Exploring the Interactions between Plant Proanthocyanidins and Thiabendazole: Insights from Isothermal Titration Calorimetry.

Anthelmintic resistance in gastrointestinal nematodes produces substantial challenges to agriculture, and new strategies for nematode control in livestock animals are called for. Natural compounds, including tannins, with proven anthelmintic activity could be a functional option as structurally diverse complementary compounds to be used alongside commercial anthelmintics. However, the dual use of two anthelmintic components requires an understanding of the pharmacological effects of the combination, while information concerning the interactions between plant-based polyphenols and commercial anthelmintics is scarce. We studied the direct interactions of proanthocyanidins (PAs, syn. condensed tannins) and a commercial anthelmintic thiabendazole, as a model substance of benzimidazoles, by isothermal titration calorimetry (ITC). Our results show evidence of a direct interaction of an exothermic nature with observed enthalpy changes ranging from 0 to -30 kJ/mol. The strength of the interaction between PAs and thiabendazole is mediated by structural characteristics of the PAs with the strongest positive correlation originating from the presence of galloyl groups and the increased degree of polymerization.

Tannins Can Have Direct Interactions with Anthelmintics: Investigations by Isothermal Titration Calorimetry.

Plant tannins are known for their anthelmintic and antiparasitic activities and have been increasingly studied to battle the ever-growing problem of anthelmintic resistance. While tannins have been shown to exhibit these activities on their own, one approach would be to use them as complementary nutrients alongside commercial anthelmintics. So far, research on the interactions between tannins and anthelmintics is limited, and few studies have reported both synergistic and antagonistic effects depending on the type of tannin and the method used. These interactions could either strengthen or weaken the efficacy of commercial anthelmintics, especially if tannin-rich diets are combined with anthelmintics used as oral drenches. To study these interactions, a series of hydrolysable tannins (HTs) was selected, and their direct interactions with thiabendazole (TBZ) were evaluated by isothermal titration calorimetry (ITC), which allowed the detection of the exothermic interaction but also the roles and significances of different structural features of HTs in these interactions. Our results show that HTs can have a direct interaction with the benzimidazole anthelmintic TBZ and that the interaction is strengthened by increasing the number of free galloyl groups and the overall molecular flexibility of HTs.

Variability in Foliar Ellagitannins of Hippophaë rhamnoides L. and Identification of a New Ellagitannin, Hippophaenin C.

Berries of common sea-buckthorn (Hippophaë rhamnoides L.) are well-known and used for their bioactive components, and while there is a considerable amount of research on the leaves as well, their ellagitannins (ETs) have not been a prominent focus of research. We identified and quantified ten major hydrophilic polyphenols, all ETs, in H. rhamnoides leaves and compared their abundance between 58 plant individuals. Of these compounds, hippophaenin C was characterized as a new ellagitannin by various spectrometric methods. The total concentrations of ETs ranged from 42.5 mg g-1 dry weight (DW) to 109.1 mg g-1 DW between individual plants. Among the ETs, hippophaenin C, stachyurin, and casuarinin were on average the most abundant compounds. Sexes did not differ significantly, while cultivars showed variation in some ETs. These results suggest that H. rhamnoides leaves could be a potential and rich source of several ETs.

Biological activity of ellagitannins: Effects as anti-oxidants, pro-oxidants and metal chelators.

Ellagitannins are a subclass of hydrolysable tannins that have been suggested to function as defensive compounds of plants against herbivores. However, it is known that the conditions in the digestive tracts of different herbivores are variable, so it seems reasonable to anticipate that the reactivities and modes of actions of these ingested defensive compounds would also be different. A previous study on a few ellagitannins has shown that these polyphenolic compounds are highly oxidizable at high pH and that their bioactivity can be attributed to certain structural features. Herein, the activities of 13 ellagitannins using the deoxyribose assay were measured. The results provided information about the anti-oxidant, pro-oxidant and metal chelating properties of ellagitannins. Surprisingly, many of the tested ellagitannins exhibited pro-oxidant activities even at neutral pH and only moderate to low radical scavenging activities, although the metal chelating capacities of all tested ellagitannins were relatively high.