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IOSR Journal of Pharmacy (IOSRPHR)
ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 81-83
www.iosrphr.org

Broncho-relaxant activity of nigella sativa versus anthemis nobilis in
    chronic bronchial asthma; a comparative study of efficacy
     Faruk H Al-Jawad1, Rafi AM Al-Razzuqi1, Hashim M Hashim2, Ahmed H
                                   Ismael3
            1
                Departments of Pharmacology and Therapeutics, Al-Yarmouk University, Baghdad, Iraq.
                           2
                             Department of Medicine, Al-Nahrain University, Baghdad, Iraq.
                3
                  Department of pharmacology and Therapeutics, Al-Nahrain University, Baghdad, Iraq.


Abstract––Background: Bronchial asthma (BA) is a clinical syndrome with variable causes. It
characterizes by episodes of broncho-constriction which leads to shortness of breath. In traditional
medicine, some medicinal plants have been used to cure the asthmatic symptoms.
Objective: To evaluate the broncho-relaxant activity of Anthemis nobilis (Chamomile) and Nigella sativa
(Black seeds) then to choose the better.
Methods: An open study was conducted on 54 patients with chronic bronchial asthma. After clinical
assessment, estimation of pulmonary function tests and serum electrolytes: calcium, magnesium, potassium
and selenium were done before and after the study. Anthemis nobilis was given to 18 patients and nigella
sativa to another 18 patients for 21 days.
Results: The comparative study showed that the tested plants have significant elevation in the values of
forced expiratory volume in first second (FEV1%) and forced volume capacity (FVC) with marked
reduction in asthmatic attacks, but showed better symptomatic improvement with black seeds as compared
to chamomile. Conclusion: The results of all parameters of efficacy prove the superiority of nigella sativa
over anthemis nobilis for CBA.

Keywords––Black seeds, chamomile, magnesium, pulmonary function tests

                                           I.        INTRODUCTION
          Bronchial asthma is an inflammatory syndrome characterized by paroxysmal or recurrent episodes of
bronchial obstruction causing shortness of breath, cough, chest tightness, wheezing and rapid respiratory rate. [1]
Many factors are involved like air pollutants, mold species[2], emotional factors [2], obesity [3] and some
medications as β- blockers and non-steroidal anti-inflammatory drugs.[4] Although the pathogenesis of chronic
bronchial asthma (CBA) is complex, reactive oxygen species (ROS) have been shown to be directly associated
with asthma pathogenesis and an oxidant-antioxidant imbalance.[5]ROS evoke bronchial hyperactivity through
releasing both histamine from the mast cells and mucus from airway epithelial cells .[6]
N. sativa (black cumin) is an annual plant, contains numerous black seeds which were used in folk medicine for
the treatment of asthma, diarrhea, and dyslipidaemia. [7]Black seed contains[8]: β-sitosterol, nigelline, nigellone (has
anti-histamine activity), and thymoquinone (the major component that blocks cancer cell growth). A. nobilis
(chamomile) is a fragrant, perennial herb, with daisy-like white flowers, found around gardens and cultured
grounds.[9] In traditional medicine, it was extensively used as perfumes and for treatment of indigestion. A. nobilis
contains[10]: fragranced essential oil (the source of its activity), Anthemene, Antheminic acid (has anti-
inflammatory property), flavonoids, tannin, and resin.
          The relative absence of data in this domain is an incentive to evaluate the potential smooth muscle
relaxation effect of these medicinal plants in CBA.

                                  II.      SUBJECTS AND METHODS
         Plant material:-The test medicinal plants were purchased from a well-known bureau for herbs (Al-
Medina) in Baghdad and were identified and authenticated by Iraqi National center for Herbs. The chamomile and
black seeds were cleaned to remove the debris, dried then were stored in airtight container at room temperature.
On use, chamomile and black seed were boiled and immediately used by inhalation for 5-10 minutes using vapor
machine.




                                                         81
Broncho-relaxant activity of nigella sativa versus….

         Subjects:-Fifty four patients of CBA, 33 males and 21 females, aged from 22-56 years (mean 38.16
± 1.9 SD), participated in this randomized, open, and comparative clinical study. The participants were recruited
from the outpatient clinic of Department of Medicine of Al-Kadhemiya Teaching Hospital from August 2009 to
June 2010 excluding pregnant women, cigarette smokers, alcohol consumers and any disease other than chronic
asthma. The trial was explained to all subjects and their consent was obtained.
         Experimental protocol:-Approval to conduct this study was granted by the ethical committee in College
of Medicine/Al-Nahrain University (Registration No.HEC/42/09/CMANU). The patients were advised to stop
medication and prevent any exercise or exposure to any allergen at least 24hrs prior to test. They were randomly
allocated to three groups of 18 patients each and received daily one dose of the following for three weeks
Group I                -served as positive control – received 0.15 mg/kg/day of
                         prednisolone as a single dose.
Group II                                                 - received 100 mg/kg of chamomile by inhalation
Group III              - received 100 mg/kg of black seeds by inhalation

          Biochemical estimations:-Blood samples were taken before and at the end of experiment from all the
participants. Serum magnesium (Mg+2) and serum selenium (Se+2) were estimated by using GFA-4B graphite tube
with auto sample absorption photometer. Serum calcium (Ca +2) and serum potassium (K+) were measured by
using flame emission spectrophotometer.
          Functional tests:-Pulmonary function tests (forced volume capacity FVC and forced expiratory volume
in first second FEV1%) were performed using a computerized spirometer (Autospiron chest corporation Tokyo-
Japan).
          Statistical analysis:-All the results were expressed as mean ± standard error mean (SEM). The
difference among means has been analyzed by student's t test. A probability value of P<0.05 was considered to be
statistically significant.

                                                       III.       RESULTS
         The results revealed significant elevation in FEV1% of chamomile and black seeds as (79.33 ± 4.40 vs
77.41 ± 3.30, and 74.91 ± 5.28 vs 53.80 ± 7.49) respectively. Also, significant elevation was showed in FVC/L of
chamomile and black seeds in addition to prednisolone as (2.75 ± 0.32 vs 2.38 ± 0.27, 3.54 ± 0.05 vs 1.36 ± 0.12,
and 2.25 ± 0.16 vs 1.05± 0.15) respectively, but with superiority to black seeds (Table 1). Elevations in serum
electrolyte levels were also significantly confirmed the above obtained results (Table 2).

                                                    IV.        DISCUSSION
          Bronchial asthma is an inflammatory condition with episodes of bronchial muscle contraction resulted
from releasing of leukotrienes (LTs). Prednisolone which is used in group I, produces bronchial muscle relaxation
indirectly through inhibiting the release of LTs and reversing mucosal edema.[11]In group II with chamomile,
significant is poor when given by inhalation. No real improvement occurs in asthmatic symptoms in spite of its
relaxant effect on rabbit tracheal muscle contraction when given by inhalation. [12]In group III with black seeds,
significant relaxing effect occurred when given by inhalation. This action is related to its active
constituent''nigellone'' that prevents histamine release from mast cells, [13] besides its well known antioxidant
activity.[14]Changes of serum electrolytes levels in asthmatic patients showed positive correlation between serum
Se+2 and Mg+2 levels and each FEV1% and FVC. Our results agreed with a study showed that if serum Se+2 and
Mg+2 levels decreased the possible risk of asthma would be increase due to reduction in glutathione peroxide and
antioxidant activity and vice versa. [15] Most of the asthmatic patients recorded low levels of serum Ca +2 before
treatment and this is due to increased intracellular Ca +2 in leukocytes that directly correlated with severity of
asthma.[16]

REFERENCES
  [1].   Drazen JM. Respiratory disease. In Cecil. Textbook of medicine, 21st edition; WB Sanders Comp; 2004. pp.504-8.
  [2].   Homer A., Bertream G. Katzung: drugs used in asthma ; Basic and clinical pharmacology. 10th edition: Mcgraw Hill; 2010. pp
         319.
  [3].   Guerra S, Sherrill DL, Bobadilla A. and Martinez F. The relation of body mass index to asthma, chronic bronchitis. Chest 2002;122
         (4) :1256-63.
  [4].   Szczeklik A, Stevenson DD. Aspirin-induced asthma advances in pathogenesis, diagnosis and management. Allergy din Immunol.
         2003; 111: 913-21.
  [5].   Repine JE, Bast A, Lankhorst I. oxidative stress in chronic obstructive stress in chronic obstructive pulmonary disease, oxidative
         stress study group. Am J Respir Orit Care Med. 1997; 156: 341-57.
  [6].   Cortigo J,Marti-Cabrera M, Dela Asuncion JG, Pallardo FV, Estero A. et al . Contraction of human airways by oxidative stress
         protection by N-acetylcysteine. Free Radical Biol. Med. 1999; 27: 392-400. Kokate CK, Purohit AP, Gokhale SB. Text book of
         Pharmacognosy, 4th ed. Nirali Prakashnan; 2006. pp. 593-7. Ali BH, Blundeu G. pharmacological & toxicological properties of
         Nigella sativa. Phytother Res 2003;17: 299-305.


                                                                 82
Broncho-relaxant activity of nigella sativa versus….

  [7].    Gualtiero E and Simonetti J. In Stanley Schuler. Simon & Schuster's Guide to Herbs and Spices, 2nd ed; Simon & Schuster; 1990.
          pp. 261-78.
  [8].    Charles D F. Phillips. Materia Medica And Therapeutics- Vegetable Kingdom, 3rd ed; Medical economic comp; New Jersey; 2001.
          pp. 57-82
  [9].    Kulkarni RR, Patki PS, Jog VP, and et al. Treatment of osteoarthritis with a prednisolone formulations: a double-blind, placebo-
          controlled, cross-over study. J Ethnopharm 1991;33:91-5.
  [10].   Al- Jawad FH and Al-Jumaily W. The relaxant effect of some drugs and aqueous extract of medicinal plants on bronchial smooth
          muscle in rabbits . Tikrit J of Pharma Sciences 2005;1:58-63.
  [11].   Mansour M and Tornhamre S. Inhibition of 5-lipoxygenease and Leukotriene C4 synthase in human blood cells by nigellone. J
          Enzyme Inhib Med Chem 2004;19:431-6.
  [12].   Al-Jawad FH, Al-Atabee HG, and Salih A. useful uses of antioxidant drugs in bronchial asthma, Pak J Physiol 2010;6(2):18-21.
  [13].   Al-amoudi OSB: hypomagnesemia and reduced selenium are chronic stable asthmatic prevalence. Correlation with severity and
          hospitalization. Eur Res 2000;16: 427-31.
  [14].   Chhabra SK, Khanduja A, Jain D. increased intracellular Ca+2 and decrease activities of Na, K ATPase and Ca ATPase in asthma.
          Clin Sci 1999; 97:595-601

Table 1: The effect of Nigella sativa, Anthemis nobilis and Prednisolone on pulmonary function parameters
in chronic asthmatic patients
Groups                                    FEV1%                          FVC / L

Before usage         After usage            Before usage             After usage

I (prednisolone/ positive control)        72.75± 0.09           78.63±3.34*           1.05 ± 0.15              2.25 ± 0.16*

II (Anthemis nobilis- received)           77.41 ± 3.30          79.33 ± 4.40           2.38 ± 0.27             2.75 ± 0.32

III (Nigella sativa-received)              53.80 ± 7.49         74.91 ± 5.28*          1.36 ± 0.12             3.54 ± 0.05*

Values are mean ± SEM, n=18 patients for each group, *P<0.05 compared with before treatment


Table 2: The effect of Nigella sativa, Anthemis nobilis and Prednisolone on serum electrolytes levels in
chronic asthmatic patients
S. Mg+2               S. Se+2             S. Ca+2            S. K+
(mmol/L)               (μg/L)             (mmol/L)          (mmol/L)

Material use before after before after before after before After
I (prednisolone) 0.73±0.05 0.81± 0.15* 44.62±6.35 49.17±4.96* 1.97± 0.07                                    2.10±0.10         3.5± 0.24
3.50 ±0.08

II (Anthemis         0.78±0.02        0.80±0.02         54.66±1.32         60.05±3.16* 2.06±0.06             2.17±0.07       3.94±0.05
3.61±0.09
nobilis)
III (Nigella          0.90±0.07       1.08±0.02*         28.03±7.01       42.10±9.18* 1.97±0.03              2.10±0.04* 3.00±0.18
3.70±0.06*
sativa)

Values are mean ± SEM, n=18 patients for each group, *P<0.05 compared with before treatment. S. Mg+2 =serum
magnesium, S. Se+2 = serum selenium, S. Ca+2 = serum calcium, S. K+ = serum potassium




                                                                 83

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  • 1. IOSR Journal of Pharmacy (IOSRPHR) ISSN: 2250-3013, Vol. 2, Issue 4 (July2012), PP 81-83 www.iosrphr.org Broncho-relaxant activity of nigella sativa versus anthemis nobilis in chronic bronchial asthma; a comparative study of efficacy Faruk H Al-Jawad1, Rafi AM Al-Razzuqi1, Hashim M Hashim2, Ahmed H Ismael3 1 Departments of Pharmacology and Therapeutics, Al-Yarmouk University, Baghdad, Iraq. 2 Department of Medicine, Al-Nahrain University, Baghdad, Iraq. 3 Department of pharmacology and Therapeutics, Al-Nahrain University, Baghdad, Iraq. Abstract––Background: Bronchial asthma (BA) is a clinical syndrome with variable causes. It characterizes by episodes of broncho-constriction which leads to shortness of breath. In traditional medicine, some medicinal plants have been used to cure the asthmatic symptoms. Objective: To evaluate the broncho-relaxant activity of Anthemis nobilis (Chamomile) and Nigella sativa (Black seeds) then to choose the better. Methods: An open study was conducted on 54 patients with chronic bronchial asthma. After clinical assessment, estimation of pulmonary function tests and serum electrolytes: calcium, magnesium, potassium and selenium were done before and after the study. Anthemis nobilis was given to 18 patients and nigella sativa to another 18 patients for 21 days. Results: The comparative study showed that the tested plants have significant elevation in the values of forced expiratory volume in first second (FEV1%) and forced volume capacity (FVC) with marked reduction in asthmatic attacks, but showed better symptomatic improvement with black seeds as compared to chamomile. Conclusion: The results of all parameters of efficacy prove the superiority of nigella sativa over anthemis nobilis for CBA. Keywords––Black seeds, chamomile, magnesium, pulmonary function tests I. INTRODUCTION Bronchial asthma is an inflammatory syndrome characterized by paroxysmal or recurrent episodes of bronchial obstruction causing shortness of breath, cough, chest tightness, wheezing and rapid respiratory rate. [1] Many factors are involved like air pollutants, mold species[2], emotional factors [2], obesity [3] and some medications as β- blockers and non-steroidal anti-inflammatory drugs.[4] Although the pathogenesis of chronic bronchial asthma (CBA) is complex, reactive oxygen species (ROS) have been shown to be directly associated with asthma pathogenesis and an oxidant-antioxidant imbalance.[5]ROS evoke bronchial hyperactivity through releasing both histamine from the mast cells and mucus from airway epithelial cells .[6] N. sativa (black cumin) is an annual plant, contains numerous black seeds which were used in folk medicine for the treatment of asthma, diarrhea, and dyslipidaemia. [7]Black seed contains[8]: β-sitosterol, nigelline, nigellone (has anti-histamine activity), and thymoquinone (the major component that blocks cancer cell growth). A. nobilis (chamomile) is a fragrant, perennial herb, with daisy-like white flowers, found around gardens and cultured grounds.[9] In traditional medicine, it was extensively used as perfumes and for treatment of indigestion. A. nobilis contains[10]: fragranced essential oil (the source of its activity), Anthemene, Antheminic acid (has anti- inflammatory property), flavonoids, tannin, and resin. The relative absence of data in this domain is an incentive to evaluate the potential smooth muscle relaxation effect of these medicinal plants in CBA. II. SUBJECTS AND METHODS Plant material:-The test medicinal plants were purchased from a well-known bureau for herbs (Al- Medina) in Baghdad and were identified and authenticated by Iraqi National center for Herbs. The chamomile and black seeds were cleaned to remove the debris, dried then were stored in airtight container at room temperature. On use, chamomile and black seed were boiled and immediately used by inhalation for 5-10 minutes using vapor machine. 81
  • 2. Broncho-relaxant activity of nigella sativa versus…. Subjects:-Fifty four patients of CBA, 33 males and 21 females, aged from 22-56 years (mean 38.16 ± 1.9 SD), participated in this randomized, open, and comparative clinical study. The participants were recruited from the outpatient clinic of Department of Medicine of Al-Kadhemiya Teaching Hospital from August 2009 to June 2010 excluding pregnant women, cigarette smokers, alcohol consumers and any disease other than chronic asthma. The trial was explained to all subjects and their consent was obtained. Experimental protocol:-Approval to conduct this study was granted by the ethical committee in College of Medicine/Al-Nahrain University (Registration No.HEC/42/09/CMANU). The patients were advised to stop medication and prevent any exercise or exposure to any allergen at least 24hrs prior to test. They were randomly allocated to three groups of 18 patients each and received daily one dose of the following for three weeks Group I -served as positive control – received 0.15 mg/kg/day of prednisolone as a single dose. Group II - received 100 mg/kg of chamomile by inhalation Group III - received 100 mg/kg of black seeds by inhalation Biochemical estimations:-Blood samples were taken before and at the end of experiment from all the participants. Serum magnesium (Mg+2) and serum selenium (Se+2) were estimated by using GFA-4B graphite tube with auto sample absorption photometer. Serum calcium (Ca +2) and serum potassium (K+) were measured by using flame emission spectrophotometer. Functional tests:-Pulmonary function tests (forced volume capacity FVC and forced expiratory volume in first second FEV1%) were performed using a computerized spirometer (Autospiron chest corporation Tokyo- Japan). Statistical analysis:-All the results were expressed as mean ± standard error mean (SEM). The difference among means has been analyzed by student's t test. A probability value of P<0.05 was considered to be statistically significant. III. RESULTS The results revealed significant elevation in FEV1% of chamomile and black seeds as (79.33 ± 4.40 vs 77.41 ± 3.30, and 74.91 ± 5.28 vs 53.80 ± 7.49) respectively. Also, significant elevation was showed in FVC/L of chamomile and black seeds in addition to prednisolone as (2.75 ± 0.32 vs 2.38 ± 0.27, 3.54 ± 0.05 vs 1.36 ± 0.12, and 2.25 ± 0.16 vs 1.05± 0.15) respectively, but with superiority to black seeds (Table 1). Elevations in serum electrolyte levels were also significantly confirmed the above obtained results (Table 2). IV. DISCUSSION Bronchial asthma is an inflammatory condition with episodes of bronchial muscle contraction resulted from releasing of leukotrienes (LTs). Prednisolone which is used in group I, produces bronchial muscle relaxation indirectly through inhibiting the release of LTs and reversing mucosal edema.[11]In group II with chamomile, significant is poor when given by inhalation. No real improvement occurs in asthmatic symptoms in spite of its relaxant effect on rabbit tracheal muscle contraction when given by inhalation. [12]In group III with black seeds, significant relaxing effect occurred when given by inhalation. This action is related to its active constituent''nigellone'' that prevents histamine release from mast cells, [13] besides its well known antioxidant activity.[14]Changes of serum electrolytes levels in asthmatic patients showed positive correlation between serum Se+2 and Mg+2 levels and each FEV1% and FVC. Our results agreed with a study showed that if serum Se+2 and Mg+2 levels decreased the possible risk of asthma would be increase due to reduction in glutathione peroxide and antioxidant activity and vice versa. [15] Most of the asthmatic patients recorded low levels of serum Ca +2 before treatment and this is due to increased intracellular Ca +2 in leukocytes that directly correlated with severity of asthma.[16] REFERENCES [1]. Drazen JM. Respiratory disease. In Cecil. Textbook of medicine, 21st edition; WB Sanders Comp; 2004. pp.504-8. [2]. Homer A., Bertream G. Katzung: drugs used in asthma ; Basic and clinical pharmacology. 10th edition: Mcgraw Hill; 2010. pp 319. [3]. Guerra S, Sherrill DL, Bobadilla A. and Martinez F. The relation of body mass index to asthma, chronic bronchitis. Chest 2002;122 (4) :1256-63. [4]. Szczeklik A, Stevenson DD. Aspirin-induced asthma advances in pathogenesis, diagnosis and management. Allergy din Immunol. 2003; 111: 913-21. [5]. Repine JE, Bast A, Lankhorst I. oxidative stress in chronic obstructive stress in chronic obstructive pulmonary disease, oxidative stress study group. Am J Respir Orit Care Med. 1997; 156: 341-57. [6]. Cortigo J,Marti-Cabrera M, Dela Asuncion JG, Pallardo FV, Estero A. et al . Contraction of human airways by oxidative stress protection by N-acetylcysteine. Free Radical Biol. Med. 1999; 27: 392-400. Kokate CK, Purohit AP, Gokhale SB. Text book of Pharmacognosy, 4th ed. Nirali Prakashnan; 2006. pp. 593-7. Ali BH, Blundeu G. pharmacological & toxicological properties of Nigella sativa. Phytother Res 2003;17: 299-305. 82
  • 3. Broncho-relaxant activity of nigella sativa versus…. [7]. Gualtiero E and Simonetti J. In Stanley Schuler. Simon & Schuster's Guide to Herbs and Spices, 2nd ed; Simon & Schuster; 1990. pp. 261-78. [8]. Charles D F. Phillips. Materia Medica And Therapeutics- Vegetable Kingdom, 3rd ed; Medical economic comp; New Jersey; 2001. pp. 57-82 [9]. Kulkarni RR, Patki PS, Jog VP, and et al. Treatment of osteoarthritis with a prednisolone formulations: a double-blind, placebo- controlled, cross-over study. J Ethnopharm 1991;33:91-5. [10]. Al- Jawad FH and Al-Jumaily W. The relaxant effect of some drugs and aqueous extract of medicinal plants on bronchial smooth muscle in rabbits . Tikrit J of Pharma Sciences 2005;1:58-63. [11]. Mansour M and Tornhamre S. Inhibition of 5-lipoxygenease and Leukotriene C4 synthase in human blood cells by nigellone. J Enzyme Inhib Med Chem 2004;19:431-6. [12]. Al-Jawad FH, Al-Atabee HG, and Salih A. useful uses of antioxidant drugs in bronchial asthma, Pak J Physiol 2010;6(2):18-21. [13]. Al-amoudi OSB: hypomagnesemia and reduced selenium are chronic stable asthmatic prevalence. Correlation with severity and hospitalization. Eur Res 2000;16: 427-31. [14]. Chhabra SK, Khanduja A, Jain D. increased intracellular Ca+2 and decrease activities of Na, K ATPase and Ca ATPase in asthma. Clin Sci 1999; 97:595-601 Table 1: The effect of Nigella sativa, Anthemis nobilis and Prednisolone on pulmonary function parameters in chronic asthmatic patients Groups FEV1% FVC / L Before usage After usage Before usage After usage I (prednisolone/ positive control) 72.75± 0.09 78.63±3.34* 1.05 ± 0.15 2.25 ± 0.16* II (Anthemis nobilis- received) 77.41 ± 3.30 79.33 ± 4.40 2.38 ± 0.27 2.75 ± 0.32 III (Nigella sativa-received) 53.80 ± 7.49 74.91 ± 5.28* 1.36 ± 0.12 3.54 ± 0.05* Values are mean ± SEM, n=18 patients for each group, *P<0.05 compared with before treatment Table 2: The effect of Nigella sativa, Anthemis nobilis and Prednisolone on serum electrolytes levels in chronic asthmatic patients S. Mg+2 S. Se+2 S. Ca+2 S. K+ (mmol/L) (μg/L) (mmol/L) (mmol/L) Material use before after before after before after before After I (prednisolone) 0.73±0.05 0.81± 0.15* 44.62±6.35 49.17±4.96* 1.97± 0.07 2.10±0.10 3.5± 0.24 3.50 ±0.08 II (Anthemis 0.78±0.02 0.80±0.02 54.66±1.32 60.05±3.16* 2.06±0.06 2.17±0.07 3.94±0.05 3.61±0.09 nobilis) III (Nigella 0.90±0.07 1.08±0.02* 28.03±7.01 42.10±9.18* 1.97±0.03 2.10±0.04* 3.00±0.18 3.70±0.06* sativa) Values are mean ± SEM, n=18 patients for each group, *P<0.05 compared with before treatment. S. Mg+2 =serum magnesium, S. Se+2 = serum selenium, S. Ca+2 = serum calcium, S. K+ = serum potassium 83