Review
Ginsenosides, catechins, quercetin and gut microbiota: Current evidence of challenging interactions
Introduction
Over the last decades, several studies have focused on the cytoprotective effects of dietary supplements, thus raising the idea that a daily intake of these products improves the quality of life (Aiello et al., 2016; Corbi et al., 2016). According to the current regulation, herbal products (e.g., crude or commercial preparations of herbs) are considered as dietary supplements (Brown, 2017). The beneficial effects of herbal products depend on the abundance of phytochemicals (e.g. polyphenols and terpenes) with complex mechanisms of cytoprotection, including both the free radical-scavenging activity and enhancement of the cell stress response (Bjørklund and Chirumbolo, 2017; Davinelli et al., 2016; Mancuso, 2015; Hun Lee et al., 2013). However, the variable bioavailability of some phytochemicals, mainly polyphenols, has complicated the ability of randomized clinical trials to evaluate the therapeutic effects of these compounds in many diseases, thus preventing the accumulation of unambiguous evidence on their utility in humans (Mancuso et al., 2015, 2012; Lewandowska et al., 2013).
Quite recently, some papers have appeared in the scientific literature on the role played by the gut microbiota in favoring the beneficial effects of herbal products (Xu et al., 2017; Chen et al., 2016a). According to these studies, intestinal microbiota exerts effects at the pharmacokinetic and/or pharmacodynamic levels. By producing glycosidases and other enzymes catalyzing phase I reactions (e.g., oxygenation or hydrolysis), gut bacteria transform phytochemicals, very often bound to sugar moieties, into smaller molecules easily absorbed or in metabolites endowed with pharmacological effects (Espin et al., 2017; Xu et al., 2017). Although clinical studies unequivocally demonstrate the formation of these metabolites, their activity, in terms of modulation of specific cytoprotective targets, is essentially supported by in vitro studies.
Ginseng-derived ginsenosides and green tea-derived catechins have been taken as an example to discuss the multifaceted role of gut microbiota on herb-derived phytochemicals. One of the reasons why we have focused on these herbs, is that they are widely used, not only in the East, but also in the West and their beneficial effects have been extensively advertised. In addition, we have decided to describe the effects of gut microbiota on the flavonoid aglycon quercetin, which exists in nature bound to several sugars (see below) and is very abundant in roots and vegetables (e.g., lettuce, onions, etc.). Another reason that has led us to pick these phytochemicals is the fact that the bacteria involved in their intestinal biotransformation have been clearly identified and fully characterized, as well as the final metabolites formed through these activities. Undoubtedly, in making this choice we had to avoid diffusing general information on the chemical and pharmacological properties of ginsenosides, catechins and quercetin, for which we refer to extensive reviews available in the literature (e.g., Mancuso and Santangelo, 2017; Saeed et al., 2017; Anand David et al., 2016). Indeed, the goal of this review is to provide specific information about the changes performed by the gut microbiota on ginsenosides, catechins and quercetin and whether or not these modifications generate metabolites with biological effects.
Section snippets
Gut microbiota
In adults, the intestine is colonized by an extremely high number of bacteria, to the point that the intestinal microbiota is considered as a real organ, which performs digestive along with metabolic and endocrine functions (Goulet, 2015). The small intestine (duodenum, jejunum and ileum) contains a number of bacteria ranging from 104/ml content to 106-107/ml at the ileocecal junction, while the large intestine has a number of bacteria ranging between 1011 and 1012/g, most of which are
Ginsenosides
Ginseng is very popular in the Far East, in particular China and Korea, although ginseng-based products, such as some types of tonic beverages, are also highly diffused in the West (Baeg and So, 2013; Yun, 2001). The commercially available preparations of ginseng can be derived from several species of the Panax genus. Among these, the most widely used are raw preparations or extracts of P. ginseng, the Chinese or Korean species, and P. quinquefolius, considered the American species (Baeg and
Catechins
Tea is one of the most popular drinks in both the Eastern and Western countries. Two are the main types of teas consumed, black tea, which accounts for 60% of the whole product, and green tea accounting for 30% (Clifford et al., 2013). In both cases, the product originates from dried leaves of Camelia sinensis in non-fermented (green tea) or fermented (black tea) forms (Schantz et al., 2010). Green tea is rich in polyphenols (about 30% dry weight), among which the (˗)-epigallocatechin-3-O
Quercetin
Although quercetin is not an herbal product per se, it is the most common flavonoid present in many consumer foods, such as lettuce, red onion, radish leaves, cranberry and several others, and plants, including lovage, buckwheat, coriander and others more (Guo and Bruno, 2015; Formica and Regelson, 1995). Quercetin is found in nature conjugated to sugar moieties, such as rhamnose or rutinose, giving rise to the corresponding glycosides quercitrin and rutin (Guo and Bruno, 2015). The average
Conclusions
The first conclusion that can be drawn, by observing the evidence so far provided, is that the gut microflora becomes an important site for metabolic reactions by transforming ginsenosides, catechins and quercetin into active metabolites. This evidence supports the possibility that age-related or antibiotic-induced modifications of gut microflora, can cause important changes in terms of biotransformation of herbal products, thus affecting some of the expected beneficial effects. This is the
Conflicts of interest
The Authors have nothing to disclose.
Funding and sponsorship
This work was supported by Università Cattolica del Sacro Cuore grants “Fondi Ateneo” to C.M. and A.S.
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These authors have equally contributed to this work.