Possible Mechanisms for Functional Antagonistic Effect of Ferula assafoetida on Muscarinic Receptors in Tracheal Smooth Muscle

Abstract

Background: The contribution of histamine (H1) receptors inhibitory and/or β-adrenoceptors stimulatory mechanisms in the relaxant property of Ferula assa-foetida. (F. asafoetida) was examined in the present study.

Methods: We evaluated the effect of three concentrations of F. asafoetida extract (2.5, 5, and 10 mg/mL), a muscarinic receptors antagonist, and saline on methacholine concentration-response curve in tracheal smooth muscles incubated with β-adrenergic and histamine (H1) (group 1), and only β-adrenergic (group 2) receptors antagonists.

Results: EC50 values in the presence of atropine, extract (5 and 10 mg/mL) and maximum responses to methacholine due to the 10 mg/mL extract in both groups and 5 mg/mL extract in group 1 were higher than saline (P < 0.0001, P = 0.0477, and P = 0.0008 in group 1 and P < 0.0001, P = 0.0438, and P = 0.0107 in group 2 for atropine, 5 and 10 mg/mL extract, respectively). Values of concentration ratio minus one (CR-1), in the presence of extracts were lower than atropine in both groups (P = 0.0339 for high extract concentration in group 1 and P < 0.0001 for other extract concentrations in both groups).

Conclusion: Histamine (H1) receptor blockade affects muscarinic receptors inhibitory property of F. asafoetida in tracheal smooth muscle.

Keywords: Ferula extract; muscarinic receptors; muscle relaxation.

Figure 1

Concentration-response curves of metacholin in tracheal smooth muscle, in the presence of three concentrations from F. asafoetida extract, saline and 10 nM atropine. (a) Incubated tissues with 1 μM chlorpheniramine and 1 μM propranolol, (group 1, filled, n = 6). The curves showed right ward in the presence of atropine and two higher concentrations of the extract but maximum response to methacholine in the presence of the extract was not achieved in the presence of high extract concentration. (b) Tissues incubated with propranolol, (group 2, open symbols, n = 7). The curves showed right-ward shift in the presence of atropine and two higher concentrations of the extract and maximum response to methacholine in the presence of the extract was achieved.

Figure 2

Methacholine EC₅₀ values in the presence of three concentrations from F. asafoetida extract, saline and 10 nM atropine. (a) Tissues incubated with 1 μM chlorpheniramine and 1 μM propranolol (group 1, filled symbols, n = 6). (b) Tissues incubated with propranolol (group 2, open symbols, n = 7). * P < 0.05, *** P < 0.001 compared to saline. +++ P < 0.001 compared to atropine. # P < 0.05, ## P < 0.01, ### P < 0.001 compared to high extract concentration (10 mg/mL). EC₅₀ values increased in the presence of high extract concentrations and atropine in both groups.

Figure 3

The values of (CR-1) in the presence of three concentrations from F. asafoetida extract, saline and 10 nM atropine. (a) Tissues incubated with 1 μM chlorpheniramine and 1 μM propranolol (group 1, filled symbols, n=6). (b) Tissues incubated with propranolol (group 2, open symbols, n = 7). + P < 0.05; +++ P < 0.001, compared to atropine. ## P < 0.01, ### P < 0.001, compared to high extract concentration (10 mg/mL).