An Experimental and Clinical Evaluation of Anti-Asthmatic Potentialities of Devadaru Compound (Dc)

A.       V. SEKHAR*, D. N. GANDHI**, N. MOHAN RAO**
AND U. D. RAWAL***
*Ayurvedic Medical College, Bidar - 585 403,
**National Institute of Occupational Health (ICMR),
Meghaninagar, Ahmedabad - 380 016
and
***Government Akhandanand Ayurvedic College,
Ahmedabad - 380 001
(Received on June, 15, 2001)

 

Abstract : Devadaru compound was shown to be beneficial in Tamak Swasa (Bronchial asthma).  Clinical findings revealed higher percentage of relief in cardinal and general symptoms with decrement in the pulse rate and in the respiration rate.  A significant linear increase in PEFR value was observed before and after treatment and an increase in FEV₁, values measured in Group I subjects.  There was relief of all symptoms in a significant number of patients.  Occurrence of relief was observed only among patients who suffer less than 10 years duration with Tamak Swasa and among those the frequency of attacks of Tamak Swasa was at fortnightly or monthly intervals.  Antispasmodic activity of Devadaru Compound (DC) on acetylcholine (Ach) induced contractions using rat ileum preparation was studied.  The results demonstrated that DC inhibits Ach induced contractions significantly and bears a dose-response relationship.  This suggests that DC has got anti-spasmodic activity and corroborates the clinical findings.  The clinical findings and experimental studies show that DC is of significant use in the treatment of Tamak Swasa (Bronchial Asthma) and superior to the standard and placebo therapy.

 

Key words: devadaru compound (DC), antispasmodic activity, acetylcholine (Ach), bronchial asthma

 

 

INTRODUCTION
METHODS
RESULTS
DISCUSSION
REFERENCES

 

INTRODUCTION

Inula racemosa (Pushkarmul), Terminalia belleria (Vibhitak) and Ocimum sanctum (Tulsi)-ayurvedic medicinal plants have been long before described to be useful agents in the treatment of various bronchial affections including bronchial asthma (1, 2). Singh and co-workers (3, 4) described the anti-asthmatic effects of these plants in experimental models of asthma.  Tamak Swasa (Bronchial Asthma) is a common disorder with varied clinical signs and symptoms.  Presently various anti-asthmatic drugs are the main stay in this condition, however, they may have limitations for a long term therapy (5, 6).  Hence, there is a need for drugs having good efficacy in asthmatic disorders.  A number of indigenous drug such as Abrak Bhasma, Tambra Bhasma, Swasa-Kutar Ras have been claimed to be effective in the treatment of asthma (7, 8) but their claims have not been largely substantiated in well controlled clinical trials.  The formulation under investigation Devadaru Compound (DC) is one such preparation which has been prepared on the basis of Indian Medicinal System of Ayurveda (9), which mentioned its use in the treatment of Swasa Roga.

 

The drug DC contains a number of ingredients out of them Devadaru has got expectorant and anti-spasmodic activity on the bronchial muscles in Guinea pigs (10), anti-spasmodic activity of Katphal in isolated guinea pig ileum (11) and Pushkarmool contains anti-spasmodic, anti-histaminic and improvement in pulmonary function and general health in chronic spasmodic bronchitis 12).  The recent clinical study of DC indicated its beneficial effect in Tamak Swasa patients (13).  Considering the long term use of these agents in Indian traditional medicine, it was thought worthwhile to conduct a preliminary, clinical trial in patients of known bronchial asthma as well as in experimental studies using isolated rat ileum smooth muscle preparation.
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METHODS

Before conducting this experiment, the details of composition of Devadaru Compound (DC) and their Latin names, the beneficial effects observed in the cardinal symptoms in Tamak Swasa by DC therapy were obtained.  The present study was conducted in clinically proved 60 cases of' uncomplicated bronchial asthma selected from indoor and out door patients of Government Akhanand Ayurvedic College & Hospital, Ahmedabad (Gujarat).  Patients of either sex were taken with duration of their illness ranged from 6 months to 24 months.  Devadaru Compound (DC) is administered to Tamak Swasa patients 3 Tab/TDS (each tablets 250 mg) for the duration of six weeks.  Before administering the drug, the detailed personal and occupational history, clinical signs and symptoms, Nidana, Proorva Rupa, precipitating factors, past illness, family history, Dasavidha pariksha, Agni assessment, sortas examination, blood pressure, pulse rate, respiratory rate, hematological examination, urine, stool, sputum examination, X-rays findings, measurement of peak expiratory flow rate (PEFR) by using Wright's peak flow meter, chest expansion, breath holding time, spirometric values by Vitallograph were evaluated.  The scoring was done for all the above mentioned investigations weekly for a duration of six weeks.  These measurements were done at a fixed time of the day throughout the, study to avoid diurnal variations of the measured parameters.

This clinical study was conducted in dividing the Tamak Swasa patients in to three groups.

Group-I:           Twenty patients receiving trial drug -Devadaru Compound 3 Tab/TDS (each tablet-250 mg).

 

Group-II:          Twenty patients receiving standard drug- Swasa Kutar Rasa (250 mg/TDS) and Bharangyadi Kwath (20 ml/TDS).

 

Group-III:Twenty patients receiving Placebo Therapy- 2 capsule/ TDS (each capsule 250 mg roasted wheat powder).  In all these groups the disappearance of symptoms and improvement in PEFR value was considered as positive result.

In experimental study, albino rats (Wistar Strain) weighing 250 to 300 gm were used.  These animals were killed by a blow on the head and were dissected.  Ileum was taken out immediately and placed in a petridish containing Tyrode physiological salt solution (PSS).  During the experiment, the organ bath was continuously bubbled with 95% oxygen and 5% carbon dioxide, maintained at 37°C.  The preparation was allowed to stabilize for 30 minutes.  The contractions were recorded on a smoked drum with an isotonic frontal writing lever, which was under 500 mg tension and gave ten fold magnification.

The effect of DC on rat ileum was based on the concentration-response curve of acetylcholine (Ach)   (9.13 x 10^-8M  to 1.65 x 10^-6M). Following this, the preparation was exposed to DC for 30 minutes and dose response curve of Ach at 333 mg, 666 mg and 999 mg was carried out.  The drug DC was added in the organ bath and allowed to remain in contact for 30 minutes before eliciting contraction with Ach.  The drug was added in the dose of 10 mg, 20 mg and 30 mg in bath of 30 ml capacity, which becomes 333 mg, 666 mg and 999 mg dose respectively.  In this experiment whether there is any dose-response dependent on the degree of inhibition of' contractions was there or not, was assessed.
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RESULTS

In Table I, the composition of the Ayurvedic formulation of 250mg tablet of Devadaru Compound (DC) is given.  In the preparation of this compound, one part of' course powder of each mentioned ingredient of the drug where added to sixteen parts of water and boil till water was reduced to one-fourth part.  This decoction was further boiled until it was converted in to thick consistent form.  From this substance, each tablet 250 mg was prepared.  Table II showed that 20 (33.3%) had Tamak Swasa from more than 15 years; 14 (22.3%) from 11-15 years; 8 (13.3%) from 7-10 years; 5 (8.3%) from 4-6 years and 7 (11.7%) from 1-3 years.  The remaining 6 (10%) are suffering from Tamak Swasa for only one year.  This suggested that the majority of them were chronic patients.  With regards to the frequency of attack of Tamak Swasa as shown in Table III, the patients reported at no specific time in 26 (43.3%); weekly attack in 14 (23.3%); daily 10 (16.7%); monthly among 6 (10%) and fortnightly in 4 (6.7%) patients.

 

Table I click to view full image

Table I: Composition of Ayurvedic formulation of 250mg tablet devadaru compound (DC).

 

Table II click to view full image

Table II: Chronicity of Tamak Swasa among 60 patients.

 

 

Table III click to view full image

Table III: Frequency of attacks of Tamak Swasa among 60 patients

 

The occupational history of these patients presented in the Table IV, reveals that majority of them 26 (43.3%) are textile mill workers.  Out of 30 patients, 23 patients are beedi smokers and 7 are cigarette smokers.  In beedi and cigarette smokers, the percentage of patients that smoke more than 20/day were found more.  The smoking Index (S.I.b and S.I.c) as calculated (number per day X duration in years) is categorized as mild, moderate and heavy in Table V. All patients belong to the heavy category of smoking index.  This shows that they are chronic smokers.

 

Table IV click to view full image

Table IV: Occupation of 60 patients of Tamak Swasa.

 

Table V click to view full image

Table V: Smoking index.

 

Relief observed in cardinal symptoms occurred to scoring pattern for the three different groups of patients.  The average scoring percentage is very much higher in Group-I Patients (50.1%) as compared to Group-II (30.6%) and Group-III (11.1%). This definitely demonstrated that the present drug produced better relief in various cardinal symptoms in comparison to standard and placebo (Table VI).

 

Table VI click to view full image

Table VI: Comparison of relief observed in cardinal symptoms of 60 patients of Tamak Swasa according to scoring pattern.

 

 

The base line PEFR value i.e. the values obtained before treatment was compared with the normal values and their percentage of predicted values were presented in Table VII.  A significant decrease in PEFR values in both male and female Tamak Swasa patients in all the three groups were observed; this was also reflected in the wide deviation of percentage predicted values in Tamak Swasa patients.  This suggests that there is ventilatory function impairment in Tamak Swasa patients contributed by the relief from obstruction in the airways.

 

Table VII click to view full image

Table VII: Peak expiratory flow rate (PEFR) values in normal and Tamak Swasa patients.

 

 

The spirometric findings before and after treatment showed 0.23 Lit (10%) improvement in FVC, 0.35 Lit (23.6%) increase FEV₁ values, 9.5 Lit (14.8%) improvement in FEV₁% after treatment compared to before treatment.  All these values were significant and again demonstrated that the improvement in FEV₁ was better than FVC (Table VIII).

 

Table VIII click to view full image

Table VIII: Spirometric findings before and after treatment in Tamak Swasa (Mean ± S.D.).

 

 

A comparison in relief from Tamak Swasa with that of no relief-mild, moderate and marked relief was made.  In Group-I patient showed significant results in relieving the disease in comparison to placebo treatment.  In Group-II patients no significant results were occurred, but the percentage of subjects that got relief from the disease is definitely more in Group-I than Group-II.  Similar comparison made between Group-III and Group-II revealed no significant changes.  However, the percentage of patients where complete relief was exhibited was more in Group-II than Group-III (Table IX).  These results provide conclusive evidence that DC Compound is of significant value in causing complete relief from Tamak Swasa.

 

Table IX click to view full image

Table IX: A comparison of drug effect in relieving symptoms of Tamak Swasa.

 

 

The effect of DC on percentage of maximum contraction on isolated rat ileum preparation was assessed and presented in Table X. In this, the contraction induced by Ach is taken 100%.  When DC at different doses was compared with Ach control, there was linear significant decrease in contractions.  This clearly suggests that a dose response relationship exists in the inhibition of Ach-induced rat ileum contraction (Fig. 1) which suggests that DC has got anti-spasmodic activity.

 

Table X click to view full image

Table X: Effect of Devadaru compound (DC) on percentage of maximum contraction of acetylcholine on isolated rat ileum preparation (Mean ± S.D.).

 

Fig. 1 click to view full image

Fig. 1: Dose response of Devadaru compound against acetylcholine induced contraction of rat ileum.

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DISCUSSION

Recently a number of ayurvedic drugs has been screened for their physiological and pharmacological activity.  The clinical use of Tylophora Asthmatica (TA) in the treatment of bronchial asthma is based on its use in indigenous medicine (12) and its reported anti-spasmodic activity on isolated tissue (13).  Data showed that 20 (33.3%) had Tamak Swasa from more than 15 years, 14 (22.3%) from 11-15 years, 8 (13.3%) from 7-10 years, 5 (8.3%) from 4-6 years and 7 (11.7%) from 1-3 years.  The remaining 6 (10%) are suffering from Tamak Swasa for only one year.  This suggested that the majority of them were chronic patients.  With regard to the frequency of attack of Tamak Swasa, patients reported at different intervals, i.e. no specific time in (43.3%), daily (16.7%), weekly attack in (23.3%), fortnightly in (6.7%) and monthly among (10%).  The occupational history of these patients reveals that majority of them 26 (43.3%) were textile mill workers.  Since smoking play an important role in asthma, out of 30 patients, 23 patients were beedi smokers and 7 were cigarettes smokers.  In both these categories, the percentage of patients who smoke more than 20 beedis per day were found more.  All patients were found to be from heavy category of smoking index and they were chronic smokers.

Relief in cardinal symptoms occurred to scoring pattern for the three different groups of patients.  The average scoring percentage is very much higher in Group I (50.1%) when compared to Group-II (30.3%) and Group-III (11.1%). This definitely demonstrated that the present drug produced better relief in various cardinal symptoms in comparison to standard and placebo.  A significant decrease in PEFR values in both male and female Tamak Swasa patients in all the three groups was observed.  This was also reflected in the wide deviation of percentage predicted values in Tamak Swasa patients.  This suggests that there was ventilatory function impairment in Tamak Swasa patients contributed by the relief from obstruction in the airways. The spirometric findings before and after treatment showed 0.23 Lit (10%) improvement in FVC, 0.35 Lit (23.6%) increase in FEV₁ values, 9.5 Lit (14.8%) improvement in FEV₁% after treatment compared to before treatment.  All these values were significant and again demonstrated that the improvement in FEV₁ was better than FVC.  These results shows that Devadaru Compound is of significant use in complete relief from Tamak Swasa.

The clinical use of Tylophora Asthmatica (TA) in the treatment of bronchial asthma is based on its use in indigenous medicine (12) and its reported anti-spasmodic activity in isolated tissue (13) of DC.  In experimental study, the anti-spasmodic activity of DC against the contractions induced by Ach suggested that anti-cholinergic actions are involved.  In bronchial asthma, cholinergic mechanisms play an important role for induction of bronchoconstrictions (14).  This indicate that bronchodilatation produced by DC in Tamak Swasa might be due to its anti-cholinergic action and the drug review also showed that some of the ingredients of DC has got anti-spasmodic activity (10, 11).  Present experimental study on isolated rat ileum preparation as well as clinical findings such as higher percentage of relief in cardinal and general symptoms, a significant decrease in PEFR values and the spirometric findings revealed that DC has got anti-spasmodic activity and it can be very useful drug for the treatment of bronchial asthma.

REFERENCES  

1.          Kirtikar PK, Basu BD.  Indian Medicinal Plants 1944; 1-10.

2.          Dixit KS, Singh SP, Sinha KN, Singh N, Kohli RP. Inula Racemosa (Pushkarmul), Terminalia Bellerica (Vibhitak) and Ocimum Sanctum (Tulsi) - A preliminary clinical trial in Asthmatic patients.  Proceeding of the International Seminar on Clinical Pharmacology in Developing Countries, Lucknow (1) 13 and 14th January, 1986.  Vol. 11.  Ed., by R.C. S,ixena, T.K. Dixit. pp.22-27.

3.          Singh N, Nath R, Tripathi SN, Sliat-ma VK, Kohli RP. Pharmacological studies on India receinosa Pushkarniul.  Res Ind Med 1976: III: 25-32.

4.          Singh N, Nath R, Gupta ML, Kohli RP.  An experimental evaluation of anti-asthmatic potentialities of Inula recemosa (Pushkarmul). Quart J Crude Drug Res 1980; 18: 86-96.

5.          Cushley MJ, Holgate ST.  Bronchiaodilator actions of xanthine derivatives administered by inhalation in Asthma.  Thorax 1985; 40: 176-179.

6.          Smyllie HC, Connolly CK.  Incidence of serious complications of corticosteroids therapy in respiratory diseases - A retrospective Survey of Patients in Brompton Hospital.  Thorax 1968; 23: 571-581.

7.          Jindal MN, Patel VA, Pandya KH, Doctor PB.  Inquiry into anti-asthmatic properties of some indigenous drugs. Nagarjun 1966; 3: 18-25.

8.          Purrshottini Acharyulu G. Effect of Apainargi (Achyranthes Aspera) antara Dhooma Bhasma on cases of Tamak Swasa. Ind J Pharm Sci 1982; 44: 131-135.

9.          Yoga Ratnakar-Communications in Hindi Chaukhaniba Sanskrit series, Varanasi, 1991.

10.      Singh N, Nath R, Gupta ML, Kohli RP.  A clinical assessment of Inula Racemosa in cases of Bronchial asthma and chronic spasmodic bronchitis (Abstract)-Paper presented at Asian Conference of Traditional Medicine, Bombay. (Abst No. C-24) 1983, March 6-9.

11.      Sekhar AV.  Clinical study of Devadaru compound in Tamak Swasa. - M.D. Thesis, Gujarat Ayurvedic University, Jamnagai- 1991.

12.      Shivapuri DN, Menon MPS, Ilrak.,ish DJ.  Preliminary studies of Tylophora Indica in the treatment of asthma and allergic rhinities.  J Assoc Physicians of India 1968; 16: 9 15.

13.      Harnath PSK, Shyamalakumari S. Experimental study on mode of action of Tylophora Asthmatica in bronchial asthma.  Ind J Med Res 1975; 63(5): 661-670.

14.      Clarke TJH.  Godfrey (Ed) Asthma. 2nd Edition, Chapman Hall, London 1983.

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