Allergen-free extracts from birch, ragweed, and hazel pollen activate human and guinea-pig submucous and spinal sensory neurons.

BACKGROUND: Non-allergenic, low molecular weight components of pollen grains are suspected to trigger changes in gut functions, sometimes leading to inflammatory conditions. Based on extensive neuroimmune communication in the gut wall, we investigated the effects of aqueous pollen extracts (APE) on enteric and spinal sensory neurons. METHODS: Using Ca2+ and fast potentiometric imaging, we recorded the responses of guinea-pig and human submucous and guinea-pig dorsal root ganglion (DRG) neurons to microejection of low (<3 kDa) and high (≥3 kDa) molecular weight APEs of birch, ragweed, and hazel. Histamine was determined pharmacologically and by mass spectrometry (LC-MS/MS). KEY RESULTS: Birch APE<3kDa evoked strong [Ca+2 ]i signals in the vast majority of guinea-pig DRG neurons, and in guinea-pig and human enteric neurons. The effect of birch APE≥3kDa was much weaker. Fast neuroimaging in human enteric neurons revealed an instantaneous spike discharge after microejection of birch, ragweed, and hazel APE<3kDa [median (interquartile range) at 7.0 Hz (6.2/9.8), 5.7 Hz (4.4/7.1), and 8.4 Hz (4.3/12.5), respectively]. The percentage of responding neurons per ganglion were similar [birch 40.0% (33.3/100.0), ragweed 50.8% (34.4/85.6), and hazel 83.3% (57.1/100.0)]. A mixture of histamine receptor (H1-H3) blockers significantly reduced nerve activation evoked by birch and ragweed APEs<3kDa , but was ineffective on hazel. Histamine concentrations in ragweed, birch and hazel APE's < 3 kDa were 0.764, 0.047, and 0.013 µM, respectively. CONCLUSIONS: Allergen-free APEs from birch, ragweed, and hazel evoked strong nerve activation. Altered nerve-immune signaling as a result of severe pollen exposure could be a pathophysiological feature of allergic and non-allergic gut inflammation.

Peppermint and caraway oils have muscle inhibitory and pro-secretory activity in the human intestine in vitro.

BACKGROUND: Herbal medicinal products with a broad activity spectrum may be promising alternatives to treat functional gastrointestinal disorders (FGD). Menthacarin® is a drug with a fixed combination of peppermint and caraway oils, which is clinically used to treat FGD-associated symptoms. MATERIALS: We studied the effects of peppermint and caraway oils on contractile and secretory activity in 255 human small and large intestinal preparations derived from surgical resections (73 patients). Motility was recorded in circular smooth muscle strips and secretion with the Ussing chamber-voltage clamp technique. Electrical field stimulation evoked nerve induced contractile responses. KEY RESULTS: Peppermint and caraway oil concentrations dependently inhibited muscle contractility as indicated by sustained muscle relaxation and decrease in phasic contractility. These effects occurred in small and large intestinal preparations with IC50 values ranging between 17 and 90 µg/mL for peppermint oil and between 7 and 127 µg/mL for caraway oil. Neither peppermint nor caraway oil influenced the nerve evoked contractile response. The inhibition of contractile activity, but not the muscle relaxation, was prevented by the L-type calcium channel activator Bay K8644 but not by the neurotoxin tetrodotoxin. Both peppermint oil and caraway oil increased epithelial secretion, which remained in tetrodotoxin. CONCLUSION & INTERFERENCE: The findings revealed a strong muscle inhibitory and pro-secretory action of peppermint and caraway oils at clinically relevant concentrations. Both actions were nerve-independent. The inhibition of contractility was mediated by inhibition of L-type calcium channels. The effects on muscle and epithelial activity may contribute to the beneficial effects observed in patients with FGD.