Multifaceted role of plant polyphenols in human health: a comprehensive review

Abstract

The work culture of human beings is going fast and exhaustive because of innovative technology and improving expectations. To meet expectations and maintain health, society is incorporating functional food into their diets. Previously, people preferred supplementary food diets, which is pure, processed and costly. Now, the diet trend is shifting to add functional food or health benefitted food to a regular diet. Food which includes vegetables, fruits, herbal drinks and spices having many beneficial secondary metabolites for human beings. Plants produce polyphenols, which are crucial functional foods for human diet. The significant potential of polyphenols for use in food preservation and medicinal benefit accounts for their enormous interest. In the twenty-first century, the importance of the functioning of food is enhanced drastically due to its great impact on maintaining health and avoiding risk of chronic diseases. Polyphenols are considered a key plant’s secondary metabolites for the prevention of degenerative diseases. Polyphenols, known for their strong antioxidative, anti-diabetic, antihypertensive, cardioprotective, neuroprotective, and anticancer properties, are used in treating various health conditions and as bio-preservatives in the food industry, helping protect cells and organs from oxidative damage through diverse mechanisms. Moreover, food processing and their form either free or conjugated in food matrices determines the bioavailability of these compounds. Recent findings are uncovering the complex interactions between plant polyphenols and cellular homeostasis, including metabolic balance, redox stability, and inflammation, providing a stronger molecular foundation for their health benefits. This review highlights current insights into polyphenol types, their dietary sources and quantitative consumption, protective mechanisms against major diseases as well as factors affecting polyphenols availability.

Introduction

Plant food like fruits and vegetables are a major source of nutrition and also provide calories to the human body and significantly contribute in human health (Li et al., 2014). Over the last few years, research on secondary metabolites of the plants has been conducted, which confirmed their potential role in the improvement of human health. Secondary metabolites are small entities which play an important role in improving plant fitness with diverse chemical structures and produced by plants for defense against biotic and abiotic stresses, attraction, and communication purposes (Yeshi et al., 2022). Such phytochemicals have been recognized to give essential contribution for the plant adaptations to the environment, as well as for the vital source of active pharmaceuticals (González-Vallinas et al., 2013). Phytochemicals like polyphenols are distinct, ubiquitous and bioactive class of plant secondary metabolites which are produced by the plants to protect themselves by acting as free radical scavengers (Stiller et al., 2021). The majority of the elements present in all vegetative organs, fruits, and flowers are polyphenols (Güneş Bayir et al., 2019).

Polyphenols in plants also being generally involved in the attraction of pollinators, the execution of structural functions, the defense against ultraviolet radiations etc. (Bertelli et al., 2021). Due to their significant biological activities, they encompass a major part of human diet (Araújo et al., 2011; Kumar et al., 2019). Various studies have been conducted to examine the health benefits of such phytochemicals in the previous decades. The consistent consumption of the polyphenolic rich food triggers the inhibition of the prevalence of obesity, diabetes, cardiovascular diseases, liver disorders etc. (Kumar et al., 2019). The major benefits of polyphenols are their different biological activities and their less toxic nature. But fast metabolism is the major drawbacks of these compounds (Asensi et al., 2011). Stefania et al. (2021) found that intake of polyphenols significantly helpful in preventing obesity by regulating the expression of genes involved in the development and progression of obesity such as fatty acid synthase (FAS) and lipoprotein lipase (LPL) genes. By blocking important enzymes involved in the breakdown of carbohydrates into glucose, polyphenols play a vital role in carbohydrate metabolism and also augment the glucose uptake for combating type 2 diabetes (Shahwan et al., 2022). Cyclooxygenase 1 which induce the platelet aggregation and thromboxane A2 production, is inhibited by resveratrol by suppressing platelet aggregation (Senoner and Dichtl, 2019).

The complex mixture of phytochemicals processed by the plant foods and their concentrations in plants and food items are influenced by biochemical and environmental factors including storage, culinary processes, sun light intensity, rainfall etc. The polyphenolic group approximately clusters ten thousand different compounds, which come from a variety of herbs, vegetables and fruits (Sharma et al., 2019, 2020). Phenolic ring is the elementary monomer of polyphenols and these can be further categorized into phenolic alcohols and phenolic acids. The categorization of polyphenols in different classes is based on the strength of the phenol ring. Flavonoids, phenolic acids and lignans exist among major classes (Dai and Mumper, 2010).

In these polyphenols, mainly glycosides which are the phenolic alcohols, constitute the chief secondary metabolites in the human diet, providing major health benefits (Konczak and Zhang, 2004). As these are the compounds of natural sources, therefore contribution have been proved significantly important in the pharmaceutical and nutraceutical industries. Additionally, to improve their effectiveness and bioavailability, these compounds are utilized in the experimentation of pharmaceutical laboratories. Besides, these polyphenols also have organoleptic properties (Lambert et al., 2005; Mocanu et al., 2015). But most of the reports confirm that polyphenols possess anti-bacterial, anti-tumor, anti-fungal and anti-inflammatory properties, which reflect their intensive benefits for human societies (Manach et al., 2004, 2005).

The proper reference intake values of polyphenols cannot be determined as deficiency disorders do not occur by inadequate intake of polyphenols (Lupton et al., 2014). Despite this knowledge gap, several of these compounds have been discovered, and some have shown promising benefits in observational studies. Due to their abundance in plant-based foods and potential to reduce cancer, diabetes, and cardiovascular risks, polyphenols have gained attention, leading to growing research on their use in functional foods with added value (Bertelli et al., 2021). However, the mechanisms through which these compounds have positive impacts on human health are less understood. Global food education in reducing obesity, hyperglycemia, and other metabolic disorders, can be enhanced by carrying research on polyphenol consumption and other natural nutrients (Siroma et al., 2022). This review seeks to address the current challenges of polyphenols and enhance their understanding and applications. Therefore, present review aims to provide a comprehensive overview of various types of polyphenols, their dietary sources and variability, quantitative consumption and their potential functionality on various aspects of human health. Moreover, various factors affecting polyphenols availability present in plant foods has also been discussed.

Types of polyphenols

As discussed above, dietary polyphenols establish one of the major and extensively dispersed groups of natural products of the plant kingdom (Singla et al., 2019). This group of polyphenols are very diverse containing further sub-category of phenols. Their variety and extensive dispersal in plants trigger the various ways of classifying these naturally occurring compounds. These compounds are categorized by the source of origin, biological activities, and their chemical structure (Durazzo et al., 2019). Various classes of polyphenols have been shown in Fig. 1.

Fig. 1.

Different classes of polyphenols

Flavonoids

Till now approximately 8000 polyphenols are well known, and among them 4000 are flavonoids, which have been recognized in plants such as Apium graveolens, Capsicum annuum, Mentha etc. (Singla et al., 2019). Flavonoids are made up of two benzene rings which are linked with three carbon chain from the adjacent pyran ring. There are six different categories of flavonoids which have been classified on the basis of oxidation state of central carbon (Chandrasekara and Shahidi, 2010; Kim et al., 2006). The categories of flavonoids involve flavanones, flavanols, flavonols, isoflavons, flavons, and anthocyanidins (Singla et al., 2019).

In the flavonols, a hydroxyl group is linked with C3 and a double bond is found in between C2 and C3. Flavonols are the chief flavonoids which is present in various types of food like Allium cepa, Vitis vinifera, Malus domestica and Rubus spp. etc. Onions contain a high quantity of this compound, whereas other food sources like broccoli and leeks also possess these polyphenols (Duda-Chodak et al., 2015). Chalcones are also a type of flavonoids even though they do not have C ring, however Malus domestica and Humulus lupulus are the main sources for chalcones. Glycones are the ultimate structures, and plants possess these structures as glycosides (Dueñas et al., 2015).

Isoflavones possess beneficial health effects and an important food source of isoflavones is Glycine max. Daidzein and genistein are the major isoflavones which are present in soy along with glycetein (Soliman et al., 2014). Trifolium pratense are an important example of food source containing daidzein and genistein, which is having phytoestrogenic property against menopausal complaints. Majorly 7-O-glucosides and 6″-O-malonyl-7-O-glucosides are the furthermost profuse kind of isoflavone-aglycones. Dalbergin is another chief neo-flavonoid entrenched in the food stuff obtained from the plants like Dalbergia sissoo which has osteoprotective functions (Abbas et al., 2017; Kim et al., 2016). These do not exist in glycosylated form in the human diet like other flavonoids. Catechins and epicatechins are the main representatives of this class (Klinder et al., 2016). Flavonones have 3 saturated C-ring and contain an oxygen molecule at C4. Flavonones are mainly possessed by citrus fruits, however, aromatic plants also have their small quantity like Citrus sinensis and Citrus limon possess these compounds in the form of hesperidin and eriodictyol respectively (Bahadoran et al., 2012; Ozdal et al., 2016).

Phenolic acids

Phenolic acids are polyphenols which are non-flavonoid in nature and benzoic acid and cinnamic acid derivatives are their two major types based on C1–C6 and C3–C6 backbones. Various free phenolic acids are present in fruits and vegetables whereas its bound form is found in grains and seeds specifically in the bran or hull (Kim et al., 2006). Such phenolic acids can be hydrolyzed by using alkaline or acid substances and also through enzymatic action. Typical phenolic acid in food includes cinnamic acid and benzoic acid (Chandrasekara and Shahidi, 2010). Corn salad, sweet fennel, parsley and spinach contain phenolic compounds such as hydroxybenzoic acid derivatives (salicylic, gentisic and vanillic acid) are found in small quantities (Rashmi and Negi, 2020). Gallic acid is present in minor quantities in rhubarb while p-hydroxybenzoic acid is the major phenolic acid in corn salad (Rashmi and Negi, 2020). The highest concentration of protocatechuic acid was found in the outer dry skin of onions whereas minor amounts in the endogenous pulpy tissue and also contain p-hydroxybenzoic and vanillic acid (Mattila and Hellström, 2007). Large amounts of phenolic acids such as chlorogenic acid and chicoric acid were found in baby leaf lettuce varieties (Santos et al., 2014). Vegetables like watercress, garden cress, mizuna and red mustard showed the presence of ferulic and sinapic acid derivatives (Santos et al., 2014).

Lignans and stilbenes

Lignans are traditionally a class of secondary metabolites and are made up of oxidative dimerization of 2-phenyl propane units. Linseed is a rich source of these compounds, which contains secoisolariciresinol up to 3.7 g/kg dry weight and less amount of matairesinol. Other food sources like fruits, cereals, vegetables, and grains also contain small amounts of lignans (Barker, 2019). Whereas stilbenes are present in very trace amounts in the human diet. These are phenolic metabolites, possessed by berries, Arachis hypogaea etc. Resveratrol is one of the stilbenes which is having anticarcinogenic properties recognized during screening of medicinal plants. These are the important chemical constituents of various phenolic structures and act as a determining agent of absorption and metabolic rate (El Khawand et al., 2018). Plant sources such as flaxseeds and sesame seeds contain rich content of lignans (Oluwole et al., 2022) among which about 8000 µg g⁻¹ lignans are present in flaxseeds. Anticancer and antioxidant characteristics are shown by flaxseed lignans (Wu et al., 2021).

Food sources and variability of polyphenols

There are many higher plants from which polyphenols have been detected and such polyphenolic structures with certain variability are found to exist in various plants that can be eaten(Arts et al., 2000). Apart from six major functional categories of heterocyclic phenolic acids, polyphenols are also linked with organic acids and carbohydrates (Lakenbrink et al., 2000).

Derivatives of cinnamic and benzoic acid are two important classes of phenolic acids. In the edible parts of plants, hydroxybenzoic acid content is very less, except some red coloured fruit, Allium cepa and Raphanus sativus, and that is having approximate doses of a few tens of milligrams per kilogram fresh weight (Manach et al., 2004). Certain fruits and plants have been found to contain higher concentrations of benzoic acid, with most berries containing up to 500 mg/kg, mature fruits of the Vaccinium species containing up to 1300 mg/kg, and resin from Styrax trees containing up to 200 mg/kg (Del Olmo et al., 2017). Gallic acid is one of the major example of trihydroxybenzoic acid and is obtained from tea leaves, which possess approximately 4–5 g/kg fresh weight of gallic acid (Tomás‐Barberán and Clifford, 2000). Except for brinjal, orange, carrot and spinach, almost all vegetables contain gallic acid while all fruits show the presence of gallic acid except kinnow. Greater content of gallic acid has been found in beetroot and black carrot than in other vegetables (Singh et al., 2016). Moreover, hydroxybenzoic acids are considered as constituents of complex structures like hydrolysable tannins (Clifford, 2000). As certain free and esterified hydroxybenzoic acids have not been studied widely and even they do not possess much nutritional value, but these are edible in nature as they are contained by certain plants like Citrus paradise, Mespilus germanica, Olea europaea etc.

The most profusely present phenolic compound is caffeic acid in both of its free and esterified forms and it shows approximately 75–100 percent of total hydroxycinnamic acid level possessed by the fruits. According to a study, highest levels of caffeic acid was found in oregano, rosemary, sage, basil and cilantro among 22 of the studied samples (Meinhart et al., 2019). In the cereals, ferulic acid is present abundantly, which also acts as an important phenolic compound. In the wheat, approximately 2.0 g/Kg dry weight of ferulic acid is present maximum, that form up to 90% of total polyphenolic content (Es-Safi et al., 2002; Heinonen et al., 2001). It is also present in the exterior part of the grain. A large amount of ferulic acid is present in the pericarp and the aleurone layer of wheat. In the wheat flour, polyphenols are chiefly present in the bran (Kumpulainen, 2001). A similar amount of phenolic contents is possessed by rice and oat flours also as contained in wheat flour, whereas, in maize flour, it is 3 times more (Heinonen et al., 2001). Ferulic acid undergoes into esterification and form hemicellulose and arabinoxylans in pericarp and aleurone (Clifford, 2000). There are different dimers of ferulic acid which occur in cereals and give rise to the formation of bridge structures between the chains of hemicellulose.

Quercetin is one of the polyphenols present in different plants including cereal grains, fruits, juice, tea, legumes, etc. However certain special polyphenols such as phloridzin, flavonone, isoflavone, etc. are contained in apples, citrus fruits and soya respectively. Malus somestica is one of the intermittent plant foods in which polyphenolic content is present. There is variation in the level of these compounds in different species of Malus (Kumpulainen, 2001).

Quantitative consumption of polyphenols

Reports suggested more specific information regarding the consumption of different types of polyphenolic content by the organisms. It was analyzed that in certain countries like Holland or Denmark etc., the average intake of these compounds is approximately 25 mg/day (Berman et al., 2017). Whereas data taken from Italy represented the average of polyphenol intake is approximately 35 mg/day. Similarly, consumption of flavanones is estimated more as compared to flavonols, i.e., at an average of 28.3 mg hesperetin/day in Finland (Lee et al., 2006). The main source of flavanones is citrus fruit and their intake is higher where production of such fruits occurs like in southern Europe. Anthocyanins, a highly concentrated group of polyphenols in foods with an average concentration of 115 ± 259 mg 100 g⁻¹ are abundant in black elderberries, black chokeberries, and black currants, as well as in red fruits, wine, certain beans, and vegetables like red lettuce and onions, with daily intake varying globally from 6.8 mg in Brazil and Australia to 133 mg in Italy due to dietary and cultural differences (Di Lorenzo et al., 2021). Anthocyanin bioavailability is very low, with only 1–2% retaining their original form after ingestion, as their chemical structure changes with pH existing as flavylium cations in the acidic stomach (pH 1.5–3) and shifting to less absorbable carbinol forms in the intestines—while undergoing additional transformations through enzymatic activity, microbiota metabolism, and phase II processes like glucuronidation, sulphation, and methylation (Di Lorenzo et al., 2021). Similarly, the intake of anthocyanins was studied in Finland only, where consumption of berries is more, i.e., an average of 80 mg/day, which may extend to 200 mg/day (Pacheco‐Ordaz et al., 2018). Human studies on bioavailability are limited, as plasma concentrations of single phenolic compounds rarely exceed 1 µM after doses of 10–100 mg, though total phenol levels may increase due to tissue or gut microflora metabolism, which is influenced by the polyphenol’s chemical structure (Stromsnes et al., 2021). Human studies indicate that urinary recovery of intact phenolic compounds varies from 0.3–1.4% for rutin and quercetin glucosides to 3–26% for catechins, isoflavones, flavanones, and anthocyanidins, while the majority (75–99%) remain unexcreted, suggesting limited absorption and metabolism (Scalbert and Williamson, 2000).

On the other hand, the intake of catechins and proanthocyanidin is analysed approximately as 25 mg/day, which can be obtained from apples, grapes, and wine, etc. (Santhakumar et al., 2018). These flavonols can be taken from apples, pear or chocolates and the average intake was noted as 50 mg/day (de Souza et al., 2019). Polymerized form of proanthocyanidins can be consumed more i.e., 100 mg/day (Barker, 2019). Whereas intake of hydroxycinnamic acid changes according to the doses of coffee consumed. People who drink large amounts of coffee in a day can consume an average of 600 mg/day of hydroxycinnamic acid/day, however those who are not taking it and are only dependent on fruit and vegetables hardly can consume 25 mg/day of this compound (Dai and Mumper, 2010). According to a German report, the average intake of hydroxycinnamic acids is 200 mg/day and hydroxybenzoic acids 10 mg/day. Caffeic acid is mainly obtained from coffee, containing 92% of this compound, which is approximately consumed 200 mg/day and principal sources were coffee, whereas 59% of this polyphenol is contained in fruits (Del Rio et al., 2013).

In Asian countries, the average consumption of polyphenols namely isoflavones is approximately 100 g/day due to the intake of soya (El Khawand et al., 2018). People from Europe and America possess a few mg of isoflavones as they eat less amount of soya. Increasing the amount of soya in the synthesized food stuff may enhance the consumption of isoflavones. In certain cases during the phytoestrogen replacing treatment of women after menopause can ingest these phenols approximately 50 mg/day (González-Sarrías et al., 2017). All such changes are due to variations in food habits. Ingestion of polyphenolic content depends upon the type of food consumed like coffee, berries, etc. which are rich sources of hydroxycinnamic acid or anthocyanins respectively. Reports indicated that in the western population, it was estimated that the average ingestion of polyphenols such as flavanols, flavanones, anthocyanins, etc. is 150 mg/day. On average, polyphenolic content consumed by people is 1 g/day, which they are getting from vegetables and fruits (Ávila-Gálvez et al., 2018). Intake quantity of various polyphenols vary with the type of plant food consumed. Therefore, effective amount of polyphenol intake cannot be determined. Estimating the average daily intake of polyphenols is highly challenging due to structural diversity, a lack of standardized analytical techniques, and variations in the quantity of a given diet (Scalbert and Williamson, 2000). A systematic review of over 90 human studies estimated daily polyphenol intake at 0.9 g, primarily from coffee, tea, wine, fruits, and vegetables, with flavonoids and their subclasses linked to lower risks of cardiovascular diseases, type 2 diabetes, and all-cause mortality, though bioavailability was not assessed (Del Bo’ et al., 2019). However, it can be concluded from these studies that consuming an effective number of polyphenols can actually yield beneficial effects. Various polyphenols consumed through different food sources along with the quantity have been mentioned in Table 1.

Table 1.

Consumption of polyphenols through different food sources

Continent	Country	Consumption (mg/day)	Source	Reference
Asia	India	929–1508	Vegetables, legumes, cereals, dairy products and fruits	Niyogi (2016)
	Japan	1492	Beverages (coffee, green tea, black tea etc.), Fruits (apple, banana, orange), vegetables (potato, cabbage, soybean etc.)	Taguchi et al. (2015)
	Malaysia	1218–4323	Fruits and vegetables, legumes, Anacardium occidentale, Centella asiatica, Colubrina asiatica,	Niyogi (2016)
	China	331.7	Fruits (apple, plum, pear, and peach, durian, grapes, and citrus), cabbage, soybeans, lotus root and taro	Li et al. (2013)
	Korea	318	Fruits, vegetables, legumes	Jun et al. (2016)
	Iran	1780	vegetables, fruit and legumes, nuts, whole grain, refined grain	Sohrab et al. (2013)
Europe	Denmark	1626–1786	Legumes	Niyogi (2016)
	Mallorca	332.8	Cereals, fruits, oils and seeds, nuts, legumes, beverages	Karam et al. (2018)
	Spain	820	Fruits (Oranges, apples, cherries), Vegetables (Potato, spinach, onion, lettuce), cereals, legumes, beverages (coffee, tea, orange juice)	Tresserra-Rimbau et al. (2013)
	Finland	863	Fruits, berries, cereals, and vegetables	Ovaskainen et al. (2008)
	France	1193	Fruits (apples, strawberry, plums, cherries), vegetables (potatoes, onion, spinach, green chicory) and cereals (Refined wheat-flour products, whole-grain wheat-flour products). Seeds of walnut, hazlenuts, chestnuts	Perez-Jimenez et al. (2011)
	UK	1521	Tea, coffee, fruits, seeds,	Zamora-Ros et al. (2018)
	Poland	1765	Fruits (apples, raspberries), coffee, tea, vegetables oils, seeds, plums, carrots, beans	Grosso et al. (2014)
North America	Mexico	445–1240	Vegetables (tomato, garlic, broccoli, pea, potato, onion etc.), Fruits (orange, apple, pineapple, guava, papaya etc.)	Hervert-Hernández et al. (2011)
	USA	1000	Fruit, vegetables, cereals, leguminous plants, fruit juices, infusions, beverages such as tea and red wine	Manach et al. (2005)
	California	750	Coffee, apples, oranges, strawberries, mamey, zapote, papaya, sweet potato and prickly pears, nopal, guava, and squash blossoms, beans, spinach, peanuts, plums	Zamora-Ros et al. (2016)
South America	Brazil	377.5	Coffee, legumes, potatoes, onion, beans, nuts, cocoa, berries, citrus fruits, flours, olive oil etc	Miranda et al. (2016)
Australia	Australia	678.69	Soy and soy products	Del Bo’ et al. (2019)

Mechanism of action

It is not necessary that the polyphenolic content present in the dietary food stuff of human beings always remain functionally active. Generally, polyphenols exist in the forms of glycoside or ester in the food stuffs, whereas after polymerization these can be absorbed in innate form (Ávila-Gálvez et al., 2018; Del Rio et al., 2013). Before absorption, the enzymes of intestine like α-glycosidase or some microflora such as Eubacterium ramulus and Bacteroides distasonis hydrolyze them. Involvement of microflora decreases the tendency of absorbing them, as the flora contributes to the degradation of aglycones, which is released by them, consequently, different aromatic acids are synthesized during the activity. Polyphenols undergo conjugation with the small intestine and then followed by liver (González-Sarrías et al., 2017). Activities like the addition of methyl or sulfur group and glucuronide are involved in it. Such type of activity involves the mechanism which detoxifies the effects of xenobiotics by facilitating the elimination of these toxins through bile and urine. For the same, conjugation strategy is very potential, and after the absorption of nutrition, aglycones remain usually at very little concentration or are sometimes absent in the blood. Polyphenols broadly bind to the albumin as these are conjugated derivatives. Accumulation of polyphenols in the particular tissue must be examined, though they can enter inside the tissue and further get translocated (Ávila‐Gálvez et al., 2019) (Fig. 2). Absorption and metabolism of polyphenols within the gastrointestinal tract decide their biological activity. Only those released in small and large intestines are absorbed. Polyphenols exist mainly as esters, glycosides, and polymers in foods, and they are needed to be hydrolyzed enzymatically or microbially before absorption. Approximately 48% are metabolized in the small intestine, 42% in the large intestine, and 10% are not digested. These unabsorbed polyphenols make their way to the colon, where gut microflora convert them into phenolic acids (Tarko et al., 2013). Bacterial enzymes hydrolyze glycosides to release aglycones, which are then converted into different acids by β-glucosidase, β-rhamnosidase, and esterases. Microflora in the gut have the ability to break flavonoid chains to simple units as well as perform hydrolysis, dehydroxylation, demethylation, and decarboxylation, unlike indigenous enzymes. On the basis of their structure, polyphenols yield different metabolites: flavonols form hydroxyphenylacetic acids, flavones and flavanones produce hydroxyphenylpropionic acids, while flavanols form phenylvalerolactone as well as hydroxyphenylpropionic acids. These intermediates ultimately result in benzoic acid, which, once absorbed, binds to albumin and is carried to the liver for further metabolism by hydroxylation, demethylation, o-methylation, and conjugation. Certain metabolites are subsequently excreted back into the gut through bile or excreted via the faeces (Tarko et al., 2013).

Fig. 2.

Mechanism of action of polyphenolic compounds

Influences of polyphenols on the human health depend on how much they are consumed and after understanding about their availability. Many of the polyphenols are abundantly present in our diet, but still some of them like proanthocyanidins cannot be absorbed properly, hence their activities are limited to the intestine only. Similarly, anthocyanin is ingested appropriately, whereas its metabolites are not even recognized (Zhang et al., 2017). Ingestion of certain other polyphenols like flavonols, flavones, and flavanols is comparatively less, and their content in plasma membrane is not exceeding 1 mol/L, as these are absorbed at a very small amount, whereas release occurs at very high rate. However, flavanones and isoflavones have great bioavailability potential, and in plasma concentrations, their concentrations can be up to 5 mol/L (Ofori and Peggy, 2013). These compounds are widely present in soya or in many citrus fruits. On the other hand, hydroxycinnamic acid is present in diverse range of food stuff at very great amounts whereas, esterification leads to a reduction in their absorption through intestine (Pojer et al., 2013). Generally, polyphenolic metabolites are quickly removed from plasma, indicating that the regular intake of plant products is essential to retaining more doses of metabolites in the blood (Weiskirchen and Weiskirchen, 2016).

To find out the assistance of these compounds for the health, much information regarding their bioavailability is required. Aglycones must be neglected, as they are not key metabolites in the blood due to their widespread intestinal and hepatic conjugation. Whereas in vitro analysis on various strategies of polyphenols focuses on aglycones or glycosides apart from the identified metabolites, frequently at doses which may not credibly be achieved in the body. Therefore, it is mandatory to approve the possessions estimated with aglycones via studying the physiologic doses of metabolites that are essentially present in the body (Zanotti et al., 2015). Moreover, the actions of microbial metabolites should be studied in the future to find out the dynamic structure, existing doses, and possible inflection of the potential of the microflora to synthesize the metabolites like them (Taranto et al., 2017).

Polyphenols and its potential health benefits

Epidemiological studies have frequently indicated a reverse correlation between chronic human disease incidence and the consumption of a polyphenol rich diet (Williamson and Holst, 2008). Phenolic groups in polyphenols may admit the electron forms quite stable phenoxyl radicals, thus upsetting chain oxidation reactions in cellular components (Guo et al., 2013). It is well proven that foods and beverages rich in polyphenols may raise the capability of plasma antioxidants. This growth in the antioxidant potential of plasma ensuing the consumption of foods rich in polyphenols can be explicated also by the presence of reduced polyphenols and their plasma metabolites; their implications on quantities of other reduction agents or on the absorption of pro-oxidant food components such as iron (Xiao and Hogger, 2015). Figure 3 indicates the different health benefits of polyphenols.

Fig. 3.

Health effects of polyphenols through dietary intake

Anti-cancerous properties

The influence of polyphenols on cell lines of human cancer is generally defensive and leads to a lessening in the growth of tumours (Dai and Mumper, 2010). Such effects have been observed in different parts of body like mouth, stomach, liver, lungs, mammary glands etc. Several polyphenols including quercetin, catechins, isoflavones, flavanones, ellagic acid, and curcumin have shown defensive actions in some models, even though their mechanisms is different (Azzini et al., 2017). Numerous approaches of action for the chemical preclusion of polyphenols have been detected, such as estrogenic / antiestrogenic activity, antiproliferation, and triggering of apoptosis, anticipation in oxidation, stimulation of detoxification enzymes, control of the host immunity, anti-inflammatory activity and shifts in cell signalling (Selby-Pham et al., 2017a).

It has also been shown that theaflavins and arubigins, the plentiful polyphenols in black tea exhibit strong anticancer properties. Black tea polyphenols have been observed to hinder proliferation and raise apoptosis in 145 carcinoma cells in the prostate (Rains et al., 2011). Advanced insulin levels such as growth factor-1 (IGF-1) have been analyzed to be linked with a greater risk for prostate cancer development. IGF-1 is a binding element of the signalling pathway to its receptor that initiates cell proliferation. The addendum of black tea polyphenols was noticed to impede IGF-1 induced cell progression into S cell cycle phase in prostate carcinoma cells. It was reported that quercetin also has anticancer activity in mice against benzopyrene stimulated lung cancer, an effect attributable to its free radical quenching activity (Miyatake et al., 2012).

Resveratrol helps in the termination of cancer development at different stages and has been observed to be effective in most of cancer types such as lung, skin, breast, prostate, gastrointestinal and colorectal cancer. Polyphenols impact pro-carcinogenic metabolism by lowering the expression of cytochrome P450 enzymes involved in their activation to carcinogenic agents. They may also ease their excretion by raising the expression of conjugating enzymes in phase II. The stimulation of phase II enzymes might have their roots in polyphenol toxicity (Xiao and Hogger, 2015). Polyphenols may form possibly noxious quinones in the body that act as substrates for these enzymes. The consumption of polyphenols activates these enzymes for their own detoxification and lead to a general upsurge in our defense against toxic xenobiotics. Tea catechins capsules used by men with high-grade prostate intraepithelial neoplasm (PIN) have been shown to reveal cancer prevention by hindering the conversion of high-grade PIN lesions to cancer (Meydani and Hasan, 2010).

Anti-diabetic effect

Numerous studies have reported the antidiabetic effects of polyphenols. Polyphenols regulate glycemia through a variety of mechanisms, which includes retardation in intestinal glucose absorption or peripheral tissue uptake. The hypoglycemic effects of diacetylated anthocyanins at a diet dose of 10 mg / kg were observed with maltose as a source of glucose but not with sucrose or glucose after 120 min of treatment in male 8-week-old Sprague Dawley (SD) rats (Matsui et al., 2002; Sahebkar, 2013; Szkudelska et al., 2009). It means these results are due to the α-glucosidase inhibition in the gut mucosa. Also reported inhibition of α-amylase and sucrase by catechin in rats at a dose of approximately 50 mg / kg diet or greater. Tea catechins have also been reported to possess anti-diabetic potential (Szkudelska et al., 2009). Individual polyphenols such as catechin, epicatechin, epigallocatechin, isoflavones, tannins, and saponins also decrease S-Glut-1 mediated glucose transport in the intestine. Apart from this, saponins also check the transfer of glucose from stomach to the small intestine (Shao et al., 2012).

Resveratrol also act as a vital anti-diabetic agent. A recent study indicated that quercetin during oxidative stress can defend the changes in diabetic patients. For diabetics, quercetin has markedly preserved the lipid peroxidation and antioxidant inhibition mechanism (Vendrame et al., 2011). Polyphenols present in the Hibiscus sabdariffa extracts lessen diabetic nephropathy, which includes pathology, serum lipid profile and kidney oxidative markers (Mena and Del Rio, 2018).

Cardio-protective effect

The use of polyphenols restricts the prevalence of coronary heart diseases (Ofori and Peggy, 2013). Reports suggested that tea catechins reduce the invasion and proliferation of the smooth muscle cells in the arterial wall, which contributes to slow atheromatous lesion formation (Selby-Pham et al., 2017b). Resveratrol inhibits platelet aggregation via preferential inhibition of cyclooxygenase-1 activity (which produces thromboxane A2, a stimulator of platelet aggregation and vasoconstrictor) (Kim et al., 2011). Several epidemiological studies also examined the connotation between polyphenol consumption and instances of cardiovascular diseases (Guo et al., 2013), which indicated that the consumption of polyphenol-rich diets was associated with a lower risk of myocardial infarction (Potì et al., 2019).

Anti-aging effect

Extracts of fruit and vegetables rich in flavonoids such as spinach, berries etc. exhibit high antioxidant activities. Such dietary supplementations have been reported to actively reverse age-related brain deficits and behavioral functions in aged rats. A recent study shows that tea catechins have strong anti-aging activity and consumption of green tea rich catechins triggers the delaying of aging (Tomás‐Barberán and Clifford, 2000). Also, polyphenols are useful in improving the adverse effects of aging on the nervous system or brain. In controlling the aging of brain, the polyphenols have the potential to cross the blood–brain barrier which strictly regulates the influx of metabolites and nutrients as well as drugs into the brain (Dong and Qin, 2011). Resveratrol was found to reliably lengthen the life span; its activity is associated with caloric restriction and partial deprivation of food (Kim et al., 2019).

Neuro-protective effects

In neuro-degenerative diseases, oxidative stress and brain damage play a significant role. As polyphenols possess antioxidative characteristics, their intake may play a vital role in providing protection against such nervous disorders (Yang et al., 2015). Resveratrol is one of the important polyphenols, which is majorly present in red wine and triggers the scavenging of hydroxyl radicals and superoxide ions. These compounds also play a crucial role in the inhibition of nuclear factor κB signaling and hence protect against Alzheimer’s disease. It has also been reported that the intake of polyphenols like catechin through green tea may reduce the risk of Parkinson’s disease (Liperoti et al., 2017). The catechins lead to the chelation of iron during Parkinson’s disease. This characteristic of the compound represents its antioxidant property by terminating the redox-active transition metal from activating free radicals’ synthesis (Aquilano et al., 2008). Furthermore, the antioxidative activity is also associated with the initiation of the countenance of antioxidants and detoxification of enzymes predominantly in the brain (Tibaut et al., 2019). Apart from this, ferulic acid an important polyphenol, which is present in the maize bran is also reported to be helpful in providing protection against Alzheimer’s disease. These impacts are due to its antioxidant and anti-inflammatory properties (Guo et al., 2013). There is a variety of foodstuff that are rich in various types of polyphenols and they may possess different biological influences such as antioxidative, anti-proliferative, anti-adhesive properties etc. described in Table 2.

Table 2.

Polyphenols: Sources and biological effects

S. No	Food Sources	Polyphenols	Effects of Polyphenols	References
1	Tea, chocolate, fruits	Flavonoids & catechins	Antioxidative, anti-proliferative, inhibition of growth, antimutagenic, anti-inflammatory, reduction of telomerase activity and lipid peroxidation, enhancement of estrogen activity and reversal of epigenetic changes	Li et al. (2014)
2	Red wine, grapes, berries, peanuts	Stilbenes	Antioxidative, anti-inflammatory, anti-cyclooxygenase, stimulation of lipid metabolism	Dai and Mumper (2010)
3	Turmeric, mustard	Curcumin	Antioxidative, anti-adhesive, tumor growth suppression, anti-inflammatory, reversal of epigenetic changes	Manach et al. (2005)
4	Herbs of Lamiaceae family	Rosmarinic acid	Antioxidative, stimulation in epigenetic changes	Barker (2019)
5	Berries, pineapples, bananas, lemons, wines	Gallic acid	Antioxidative, antibacterial, antiviral, antimutagenic, inhibition of tumor growth, reduction of tumorigenesis, anti-angiogenic, modulation of androgen receptor	El Khawand et al. (2018)
6	Legumes, especially soya	Genistein	Antioxidative, anti-invasive, anti-inflammatory, delaying of tumor growth, suppression of tumor multiplicity, antiproliferative, estrogenic activity, epigenetic changes	Arts et al. (2000)
7	Citrus fruits, tomatoes, aromatic plants	Hesperetin	Antiviral, anti-inflammator, antioxidative	Lakenbrink et al. (2000)
8	Hops, beer	Xanthohumol	Antioxidative, anti-inflammatory, anti-estrogenic, stimulation of enzymatic action, pro-apoptotic, anti-invasive, suppression of tumor growth, anti-proliferative, targeting several processes	Tomás‐Barberán and Clifford (2000)
9	Vegetables (onions, broccoli), fruits (apples, apricots, berries), nuts, seeds, tea, wine, cocoa	Quercetin	Strongly antioxidative; antiviral, reduction in tumor formation and migration, anti-proliferative, antimetastatic, retarded lipid peroxidation, suppression of tumor development and multiplicity, epigenetic changes	Clifford (2000)
10	Strawberries, apples, persimmons, grapes, onions and cucumbers	Fisetin	Antioxidative, pro-apoptotic, stimulation of cell cycle arrest, reduction of androgen signaling and tumor growth, antiproliferative, inhibition in viability of tumor cells	Manach et al. (2004)

Polyphenols as anti-nutritional factor

Most of the studies on polyphenols showed their protective effects against various diseases. Polyphenols may enhance the exhaustion of iron in individuals who have marginal iron status (Tresserra-Rimbau et al., 2018). Most importantly, the polyphenols that are being taken through tea, coffee or wine may increase the non-heme iron intake as these sources do not possess vitamin- C (van Waalwijk van Doorn-Khosrovani et al., 2007). Besides, condensed tannins like proanthocyanidins and ellagitannins also act as anti-nutritional compounds, specifically in animal nutrition due to their tendency of interacting with some proteins and consequently, retard the activities of certain enzymes (Ross, 2000). It was reported that the intake of proanthocyanidin-rich fava beans caused the inhibition of net protein utilization in Egyptian boys which was further reinstated with de-hulling of the beans (Spector et al., 2005). These specific effects are implausible to happen with frequent Western diets that are illustrated by very little tannin consumption (Lu et al., 2004).

Similarly, flavonoids were found to be involved in the chelation of metals e.g. zinc (Zn) or iron (Fe) at high doses and hence caused inhibition in the absorption of nutrients. Apart from this, their involvement was also observed in protein metabolism, where they suppress digestive enzymes. Reports also suggested that the flavonoids stimulate DNA mutations in MLL gene as (common findings in neonatal acute leukemia) they act as topoisomerase inhibitors (Akiyama et al., 2001). Alterations in DNA were enhanced when high flavonoid doses were applied to cultured blood stem cells (Kolodziej and Kiderlen, 2005). In another study, it was analysed that the high concentration of flavonoids in mother’s diet may enhance the risk of MLL + acute myeloid leukemia in neonates. Though these findings were not statistically significant and when the information from different types of leukemia studies were collected, a favorable influence of the high-flavonoid diet was also observed (Ferrell and Thorington Jr, 2006). Many of these effects have been observed in animals or in vitro, and still, it is not clear that these effects may also occur in human beings. However, the absorption of the polyphenols through the regular diet is very low and the food matrix can also stimulate the effects of polyphenols (McGee, 2007).

Factors affecting polyphenols present in plant food

Polyphenols such as phenolic acids play a significant role against various stress conditions, where they help in recovering deteriorated parts by the process of lignification as their concentration stimulates with the stress and also, they have antimicrobial features (Es-Safi et al., 2002). There is a scarcity of information regarding the synthesis of polyphenolic content in the case of vegetables through sustainable agricultural practices more in comparison to those grown under normal conditions including hydroponic culture or other conventional methods. This was reported in corn, strawberries, blackberries, etc. (Heinonen et al., 2001).

Storage conditions

Polyphenolic content is affected by storage which leads to their oxidation. Oxidized polyphenols further trigger the synthesis of certain substances that occur in polymerized form which can cause the alteration of food quality, organoleptic and color of the food. Alterations like this can be useful or may cause damaging effects depending upon the acceptance of the consumers. Browning of fruits indicates the harmful effects, whereas black tea is the case of beneficial consequences. Significant deterioration of phenolic compounds occurs in the stored wheat (Kumpulainen, 2001). Constant phenolic compounds are observed qualitatively in flours after the storage of 6 months, whereas 70% loss in the concentrations was found. However, polyphenolic content remains preserved in onion or in apple in the cryopreservation. A 60% reduction in quercetin content along with complete loss of procyanidin was observed in the apple juice after storing at 25 °C, even though these compounds are considered stable in the fruit juice (Berman et al., 2017).

Industrial processing

Polyphenolic content is also affected by industrial food processing. During the different development processes like peeling off the fruits or by the removal of the seed hull, surface layer, membrane or the fibrous cover of the organs and production of flowering stem, polyphenolic content is lost. Even when the tissues are crushed, oxidative damage to the polyphenols is caused. As a consequence, these compounds may convert into brownish pigments, where they undergo polymerization at different degrees. This type of unusual activity may occur at the time of certain product formation from fruits like jam. Fruit juice formation includes the removal of flavonoids, which may lead to haze production and colour dullness. Therefore, fruit juices, which are synthesized may have fewer flavonoids. Esters of hydroxycinnamic acid can be hydrolyzed by pectinolytic enzymes (Clifford, 2000). Polyphenolic diffusion in the juice is facilitated by the maceration which is due to the vinification of red wine. However, the polyphenols in red wines are 10 times higher in comparison to the white wines as well as from grape juice (Lee et al., 2006).

Polyphenols are a large and varied group of secondary plant metabolites, and are therefore plenteous in most fruits and vegetables, even in greater quantities than vitamins. They should constitute important human nutrients, having multiple biological effects. Their biological activities can provide us with effective protection or even cure for several prevalent diseases, particularly cancer of various types. Omnipresence, response specificity and absence or low toxicity are essential benefits of polyphenols as anticancer agents. Agricultural residues have great potential as an antioxidant source, many of which belong to polyphenols. The removal of polyphenols from agricultural waste seems to be an appropriate technique for isolating these highly valuable, thermolabile compounds. Polyphenol bioavailability research must ultimately enable us to correlate polyphenol intakes with one or more accurate bioavailability measures (such as plasma and tissue concentrations of key bioactive metabolites) and with potential bioavailability measures. Knowledge of these correlations must be acquired despite the difficulties associated with the high diversity of polyphenols, their different bioavailability, and the high interindividual variability observed in certain metabolic processes, particularly those involving the microflora.

Besides this, the study results outlined in this review provide an up-to-date understanding of the biological effects of polyphenols and their relevance to human health. Polyphenols or diets rich in polyphenols provide substantial protection against the development and progression of many chronic diseases including cancer, diabetes, cardiovascular problems and aging. Although it is possible to scientifically explain several biological effects based on epidemiological studies, the mechanism of action of some of the polyphenols’ effects is not fully understood. Improved knowledge of some variables of the bioavailability of polyphenols, such as the kinetics of absorption, accumulation, and elimination will facilitate the design of such trials. While polyphenols show promising properties, further research is needed to clarify their mechanisms, interactions, and applicability, along with clinical trials to ensure their effectiveness and safety for human health. The role of polyphenols in human health remains a fertile research area. Based on our current understanding of science, polyphenols offer great hope in preventing chronic human diseases. In recent years, there has been a continuous exploration of polyphenols from novel plant sources for their potential applications in the functional food industry, significantly expanding the range of available polyphenol sources. Furthermore, advancements in emerging technologies, such as multi-omics, bioinformatics, and artificial intelligence, provide promising opportunities to elucidate the precise molecular mechanisms through which polyphenols contribute to the management of chronic diseases. Furthermore, use of advanced biotechnologies, including phenotyping, genotyping, and genome editing like CRISPR-Cas9, can enhance polyphenols production in crops. Domesticated crops have limited genetic diversity, whereas wild species possess greater variation, driving interest in their study for resilience to adverse environmental conditions. Future research on dietary polyphenols should focus on exploring new sources, optimizing preparation processes and quality standards, developing rapid identification methods for phenolic compounds, investigating their bioavailability and interactions with other bioactive components, and uncovering their molecular mechanisms in combating chronic diseases.

Funding

There is no research funding to address.

Declarations

Conflict of interest

Authors declare no conflict of interest.

Ethical approval

Not applicable.