Polyphenol-Rich Dry Common Beans (Phaseolus vulgaris L.) and Their Health Benefits

Polyphenols are plant metabolites with potent anti-oxidant properties, which help to reduce the effects of oxidative stress-induced dreaded diseases. The evidence demonstrated that dietary polyphenols are of emerging increasing scientific interest due to their role in the prevention of degenerative diseases in humans. Possible health beneficial effects of polyphenols are based on the human consumption and their bioavailability. Common beans (Phaseolus vulgaris L.) are a greater source of polyphenolic compounds with numerous health promoting properties. Polyphenol-rich dry common beans have potential effects on human health, and possess anti-oxidant, anti-diabetic, anti-obesity, anti-inflammatory and anti-mutagenic and anti-carcinogenic properties. Based on the studies, the current comprehensive review aims to provide up-to-date information on the nutritional compositions and health-promoting effect of polyphenol-rich common beans, which help to explore their therapeutic values for future clinical studies. Investigation of common beans and their impacts on human health were obtained from various library databases and electronic searches (Science Direct PubMed, and Google Scholar).


Introduction
Plants synthesize secondary metabolites that often have widespread bioactivities, and are known as phytochemicals. Polyphenol is one of the phytochemicals containing large bioactive structural phenolic units. It has a wide range of classification and possesses various pharmacological and health-promoting effects [1]. Polyphenols are largely found in fruits, cereals, vegetables, food legumes, herbs, spices, nuts, wine, olive oil, tea, coffee, and chocolate. Polyphenols are classified into different groups based on the function of several phenyl rings, including flavonoids (flavones, flavonols, flavanones, isoflavones, anthocyanins, chalcones, dihydrochalcones, and catechins), phenolic acids (hydroxybenzoic hydroxyphenyl acetic, hydroxyphenyl pentanoic and hydroxyl cinnamic acids), stilbenes, and lignans [2]. The primary functions of polyphenols are as anti-oxidants involved in the prevention of degenerative diseases such as cancer and metabolic syndromes [2]. The health-promoting effects of polyphenols depend on the quantity consumed in the diet and their bioavailability. In addition, polyphenols are the active substances in many food legumes, which regulate the activity of a broad spectrum of cell receptors, enzymes and gene expression [3]. Animal experimental studies showed that polyphenol in common beans possess anti-oxidant properties and have various biological activities including anti-diabetic, anti-obesity, anti-inflammatory, antimicrobial, anticancer, hepatoprotective, cardioprotective, nephroprotective, neuroprotective, and osteoprotective [4][5][6][7][8][9][10][11].
these substances have been known as anti-nutritional factors. These substances can reduce protein digestibility, diminish nutrient absorption and mineral bioavailability, which may cause flatulence in human [51]. However, these anti-nutritional factors have antioxidant and prebiotic activities, and protect DNA damage against various cancers [52][53][54][55][56]. Hence, common beans are nutritionally complementary with respect to essential amino acids, vitamins, minerals, and anti-nutritional factors, and the consumption of common beans could alleviate deficiency status, ensuring in the balanced diet [47,57]. Table 1. Nutritional compositions of common beans in 100 g of edible portion [58][59][60].

Polyphenols in Common Beans
The dry bean contains plenty of polyphenols. Studies have demonstrated that phenolic compounds are predominantly located in the seed coat of the bean than in the cotyledon and testa [61]. The content of the phenolic compound is about 145 mg/g and represents about 11% of the total seed [62]. The phenolic compounds in the seeds are flavones, monomers, and oligomers of flavanols, flavanones, isoflavonoids, anthocyanins, chalcones, and dihydrochalcones [61,[63][64][65][66]. However, the phenolic acids and non-flavonoid phenolic compounds (hydroxybenzoic and hydroxycinnamic acid) are mainly found in cotyledons of the bean [67]. Based on their chemical structure, they are a highly diverse group ranging from simple molecules such as phenolic acids to complex polymers such as tannins and lignin [68]. The testa of the beans contains greater quantities of proanthocyanidins and anthocyanins [61]. Condensed tannins (10.65 mg catechin equivalents/g) and cyanidin 3-glucoside (3.75 mg catechin equivalents/g) are also mainly present in seed coats of the bean [69,70]. These phenolic compounds are generally varied, based on the seed coat color pattern and types of the cultivar of the beans. The color of the seed coat is based on the presence of polyphenols including anthocyanins, flavonols glucosides, and condensed tannins. Dark-colored beans normally have the highest anthocyanins content [71]. In addition, red, black and pink-colored varieties confer color to the bean seed coat due to their anthocyanins. The colors of light yellow or pink spot of the seed coat are generally based on the presence of condensed tannins [70].
Lima et al. [82] and Guajardo-Flores et al. [80] have analyzed in Brazilian beans containing non-glycosylated forms of isoflavonoids including daidzein (0.0082-0.1291 mg/g) and genistein (0.0026-0.0097 mg/g). Among them, black type of beans showed the highest concentrations of isoflavonoids and daidzein was the predominant compound. Raw and cooked beans contain phenolic acids, which may be derived from benzoic acid (vanillic, p-hydroxybenzoic, and gallic acids) and those derived from cinnamic acid (ferulic, p-coumaric, and chlorogenic acids). Among them, ferulic acid is the predominant phenolic acid on the dry common beans [78]. Studies have demonstrated that cooking of common beans at high temperature does not change the content of phenolic acids [83]. Raw common beans contain p-hydroxybenzoic acid (0.0045-0.0086 mg/g), vanillic acid (0.0052-0.0166 mg/g), coumaric acid (0.0032-0.0068 mg/g), and ferulic acid (0.0017-0.0036 mg/g) [84]. The polyphenols present in the common beans are illustrated in Table 2.

Health Promoting Effects of Polyphenol-Rich Dry Beans
The consumption of dry common bean has been greatly connected with many physiological and health promoting effects such as prevention of cardiovascular diseases, obesity, diabetes mellitus and cancers [86,88]. The anti-oxidant properties of polyphenol lie in their ability to neutralize free radicals and the chelation of transition metals, thus they counteract the initiation and propagation of oxidative processes [83]. Health promoting effects of polyphenol-rich dry common beans are illustrated in Figure 1.

Health Promoting Effects of Polyphenol-Rich Dry Beans
The consumption of dry common bean has been greatly connected with many physiological and health promoting effects such as prevention of cardiovascular diseases, obesity, diabetes mellitus and cancers [86,88]. The anti-oxidant properties of polyphenol lie in their ability to neutralize free radicals and the chelation of transition metals, thus they counteract the initiation and propagation of oxidative processes [83]. Health promoting effects of polyphenol-rich dry common beans are illustrated in Figure 1.

Anti-Oxidant Activity
The dry common beans have excellent anti-oxidant activities because of its phenolic acids, flavonoids, stilbenes, and tannins. These anti-oxidant activities are primarily due to the reducing capacity of polyphenols as they play vital functions in neutralizing free radicals and scavenging radicals or suppressing lipid peroxidation [89]. In addition, polyphenols involve chelation of metal ions, causing impairment/cessation of oxidative mechanisms. Generally, the anti-oxidant activity is elevated during digestion and absorption of the common beans in the intestine. Normally, phenolic compounds are released higher in the stomach due to its acidic environment, and the acid medium and enzyme-mediated hydrolysis facilitate the higher solubility of polyphenols along with starch and proteins [65]. Common beans containing polyphenols have demonstrated the highest total anti-oxidant capacity measured by in vitro methods of 2,2'-Diphenyl-1-picrylhydrazyl (DPPH), β-carotene bleaching, ferric reducing anti-oxidant power, oxygen radical absorbing capacity, Trolox equivalent anti-oxidant capacity, and total radical-trapping anti-oxidant parameters [63,64,80,85,[90][91][92][93]. Animal studies have also confirmed that common beans possess the highest anti-oxidant capacity, as measured in various biochemical parameters including thiobarbituric acid reactive substances (TBARS), hydroperoxides, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST) [26,61,93,94]. In vitro and in vivo studies of common beans exerting anti-oxidant activity are summarized in Table 3.

Anti-Oxidant Activity
The dry common beans have excellent anti-oxidant activities because of its phenolic acids, flavonoids, stilbenes, and tannins. These anti-oxidant activities are primarily due to the reducing capacity of polyphenols as they play vital functions in neutralizing free radicals and scavenging radicals or suppressing lipid peroxidation [89]. In addition, polyphenols involve chelation of metal ions, causing impairment/cessation of oxidative mechanisms. Generally, the anti-oxidant activity is elevated during digestion and absorption of the common beans in the intestine. Normally, phenolic compounds are released higher in the stomach due to its acidic environment, and the acid medium and enzyme-mediated hydrolysis facilitate the higher solubility of polyphenols along with starch and proteins [65]. Common beans containing polyphenols have demonstrated the highest total anti-oxidant capacity measured by in vitro methods of 2,2'-Diphenyl-1-picrylhydrazyl (DPPH), β-carotene bleaching, ferric reducing anti-oxidant power, oxygen radical absorbing capacity, Trolox equivalent anti-oxidant capacity, and total radical-trapping anti-oxidant parameters [63,64,80,85,[90][91][92][93]. Animal studies have also confirmed that common beans possess the highest anti-oxidant capacity, as measured in various biochemical parameters including thiobarbituric acid reactive substances (TBARS), hydroperoxides, glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST) [26,61,93,94]. In vitro and in vivo studies of common beans exerting anti-oxidant activity are summarized in Table 3.

Anti-Diabetic Activity
Venn and Mann [150] have strongly suggested that the regular consumption of dry common beans is beneficial in the prevention and management of diabetes. Clinical studies show that consumption of three or more servings of beans in a week decreases the menace of diabetes almost by 35%, as compared to less or non-consumption of beans [151]. In vitro anti-diabetic studies of common beans have showed a greater inhibition of α-amylase, α-glucosidase and dipeptidyl peptidase-IV, which have found to be anti-hyperglycemic activities due to their phenolic compounds such as flavonoids and their glucosides of delphinidin, petunidin, and malvidin, anthocyanins, catechin, myricetin 3-O-arabinoside, epicatechin, vanillic acid, syringic acid, and O-coumaric acid [23,101,152,153].
In vivo studies have also demonstrated that beans containing phenolic compounds reduce blood glucose, glycosylated hemoglobin and elevated insulin levels in the animals [104][105][106]131]. Similarly, Roman-Ramos et al. [154] have demonstrated that anti-hyperglycemic effect of kidney beans in healthy rats revealed 21% reduction in the graph plot under glucose tolerance curve when compared with 16% of the standard diabetic drug. Epidemiological studies associated with Chinese population have shown that regular intakes of common beans are inversely connected with the risk of type-2 diabetes [155]. Gupta et al. [103] and Tang et al. [156] have also studied in 56 diabetic subjects based on traditional and Ayurvedic principles, which have revealed that the regular consumption of black bean for three months reduces plasma glucose and glycosylated hemoglobin. The results showed that black bean ameliorates type-2 diabetes, which is due to black beans containing total phenolic, tannins and anthocyanins. In vitro and in vivo studies of common beans exerting anti-diabetic activities are summarized in Table 3.

Anti-Obesity and Cardioprotective Activity
Metabolic syndrome is the set of metabolic conditions connected with the threat of cardiovascular diseases, increased triglycerides (TG), total cholesterol (TC), low density lipoprotein (LDL), very low density lipoprotein (VLDL), blood pressure (BP), and glucose as well as lower levels of HDL and central adiposity [157,158]. Regular intake of dry common beans has proven to be favorable for healthy subjects as well as obese individuals by decreasing serum TC and LDL and elevating HDL [159]. Epidemiological and clinical studies have demonstrated that consumption of common beans inversely connected with the risk of cardiovascular and coronary arterial diseases [158,160]. Further, these studies revealed that consumption of beans four or more times per week reduced the risks of coronary arterial diseases (22%) and cardiovascular diseases (11%): serum TC declines of about 1% decrease the risk of coronary heart disease by 2%, while serum LDL declines of about 1% reduce the risk of both diseases by about 1% [160]. Two weeks of regular consumption of baked beans by hypercholesterolemic individuals showed a significant reduction of TC (12%) and LDL (15%) [161]. Another clinical trial has also investigated on the hypercholesterolemic subjects with consumption of 275 g of navy beans for three weeks found a reduction of both serum TC, and LDL up to 24% [162]. Eight weeks of consumption of one cup serving baked beans by hypercholesterolemic individuals showed a marked reduction of TC (6%) and LDL (5%) [160]. Similarly, consumption of dried, cooked pinto beans (130 g) four times a week significantly decrease serum TC and LDL in healthy individuals, resulted in decreasing the risk of cardiovascular disease by 20% [158]. Azuki bean juice supplementation to young women also showed significantly decrease TC and TG levels and proved to be anti-hypercholesterolemic [163]. Similarly, consumption of one serving of cooked beans on regular basis inversely associated with the risk of myocardial infarction up to 38% [164].

Anti-Mutagenic and Anti-Carcinogenic Activities
Normally, the generation of ROS and oxidative stress damage macromolecules such as lipid, protein RNA, and DNA, which may cause chronic degenerative diseases, including cancer [166,167]. However, the occurrence of cancer can be decreased by lifestyle and dietary habit changes. Studies have also suggested that diets rich in common beans reduce the greater risk of various cancers including colon, breast, and prostate [130,134,137]. A larger study conducted in 41 countries found that the consumption of common beans reduced the morbidity by cancers such as colon, breast, and prostate [168]. Further, studies have revealed that consumption of beans two or more times per week reduced the risks of colon cancer up to 47% [107], prostate cancer about 22% [169] and breast cancer about 67% [170]. In vivo studies have also suggested consumption of beans reduced risk of various cancers [132][133][134][135][136]. Hangen and Bennink [171] investigated diets fed with black beans in rats and observed the lower the incidence of total tumor (54%) and adenocarcinoma (75%). Similarly, the effect of navy beans decreased the occurrence of total tumor (59%) and adenocarcinoma (44%). The anti-carcinogenic and anti-mutagenic activities of beans are highly associated with the presence of phenolic compounds as well as other bioactive compounds [62,93]. Phenolic compounds have the potential to inhibit mutagenic agents including polycyclic aromatic hydrocarbons, nitrosamines, and mycotoxins by inhibiting activation enzymes, provoking detoxification enzymes and intonation of commencement of mutagens [172,173]. Furthermore, common beans possess anti-carcinogenic and anti-mutagenic properties due to their phenolic compounds interacting with ultimate toxicants or mutagens, scavenging activities of phenolics, and inhibition of metabolism of the ultimate mutagen [62,76,174]. In vitro and in vivo studies on chemopreventive and anti-mutagenic activities of common beans are summarized in Table 3.

Anti-Inflammatory Activity
Common beans contain phenolic compounds (phenolic acids, flavonoids, and anthocyanins) and non-digestible fermentable components (short-chain fatty acid precursors) with demonstrated anti-oxidant and anti-inflammatory activities. Experimental studies associated with modulation of inflammatory-related cell signaling pathways by common beans have been well established. In an animal study, C57BL/6 mice fed a 20% navy bean or black bean flour-containing diet showed significantly reduced dextran sodium sulfate induced experimental colitis and inflammation-related parameters (IL-1β, TNFα, IFNγ, IL-17A, and IL-9), increased histological injury score and apoptosis, and alleviated symptoms of colitis and colon inflammation [15]. Common beans possess various bioactive compounds including flavonoids and anthocyanins, which significantly reduced the activity of murine macrophages through the inhibition of pro-inflammatory gene expression without cytotoxicity [117][118][119]. Similarly, human-randomized, controlled, crossover trials have also demonstrated that three-day intake of 100 g of black bean meal and soup improved the arthritic condition by significantly reducing pain and inflammation [119]. The immunomodulatory effects of 20% navy bean or black bean or cranberry bean administration in C57BL/6 mice for two weeks showed a significant reduction in colonic mucosal damage and inflammation in response to dextran sodium sulfate. The results further demonstrated that common bean containing bioactive compounds including phenolic acids, flavonoids, and anthocyanins provoke prominent immune response [26,120]. In vitro and in vivo studies of common beans exerting anti-inflammatory activities are summarized in Table 3.

Conclusions
Dry common beans are consumed in diets worldwide, and play a significant function in human nutrition, especially as a source rich in proteins, carbohydrates, dietary fibers, vitamins, minerals, phytochemicals and other micronutrients, as well as low saturated fat content. Besides these nutrients, common beans possess enormous quantities of polyphenols and other metabolites, have anti-oxidant activities, major role in health-promoting effects, and protect against various diseases including diabetes, CVD, cancer, and microbial infections. These health benefits of beans are generally acquired from direct attributes, including their high content of nutrients, as well as replacement in the diet, when they substitute for animal products. It can therefore be concluded that health-promoting effects are directly proportional to the increase in bean intake. In addition, long-term clinical studies are urgently needed to warrant the therapeutic benefit of polyphenols rich common beans. In addition, the synergistic effects of polyphenol-rich common bean with other bioactive compounds on biological functions would be a recommendation for further studies. This investigation proves the efficacy of bioactive compounds in common bean, and enhances the therapeutic options for various diseases.

Acknowledgments:
The work was jointly supported by two grants R201627 and R201714 from Beijing Normal University-Hong Kong Baptist University United International College, Zhuhai, Guangdong, China.
Author Contributions: Kumar Ganesan and Baojun Xu conceived and designed the review; Kumar Ganesan wrote the paper; and Baojun Xu critically revised and improved the manuscript.

Conflicts of Interest:
The authors declared that no conflicts of interest.