# Beta-adrenergic receptor stimulation, histamine receptor inhibition, and potassium channel opening contribute to the relaxant effects of crocetin on airway smooth muscle

## TL;DR

Crocetin relaxes airway smooth muscle through beta-adrenergic stimulation, histamine inhibition, and potassium channel opening.

## Contribution

The study identifies specific mechanisms through which crocetin exerts relaxant effects on tracheal smooth muscle.

## Key findings

- Crocetin and theophylline both showed concentration-dependent relaxation of tracheal smooth muscle.
- Crocetin's effects were reduced in tissues incubated with propranolol, chlorpheniramine, and glibenclamide.
- Relaxation mechanisms include ß-adrenergic stimulation, H1 histamine receptor inhibition, and potassium channel activation.

## Abstract

In the present study, the relaxant effect of crocetin on tracheal smooth muscle cells (TSM) and its possible mechanisms were evaluated.

The study was conducted on 54 male Wistar rats in 8 groups. TSM was contracted by methacholine (10 μM) and KCl (60 mM), and the relaxant effects of four cumulative concentrations of crocetin, petal extract of saffron, and theophylline were examined on non-incubated and TSM incubated with propranolol, chlorpheniramine, diltiazem, atropine, glibenclamide, and indomethacin were investigated.

In non-incubated TSM contracted by methacholine or KCl, crocetin and theophylline showed concentration-dependent relaxant effects (all, P<0.001). However, various concentrations of crocetin showed significantly lower relaxant effects compared to those of theophylline (all, P<0.001). In the methacholine-induced contraction of TSM, the relaxation effect of the last concentration of crocetin in the TSM incubated with propranolol was lower than in non-incubated TSM (P<0.05). In the incubated TSM with chlorpheniramine, the relaxant effects of the two last concentrations of crocetin were significantly lower than in the non-incubated tissues contracted by KCl (P<0.05 and P<0.0). The levels of EC50 crocetin in the incubated TSM with glibenclamide, chlorpheniramine, and indomethacin were markedly lower than in non-incubated (all, P<0.05).

The results showed potent relaxation effects of crocetin on TSM and were suggested to be through stimulation of ß-adrenergic receptors, inhibition of histamine (H1) receptors, and potassium channel opening mechanisms.