incorporated into the
Onion quercetin atherosclerotic region, acted as [61]
a complementary antioxidant
Lowered serum TAG, carotid
soybean isoflavones Chinese adults (n = 572) artery intima-media thickness, [62]
increased HDL-C
reduced ischemic heart
disease, lowered blood LDL-C,
soybean foods,
(Meta-analysis) improved endothelial function, [63]
isoflavones
slowed the progression of
subclinical atherosclerosis
Green leafy Reduced incidence of CVDs
(Meta-analysis) [29]
vegetables significantly (15.8%)
Nitrate-containing Non-hypertensive subjects Had a protective effect against
[64]
vegetables aged 20–70 years (n = 1546) development of hypertension

In summary, evidence from most epidemiological studies suggested the significant negative
relationship between vegetable consumption and the risks of CVDs. These vegetables specifically
included tomato, potato, onion, cereal and cruciferous vegetables. Several kinds of components, like
botanic protein, dietary fiber, vitamins (vitamin B1, vitamin B2, niacin and folate), essential elements
(calcium and potassium) and phytochemicals (lycopene), might contribute to the cardioprotective
effects of vegetables. However, in some studies, there were no observed significant inverse association
between CVDs risks and intake of broccoli and vegetable flavonols. In some other studies, consuming
potato, particularly badly cooked potato, could even increase the risk of CVD.

3. Experimental Research

3.1. Potatoes
People all over the word consume a large amount of potatoes per year. Potatoes have been found to
benefit the cardiovascular system, thus they are worth investigating for the treatment and prevention of
CVDs [42,43]. Researchers investigated the potential effects of a CA Mey (Hypoxidaceae) corm (African
potato) aqueous extract (APE) on the cardiovascular system in experimental animal paradigms [42]. Firstly,
Nutrients 2017, 9, 857 5 of 25

APE (25–400 mg/mL) exhibited negative inotropic effects on guinea pig isolated electrically driven left atrial
muscle preparations and negative chronotropic effects on spontaneously beating right ones, respectively,
significantly (p < 0.05–0.001) and concentration-dependently. Secondly, APE concentration-dependently
reduced or abolished the positive inotropic and chronotropic reactions of strips of atrial muscle from guinea
pig induced by noradrenaline (1–100 µM) and calcium (Ca2+, 5–40 mM), which were not modified by
exogenous administration of atropine (7.5 × 10−7 − 2.5 × 10−6 M) to the bath fluid. Thirdly, APE also
caused a reduction or cessation of the rhythmic, spontaneous, myogenic contractions of portal veins
in rats, significantly (p < 0.05–0.001) and concentration-dependently. Furthermore, APE reduced the
systemic arterial blood pressure as well as heart rates of hypertensive rats, significantly (p < 0.05–0.001)
and dose-dependently. Taken together, APE might be a natural candidate for cardiac dysfunction and
essential hypertension remedy. In another study, cholesterol and triglyceride (TG) levels in plasma
(−30%, p < 0.0001 and −36%, p < 0.05, respectively) and cholesterol levels in the liver (−42%, p < 0.0001)
were significantly reduced in rats after three weeks of a potato-enriched diet [43]. Antioxidant status
was also improved due to the intake of potato; additionally, thiobarbituric acid reactive substances
(TBARS) levels in the heart were lowered and the vitamin E/TG (VE/TG) ratio in plasma was
improved. These effects indicated that consumption of cooked potato could be a way of preventing
CVDs. However, when researchers investigated the effects of soluble fiber extracted from potato pulp
on risk factors for diabetes and CVDs in Goto–Kakizaki rats, no difference in hematological parameters
was found; only the postprandial plasma TG concentration of rats was reduced, significantly but
modestly [65]. These results might lead to a conclusion that plasma cholesterol or glycemic response
could not be reduced by increased fermentation and production of propionate with diet-soluble fiber.

3.2. Soybeans
Soybeans are a common vegetable that can be used to extract oil and make soy milk. Polyphenols,
mainly including phenolic acid and flavonoids like flavones and flavonols, are among the most
important bioactive components extracted from soybeans. It was reported that phenolic acid mainly
contributed to the antioxidant capacities of many natural products [66–71]. Many researchers suggested
that polyphenols possessed biological effects like antioxidation and anti-inflammation, which in turn
provided cardiovascular protection [37,44,45,72–75]. In an in vitro study, phenolic-rich extracts from
soybeans were found to inhibit the activities of α-amylase, α-glucosidase, and angiotensin-I converting
enzyme (ACE), which are key enzymes linked to diabetes and hypertension [44]. Thus, researchers
came to the conclusion that soybeans have health-promoting effects including anti-diabetes and
anti-hypertension. Another study investigated the effects of saponin (2-phenyl-benzopyrane), a
soybean flavonoid, on glucose tolerance and risk factors for atherosclerosis [45]. In saponin-treated
animals, the LDL-C/TG ratio was increased, and TG, very low-density lipoprotein cholesterol
(VLDL-C), lipid hydroperoxide, and TC/HDL-C ratio were decreased. However, no effects were
found on glucose tolerance, LDL-C, superoxide dismutase (SOD), and glutathione peroxidase (GPx) in
the experimental groups. These observations indicated that saponin from soybeans might improve the
serum lipid profile due to direct antioxidant activity.
It was also reported that soybeans contain considerable phytoestrogens, like isoflavones (mainly
genistein and daidzein) and lignans, which are safe and natural estrogen receptor modulator
alternatives to hormone therapy and possess antioxidant and cardioprotective effects [31,32,76].
Researchers analyzed the functional and anatomopathological effects of soybean extract and isoflavone
on post-MI [76]. It was found that in the soybean extract group, a protective effect was observed
30 days after the MI. In another study, the cardioprotective effects of genistein from soybean extract on
isoproterenol-treated H9c2 cardiomyoblast cells were investigated [31]. Results indicated that genistein
administration could downregulate the expression of mitochondrial pro-apoptotic proteins such as
Bad, caspase-3, caspase-8, and caspase-9 in H9c2 cells. Additionally, several survival proteins were
expressed in H9c2 cells, including phosphor (p)-Akt, p-Bad, and p-Erk1/2. Moreover, researchers
reported that genistein exerted cardioprotective effects partially due to the regulation of Erk1/2, Akt,
Nutrients 2017, 9, 857 6 of 25

and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) proteins by inhibiting related
pathways. It was also pointed out that genistein from soybeans not only reversed preexisting severe
pulmonary hypertension but also prevented its progression into heart failure (HF) [32]. When genistein
and daidzein were administered, significant neuroprotective effects and antioxidant activities were
observed both in vitro and in vivo in ischemia/reperfusion (I/R)-like conditions [77]. Moreover, the
effects of genistein from soybeans on blood pressure were evaluated in fructose-induced hypertensive
rats [78]. Results showed that genistein administration could lower blood pressure and restore ACE,
protein kinase C-β II, and nitric oxide (NO) synthase (NOS) expression.
Soybean protein is a well-known botanical protein that is regarded as a kind of complete protein,
highly valuable in promoting health [79,80]. The cardioprotective effects of soybean protein have been
proven by evaluating the association between dietary protein source, protein level, and serum lipid
profile in male rats [79]. It was found that the total serum TG level was significantly lowered after
long-term intake of soybean protein, indicating the possibility of reducing the risks of atherosclerosis.
It was also reported that soybean protein possessed cardioprotective effects, partially by improving
serum lipids via modifying the expression of sterol regulatory element-binding protein-2 and its
downstream genes (hydroxymethylglutaryl-coenzyme A reductase and LDL receptor), and increasing
the antioxidant activities of SOD and catalase [80].
It was reported that soybean products could be enhanced in nutritional value after
fermentation [81]. For instance, doenjang was more effective at preventing diet-induced visceral
fat accumulation than non-fermented soybeans in rats, by stimulating carnitine palmitoyltransferase-1
activity and suppressing fatty acid synthase activity, possibly due to the higher content of aglycone
isoflavones [82]. Additionally, it was evaluated that regular intake of miso soup, a Japanese soybean
paste, could alleviate salt-induced sympathoexcitation in mice with chronic pressure overload via
inhibiting the hypothalamic MR–AT1R pathway [83]. Moreover, the effects of probiotic-fermented
genetically modified (GM) soybean milk on hypercholesterolemia in hamsters were explored [84].
The observations suggested that serum total TG level decreased significantly (p < 0.05) after treatment
with four kinds of soy milk (GM or non-GM; with or without probiotic fermentation), compared to the
control group in a diet with high cholesterol. In addition, there was a significant difference between
the GM and non-GM soy milk groups (p > 0.05) in total TG levels. Furthermore, the GM soy milk was
found to reduce the risk of developing atherosclerosis by alleviating oxidative stress and diminishing
atherosclerotic plaque formation in the aorta.
There are some other bioactive components in soybeans, such as unsaponifiables and
oligosaccharides, which are beneficial to the cardiovascular system [85,86]. The protective effects
of soybean unsaponifiables on the prefrontal cortex after global brain I/R injury in rats were
investigated [85]. The results indicated that malondialdehyde (MDA) and tumor necrosis factor-α
(TNF-α) levels, as well as the number of apoptotic neurons, were significantly decreased, while
SOD activities were significantly increased, suggesting that soybean unsaponifiables had antioxidant
and neuroprotective effects. In addition, the protective effects of soybean oligosaccharides on heart
function against myocardium I/R injury were assessed in rats [86]. MDA level was upregulated, while
antioxidant enzyme activities and the expression of p-JAK2 and p-STAT3 proteins were increased in
the soybean-oligosaccharide-treated group. When rats were fed with soybean oligosaccharides, the
cardiac contractile function was significantly recovered, the infarct size was reduced, and creatine
kinase, aspartate transaminase, and lactate dehydrogenase activities were decreased as well.

3.3. Sesame
It has been demonstrated that extracts of sesame possessed strong antioxidant, anti-atherogenic,
anti-thrombotic, and anti-hypertensive activity; thus, regularly consuming sesame whole grains or
purified bioactive components would offer effective protection against CVDs [33–35]. In a study,
chemical and biological model systems were used to access the free radical scavenging capacity and
anti-atherogenic activity of Sesamum indicum seed extracts [33]. By Fe3+ /ferricyanide complex and
Nutrients 2017, 9, 857 7 of 25

ferric reducing antioxidant power assays, it was reported that any dose (25–1000 µg/mL) of aqueous
and ethanolic extracts significantly scavenged the NO, superoxide, 1-diphenyl-2-picrylhydrazyl,
2,20 -azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)1, and hydroxyl radicals. In biological models,
metal-induced lipid peroxidation in mitochondrial fractions, human serum, and LDL oxidation
models was inhibited by both extracts. Moreover, in a lipoprotein kinetics study, the lag phase
time was significantly (p < 0.05) increased by both extracts, while the oxidation rate as well as the
conjugated dienes production was reduced. In another study, the anti-hypertensive effects of ACE
inhibitory peptides from a sesame protein hydrolysate in spontaneously hypertensive rats (SHRs)
were investigated [34]. The systolic blood pressure in SHRs was significantly and temporarily lowered
by sesame peptide powder at 1 and 10 mg/kg, which might be due to ACE inhibitory activity.
Moreover, the ACE activity was competitively inhibited by the representative peptides (Leu-Val-Tyr,
Leu-Gln-Pro, and Leu-Lys-Tyr) isolated from sesame peptide powder at Ki = 0.92 µM, 0.50 µM, and
0.48 µM, respectively. According to the content ratio in sesame peptide powder, it was evident that a
reconstituted sesame peptide mixture of Leu-Ser-Ala, Leu-Gln-Pro, Leu-Lys-Tyr, Ile-Val-Tyr, Val-Ile-Tyr,
Leu-Val-Tyr, and Met-Leu-Pro-Ala-Tyr exhibited a strong anti-hypertensive effect on SHRs at doses
of 3.63 and 36.3 µg/kg, which were responsible for more than 70% of the corresponding dosage for
hypotensive effects induced by the sesame peptide powder. Furthermore, researchers focused on the
anti-thrombotic effects of sesame, and found that Col/Chichibu/Maruteru-2/1995 and T016 varieties
of sesame exhibited significant anti-thrombotic activity, while 00037803 was pro-thrombotic [35]. It was
also observed that sesamol was the most effective component, followed by sesamolin and sesamin,
which showed significant acute anti-thrombotic effects.
Although it was the fat-soluble constituents in the sesame that were thought to benefit the
cardiovascular system, some studies demonstrated that defatted sesame seed extracts (DSSE) also
possessed protective effects [87,88]. In a study, researchers evaluated the positive effects of DSSE using
ischemia models [87]. It was found that DSSE (0.1–10 µg/mL) significantly blocked cell death and
prevented lipid peroxidation induced by oxygen–glucose deprivation followed by reoxygenation.
It was also evident that brain infarct volume was reduced in a dose-dependent manner, while sensory
and motor function were improved by DSSE (30, 100, and 300 mg/kg, orally) administrated 0 h and
2 h after the onset of ischemia. Therefore, it could be concluded that DSSE might be effective in
ischemia models due to the antioxidant activity. In another study, researchers investigated whether
the neuroprotective effects of DSSE were related to brain edema [88]. The results showed that water
content leakage was reduced by DSSE (30, 100, and 300 mg/kg, orally), but not Evans blue leakage.
The Aquaporin 4 expression was inhibited by DSSE at 4 h but not at 24 h after ischemia. No effect on
matrix metalloproteinase expressions and activities was observed. Herein, DSSE might be effective on
brain edema due to the regulation of Aquaporin 4 during the acute phase of ischemia.

3.4. Tomatoes
Tomatoes were thought to have a considerable protective role in CVD; in particular, their bioactive
component, lycopene, was found to exhibit significant antioxidant, anti-hypertensive, hypolipidemic,
and anti-atherogenic effects in vivo and in vitro [36,39]. In a study, it was showed that the increase in
serum MB-isoenzyme of creatine phosphokinase (CPK-MB) was prevented and cardiac cell injury was
ameliorated by lycopene (1.7 and 3.5 mg/kg, intraparietally) and tomato extract (1.2 and 2.4 g/kg,
intraparietally), respectively [36]. These results suggested that lycopene and tomato extract inhibited
the cardiotoxicity induced by doxorubicin and could be used in combination with doxorubicin to
alleviate the organ injury induced by free radicals. In another study, researchers investigated the
effects of tomato extracts and carotenoids, like lycopene and lutein, on physiological function and
NF-κB signaling in endothelial cells [39]. All carotenoids could cause a significant improvement in
primary endothelial function, which was related to increase NO and decreased endothelin release. In
addition, carotenoids effectively attenuated inflammatory NF-κB signaling, including reducing the
adhesion of leukocytes induced by TNF-α, expression of adhesion molecules (AM) like inter-cellular
Nutrients 2017, 9, 857 8 of 25

adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), nuclear translocation
of NF-κB components, and reverting the inhibitor of κB ubiquitination. Additionally, carotenoids
played a role in inhibiting NF-κB activation in transfected endothelial cells. Moreover, lutein combined
with oleoresin synergistically precluded leukocytes’ adhesion.
Sapogenol, another major bioactive component in tomatoes, exhibited anti-atherogenic activities
endowing tomatoes with cardioprotective effects [89,90]. It was reported that esculeogenin A,
a new tomato sapogenol, ameliorated hyperlipidemia and atherosclerosis in ApoE-deficient mice
via restraining cholesterol acyl-transferase [89]. Esculeogenin A markedly blocked the accumulation of
cholesterol ester induced by acetylated LDL in human monocyte-derived macrophages and Chinese
hamster ovary cells, dose-dependently. In addition, esculeogenin A prevented the expression of
acyl-coenzyme A: cholesterol acyl-transferase (ACAT)-1 protein, and suppressed the activities of
both ACAT-1 and ACAT-2. The levels of serum cholesterol, TG, LDL-C, as well as the proportion of
atherosclerotic lesions in ApoE-deficient mice were significantly decreased by oral administration of
esculeoside A, without any detectable side effects. In a similar study, tomatidine, a tomato sapogenol,
was reported to significantly suppress the activity of cholesterol acyl-transferase and led to the
reduction of atherogenesis [90].
In addition, the n-hexane extract of tomato exerted a protective effect against adrenaline-induced
MI in rats [91]. The levels of MDA in heart and aspartate aminotransferase in serum were both
significantly lowered in adrenaline-treated rats given a pre-treatment of tomato extract (1 mg/kg,
2 mg/kg) and vitamin E (50 mg/kg), which also significantly blocked myocardial necrosis. It could
be concluded that the n-hexane extract of tomato possessed an antioxidative potential that might in
turn prevent MI induced by catecholamine. Additionally, the anti-hypertensive effects of a tomato
cultivar (DG03-9) rich in gamma-aminobutyric acid (GABA) were investigated in SHRs [92]. DG03-9
caused a significant reduction in systolic blood pressure with both single and chronic administration
compared to the control. Moreover, researchers found that DG03-9 elicited a higher anti-hypertensive
effect than the commonly consumed cultivar (Momotaro) did, and GABA exhibited a similar effect
to DG03-9 in a comparable dose. Furthermore, it was reported that consuming cooked tomato sauce
could preserve coronary endothelial function; improve HDL, apolipoprotein A-I, and apolipoprotein
J protein profile; enhance endothelial NOS transcription and activation; and reduce DNA damage
in the coronary arteries in dyslipidemic animals [93]. These bioactivities were responsible for the
beneficial effects of cooked tomato sauce, i.e., lowing lipid peroxidation, increasing HDL antioxidant
potential, and preventing diet-induced impairment of receptor-operated and non-receptor-operated
endothelial-dependent coronary vasodilation.

3.5. Dioscorea
Dioscorea is a common vegetable widely used as traditional Chinese medicine, and
contains a variety of bioactive components, like saponins, diosgenin, and flavonoids; it has
been demonstrated that saponins have anti-thrombotic activity [40,41]. In a study, the total
steroidal saponins derived from Dioscorea zingiberensis rhizomes blocked platelet aggregation
and thrombosis dose-dependently, leading to prolonged activated partial thromboplastin time
(APTT), thrombin time (TT), and prothrombin time (PT) in rats and prolonged bleeding time
and clotting time in mice, suggesting ability to decrease CVD risk [40]. In another study,
researchers evaluated the anti-thrombotic effects of four kinds of diosgenyl saponins [41].
The observations indicated that diosgenyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside, a novel
disaccharide saponin, exhibited outstanding efficiency in prolonging bleeding time. Moreover,
it could significantly and dose-dependently block platelet aggregation, prolong APTT, and
inhibit factor VIII activities in rats. Taken together, a conclusion could be drawn that
diosgenyl β-D-galactopyranosyl-(1→4)-β-D-glucopyranoside had considerable anti-thrombotic activity.
Moreover, the beneficial effects of total saponins exacted from three medicinal species of dioscorea,
Dioscorea nipponica Makino, Dioscorea panthaica Prain et Burkill, and Dioscorea zingiberensis, against
Nutrients 2017, 9, 857 9 of 25

isoprenaline-induced myocardial ischemia were further investigated [94]. It was found that the
total saponins from the three dioscorea significantly reduced activities of creatine kinase, lactate
dehydrogenase, and aspartate aminotransferase; lowered the concentration of MDA; and increased
activities of total SOD, catalase, GPx, and total antioxidant capacity, which was comparable
between these three dioscorea. Additionally, heart tissue from total saponins groups revealed
less severe histological damage. These results might partially explain why total saponins possess
a cardioprotective efficacy for myocardial ischemia. Furthermore, saponins exhibited a potent
neuroprotective property in attenuating severe injury induced by transient focal cerebral I/R, and
the mechanism included anti-inflammatory and anti-apoptotic action [95]. It was reported that
saponins markedly decreased neurological deficit scores, cerebral infarct volume, and brain edema
in rats. Additionally, saponins increased neuron survival (Nissl bodies) and decreased caspase-3
in the hippocampal cornu Ammons 1 and cortex hemisphere of the ipsilateral ischemia. Moreover,
pre-administration of saponins significantly decreased the inflammatory cytokines in serum induced
by the middle cerebral artery occlusion, and markedly inhibited the downregulating anti-apoptotic
Bcl-2 and upregulating proapoptotic Bax proteins.
It was reported that dioscorea, and its bioactive compound diosgenin in particular, exerted
anti-thrombosis activity, possibly via promoting the anti-coagulation function and blocking platelet
aggregation [96,97]. In a study, it was found that platelet aggregation, thrombosis and APTT, TT, and PT
in rats were dose-dependently inhibited by diosgenin, while the bleeding time and clotting time were
dose-dependently prolonged in mice [96]. It could be concluded that diosgenin extracted from Dioscorea
zingiberensis possessed anti-thrombosis activities with a potential for CVD treatment. In another study,
diosgenin was observed to alleviate cardiotoxicity induced by doxorubicin in mice [97]. In the
heart tissue, diosgenin recovered the reduced activities of antioxidant enzymes, involving SOD and
GPx. In addition, diosgenin significantly lowered the serum levels of cardiotoxicity markers, cardiac
levels of TBARS and reactive oxygen species (ROS), caspase-3 activation, mitochondrial dysfunction,
and the expression of NF-κB. Moreover, diosgenin increased the cardiac levels of cyclic guanosine
monophosphate by modulating phosphodiesterase-5 activity and attenuating myocardial fibrosis.
Meanwhile, it was confirmed that regulating protein kinase A and p38 could mediate the health
benefits of diosgenin. These results implied that diosgenin possessed antioxidant and anti-apoptotic
activities, as well as cyclic guanosine monophosphate modifying effects, which in turn protected the
heart from cardiotoxicity induced by doxorubicin.
There are some other studies focusing on the beneficial effects of dioscorea on cardiovascular
protection as well. More promisingly, other bioactive compounds contained in dioscorea have been
identified, which might protect against MI and atherosclerosis [98,99]. In a study, results suggested
that the flavonoid-rich portion of Dioscorea bulbifera Linn. could attenuate lipid peroxidation due
to the capacity to scavenge free radicals and modulate energy-producing mitochondrial enzymes,
suggesting a cardioprotective effect on isoproterenol-induced MI [98]. In another study, researchers
arrived at the conclusion that an extract of Chinese yam, rich in β-sitosterol and ethyl linoleate,
had the capability to prevent atherosclerosis, thus it could be a candidate for functional foods.
It was reported that such extracts could inhibit the expression of inflammatory mediators, including
TNF, NO, and inducible NOS, and the development of atherosclerotic lesions [99]. In addition,
several studies also suggested the cardioprotective effects of dioscorea, of which the bioactive
compounds might not have been identified [100,101]. In a study, it was confirmed that dioscorea
rhizome exhibited antioxidative and anti-atherogenic effects on hyperlipidemic rabbits, suggesting
that supplementation with dioscorea rhizome might be a possible way to reduce oxidative stress
and attenuate atherosclerosis [100]. In another study, Dioscorea opposita Thunb. was found to exhibit
anti-hypertensive effects on hypertensive rats through inhibiting the endothelin-converting enzymes
as well as antioxidant activity [101]. After treatment, Dioscorea opposita Thunb. caused significant
reductions in mean blood pressure, plasma endothelin and MDA concentration, plasma angiotensin-II
activity, left ventricular hypertrophy, and cardiac mass index, while increasing the plasma SOD activity.
Nutrients 2017, 9, 857 10 of 25

3.6. Onions
Onions are a commonly consumed vegetable all over the world, and contain bioactive components
like phytochemicals. Onion extracts exhibited potent anti-atherogenic effects that were related to a
variety of bioactivities [102,103]. In a study, onion (Allium cepa L.) extracts as well as the bioactive
components quercetin and catechin were observed to enhance paraoxonase 1 activity and radical
scavenging activity, which in turn prevented LDL oxidation and lipid peroxidation in male Wistar
rats subjected to oxidative stress caused by mercuric chloride [102]. In another study, [103] onion
extract was found to lessen atherosclerotic lesions, increase endogenous aortic hydrogen sulfide
(H2 S) production, and decrease plasma adrenomedulin content, aortic adrenomedulin content, aortic
calcitonin receptor-like receptor, and receptor activity-modifying protein 1/2 mRNAs. Additionally,
plasma GPx level, SOD activity, plasma endothelial NOS activity, and NO content were increased,
while MDA and inflammatory response were reduced by onion extract. All of these effects made
onions a potential candidate for anti-atherogenic therapy.
Some experimental studies have suggested that onions have anti-thrombotic effects via platelet
inhibitory response and inhibiting mitogen-activated protein kinase (MAPK) activation. Therefore,
onion intake might have a capacity for preventing platelet-mediated CVDs [104–106]. In a study, results
showed that onion could inhibit thrombosis induced by platelets in dogs [104]. It was demonstrated
that periodic platelet-mediated thrombus formation followed by embolization caused a reduction
in cyclic flow. However, in five dogs, 0.09 ± 0.01 mL/kg onion juice administered intravenously
attenuated cyclic flow reductions within 20 min, followed by a 60 ± 14% (p = 0.002) reduction in
collagen-induced ex vivo whole blood platelet aggregation. In addition, in six dogs given 2.0 g/kg
onion homogenate intragastrically, cyclic flow reductions were lessened within 2.5–3 h in five of
the dogs, accompanied by a 44 ± 24% (p = 0.04) reduction in ex vivo aggregation. Moreover, as
measured by thrombosis/thrombolysis models in rodents in another study, a variety of onion cultivars
exhibited natural anti-thrombotic effects [105]. First of all, researchers confirmed that Toyohira exerted
marked anti-thrombotic activities as well as anti-platelet effects accompanied by thrombolytic activity.
Meanwhile, Super Kita Momiji, 2935A, and K83211 exhibited only thrombolytic activity. Furthermore,
researchers found no significant association between quercetin concentration and anti-thrombotic
activity. Interestingly, the anti-thrombotic effects of quercetin-rich onion peel extracts (OPE) on arteries
in rats were stated in another study [106]. The OPE markedly reduced blood TG and glucose without
affecting blood cholesterol levels. In addition, in vivo arterial thrombosis was significantly abolished
in groups fed with 2 mg and 10 mg OPE. Additionally, thrombin-induced expression of tissue factor
in human umbilical vein endothelial cells, a coagulation initiator, was greatly diminished by the
OPE. Furthermore, extracellular signal-regulated kinase (ESRK) and c-Jun N-terminal kinase (CJNK)
signaling pathways activated by thrombin treatment were blocked by pre-treatment with OPE.
Onions were also found to have anti-hypertensive effects in some other experiments [107,108].
For instance, dietary onion decreased the TBARS in plasma in N(G)-nitro-L-arginine methyl ester
(L-NAME)—induced-hypertensive rats and stroke-prone SHRs [107]. In addition, onions improved
the nitrate/nitrite (products of NO) excreted in urine and the NOS activities in the kidneys in
stroke-prone SHRs, but not in L-NAME- induced-hypertensive rats. These results might in part
explain the mechanisms by which onion exerted an anti-hypertensive effect on these hypertensive
rats. In addition, the anti-hypertensive effects of onion were observed with different mechanisms [108].
OPE was demonstrated to concentration-dependently reduce the aorta contractions induced by KCl
or phenylephrine (p < 0.001). Moreover, the OPE activity could not be attenuated by removing
aorta endothelium, or the inhibition of NO, cGMP and prostaglandin synthesis induced by L-NAME
(100 µM), methylene blue (10 µM) and indomethacin (10 µM), respectively. In addition, the relaxation in
phenylephrine-precontracted aorta mediated by OPE was not abolished by atropine, which blocked the
acetylcholine-induced relaxation. Furthermore, after three weeks’ intervention with OPE, a reduction
of blood pressure was observed in the hypertensive rats fed with fructose (p < 0.001).
Nutrients 2017, 9, 857 11 of 25
Nutrients 2017, 9, 857 11 of 25

3.7. Other Vegetables

3.7. Other Vegetables
Besides
Besides the
the vegetables
vegetables investigated above, there
investigated above, there are
are others
others that
that have
have beneficial
beneficial effects
effects onon the
the
cardiovascular system. Evidence from experimental research has suggested cardioprotective
cardiovascular system. Evidence from experimental research has suggested cardioprotective effects effects
and
and mechanisms
mechanisms (Table
(Table 2).
2).
In summary,
In summary, numerous
numerous experimental
experimental studies
studies have
have indicated
indicated that
that vegetable
vegetable consumption
consumption is is
potentially beneficial in preventing and treating CVD. As demonstrated, vegetables
potentially beneficial in preventing and treating CVD. As demonstrated, vegetables like potatoes, like potatoes,
soybeans, sesame, tomatoes,
soybeans, sesame, tomatoes, dioscorea,
dioscorea, and
and onions
onions possess
possess cardioprotective
cardioprotective effects,
effects, for
for which
which aa
variety of bioactive components including vitamins, essential elements, dietary
variety of bioactive components including vitamins, essential elements, dietary fiber, botanical fiber, botanical
proteins,
proteins, and
and phytochemicals
phytochemicals are are responsible.
responsible. In
In addition,
addition, the
the cardioprotective
cardioprotective effects
effects might
might include
include
antioxidation, anti-inflammation, anti-platelet,
antioxidation, anti-inflammation, anti-platelet, lowering
lowering blood
blood pressure,
pressure, modifying
modifying lipid
lipid metabolism,
metabolism,
regulating bloodglucose,
regulating blood glucose, improving
improving endothelial
endothelial function,
function, and attenuating
and attenuating myocardial
myocardial damagedamage
(Figure
(Figure 1). Moreover,
1). Moreover, the mechanisms
the mechanisms of action
of action might might
involveinvolve modulating
modulating relatedrelated
enzyme enzyme activity,
activity, gene
gene expression,
expression, and signaling
and signaling pathways
pathways as wellasaswell
someas other
some biomarkers
other biomarkers associated
associated with CVD withrisk
CVD risk
(Table
(Table
3). 3).

Figure 1. The
Figure 1. The cardioprotective effects of
cardioprotective effects of vegetables.
vegetables.
Nutrients 2017, 9, 857 12 of 25

Table 2. Other vegetables and their effects on CVDs.

Vegetables Subjects Effects and Mechanisms References

Apium graveolens (seed) Rats Decreased blood pressure, increased heart rate [109]
Lessened lipid droplets and TC content, decreased secretion of inflammatory
Celery (seed) RAW264.7 macrophages cytokine TNF-α and interleukin (IL)-6, promoted cell viability, inhibited [110]
apoptosis, suppressed NF-κB, p65 and notch1 protein expressions
Apium graveolens (leaf) Sprague Dawley rats Decreased systolic blood pressure, cholesterol, TG, LDL and VLDL [111]
Lowered systolic blood pressure, urinary protein excretion/creatinine
Asparagus officinalis SHRs [112]
excretion ratio, creatinine clearance and ACE activity
Decreased LDL/HDL ratio and liver cholesterol levels, increased fecal total
Lettuce Rats steroid excretion, depressed apparent absorption of dietary cholesterol, [113]
improved VE/TG ratio in plasma, limited lipid peroxidation in heart
Modulated liver fatty acid composition, protected against elevations in
Collard greens SHRs [114]
atherogenic fatty acids
Brassica oleracea L. In vitro thrombolytic model Showed clot lysis activity [115]
Rape (seed) SHRs Inhibited ACE, dilated mesenteric artery [116]
Rape (seed) SHRs Inhibited ACE and renin activities, lowered blood pressure [117]
Reduced surface hydrophobicity, scavenged oxygen radicals, inhibited ACE,
Rape (seed) SHRs [118]
lowered blood pressure
Decreased catalase, increased SOD activities, protected against
Spinach Balb/c mice [119]
doxorubicin-induced heart injury
Spinach SHRs Exerted anti-hypertensive activity [120]
Spinach (leaf) SHRs Inhibited ACE, exerted anti-hypertensive activity [121]
Antioxidant, inhibited α-glucosidase and ACE, anti-diabetic- and
Pumpkin In vitro [122]
anti-hypertension
In vitro, normotensive anesthetized Lowered arterial blood pressure, inhibited spontaneously beating guinea pig
Daucus carota [123]
rats atria and K+ -induced contractions of rabbit aorta
Increased total neutral sterols fecal excretion, increased antioxidant status and
Lyophilized carrot C57BL/6J mice [124]
VE/TG ratio, lowered lipemia, regulated cholesterol metabolism
Carrot In vitro, mice Anti-thrombosis [125]
Broccoli stroke-prone SHRs Attenuated oxidative stress, hypertension and inflammation [126]
Nutrients 2017, 9, 857 13 of 25

Table 2. Cont.

Vegetables Subjects Effects and Mechanisms References

Protected mammalian hearts, activated survival proteins, improved
post-ischemic ventricular function and pro-caspase 3 activities and redox
Broccoli Rats [127]
cycling of thioredoxins, reduced myocardial infarct size, cardiomyocyte
apoptosis and cytochrome c release
Protected against myocardial oxidative damage and cell death during I/R,
Broccoli Rats [128]
inhibited markers of necrosis and apoptosis, decreased oxidative stress
Improved post-ischemic ventricular function, reduced MI and
Broccoli Rats [129]
cardiomyocyte apoptosis
Corn SHRs, in vitro Inhibited ACE, lowered systolic blood pressure [130]
Antioxidant, inhibited a-glucosidase and ACE, anti-diabetic- and
Corn In vitro [122]
anti-hypertension
Purple corn SHRs Decreased blood pressure and heart rate [131]
Reduced infarct size, increased myocardial glutathione levels, modulated
Maize Wistar rats [132]
cardiac antioxidant defenses
Reduced MDA, tissue calcium concentration, myeloperoxidase and apoptosis
Pea Rats [133]
indicator caspase-3, protected hearts from I/R injury
Hindered free radical-mediated tissue injury, endothelial dysfunction and
Latyrus cicera Rats leukocyte recruitment, protected against splanchnic artery I/R-induced [134]
splanchnic injury
Pea In vitro Inhibited α-amylase and α-glucosidase and ACE [135]
Pea Weanling Han:SPRD-cy rats Lowered serum creatinine and renal chemokine receptor 2 level [136]
Pea Rats lowered plasma TC concentrations, affected cellular cholesterol homeostasis [137]
Nutrients 2017, 9, 857 14 of 25

Table 3. The mechanisms involved in the cardioprotective effects of vegetables.

Cardioprotective Effects Mechanisms

Inhibit ACE activity and hypothalamic MR-ATIR pathway, alleviate
sympathoexcitation; improve protein kinase C-β II activity; modify relative
Lower blood pressure
telomere length of peripheral leucocyte, increase NOS expression; inhibit
Ca2+ influx and K+ -induced contractions.
Decrease TC, TG, TAG, VLDL-C, TC/HDL-C ratio and atherosclerotic
plaque formation, increase LDL-C/TG and VE/TG ratio; inhibit fatty acid
Regulate lipid metabolism synthase and ACAT activity, modulate energy producing mitochondrial
enzymes; modify expression of ACAT and sterol regulatory
element-binding protein-2 and its downstream genes.
Scavenge free radicals (NO, superoxide, hydroxyl, TBARS); increase
Antioxidant endogenous aortic H2 S production; improve SOD, catalase, GPx, carnitine
palmitoyltransferase-1 and paraoxonase 1 activity.
Decrease endothelin and artery intima-media thickness, increase NO,
Improve endothelial
improve apolipoprotein A-I and apolipoprotein J protein profile; inhibit
function
endothelin-converting enzyme; diminish DNA damage.
Attenuate TNF-α induced leukocytes adhesion; reduce NF-κB, IL-6; inhibit
Anti-inflammatory
expression of AM.
Prolong APTT, TT, PT, bleeding time and clotting time; inhibit MAPK,
Anti-platelet
ESRK, factor VIII activities and c-Jun N-terminal kinase signaling pathways.
Decrease MDA, water content leakage and infarct size, increase cyclic
guanosine monophosphate; inhibit creatine kinase, aspartate transaminase,
Attenuate myocardial lactate dehydrogenase and CPKMB activity, modulate protein kinase A, p38,
damage and phosphodiesterase-5 activity; inhibit Bad, Bax, caspase-8, caspase-9,
and caspase-3 and aquaporin 4 expression, increase phosphor (p)-Akt,
p-Bad, p-Erk1/2, Bcl-2, p-JAK2 and p-STAT3.
Inhibit α-amylase and α-glucosidase activity; improve hemoglobin A1c and
Regulate blood glucose
high fasting blood sugar level.

4. Clinical Trials

4.1. Whole Soybeans and Soy Milk

In addition to the findings in the abovementioned studies that soybeans possess a variety
of bioactivities to prevent CVD, the results of many clinical trials have supported that soybean
consumption might be a way to lower CVD risk and maintain cardiovascular health [46–49]. Soybeana
had an effect on biomarkers of CVDs in elderly women with metabolic syndrome [46]. Compared
to mean changes from baseline with the control group, LDL-C, VLDL-C, and apolipoprotein B100
levels were significantly improved in the whole soybean (35 g/day) intake group (p < 0.05), while
fewer, significant improvements were observed in these variables in the textured soybean protein
(35 g/day) group (p < 0.001). For apolipoprotein A-I, similar results were observed in the treatment
groups (p < 0.01), in which serum TC was significantly decreased (p < 0.005). In all, soybeans and
textured soybean protein could improve the lipid profile, but the former caused more considerable
improvements than the latter. Moreover, consumption of soybean foods was found to improve the
lipid profile in patients with hyperlipidemia [47]. According to the data measured in the separation of
the group into equol producers (n = 30) and non-producers (n = 55), similar changes from baseline
in LDL-C were observed (−9.3 ± 2.5% and −11.1 ± 1.6%, respectively, p = 0.834), with preservation
of HDL-C and apolipoprotein A-I only in equol producers compared with changes in non-producers
(HDL-C: +0.9 ± 2.7% compared with −4.3 ± 1.1%, p = 0.006; apolipoprotein A-I: −1.0 ± 1.1% compared
with −4.7 ± 1.0%, p = 0.011). Moreover, soy milk consumption significantly reduced systolic blood
pressure in type 2 diabetic patients with nephropathy when compared to cow’s milk consumption
(percent change: −4.50% vs. 5.89%, p = 0.03) [48]. Additionally, intake of soy milk significantly reduced
Nutrients 2017, 9, 857 15 of 25

serum TG (percent change: −15.22% vs. 2.37%, p = 0.02), though these effects were not significant after
adjustment for carbohydrate intake. Furthermore, data derived from another study indicated that the
use of soybean products in comprehensive early rehabilitation therapy of patients with macrofocal MI
significantly reduced the risk of arrhythmia [49].

4.2. Soybean Protein

Soybean protein could modestly improve the serum lipid profile as well as other risk factors
related to CVD, as has been affirmed in a study involved 90 moderately hypercholesterolemic
Chinese adults [138]. In a randomized controlled trial (RCT), soybean protein supplementation
gave rise to a significant mean net change (95% CI) in plasma E-selectin of −3.93 ng/mL (−7.05 to
−0.81 ng/mL, p = 0.014) compared with milk protein, and in plasma leptin of −2089.8 pg/mL (−3689.3
to −490.3 pg/mL, p = 0.011) compared with carbohydrate [139]. These observations indicated that
soybean protein supplementation could reduce E-selectin and leptin levels in plasma. However,
intake of either cow’s milk or a soy protein beverage for eight weeks did not alter soluble cell
AM concentrations in pre-hypertensive or stage 1 hypertensive individuals, suggesting that neither
beverage diminished atherosclerotic CVD risk in mildly hypertensive individuals by improving
circulating cell AM concentrations [140].

4.3. Soybean Isoflavones

Soybean isoflavones, especially genistein and daidzein, are common phytoestrogens recognized
as selective estrogen receptor modulators that possess cardioprotective effects in vitro and in vivo,
but there is a lack of promising outcomes in clinical trials. In a six-month RCT, purified daidzein
did not exhibit significant effects on body weight, body mass index, waist and hip circumferences,
waist to hip ratio, body fat percentage, fat mass, and free fat mass in equol-producing postmenopausal
women with prehypertension [141]. In the same study, it was found that purified daidzein had no
significant effect on blood pressure and vascular function [142]. However, in the above two studies
urinary isoflavones suggested good compliance of the patients with the interventions.

4.4. Combination of Soybean Isoflavones and Soybean Protein

Results from clinical trials also indicated that a combination of isoflavones and soybean protein
might not be an effective intervention to prevent CVD [143,144]. In a RCT, isoflavone soybean protein
(ISP) supplementation did not result in a significant reduction of subclinical atherosclerosis progression
in postmenopausal women [143]. While subgroup analysis indicated that ISP supplementation could
reduce subclinical atherosclerosis in healthy young women (median age: 53 years) less than five years
postmenopausal who were at low risk for CVDs. In a double-blind randomized, placebo-controlled trial
conducted among 180 postmenopausal Chinese women, soybean protein combined with isoflavones at
the provided dosage (15 g soybean protein, 100 mg isoflavones) had no significant effect on measured
cardiovascular risk factors, including serum HDL-C, LDL-C, TC, TG, and highly sensitive C-reactive
protein [144].

4.5. Other Vegetables and Their Bioactive Components

Other vegetables and their bioactive components were also studied, such as sesame, tomatoes,
broccoli, and onions, among which some were found to have properties promising for CVD prevention
and treatment (Table 4).
Nutrients 2017, 9, 857 16 of 25

Table 4. Relationship between other vegetables and CVD.

Vegetables Subjects Effects References

Overweight or obese
Sesame No improvement in markers of CVD risk [145]
men and women (n = 33)
Patients with grade-1
Tomato Decreased blood pressure and TBARS level [146]
hypertension (n = 31)
Improved serum antioxidant status,
Tomato Healthy women (n = 18) [147]
decreased vascular AM 1
Decrease plasma TC, TG and several
cellular and plasma inflammatory
Tomato Healthy subjects (n = 40) [148]
biomarkers, increase plasma HDL-C and
IL-10
No change in inflammatory markers,
Healthy middle-aged
Tomato insulin resistance and sensitivity, lipid [149]
volunteers (n = 225)
concentrations and arterial stiffness
No significant change in blood pressure
Hypertensive
Broccoli and endothelial function measured by flow [150]
individuals (n = 40)
mediated dilation
Increased the urinary concentrations of
sulforaphane metabolites and vitamin C,
Healthy Caucasian
Broccoli decreased the urinary concentrations of [151]
volunteers (n = 24)
tetranor-PGEM, 11β-PGF2α and
11-dehydro-TXB2
Improved postprandial but not fasting
Onion Healthy men (n = 23) flow-mediated vasodilation; did not alter [152]
systemic and forearm hemodynamics
Decreased 24 h, daytime and night-time
Overweight-to-obese
Onion systolic blood pressure in hypertensives; [153]
patients (n = 70)
did not affect vasoactive biomarkers

In addition, healthy dietary patterns characterized by a high content of vegetables were important
to reduce CVD risk [154,155]—for instance, the recommended Dietary Approach to Stop Hypertension
(DASH) and the Mediterranean diet. The DASH diet suggests consumption of vegetables, fruits, and
low-fat dairy products, and was found to result in a significant improvement of cardiovascular risk
factors including BP, TC, and LDL, and cause a risk reduction for CVD incidence and mortality [156,157].
The Mediterranean dietary pattern is characterized by a high content of vegetables, as well as fruits
and whole grains, and has been reported to decrease the incidence and mortality of CVDs, like CHD,
MI, and stroke [158–160].
In summary, clinical trials showed that some specific vegetables had advantages in CVD
prevention and treatment. Whole soybeans and their components (like soy protein) possessed potent
cardioprotective effects. Moreover, some other vegetables, such as sesame, tomatoes, broccoli, and
onions, were beneficial to CVD patients to some degree. On the other hand, no significant change in
some biomarkers in subjects consuming tomato, broccoli, and soybean isoflavones was observed in
some studies, so further clinical trials regarding the cardioprotective effects of vegetables are warranted.
Furthermore, it is favorable to promote a healthy dietary pattern containing a high content of vegetable
to reduce CVD risk.

5. Conclusions
The results from many epidemiological studies support the hypothesis that vegetable
consumption is inversely correlated to the risk of CVDs. Moreover, numerous studies have suggested
that many vegetables could be taken into consideration as candidates for CVD prevention and
treatment, such as potatoes, soybeans, sesame, tomatoes, dioscorea, onions, celery, broccoli, lettuce, and
Nutrients 2017, 9, 857 17 of 25

asparagus, which contain varieties of bioactive components, including vitamins, essential elements,
dietary fibers, botanical proteins, and phytochemicals. The cardioprotective effects of vegetables
might include antioxidation, anti-inflammation, anti-platelet, lowering blood pressure, modifying
lipid metabolism, regulating blood glucose, improving endothelial function, attenuating myocardial
damage, modulating related enzyme activities, gene expressions and signaling pathways, as well
as some other biomarkers associated with CVD risk. Furthermore, the cardioprotective effects of
vegetables have also been observed in some clinical trials, though evidence was limited. Thus,
consuming vegetables could help maintain cardiovascular health, and could be used as a substantial,
sustainable, and economical strategy. In the future, more vegetables should be evaluated as to whether
they have protective effects on the cardiovascular system, and bioactive components should be isolated
and identified. Underlying mechanisms of action are also worth investigating. Meanwhile, more
clinical trials should be conducted in this field.

Acknowledgments: This work was supported by the National Natural Science Foundation of China (No.
81372976), a Key Project of the Guangdong Provincial Science and Technology Program (No. 2014B020205002),
and the Hundred-Talents Scheme of Sun Yat-Sen University.
Author Contributions: Guo-Yi Tang and Hua-Bin Li conceived this paper; Guo-Yi Tang, Xiao Meng, Ya Li,
Cai-Ning Zhao, and Qing Liu wrote this paper; Hua-Bin Li revised the paper.
Conflicts of Interest: The authors declare no conflict of interest.

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