Pomegranate & Microbiota - The Health Benefits of Punicalagins

Punicalagins are bioactive compounds found in pomegranate (Punica granatum) as well as in various medicinal plants, in particular in species of the genus Terminalia. These very specific molecules belong to the ellagitannin family, a class of hydrolyzable tannins with proven health benefits.

Punicalagins are no exception: they have been identified as potentially beneficial in a myriad of health areas ranging from the cardiovascular [1-6] to the neurological spheres [7-13], but also for osteoarticular health [14-22].  They could even be of interest for therapeutic applications in the field of oncology [23-32].

 

Given that punicalagins are macromolecules whose systemic bioavailability after ingestion is far from optimal, one may wonder how this type of phytoactive is able to act beyond the digestive sphere.

In fact, these pleiotropic effects can be explained by two crucial aspects in the physiological action of punicalagins. In this article, these two aspects will be discussed in order to highlight the interest of pomegranate extracts rich in punicalagins and – by extension – other medicinal plants rich in ellagitannins such as the exotic Haritaki (Terminalia chebula – emblematic plant of Ayurveda), or our local Purple loosestrife (Lythrum salicaria).

1. THE MICROBIOTA AS A COMMON DENOMINATOR?

As previously discussed, punicalagins have been identified as active and potentially beneficial for many areas of health, all of which correspond to applications where the health potential of the intestinal microbiota has been highlighted. Enough reason to investigate the impact of punicalagins on the microbiotic ecosystem.

As hydrolyzable tannins, punicalagins are water-soluble macromolecules with an affinity for the digestive mucosa and more specifically with the proteins that make up the mucus. They are therefore able to spread more efficiently on the mucous membrane, which makes punicalagins a significant asset for a targeted action on the intestinal mucosa. Once fixed, they will act on the oxidative and inflammatory status of the mucosa (therefore promoting the balance between microbiota and organism). On-site punicalagins will also limit the progression and virulence of certain pathogenic elements – whether fungal [33-34], bacterial [35-39] or viral [40-41] – while supporting the growth of symbiotic bacteria such as Bifidobacterium [42-43].

1.1. Punicalagins & Intestinal Epithelium

The positive effects of punicalagins on the microbiotic environment may also be indirect. For example, they have repeatedly been shown to exert significant influence on autophagic mechanisms [44-47]. Such activity is characteristic of phytonutrients that promote a healthy intestinal epithelium and ultimately microbiotic balance [48-49]. Indeed, protecting the integrity of the intestinal barrier is crucial to limiting excessive inflammatory response, which can carry harmful consequences for both the microbiota and the body.

1.2. Punicalagins & Liver Function

Another interesting finding is the positive effect of punicalagins on liver health [50-52], particularly via the Nrf2 pathway [53-55]. By supporting the optimal activity of the liver, punicalagins may promote a balanced production of bile acids. It is well known that the balance between bile and microbiota is a key factor of many microbiotic benefits [56].

2. ACTIVE & PRECURSOR OF BIOACTIVE COMPOUNDS

A large portion of the world’s population has an intestinal microbiota that can metabolize punicalagins. This phenomenon leads to the release of ellagic acid, a molecule that can influence intestinal inflammation [57-59] but also shown to act at various other levels. In a third step, ellagic acid is finally converted into Urolithins, in particular into Urolithin A, a highly bioavailable molecule with direct action on the protection of the intestinal barrier [60-63], as well as numerous beneficial health properties.

This metabolic pathway characteristic of punicalagins allows them to act progressively and in the longer term, as they are metabolized from precursors to other active derivates. However, it should be noted that the maximization of this activity requires an efficient microbiota that is able to perform this conversion. This factor can lead to varying efficiency across individuals and has therefore led to the theory of metabotypes. Based on these elements, it appears that combining punicalagins with other molecules with known action on the microbiotic balance could be a good strategy to optimize the results.

3. POSSIBLE COMBINATIONS

Molecules with pleiotropic action such as punicalagins allow a large number of opportunities for synergistic combinations. However, it appears that an association with active ingredients capable of positively influencing the microbiotic environment could be of particular interest to ensure optimal efficiency.

Fast-acting molecules such as hydroxytyrosol from the olive tree (Olea europeae), chlorogenic acid found in green coffee (Coffea canephora), blueberry leaves (Vaccinium myrtillus) or even artichoke (Cynara scolymus), could allow a two-step action with a rapid effect of precursor phytoactives (hydroxytyrosol or chlorogenic acid), followed by a longer term effect of punicalagins for an efficient regulation of the microbiotic balance.

Another approach could be to combine a pomegranate extract rich in punicalagins with a fermented pomegranate extract, richer in its bioactive derivates Urolithin A and Ellagic Acid. This would allow patients to benefit from the advantages of ellagitannins and its metabolites, regardless of their microbiotic profile.

Finally, diversifying the supplemented tannins could also maximize the results: we could therefore consider combining pomegranate punicalagins with chebulagic acids of Haritaki (Terminalia chebula) or with those of Purple Loosestrife (Lythrum salicaria).

CONCLUSION

Punicalagins, like most active ingredients that promote microbiotic balance, have a variety of pleiotropic benefits on Health. They are also a good example that some molecules can have many health benefits through the microbiota despite not having significant systemic bioavailability.

A growing body of scientific evidence now points to the crucial impact of phytonutrients on the microbiotic environment, and it is suggested that the relationship between phytotherapy and the gut microbiota is anything but incidental. It could even appear as if the microbiome could be the “missing link” that would explain a large part of the benefits of medicinal plants on human health and lesser side effects.

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