The relaxant effect of some drugs and aqueous extract of medicinal plants on bionchial smooth muscle in rabbits

Histamine is a biogenic amine. that produces bronchospasm when it is used (I V) at.a.dose of 0.4 mg / kg in rabbits. It significantly reduced the ,e*- l"u"i. oi calcium (Ca) magnesium (Mg) and selenium (Se). (p < 0.05) . Forty rabbits were involved in this study. The serum ca, Mg and Se levels were measured before and after giving histamine and following [e administration oi aqueous extract of medicinal plants Cumi'um cyminum (cumin), Thymus vulgaris (thyme) and Anthemis nobilis (chamomile). ^ The serum Ca, Mg and Se levels were highly elevated after treatment with extract of cumin or chamomile in rabbits pretreated with histamine, the resurts of ca were changed lrom 8.34+ 0.40 and 8.79+ 0,27 to 33.41+ 0.50 and 97.62 ! 7.2 1tg /dl respectively while that of Mg from 20.20+ 0.37 and 19.47+ 0.31 to 74.97+ 0.ii and 89.14+ 1.41 pg /dl where as the serum level of Se was changed from 137.9g+ 0.4g and 145 36 + 0.66 ro 302.69 ! 0.6g and 245.4r,' 0.g1 pg /direspectivery .All these results were significant at p<0.05.


Introduction
Bronchial asthma is a syndrome with multiple causes that produces obstruction of the air ways as a result of contraction of bronchial smooth muscle, swelling of the bronchial mucusa and an increased quantity of tenacious sputum (l). The usual presenting complaints are of chest tightness, wheeze and dyspnea. The release of the mediators e.g. histamine, prostaglandin and leukotrienes lrom sensitized mast cells lead to prompt bronchocostriction (') . Thir study was carried out in vivo and in vitro to investigate the possible activity of aqueous extract of medicinal plants against bronchial asthma in order to develop effective, safe and less expensive therapy.

Materials and Methods
Sixty New Zealand healthy male rabbits were used in this study, weighing 1150-1250 gm. They were supplied by the animal house of medical college -Al-Nalrain University Each animal was kept in a separate cage which was provided with a wire mesh floor to avoid coprophagy.
They were fed with a standard diet (Oxoid) and were given water ad libitum ln vivo study Fofly rabbits had been used in this study; they were divided into 4 groups (10 animals for each group). All the drugs were administered at 09:00 a.m. Group I Normal rabbits were given 1ml normal saline (LV.) and considered as control group. Group 2 Rabbits were given histamine (BDH chemicals LTD U.K) 0.4 mg I kg ( i.v). Group 3 Rabbits were given histamine 0.4 mg / kg (I.V.) and then treated with 1.5 gm / kg aqueous extract of cumin orally after 30 minutes.
Group 4 Rabbits were given histamine 0.4 mg / kg (1.V.) and then treated with 1.5 gm / kg aqueous extract of chamomile orally after 30 minutes.
In vitro study Twenty rabbits had been used in this study. The animals were anesthetized by sodium pentobarbital (May and Baker LTD U.K) at a dose of 30 mg / kg (1.V.), they were killed by blow on the head. The trachea was exposed and Plants were collected, crushed and grinded. One gram was taken from each and steeped in 50 ml of distilled r.later by using of electric mixing machine for 15 minutes then the mixture was left for 24 hour. The solution was put in centrifuge of 6000 RPM for 30 minutes. The sediments was discarded and supematant was taken.This procedure was repeated three times by using the Seitz filter.
The relo-rant effect of some drugs and extrsct on bronclrisl smooth muscle in rabhits Blood samples were collected from the hearl of each rabbit before teatment and after giving histamine (I.V.) and administration of aqueous extract orally. Biochemical examination of serum Ca, Mg and Se levels was determined by using atomic absorption spectrophotometer. The obtained results were collected for analvsis and assessment.

Results
The results of this study revealed that the aqueous extract of cumin, thyme and chamomile produced relaxation of isolated tracheal rings at concentration of 0.4 mg / ml in trachea pretreated with 2x 10-3 M of Ach, Histamine or PGF2 o , these effects were compared with the action of Atropine ( 0.006) mg / ml and Diphenhydramine (0.1) mg / ml in trachea pretreated with 2 x 10-3 M Acetylcholine and Histamine respectively. The aqueous extract of cumin, chamomile were used at a dose of 1.5 gm/ kg (ln vivo) after histamine injection to protect the animals from the bronchospasm induced by histamine injection group (3,4 14' or may be related to phenolic constituents of thymol and carvacrol (6) . The relaxant action of chamomile was related to the presence of azulenes in chamomile that may interfere with action ol ACH. PGF:a and Hisramine (" . .lt may have an anti allergenic and anti-inflammatov properties (8) (e) The effect of cumin on bronchial muscle was related to phenolic constituent thymol which prevented the contracrion induced by Histamine ACH and PGFrotor . Patients with low level of serum Se may have a high risk of asthma (16,17) and this confirming the impoflant role of Mg and Se in bronchial asthma and the possibility of using medicinal plants in therapy. All these values were significant at P<0.05 Table (2) Serum Ca,Mg& Se levels(pg/dl)in rabbits given Histamine (0.amglkg)(I.V) and then treated orally by (l.5gm/kg)aqueous extract of