Medicinal plants have been used as traditional medicines for thousands of years. Their therapeutic properties are attributed to the presence of a variety of bioactive molecules such as polyphenols (e.g., flavonoids, tannins) and saponins (e.g., glycosylated triterpenes) amongst others (1, 2). Many of these health-promoting plant constituents require biotransformation by gut microbiota for intestinal absorption or to become biologically active (1, 2). Hence, composition of the gut microbiome is a key factor for the efficiency of medicinal plants (1). By applying fermentation to medicinal plants, one can bypass imbalances in the gut microbiome, since microorganisms participating in the fermentation process take charge of the biotransformation job by predigesting the plant.

Fermentation is an ancient technology based on knowledge passed down from generation to generation and used to enhance the shelf-life, digestibility, and nutritional and organoleptic qualities of food. During fermentation microorganisms predigest the plant material so that the complete plant matrix becomes more readily available to the body (2).

More specifically, complex plant compounds are degraded enzymatically and chemically and subsequently modified in biotransformation reactions, while new molecules are created (including those derived from microbial metabolism) (1-4).

The effect of fermentation on the plant matrix is specific to the microorganisms involved, depends on the unique phytochemical composition of the plant material used and can be modified by process conditions (i.e., pH, humidity, temperature) (4).

The traditional fermentation of medicinal plants has been maturing by adopting a range of fermentation control techniques to achieve desired final product properties: implementation of a closed system with sterile starting conditions, oxygen and temperature regulations, constant stirring for maximal exposure to the microorganisms, in-line process control, sterilisation to stop the process at the appropriate incubation period.

Medicinal plants are naturally fermented by food-grade bacterial and fungal strains with a safe history of use (e.g., preselected lactic acid bacteria, yeasts, acetic acid bacteria), only after thorough identification of the inoculated strains. As a result, a targeted fermentation facilitates the controlled release of bioactive components, enhances the density of those bioactive constituents, and improves product stability (1).

One of the principal events occurring during the fermentation of medicinal plants is the conversion of glycosides (i.e., plant constituents associated with a sugar moiety) into aglycones (i.e., bioactive molecules without sugar moiety) by the action of microbial enzymes. This bioconversion increases the biological activity of plant constituents. Moreover, glycosides are typically large and highly polar, and therefore poorly absorbed from the gastrointestinal tract. On the contrary, aglycones are small and highly absorbable (1, 2).

Since most of the non-medical plant constituents (i.e., starch, proteins, sugars, fats) are consumed by the microorganisms during their growth phase, fermentation is a gentle and natural method for enrichment of the bioactive components (1). Bioactivity is further enhanced by microbial conversions of bioactive components into active metabolites (1).

Fermentation exerts beneficial effects on the absorption and bioavailability of medicinal plants by facilitating the conversion of complex glycosides into smaller aglycones, depolymerization of high molecular weight phenolic compounds and the metabolization of flavonoids (through microbial bioconversion pathways) (1).

With the help of widely used intestinal permeability models it was shown that high molecular weight glycosides (e.g., astragaloside IV from astragalus root or withanoside IV from ashwagandha) (5, 6) are poorly transported across the intestinal epithelial barrier whereas the low molecular weight aglycones (e.g., cycloastragenol from astragalus and withanolide A from ashwagandha)(7),(6) are transported very rapidly.

Fermented medicinal plants are abundant in antioxidants. The observed antioxidant activity typically coincides an increase in total phenolic compounds. The fermentation process induces the structural breakdown of plant cell walls, leading to the liberation of various antioxidant compounds (e.g., flavonoids, simple phenolic compounds) (1).

Flavonoids are broken down into smaller antioxidant molecules, often called SOD-like substances. These very stable molecules have an antioxidant property like that of superoxide dismutase (SOD). SOD forms the front line of defence against oxidative stress in the body.

Moreover, the microorganisms synthesize a range of antioxidants to protect themselves against oxidative damage (e.g., glutathione, exopolysaccharides) and add these to the final product (2).

Preservation of the natural matrix adds to a completer therapeutic efficacy and safer use compared to isolated substances. Fermentation offers a good solution.

For example, due to the recent observation that curcumin-only preparations could cause acute liver injury in susceptible individuals (8), return to equally effective full matrix formulations (with lower curcumin levels) is gaining tremendous interest.

Moreover, a complete matrix of bioactive compounds offers added value. The immune regulating potential of astragalus root preparations is not solely mediated by polysaccharides, which is often believed, but saponins and flavonoids also contribute to proper immune functioning. Also, the precise phytochemicals responsible for the adaptogenic effect (non-specific resistance to stress) of rhodiola remain to be confirmed. Salidroside, p-tyrosol and rosavins are considered significant contributors, but a synergistic effect with yet unidentified components cannot be ruled out (9).