Extract of the plant Petasites hybridus

In patients with histamine intolerance accumulated or ingested histamine causes a broad range of undesirable symptoms. Food-derived histamine is degraded by intestinal diamine oxidase (DAO) and histamine-N-methyltransferase (HNMT), while the organic cation transporter 3 (OCT3) contributes to the transcellular flux of histamine. Anecdotal evidence from patients with HIT suggests an improvement of symptoms related to histamine intolerance after intake of Ze 339, a lipophilic CO₂-extract prepared from the leaves of Petasites hybridus. Thus, it was the aim of this study to investigate the influence of Ze 339 on DAO, HNMT and OCT3 using Caco-2 and MDCKII cells. Even though Ze 339 reduced mRNA levels of HNMT and DAO, there was no change in protein expression. Ze 339 changed neither the basal release nor the enzymatic activity of DAO. Testing the interaction of Ze 339 with the transcellular histamine transport, we observed a significant increase in the basal to apical flux in presence of high Ze 339 concentrations at the early phases of the experiment. Testing the influence of Ze 339 on OCT3-mediated histamine uptake in overexpressing MDCKII cells revealed a dose-dependent inhibition with an estimated IC₅₀ of 26.9 ug/mL for the extract. In conclusion, we report an effect of Ze 339 on transcellular histamine transport, where inhibition of OCT3 may contribute.

It has been shown that a lipophilic CO₂-extract prepared from the leaves of Petasites hybridus (Ze 339) inhibited leukotriene synthesis in vitro and ex vivo. The inhibition of the leukotriene synthesis was solely attributed to the sum of the petasins, namely petasin and its isomers isopetasin and neopetasin. To further investigate the influence of the extract matrix on leukotriene synthesis inhibition, we compared twelve selected batches of Ze 339 that differed significantly in the composition of the extract matrix. Quantitative analysis of the twelve extract batches revealed high contents of petasins [28.8-41.9%], fatty acids [17.1-27.2%] and crude oil and fat [17.7-44.2%]. The amount of sterols ranged between 3.0 and 4.9% and that of essential oils between 1.3 and 10.5%. Based on the quantitative analysis, 97-100% of the extract mass could be attributed to the above mentioned groups of ingredients. Despite significant differences in extract matrix composition, only the content of petasins was critical for the dose-dependent inhibition of leukotriene synthesis. However, at equal concentrations of petasins, no significant differences in 5-LOX, LTC4 synthase and LTA4 hydrolase inhibition were detected between the selected extract batches, despite differences in the composition of the petasin isomers. Our data suggest that the extract matrix of Ze 339 has no effect on leukotriene inhibitory effects of the petasins.