Phenolic Compounds Present in Yerba Mate Potentially Increase Human Health: A Critical Review.

Yerba Mate (YM) is a food product derived from Ilex paraguariensis whose constituents obtained from its extract, mainly the phenolic fraction, have been linked to numerous health benefits, such as cardiovascular protection, weight reduction, glucose control, and gene modulation. However, evidences linking phenolic compounds (PC) intake and human health are still limited and often contentious. Several researches have shown that key PC elements are poorly absorbed in humans and exist predominantly as conjugates, which may not be bioactive but may play a crucial role when interacting with the gut microbiota (GM). As the intestine is the largest microorganism-populated organ in the human body, GM has been regarded as a "microbial organ", acting as a second genome for modulating the host's health phenotype. For this reason, the study of intestinal microbiota has received considerable attention in recent years. Its impact on the development of nutrition-related diseases must motivate broader researches on the interaction between YM's PC and GM regarding the production of metabolites that may influence human health. This review aimed to gather and assess the available information about how PC from YM may impact host metabolism and the immune system and GM.

Introduction

The aging of the world’s population is placing emphasis on the development of health-care policies and research methodologies to enhance nutrition and human health relationships. Bioactive compounds (BAC) of natural origin, which are secondary metabolites derived from seeds, food, and fermentation-based metabolic products, are currently on researchers focus [1]. Several factors, including food matrix, molecule size, environmental factors, and association with gastrointestinal material, can inhibit BAC bioavailability and absorption in host cell systems and target sites. As a result, the isolation of such natural BAC can result in promising multifunctional extracts that can be used in food applications to aid in health-promoting effects in host cell systems [2].

For instance, the most common plant-based BAC from food are phenolic compounds (PC). Numerous health benefits associated to them have made the interest and demand for phenolic-rich foods, identified as preventive diets, increase. In addition, because of their antioxidant properties and mechanisms such as enzymatic activity modulation, cellular signaling, and gene expression, foods high in phenolic compounds have been linked to the prevention of several chronic diseases [3].

Nevertheless, the same emerging interest has been observed regarding yerba mate (YM) as a food product derived from Ilex paraguariensis A. St. Hil. (mate) whose constituents obtained from its extract, mainly its phenolic fraction, have been linked to numerous health benefits. In Brazil, Paraguay, Uruguay, and Argentina, it is usually consumed as a tea-like beverage [4].

It is estimated that among the countries with the largest consumption of YM, Uruguay has the greatest per capita (8–10 kg/hab/year); Argentina´s consumption is around 6.5 kg/hab/year and in southern Brazil it is ingested 3–5 kg/hab/year [5]. Nowadays, YM products are also consumed in different countries, including Germany, Syria, and the United States for the production of energy drinks and teas. More recently, the consumption of YM products has been amplified to other countries such as Italy, France, Spain, Japan, Australia, Russia, and Korea since its taste and stimulant properties are very attractive [6]. In addition, the use of mate has already surpassed the tradition of infusion, starting to be used in the manufacture of cosmetics and in the pharmaceutical industry [7].

This plant is a rich source of several bioactive chemicals that apparently have their health effects influenced in a synergistic or complementary manner. Beyond that, it seems clear that the several benefits may not be exclusively related to a specific nutrient, but rather to the interaction between them, the human body and the GM [8]. The interaction between GM and PC has been extensively addressed by a plethora of studies using animal models or in-vitro colonic models. Although the findings reveal that dietary PC increases the number of beneficial bacteria and antimicrobial activity against pathogenic bacteria on GM, the main elements of PC are poorly absorbed by animals, and are mostly present as non-active conjugates when in the bloodstream [9].

Therefore, in order to take advantage of the nutritional effects of BAC, improvements in the absorption rate of these components should be studied, at the same time as potential food sources rich in PC must be known in better details so that we can safely introduce them into our diet. GM modulation through dietary changes has proven to be a key to improvements on PC absorption by animals. Several aspects present in GM modulation, such as eating habits seem to be particularly important in defining its characteristics. Long-term diet may not only have a crucial effect on the human GM but also, slight diet changes may affect the species composition [10]. For instance, diets rich in PC are reported to change the nature of GM, which in turn, may metabolize phenolics into bioactive compounds, improving their regulatory bioavailability [11].

Despite several researches displaying interaction between GM and PC have already been published there are almost no studies on the effect of YM and its PC on the human GM. This is certainly a relevant topic that should be better investigated once YM is a potential source of PC even when compared with most beverages and food products already studied [12].

For this reason, to know better the impact of PC from YM on gut microbiota (GM) and human health, this review has gathered and assessed relevant papers selected from Science Direct, Scopus, Web of Sciences, PubMed, Scielo, and Google Scholar databases resulting in a total of 74 publications were selected, considering the novelty and the impact in the area of this review.

An Overview on Yerba Mate’s Health Benefits

Over the last two decades, clinical trials have explored the use of YM in the prevention and treatment of a variety of health conditions [13]. Figure S1, of the supplementary material, shows the processing flow for YM products and details of the production processes in different countries.

Several authors have linked YM to a wide range of health benefits, including antioxidant capabilities [8, 14], vasodilator functions [15], gene modulation and DNA damage defense [16], hypoglycemic effects [17], anti-obesity and weight loss properties [13, 18], cardioprotective effects [19], cholesterol improvement [20] and thermogenic effects [21].

Heck and Mejia [4] described that YM extracts are especially rich in CGAs (ester formed by quinic acid, QA, and caffeic acid, CA). The hydrolytic products, QA and CA are significant as chemicals of high interest and present great commercial values. For instance, CA has demonstrated antioxidant capacity, with several mechanisms concerning metal ion chelation, inhibitory effects to some specific enzymes involved in free-radical generation and free-radical scavenging [22].

Studies in vitro and in vivo have presented a wide variety of biological activities of mono and di-caffeoylquinic acids, also found on YM extracts. Caffeoylquinic acids derivatives exhibited antioxidant capacity and anti-inflammatory activity [23], apoptosis-mediated cytotoxicity and α-glucosidase inhibitory effects [24], hypoglycaemic properties [25], anti-obesity effects, and lipid metabolism improvement [26]. Table S1, of the supplementary material, presents a compilation of studies suggesting some of YM beneficial health effects.

Different chemical components responsible for YM’s health benefits have already been identified, such as organic acids, minerals, enzymes, vitamins, amino acids, xanthines, saponins, lignin, lutein, cellulose, and especially PC [27]. For instance, methylxanthines, the main stimulant compounds present in YM, have presented several biological properties, including peripheral vasoconstriction, central nervous system and myocardial stimulation, smooth muscle relaxation, neuroprotective, hypoglycemic, anti-inflammatory, diuretic, and cardioprotective effects, among other benefits [28].

Some studies have also linked the effects of YM health benefits regarding its antioxidant capacity and more recent global health outbreak. In general, the antioxidant capacity of food products is already known to be related to free radical neutralization by PC even though, their potential within the human body is still arguable [29]. However, the main antioxidant effect in YM seems to be primarily due to the PC in the extract, delocalizing electrons and forming intramolecular hydrogen bonds [4, 19].

De Lima et al. [8] investigated the ability of YM to protect rat brain from chemically induced reactive oxygen species (ROS), glutathione balance disturbance, mitochondrial dysfunction, and lipid peroxidation. Glutathione depletion and mitochondrial dysfunction were both prevented by YM, and both benefits were associated to its ability to decrease ROS formation. Their results have also suggested that the preventive properties of YM may be due to a coordinated action amongst the numerous components in the extract, rather than just the phenolic fraction.

Augusti et al. [30] have very recently published a review on the utilization of dietary bioactive substances, such as PC, as a potential supplement to decrease COVID-19 symptoms. The synthesis of PC-derived postbiotics has been hypothesized to boost host’s antioxidant and immune response against SARS-CoV-2 infection, along with GM remodeling.

Phenolic Compounds in Yerba Mate

In YM leaves, the PC fraction represents 7–10% of the dry weight. Its main PC fraction is composed by hydroxycinnamates, a family of esters formed mostly by QA and a plethora of distinct hydroxycinnamic acids, such as ferulic acid, p-coumaric acid, and CA accounting for up to 95% of the phenolic content. The remaining 5% of the PC fraction is composed by flavonols [31]. Among flavonoids found in Yerba Mate are rutin, quercetin 3-rhamnoside and 3-glucoside, kaempferol 3-rhamnoside and 3-glucoside, and luteolin diglycoside [5].

CA is considered an important biosynthetic precursor representing the main hydroxycinnamic moiety, forming mono- and dicaffeoylquinic acid isomers and counting over 90% of the total PC, with 5- caffeoylquinic acid being the main hydroxycinnamate in YM [15, 31].

In detailed research, Mateos et al. [32] found 58 PC in YM, such as four isomers of caffeoyl-2,7-anhydro-3-deoxy-2-octulopyranosonic acid, two isomers of tri methoxy cinnamoyl shikimic acid, di- and tri-methoxy cinnamoyl quinic acids and 4-sinapoyl quinic acid. In addition, 2-methylxanthines and 46 PC were also found. Alike the aforementioned ratio, in their study, hydroxy cinnamic acid derivatives and flavonols represented 90 and 10% of YM’s PC, respectively. Along with rutin (7.1–7.8%), 5-caffeoylquinic (21.1–22.4%), 4-caffeoylquinic (12.6–14.2%), 3-caffeoylquinic (26.8–28.8%), and 3,5-dicaffeoylquinic acids (9.5–11.3%) were the most abundant phenols, and caffeine was the major methylxanthine (90%) [33].

These phenolic compounds can also be obtained from numerous vegetable sources, although in different compositions and amounts when compared to those found in YM.

In particular, Meinhart et al. [12] analyzed the existence of CGAs in 89 plants infusions. They found these compounds in 93% of infusions, however, YM presented the greatest content of CGAs (52.6 mg in 100 mL), being an important source of this nutrient compared to other beverages and food products.

Likewise, according to Duarte and Farah [34], 100 mL of chimarrão has double the quantity of 3,4-dicaffeoylquinic acid, 15 times more 3,5-dicaffeoylquinic acid, and six times more 4,5-dicaffeoylquinic acid than the same volume of coffee. The values of 5- caffeoyilquinic acid in 100 ml of chimarrão are on average 100, 60, and 20 times higher than in the same amount of white, green, and black tea, respectively [35]. Similar results were obtained for tererê extract, which presented amounts 300, 100, and 50 times greater than white, green, and black tea infusions, respectively [35].

In addition, YM-based drinks produced 120 times more 5-caffeyolquinic acid than mountain tea and 15 times more than chamomile tea when aqueous extracts of YM and Mediterranean herbs were compared [36]. Infusions commonly consumed in South America, such as those prepared from macela (Achyrocline satureioides) and carqueja (Baccharis trimera) leaves, showed concentrations of dicaffeyolquinic acids isomers 100 times lower than those in chimarrão and tererê extracts [35]. Therefore, chimarrão and tererê are great alternative sources of CGAs.

Interaction Between PC and the GM

The human body provides a nutrient-rich environment for intestinal bacteria, and the microbiota, in its turn, performs essential functions not exerted by humans, such as the production of valuable nutrients, modulation of bile acid metabolism, intestinal cell barrier, and immune system regulation. The balance of gut bacteria has been associated with immunological fortification, prevention of autoimmune disorders and immune inflammation, and preservation of the integrity of the intestinal epithelium (which avoids permeation of pathogens and immune-triggering compounds into the blood circulation) [37-39]. Polyphenols might indirectly regulate these functions by modulating the composition and activity of this microbiota [38]. In addition, some polyphenols are involved with the immune system, mainly with immunoglobulin A [40].

It also plays an important role in breaking down original complex PC into phenolic metabolites that are absorbed in the small intestine region [41].

In its turn, the bioavailability and bioactive impact of PC and their metabolites seem to influence GM composition. For instance, dietary PC is able to increase the number of beneficial bacteria and antimicrobial activity against pathogenic bacteria, although most researches have been performed in animal models or in-vitro colonic models [42]. In fact, there is also a strong relationship between PC activity modifying GM and, consequently, impacting Bacteroides/Firmicutes balance. Several studies have shown the importance of this ratio since decreased values indicate lower index of insulin resistance, adiposity, and obesity [39]. This ratio changes across the lifetime. It is lower in the first years of life (0.4), rises in adulthood (10.9), and diminished during elderliness (0.6) [43].

Phenolic compounds are poorly absorbed by the stomach and the small intestine, being that the small intestine absorbs from 5 to 10% of the total phenolic intake [38, 39, 44–46]. The low absorption is due to molecular structure complex and polymerization of polyphenols, while free aglycones can be absorbed efficiently [44, 46]. Next, unabsorbed polyphenols are carried to the large intestine, where are metabolized and biotransformed by the gut microbiota [38, 44, 45, 47]. Enzymes from gut microbiota degrade polyphenols into bioactive phenolic metabolites which might regulate the metabolic functions and composition of gut microbiota [38–40, 44]. Polyphenols are metabolized via dihydroxylation, glucosidase, esterase, demethylation, and decarboxylation, resulting in more simple phenolic structures by cleavage, hydrolysis, and reduction reactions [37, 46, 48]. Some of these metabolites produced have higher bioactivity and bioavailability than their precursors, such as simple phenolic acids and lactones [44–46, 49]. This way, the interaction between polyphenols and gut microbiota promotes the production of active phenolic metabolites, which its turn results in the modulation of gut microbiota composition [38, 50]. Phenolic metabolites prompt the swap of the gut microbiota population, usually favoring the growth of beneficial over pathogenic gut microbiota [39, 47]. For this reason, phenolic compounds act as prebiotics [38, 40, 44, 47]. For instance, caffeic and ferulic acids act selectively, reducing the rates of growth of pathogens without disturbing beneficial microorganisms [39, 44]. In addition, caffeic and chlorogenic acids might reduce the firmicutes-bacteroidetes ratio of the gut microbiota [51]. Polyphenols are also related to the prevention of gut dysbiosis, caused by the imbalance of gut microbiota [38, 46]. In addition, gut bacteria produce short-chain fatty acids by fermentation of dietary fibers and resistant starch, which have several health benefits, such as supplying energy to intestinal epithelial cells, reducing inflammation, absorbing minerals, and maintaining the gut and immune homeostasis [45, 47].

According to Loo et al. [44], quercetin suppresses the development of Escherichia coli, Staphylococcus aureus, Salmonella typhimurium, and Lactobacillus rhamnosus at minimum inhibitory concentrations (MIC) ranging from 62.5 to 250 g mL− 1, however, it seems to suppress the growth of Bacteroides galacturonicus, Enterococus caccae, Lactobacillus spp., Ruminococcus gauvreauii, Bifidobacterium catenulatum, and E. coli at doses ranging from 4 to 50 g mL− 1.

Other studies have reported MIC of hydroxycinnamic acids (HCA) ranging from 125 to 1,000 µg mL− 1 to strains of S. aureus, E. coli, S. typhimurium, and L. rhamnosus [44]. HCA on GM has also been reported to increase the lactic acid bacteria growth in the human intestine as a consequence of a high dose of CGAs. At the same time, a positive effect on the adhesion of probiotic bacteria such as L. acidophilus has been proved to be caused by CA presence [39].

As it can be seen, numerous studies have shown that PC modulate the microbial intestinal community through prebiotic or antimicrobial action against pathogenic intestinal bacteria [52].

As a consequence, there has been an increase in the number of studies associating the antioxidant, anti-inflammatory, antiadipogenic, antidiabetic, cardioprotective, neuroprotective, and anticarcinogenic effects of phenolic-rich substances through interaction with GM, in recent years [53]. However, there are almost no published studies on the effect of YM and its PC on the human GM, and this is certainly a relevant topic that should be better investigated. On the other hand, different sources of PC have already been assessed regarding their beneficial impact on human GM.

For instance, Gil-Sánchez et al. [54] researched grape pomace, a wine product rich in fibers and PC, two elements of foods in which bioaccessibility involves the microbiota. In this study, the in vitro colonic digestion of grape pomace extracts was analyzed for the first time. From the release of the main bioaccessible phenolic metabolites of grape pomace extract, various benzoic, phenylacetic, and phenyl propionic acids have been identified. It was observed a significant increase in the amounts of acetic, propionic, and butyric acids posteriorly to enhanced feeding indicating microbial fermentative activity [54]. Moreover, most classes of bacteria increased during chronic feeding, with the highest increases for groups of Lactobacillus and Bacteroids.

Nash et al. [55] published an overview of recent studies in humans concerning the impact of PC from grape and red wine on GM. All studies confirmed the regulation of those ingested PC performed by the intestinal microbiota, through the increase in the number of phenolic metabolites found in blood, urine, ileal fluid, and fecal fluids. According to the authors, the consumption of grape and red wine-derived PC may modulate GM and lead to beneficial microbial ecology improving human health. In addition, GM has demonstrated to modulate grape and red wine PC, suggesting an important two-way relationship [55].

Ramírez-Pérez et al. [56] also demonstrated a two-way interaction where host metabolism may be affected by both microbial modifications of bile acids, either by altering bile acid receptors signals as well as the microbiota composition. It becomes increasingly clear that the GM of individuals may determine the health effects of PC and several other bioactive compounds.

Despite all these demonstrated benefits for the regulation of GM, the observed limitation in animal absorption of key PC elements requires researches aimed at improving the bioaccessibility of bioactive chemicals derived from plant sources [9].

Approaches to Enhance the Bioavailability of Phenolic Compounds

Researches in the digestion processes of YM and other plants revealed a modification in the number of bioactive compounds after it passes through the several compartments of the gastrointestinal tract (GIT) due to enzymatic actions, metabolic activity of the GM and pH alterations [57]. Temperature and length of digestion may also influence the final qualitative and quantitative outcome. For instance, only one-third of all CGAs amount is absorbed in the small intestine while two-thirds reach the colon where they may be metabolized by the microbiota [58].

In accordance with this finding, Gómez-Juaristi et al. [59] evaluated the bioavailability of YM’s PC in healthy humans. They found that aside from unmetabolized caffeoyl-, feruloyl-, and p-coumaroilquinic acids, more than 34 metabolites with quick onset and clearance in plasma have been discovered, implying small intestine absorption. These chemicals accounted for 13.1% of the metabolites found in urine. In addition to feruloylglycine, delayed absorption of dihydrocaffeic, dihydroferulic, and dihydrocoumaric acids and their phase II metabolites, accounting for 81.0% of excreted metabolites, revealed bacterial origin and intestinal absorption, suggesting that YM’s PC are highly metabolized, mainly by the microbiota.

Furthermore, GM not only appears to be responsible for most of the PC metabolism, but it can also be modified through specific interventions in order to favorably affect human metabolism. Notwithstanding, GM must be first maintained so as to exert its main function properly. In this regard, pre-and probiotics may play an important role.

Prebiotics such as inulin, fructooligosaccharides, and galactooligosaccharides have demonstrated to improve intestinal permeability, decrease inflammation, and improve insulin control in vivo [60].

Probiotics as Lactobacillus spp. and Bifidobacterium spp. are equally beneficial to human health even when used isolated. However, combinations of pre- and probiotics have suggested a better potential in the GM and host health than isolated consumption, since the combination of both components stimulate bacteria growth and survival in the gastrointestinal tract [61].

In addition, isolated nutrients are rarely consumed and for this reason, in recent years, science has been evaluating the ability of dietary and nutritional patterns to adjust GM in pathological conditions. It seems that a long-term adherence to a high-fiber, phenolic compounds-enriched and vegetable-protein-based diet may provide benefits to the GM composition, as well as improvement in obesity and metabolic syndrome symptoms [41].

Diet has been shown to be a primary predictor of GM composition. Different degrees of in vivo scientific evidence support nutrition as a crucial component in GM modulation since certain foods, bioactive chemicals, and dietary patterns may impact health outcomes via their effect on the GM. In this context, it is crucial to understand how specific nutrients, such as PC may act in the modulation of the GM in order to clarify their action and effect in the human body. The discovery that food may have a significant impact on host-microbe interactions suggests that future treatment techniques to change the GM and reduce dysbiosis caused by nutrition-related disorders should be pursued [41].

Nowadays, dietary polyphenols have been used as an emerging therapy in the prevention of several diseases. For instance, the association between gut microbiota and polyphenols was related to the improvement of the signs of depression, mitigation of cognitive dysfunction, improvement in blood flow and vasodilation in cerebrovascular circulation, and acting as a neuronal protector due to diminishing neuroinflammation [62, 63], with immunomodulatory effect [40]. In addition, dietary polyphenols can prevent inflammatory processes, cardiovascular diseases, obesity, cancer, and type 2 diabetes [37, 46]. These properties were also reported for yerba mate, being yerba mate tea is recommended as dietary therapy [5, 33].

It is salient to promote investigations focusing on metagenomic, transcriptomic, and proteomic that help to comprehend the interaction between dietary polyphenols and gut microbiota, for this way, to know the genes and microorganisms that participate in the metabolism of these polyphenols, and thus, elucidate how the dose and polyphenol compounds from yerba mate extract impact on the gut microbiome and the immune system [37].

Aside from the maintenance of GM, the extraction method used to obtain PC elements from plant sources has to be efficient and provide a high quantity of compounds in order to improve PC absorption by human GIT.

It is already known that different extraction conditions such as time, temperature, type of solvent, and concentration may affect PC composition. Conventional methods for bioactive compounds extraction can be an alternative to increase their bioavailability and include solvent maceration, direct boiling, distillation, compression, etc. [64], although, such processes are time-consuming and can lead to the degradation of thermolabile compounds. Traditional methods such as Soxhlet and maceration present numerous disadvantages, including the employment of large amounts of organic solvents that may be toxic and also harmful to the environment, in addition to their high consumption of energy and time [65].

The stability of bioactive compounds derived from natural sources is a crucial factor for their effective integration into various food systems. In this context, methods such as microwave-assisted extraction emerged as an alternative to reduce the exposure times of bioactive compounds to high temperatures, energy costs, and environmental degradation [65]. Ultrasound-assisted extraction represents another option for the acquisition of bioactive compounds, using acoustic energy to improve the release and diffusion of target compounds from several matrices [66].

Subsequently, as natural antioxidants are significantly sensitive to the environment, in order to have its efficacy improved, they may also be protected from the surrounding medium through several methods. Recent techniques such as encapsulation may be valuable options for this purpose. The encapsulation process packs particles with the assistance of an encapsulating material in order to protect internal compounds and their functionalities. Protective delivery vehicles may also permit targeted release in tissues such as the small intestine, in addition to encasing, protecting, and conveying the desired bioactive molecules into the circulatory system [67].

In particular, in the pharmaceutical and nutritional domains, the use of encapsulated micro and nanoparticles for efficient oral administration of biomolecules has been a growing trend. Modern bioactive carriers, which mainly apply natural dietary macromolecules as functional materials, are meant to increase bioactive component absorption, physicochemical stability, and bioavailability through several routes while not presenting safety or health risks [68]. Successful application of these bioengineered vehicles of food compounds can bring benefits beyond basic nutrition to human health.

Encapsulation may also represent an alternative to transform some of the product’s characteristics, enhancing its appearance or avoiding unpleasant interactions with the carrier food matrix [67]. Phenolics having greater water solubility may be more readily liberated from the food matrix, dissolved in digestive juice, and absorbed by the small intestine mucosa during digestion. Hydrophobic molecules, on the other hand, are more likely to interact with other food components like fibers and lipids, delaying or reducing absorption [69]. Several wall materials can be used for food encapsulation, such as fibers, proteins, and gums. However, depending on the structure and features of each encapsulating agent, the employment of multiple agents may result in varied physical attributes [70].

Several biocompatible and biodegradable polysaccharides have been designed into micro or nanoparticles in an attempt to address the absorption issues of PC. Cyclodextrins, cyclic oligosaccharides presenting a hydrophilic outer surface and a lipophilic inner chamber, are a viable choice. Likewise, chitosan is another type of polysaccharide positively charged often employed for entrapping hydrophilic molecules. Because of interactions with the negatively charged mucus layer, the chitosan-based particles promote absorption by facilitating the passage through the tight junctions [71].

Furthermore, dietary proteins such β-lactoglobulin, β-casein, gelatin, and isolated soy protein are appealing as macronutrients and functional components, making them suitable materials for carriers to efficiently transport nutraceuticals. As can be seen, by the use of electrostatic interactions, proteins and polysaccharides may be designed to produce self-assembled particles [68].

In fact, encapsulated PC compounds have already demonstrated higher bioavailability and stability [72]. According to Berté et al. [73], spray-dried YM extract presented greater amounts of phenolic acids compared to the leaves. Becker et al. [74] assessed the antioxidant capacity and clinical effects of spray-dried YM extract capsules in healthy individuals. The ingestion of the capsules increased the antioxidant biomarkers while decreasing lipid peroxidation both in the short and long term.

Concluding Remarks

Ilex paraguariensis has been shown to have several health advantages. Although many of these benefits are not yet fully established, multiple studies have shown that the plant has the potential to be a promising functional food product, mostly due to its phenolic component. Because the relationship with the GM is essential for PC metabolism, the final fraction of YM compounds ingested as well as their mode of action in the human body should be better understood.

In this context, authors should exercise caution in light of the abundance of repetitive and misleading information, since multiple poor research can dilute solid works. Interindividual variation, on the other hand, emerges within rigorous research, such as varied responses to PC utilization depending on the individual. Before precise findings can be drawn, it is necessary to determine the probable interplaying elements surrounding the PC and GM interaction in human health. Also, because PC bioavailability and effects are frequently contested, it is critical to qualify the various YM products in terms of PC, as well as understand how different extractions and modes of consumption impact the degree of phenolic migration to water as well as absorption by the human body.

Subsequently, as natural antioxidants are significantly sensible, in order to have its efficacy improved, they may also be protected from the surrounding medium through several methods. Recent techniques such as encapsulation could be valuable options for this purpose. Protective or encapsulated delivery vehicles may also permit targeted release in tissues such as the small intestine, in addition to encasing, protecting, and conveying the desired bioactive molecules into the circulatory system [67].

Below is the link to the electronic supplementary material.

Supplementary Material 1