The complex pathophysiological process involved in CVD includes the participation of platelets; these have a main role during thrombosis and progression of atherosclerosis [90]. Food supplements and/or nutraceuticals have become attractive alternatives to reduce cardiovascular events [91].

The methanolic extract of Phaseolus vulgaris L. had been considered relevant by its antiplatelet effect, especially the ability to suppress platelet secretion, using the proposed mechanism of protein kinase A (PKA) modulation and the inhibition of AKT phosphorylation [92].

It is hypothesized that some flavonoids (kaempferol, epicatechin, delphinidin, cyanidin) can inhibit the platelet function by suppressing the platelet aggregation, calcium mobilization, integrin modulation, granule secretion, and thrombus formation, using as an example the pharmacological action of nobiletin [93].

Furthermore, other proteins can increase the activation of platelets, as is the case of lectins; these are proteins sometimes referred to as an antinutrient for decreasing the body’s ability to absorb nutrients, but this review will be focusing on the lectins-induced stimulation of fresh platelets [94].

These lectins have shown effect through phospholipase C (PLC) ƴ 2 activations, using the Src/Syk and PI3K/BTK pathways, but also an increase in the reactive oxygen species (ROS), as well as superoxide anion formation and lipid peroxidation by working as an uncoupling agent with the consequent increase in oxygen consumption and decrease in adenosine triphosphate (ATP) formation [95,96]. This activation was completely inhibited by the use of penicillin G (12.5 mM) and cephalothin (12.5 mM) [97].

Another interesting discovery is the Phaseolus vulgaris L. agglutinin production of nitric oxide (NO), regulated by the Ca²⁺/calmodulin kinase/AMPK pathway in a time and dose-dependent manner. This process is dependent on the eNOS phosphorylation involving the eNOS/NO/cGMP/PKG pathway [95,98]; the NO production by the beans agglutinin can reduce the platelet aggregation, explaining the lower platelet activation compared with agglutinin from whole grain [99].

Many components from Phaseolus can help with the regulation of platelet aggregation as glycine by impeding the calcium influx [100], arginine by enhancing the nitric oxide activity in hypercholesterolemic patients [101], or anthocyanin by inhibiting the platelet-monocyte and platelet–endothelial interaction [102].

Derivatives of alpha-linoleic acid can inhibit platelet aggregation and inflammation, which has been linked to the prevention of CVD, hypertension, type 2 diabetes, chronic obstructive pulmonary disease, among others [19]. Especially, the role of omega3 and omega6 has been discussed many times for his role in platelet aggregation; many papers report the inhibitory effect of omega3 in ADP-dependent platelet aggregation [103,104], with a noticeable effect in healthy patients, unlike CVD patients who had a low increase in lag time [105]. Meanwhile, high omega 6 levels have been related to pro-inflammatory and pro-aggregatory phenotypes [106], by increasing the susceptibility of LDL to oxidate and therefore increasing the TXA2 production [107].

The ingestion of inadequately cooked beans can result in severe glycemic index tract distress; the proposed mechanism of damage prevents the repair of the epithelial cell surface disruptions, resulting in necrotic cell death. The lectins are known to inhibit the exocytosis event required to repair the plasma membrane, and that is the mechanism used to maintain and accumulate the damage in the GI tract [108].

As we discussed, the common bean is cultivated worldwide and used as a nutraceutical food, when cooking properly, but is not the only process used to gain nutritional value from these pulses. The common bean hydrolysate had reported many effects from angiotensin-converting enzyme inhibitor to antioxidant, antimicrobial, and even tumor cell inhibitor. The bioactive potential of peptides present in the indigestible fraction of common beans that protect cells from oxidative stress and inhibit the angiotensin-I converting enzyme by interacting with its catalytic cavity independently of its antioxidant capacity was demonstrated [109].

Gomes et al. explained the hydrolysate capacity to modulate lipid metabolism and prevent endothelial dysfunction in BALB/c mice; they also showed hypocholesterolemic activity helping to reduce inflammation, oxidative stress, and endothelial dysfunction [110]. Phaseolus vulgaris L. agglutinin (PHA) evidenced specific cytoplasmic staining of macrophages in rabbit vessels, monkeys, and human tissues (atherosclerotic arteries obtained in surgery). When analyzing the morphometric comparisons between PHA staining of the lesion and acid lipase as a macrophage marker, similar results were obtained. In this context, they concluded that PHA is an excellent experimental marker to differentiate and quantify macrophages in fixed and human atherosclerotic lesions [111]. The use of hydrolysates of Phaseolus vulgaris shows an interesting effect in mice, from the modulation of the lipid profile to the increase in e-NOS expression [110]; this effect can be explained by the effect of the compounds found in the bean, upon endothelial cells. This is the case of n-3 PUFAs such as omega3 that, in trials, have shown prevention of endothelial dysfunction [112], or of amino acids such as lysine, leucine, serine and glutamine that work as modulators of NO production [113].

Some studies have focused on evaluating the effect of different plants with beneficial effects on pro-inflammatory mechanisms, mainly to reduce cardiovascular risk factors [114]. Macrophages are the main source of pro-inflammatory cytokines and can be used as markers of chronic inflammation, tumor necrosis factor α (TNF-α), interleukins (IL), and prostaglandins E-2 (PGE-2), among others. TNF-α plays a fundamental role in the expansion of the inflammatory process since it induces the production of IL-1β, among other pro-inflammatory cytokines [115], and increases PGE-2 [116,117].

Peroxisome Proliferator-Activated Receptors (PPARs) are transcription factors that belong to the superfamily of ligand-activated nuclear receptors, which mainly regulate lipid metabolism [118]. PPAR-α ligands are known to have anti-inflammatory effects in various cells through apoptosis in cytokine-activated macrophages, inhibiting NFκB signaling [118,119]. It has been described that the enzymatic hydrolysis of beans produces protein hydrolysates with anti-inflammatory activity [120] that could counteract the chronic inflammatory process initiated by human macrophages [117]. Research highlights the effectiveness of total digested proteins and peptides from bean seeds against adipogenic complications and inflammation [121]. Hydrolysate protein from this legume has been shown to decrease inflammation in adult male mice fed an atherogenic diet for nine weeks [110].

Phaseolin is the main globulin reserve in bean seeds [67]. This protein is a potential therapeutic candidate for the management of inflammation. Phaseolin inhibits nitric oxide production; inducible nitric oxide synthase expression also suppresses pro-inflammatory mediators such as cyclooxygenase 2 (COX-2), interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), among others [122].

Oseguera et al. evaluated the antioxidant capacity of protein hydrolysates (rich in bioactive peptides derived from phaseolin) from the Negro 8025 and Pinto Durango varieties of Phaseolus vulgaris L. and determined their effect on the markers of inflammation in RAW 264.7 macrophages induced by lipopolysaccharides. Durango Pinto bean alcalase hydrolysates at 120 min inhibited inflammation (inhibition of cyclooxygenase (COX)-2 expression, prostaglandin E₂ production, inducible nitric oxide synthase (NOS) expression, and NO production) to a greater extent than black beans. Additionally, the hydrolysates inhibited the transactivation of NF-κB and the nuclear translocation of the p65 subunit of NF-κB [120].

Kim et al., 2016, studied the effects of adzuki beans on lipid accumulation and inflammation mediated by oxidative stress in male C57BL mice induced by a diet high in cholesterol and fat for 6 weeks. The results suggested that adzuki beans decrease lipid accumulation and inflammation induced by oxidative stress, by a mechanism of suppression of hepatic messenger RNA expression of lipogenic and inflammatory mediators. This effect could be associated with the rich anthocyanin, catechin, and saponin content of adzuki beans [123].

The effect of whole wheat flour and bean protein hydrolysate from the common bean variety Carioca on inflammation and oxidative stress was studied in BALB mice fed a diet high in fat and cholesterol. Animals fed whole bean meals showed less weight gain, higher levels of alanine aminotransferase, and low-density lipoprotein cholesterol than animals fed bean protein hydrolysate. The expression of PPAR-α was lower in the groups fed with bean protein hydrolysate and bean flour. These results could be associated with the increase in inflammation generated in diet-induced obesity since a short period was sufficient to decrease the inflammatory marker (PPAR). The positive effect on inflammation is attributable to phenolic compounds such as catechin and kaempferol present in bean flour, while in the protein hydrolysate; it is attributed to biologically active peptides and proteins such as phytohemagglutinin, alpha and beta phaseolin, alpha-amylase 1 inhibitor, and alpha-amylase 2 inhibitors [119,124].

Another study refers to how postharvest storage time influences the inflammation of Carioca, Madreperola, and Pontal beans, stored (0, 3, and 6 months), cooked, and subjected to simulated gastrointestinal digestion with pepsin–pancreatin. The study was conducted in human THP-1 macrophage-like cells. The commercial storage time did not affect the protein concentration, the degree of hydrolysis, the hydropathic, or the antioxidant capacity. All hydrolysates reduced TNF-α by about 30%. The Madreperola hydrolysates decreased IL-1β and PGE-2. Carioca beans inhibited inflammation due to their content of bioactive peptides and phenolic compounds, and it was shown that the commercial storage time did not affect the physicochemical or biological properties [117].

Studies have shown that the antioxidant and anti-inflammatory activities of bean extracts are associated with polyphenols present capable of inhibiting COX and lipoxygenase (LOX). Acetone extract made from black bean peel exhibited strong inhibitory effects of COX-1 (IC₅₀ = 1.2 μg/mL) and COX-2 (IC₅₀ = 38 μg/mL), while the aqueous extracts were stronger inhibitors of lipoxygenase, 15-LOX, versus the acetone extracts. The COX and LOX inhibitory activities of aqueous extracts such as acetone suggest that the use of bean shells in food may protect against some diseases associated with chronic inflammation [125]. People who consume beans and whole grains have been found to have a longer life expectancy and lower burden of chronic diseases, including obesity, CVD, diabetes, and cancer [126], which are characterized by having a strong chronic inflammatory component [127].

Metabolic syndrome (METS) is a simultaneous group of metabolic disorders that includes central obesity (abdomen), insulin resistance, hypertension, glucose intolerance, and dyslipidemia [128], which increases the risk of CVD. It is estimated that it affects almost 35% of the US adult population, and its prevalence increases with age [129].

A healthy lifestyle, improving eating habits, and physical activity, are the therapeutic recommendations for the treatment and management of METS, but a gold standard dietary pattern for its management has not yet been proposed [130]. In this sense, many researchers have pointed out that a diet high in unsaturated fats, (olive oil), together with the consumption of legumes, cereals (whole grains), fruits, vegetables, nuts, fish, and low-fat dairy products, can prevent and delay the development of METS and prevent CVD [131].

One of the main causes of the development of this chronic syndrome is an imbalance between caloric consumption and expenditure. METS is associated with excessive activity of glucose metabolism enzymes and inflammatory processes [132]. Thus, a diet with low glycemic index products, such as Phaseolus vulgaris L., slows down the absorption of carbohydrates due to the inhibition of alpha-amylase and glucosidase enzymes, been proven in clinical trials [133].

Products that slow the absorption of carbohydrates by inhibiting the enzymes responsible for their digestion have been described as a powerful alternative to achieving a low-glycemic diet. These products include alpha-amylase and glucosidase inhibitors, which can reduce the risk of diabetes and heart disease and its complications. The common white bean (Phaseolus vulgaris L.) inhibits alpha-amylase by the action of the alpha-amylase inhibitor protein (αAI), which has been characterized and demonstrated in various clinical studies, demonstrating the ability of beans to cause weight loss (doses between 500 to 3000 mg per day). Conversely, the ability of this legume to reduce the postprandial peak in blood glucose levels depending on the dose has also been pointed out [133,134]. Common beans have three isoforms of alpha-amylase inhibitors (alpha-A1, alpha-A12, alpha-AIL). The alpha-AI isoform has anti-amylase activity in humans. This enzyme is only found in the embryonic axes and cotyledons of the plant seed. The alpha-amylase inhibitor prevents starch assimilation by completely blocking access to the active site of the enzyme. Some factors that affect the activity of the alpha-AI isoform inhibitor are pH, temperature, incubation time, and the presence of particular ions. Several authors have pointed out that the common bean reduces the rate of carbohydrate absorption, thus reducing the glycemic index of foods, as well as weight loss when consumed at the same time with carbohydrate-containing meals [133].

The consumption of legumes such as Phaseolus vulgaris L. provides bioactive molecules with an effect on obesity and metabolic syndrome, mainly due to a decrease in weight and triglyceride levels, although more quality trials must be performed to establish clinical efficacy [135]. In this sense, overweight individuals who received Phaseolus vulgaris L. extract had a significantly greater reduction in body weight index, fat mass, adipose tissue thickness, and anthropometric measurements of waist, hip, and thigh compared to the placebo group. The authors point out that this effect is based on the activity of αAI described in the extracts of Phaseolus vulgaris [136]; furthermore, the daily consumption of baked beans (Phaseolus vulgaris L.) for 14 days as part of a regular diet significantly decreased the mean total plasma cholesterol level of the volunteers: from 5.1 to 4.5 mmol/L (p < 0.02) [137]. This is correlated with the effect of dry beans, where it was identified that they reduce serum lipid concentrations in healthy and hyperlipidemic subjects, specifically serum cholesterol and triglyceride concentrations by 10.4% (p < 0.001) and 10.8% (p < 0.025), respectively, along with reducing body weight, despite constant energy intake, contributing to the management of hyperlipidemia present in METS due to its high content of soluble fiber, which alters the absorption of lipids in the intestine, affecting the synthesis of cholesterol to hepatic level [138].

In a clinical trial with 12 adults diagnosed with METS who ate one of three meals: black beans (BB), combined fiber (FM), and combined antioxidant capacity (AM), it was found that in the group that consumed black beans, postprandial insulinemia was lower after the meal compared to the other groups (p < 0.0001), and there was an improvement in plasma antioxidant capacity (p = 0.002), which could be explained by the fiber content of beans [139]. Similar effects were seen in healthy individuals, where consumption of Phaseolus vulgaris L. extract reduced postprandial glucose, insulin, and increased satiety [140]. Finally, 12 volunteers with METS were given in three different meals: no added fiber (control (NF), extrinsic or added fiber (AF), or whole black beans as a source of intrinsic fiber (BN). The BN meal produced a significant reduction in comparison with controls (p < 0.0001), showing beneficial effects in patients with METS [141]. In the context of animal models, in METS-induced male C57BL/6 mice, Phaseolus vulgaris L. extract reduced body weight and effectively lowered blood glucose, triglycerides, and cholesterol. At the same time, histological analysis of the aorta showed protection against the development of fatty streaks in the muscle layers. The authors conclude that the mechanism of action is due to the presence of αAI and alpha-glucosidase inhibitors [142]. In another investigation, treatment with a combination of Phaseolus vulgaris L. and Cynara scolymus extracts reduced food intake and blood glucose in rats [143].

Proteins are abundant components in beans. The positive effect on blood pressure reduction of bean protein hydrolysates has been reported in hypertensive rats, which is attributed to the ability of peptides to inhibit angiotensin-converting enzyme (ACE) [110,144]. Glutelin hydrolysates show a potent ACE inhibitory activity of around 80.24%. The results show that glutelin could be an effective hypertensive in ACE [145]. Conversely, the administration of a black bean protein hydrolysate at a concentration of 200 mg/kg showed a hypoglycemic effect in rats [110,146]. Studies have highlighted that starch-enriched diets lower cholesterol levels, improving dyslipidemia and body composition. A double-blind, placebo-controlled crossover intervention showed that individuals who consumed a diet rich in starch for 12 weeks show favorable results for the promotion of these diets in public cardiometabolic health [147]. Another study examined the effect of starch on hypolipidemic actions, blood glucose, insulin levels, and humoral immune responses in healthy, overweight subjects who were fed 24 g/day of resistant cornstarch or regular cornstarch for 21 days. Reducing effects of total serum cholesterol and serum LDL cholesterol were evidenced. These results suggest that starch supplementation improves blood lipid profile and controls blood glucose levels in healthy overweight subjects [148].

Many studies suggest the effect of linoleic acid on obesity, cancer, atherosclerosis, among other health benefits. Linoleic acid has been shown to promote fat loss in rodent models [149]. Initial studies in male and female mice showed that a mixed diet supplemented with conjugated linoleic acid promotes fat loss by 60% for 30 days; this effect was attributed to increased lipolysis and fat oxidation [149,150]. Recently, it has been recognized that supplementation with this acid reduces fat stores, and dramatically decreases circulating adiponectin levels in mice [149,151].

Evidence suggests that the consumption of derivatives of Phaseolus vulgaris L. reduces food intake, body weight, lipid deposition, and blood glucose in rats due to the inhibition of α-amylase, reducing carbohydrate metabolism [152]. Together, these data in animal models and clinical trials demonstrate the potential effect of Phaseolus vulgaris L. to treat obesity and METS, consecutively decreasing the development of thrombotic events.

Studies have shown that diet attenuates atherosclerosis, the mechanisms of which are related to less atherogenic dyslipidemia, relief of intestinal dysbiosis, and suppressed inflammation [153]. The atherosclerotic process is established from the increase of pro-atherogenic and pro-inflammatory mediators that favor plaque formation and progressive stenosis [154,155]. The initial step of atherosclerosis is associated whit high levels of low-density lipoproteins (LDL), oxidation of LDL, and recruitment of monocytes [155,156]. The accumulation of cholesterol-laden macrophage foam cells is a key feature of atherosclerotic lesions. Cholesterol can enter macrophages through various pathways and induce the transformation of macrophages into foam cells [157].

Studies have shown that beans can improve lipid profiles associated with the development of atherosclerotic lesions and the prevalence of CVD. Consuming beans lower cholesterol without affecting serum triglycerides, VLDL cholesterol, or blood glucose [158]. Oxidized LDL (ox-LDL) and its interaction with the ox-LDL lectin receptor (LOX-1) determine the progression of atherosclerosis. Peptides from carioca beans have shown antiatherosclerotic properties comparable to simvastatin, through inhibition of LOX-1, MMP-9, and ICAM-1 and inhibition of 10 cytokines related to the atherosclerotic process (128). Research shows that chia, a variety of beans, is considered a good source of dietary fiber, protein, antioxidants, and bioactive lipids [159,160]. In recent years, chia seeds have gained great importance due to their high alpha-linolenic acid content (68%) and their relationship to human health and nutrition [161].

Various studies have indicated that this compound has cardioprotective properties by affecting specific biomarkers (lactate dehydrogenase; LDH) [162]. The background shows that conjugated linoleic acid has the potential to inhibit cholesterol-induced atherosclerosis in rabbits and hamsters, respectively [163]. Conjugated linoleic acid inhibits experimentally induced atherosclerosis in rabbits fed an atherogenic diet. A reduction in pre-established atheromatous lesions was evidenced [164]. Conjugated linoleic acid reduced early aortic atherosclerosis to a greater extent than linoleic acid in a hypercholesterolemic hamster population. These effects may be related to changes in the oxidative susceptibility of LDL in hypercholesterolemic hamsters [165].

The intake of dietary fiber has been associated with an inhibition of the development of atherosclerosis in animal models [88], while soluble fiber reduces serum cholesterol and LDL cholesterol concentrations [88,166]. In general, proteins of animal origin are more cholesterolemias and atherogenic than proteins of plant origin [167]. Research has highlighted that the oral administration of peptides synthesized from amino acids reduces atherosclerosis independently of plasma cholesterol in a group of mice, thus improving the capacity of high-density lipoproteins (HDL) in the study population [168]. Specific studies with different varieties of beans have shown that the consumption of this legume reduces 10% of the cholesterol levels of normal young men after ingestion of 450 g/d of canned baked beans compared to the control group [137]. A 10% reduction in serum cholesterol levels was also reported in hyperlipidemic men fed 120–162 g/d of pinto beans [138].

Celleno et al. showed that overweight subjects who consumed a dietary formula with Phaseolus vulgaris L. extract as the main ingredient, significantly decrease body fat due to the interference caused by this legume in the digestion of carbohydrates, thus contributing to the prevention of atherosclerosis by reducing fats in organs and tissues [136]. Phaseolus vulgaris L. provides micronutrients, particularly folic acid and magnesium, and its high content of fiber, sulfur amino acids, tannins, phytoestrogens, and non-essential amino acids have been linked to the prevention of atherosclerotic lesions. The prevention of atherosclerosis is a powerful tool in the prevention of cardiovascular events, as this silent pathology is responsible for about half of deaths from heart disease [19,169].