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ORIGINAL ARTICLE
Year : 2018  |  Volume : 11  |  Issue : 6  |  Page : 471-475  

Anti-tussive activity of Ashtangavaleha prepared by two different methods against sulphur dioxide induced cough in mice


1 Department of Rasashastra and Bhaishajya Kalpana, Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India
2 Department of Rasashastra and Bhaishajya Kalpana, All India Institute of Ayurveda, New Delhi, India
3 Department of Pharmacology, Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar, Gujarat, India

Date of Submission01-May-2018
Date of Acceptance24-Jul-2018
Date of Web Publication15-Nov-2018

Correspondence Address:
Harmeet B Kaur
Department of Rasashastra and Bhaishajya Kalpana Including Drug Research, Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar - 361 008, Gujarat
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/mjdrdypu.mjdrdypu_72_18

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  Abstract 


Context: Control of cough remains a major unmet medical need. There is a need to have safe and effective anti-tussive drug that can alleviate chronic cough without developing side effects. Ashtangavaleha is an effective compound formulation for combating the disease asthma. Aim: The present study was carried out to evaluate anti-tussive activity of two different samples of Ashtangavaleha prepared with classical (AC) and modified methods (AM) in sulfur dioxide (SO2)-induced cough in mice. Materials and Methods: Batches of both samples of Ashtangavaleha, namely AC and AM were prepared by following standard manufacturing procedures. Anti-tussive activity was carried out against SO2-induced cough reflex in mice. Swiss albino mice of either sex weighing 30 ± 5 g were selected and divided into four groups of six animals each. Test drugs were administered orally at a dose of 2.6 mg/kg. Recodex (Codeine phosphate [2 mg/ml] and chlorpheniramine maleate [0.8 mg/ml]) was used as standard drug. Results: Both test drugs showed significant (P < 0.001) anti-tussive activity against SO2-induced cough reflex. AC significantly reduced the number of cough reflexes by 40.18%, whereas AM reduced it to 34.97%. Conclusion: Both the trial drugs have highly significant anti-tussive effect in SO2-induced cough reflex comparable to the standard drug. Thus, both drugs AC and AM can be safely administered to alleviate cough.

Keywords: Antitussive, Ashtangavaleha, Avaleha, Ayurveda, cough


How to cite this article:
Kaur HB, Ruknuddin G, Nariya M, Patgiri B, Bedarkar P, Prajapati PK. Anti-tussive activity of Ashtangavaleha prepared by two different methods against sulphur dioxide induced cough in mice. Med J DY Patil Vidyapeeth 2018;11:471-5

How to cite this URL:
Kaur HB, Ruknuddin G, Nariya M, Patgiri B, Bedarkar P, Prajapati PK. Anti-tussive activity of Ashtangavaleha prepared by two different methods against sulphur dioxide induced cough in mice. Med J DY Patil Vidyapeeth [serial online] 2018 [cited 2018 Dec 19];11:471-5. Available from: http://www.mjdrdypv.org/text.asp?2018/11/6/471/245435




  Introduction Top


Cough is the most common complaint for which medical attention is sought and chronic cough can be both physically and mentally debilitating. There is currently no evidence supporting the use of antitussives in the treatment of resistant chronic cough. Cough is also a common symptom of diseases such as asthma, chronic obstructive pulmonary disease and lung cancer. Although the centrally acting opioids have remained the anti-tussive drug of choice for decades, they possess side effects such as sedation and gastrointestinal symptoms.[1] Therefore, there is a need to have safe and effective anti-tussive that can successfully alleviate chronic cough without developing side effects.

Looking into these inconveniences, ailing population is turning toward certain alternatives for satisfactory remedies. In such scenario, Ayurveda can offer a number of drugs through its armamentarium. Researches of recent past have proven anti-tussive activity of many herbs. In addition, certain compound herbal formulations of Ayurveda such as Vyaghri Haritaki Avaleha,[2]Vasavaleha,[3]Shirishavaleha,[4]Sitopaladi choorna,[5] and Shirisharista[6] are reported to possess significant anti-tussive activity. Ashtangavaleha is also a well-known poly herbal formulation for bronchial asthma (indicated for Shwasa and Kasa),[7] but evaluation of its anti-tussive activity has not been reported yet. Ashtangavaleha is a mixture of eight fine powdered drugs to be licked with honey. Avaleha (linctus) as dosage form is widely used and better acceptable in current days than intake of drug in the form of powder. Considering this, an attempt was made to convert powder form of Ashtangavaleha (classical method) to linctus form (modified method) and to compare them for anti-tussive activity.


  Materials and Methods Top


Test drugs

The trial drugs (AC and AM) were prepared in the departmental laboratory by following standard manufacturing procedures. The formulation composition is summarized in [Table 1] and [Table 2]. Genuine raw materials certified by the authority were procured from Pharmacy, Gujarat Ayurved University, Jamnagar. All ingredients were authenticated in the Pharmacognosy Lab at Institute for Post Graduate Teaching and Research in Ayurveda, Gujarat Ayurved University, Jamnagar. Fine powders of all nine Prakshepa Dravyas (adjuvants) were made by grinder and mixer.
Table 1: Formulation composition of Ashtangavaleha classical form

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Table 2: Formulation composition of Ashtangavaleha modified form

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Procurement of raw drugs

All the raw materials such as Katphala (Myrica esculenta Buch-Ham.), Pushkaramoola (Inula racemosa Hook. f.), Shringi (Pistacia integerrima Stew. Ex Brandis), Yavani (Trachyspermum ammi Linn.), Krishna jeeraka (Carum carvi Linn.), Shunthi (Zingiber officinale Roscoe.), Maricha (Piper nigrum Linn.), and Pippali (Piper longum Linn.) were procured from the Pharmacy and authenticated at Pharmacognosy Laboratory, Institute for Post Graduate Teaching and Research in Ayurveda (IPGT and RA), Gujarat Ayurved University, Jamnagar. After identification and authentication of the ingredients, voucher specimen of both the samples, namely Ashtangavaleha in powder form and linctus (Avaleha) form were preserved in the Pharmacognosy Laboratory, IPGT and RA, Gujarat Ayurved University, Jamnagar (No. IPGT and RA Phm 6220/16-17 for AC and IPGT and RA Phm 6221/16-17 for AM), while mature and fresh rhizomes of Ardraka (Zingiber officinalis Roscoe., family: Zingiberaceae) were procured from the local market of Jamnagar. After washing and cutting into small slices, these pieces were crushed with the help of industrial juicer to collect Swarasa (juice).

Animals

Swiss albino mice of either sex weighing 30 ± 5 g were used in the experimental study. The animals were obtained from the animal house attached to the pharmacology laboratory of the institute. Animals were exposed to natural day and night cycles with ideal laboratory conditions in terms of ambient temperature (22°C ± 2°C) and humidity (50%–60%). They were fed with Amrut brand rat pellet feed supplied by Pranav Agro Industries and tap water given ad libitum. The experiment was carried out after obtaining permission from the Institutional Animal Ethics Committee (IAEC/19/2015-38).

Animal grouping and dose selection

The selected animals were divided into four groups of six animals each. Group I received tap water and served as control. The test formulations AC and AM were administered to the groups II and III at a dose 2.6 mg/kg, respectively, extrapolating the human dose (20 g/day) to animals (2.6 g/kg) based on the body surface area ratio.[8] The test formulations were suspended in distilled water (520 mg/ml) and administered orally at a volume of 0.1 ml/10 g body weight with the help of rubber catheter of suitable size sleeved on to a syringe nozzle. Recodex (Wockhardt Ltd., Mumbai, India), which contains codeine phosphate (2 mg/ml) and chlorpheniramine maleate (0.8 mg/ml) at the dosage of 0.05 ml/10 g, was administered to Group IV orally to serve as standard control. The test drugs and standards were administered 1 h before the sulfur dioxide (SO2) exposure.

Experimental design

Anti-tussive effect of the test formulations was evaluated in mice by following the procedure of Miyagoshi et al.[9] In brief, the assembly comprises of a 500-ml three-necked flask containing aqueous saturated sodium hydrogen sulfite solution (NaHSO3; Nice Chemicals Pvt. Ltd., India). Into this bottle, concentrated sulphuric acid (H2 SO4; Merck, India) was introduced drop by drop. The reaction involved is 2NaHSO3+ H2 SO4=2SO2+ Na2 SO4+ H2O. SO2 is filled previously in the column of water manometer by opening the three-way cork such that SO2 can enter the water manometer but without any exit way until the pressure generated reads 75 mmH2O as recorded by the water manometer. Then, the three-way cork is rotated in such a way that the volume of SO2 collected in the water manometer escapes into the desiccator and not into the flask containing sodium hydrogen sulfite solution. These procedures are operated in a drift. The mouse to be tested is placed in 1l desiccator and covered with lid. Certain amount of SO2 is introduced into the desiccator by this procedure. The mice, after exposure to SO2 for 1 min in the desiccators, were taken out of the desiccator and confined in an up-turned filter funnel. The free end of the funnel is attached to a stethoscope, by the help of which the cough reflex of the mice was heard and the number of cough episodes in 5 min was enumerated. To avoid the observer bias, cough episodes were independently counted by two observers using digital counters and stopwatches.

Statistical analysis

The results were presented as mean ± standard error of the mean. Data generated during the study were subjected to student's t-test for unpaired data to assess the statistical significance. The values were considered significant at the levels of P < 0.05, 0.01, and 0.001.


  Results Top


On exposure to SO2, frequency of cough episodes in the experimental animals varied between 29.83 ± 1.97 and 54.33 ± 9.45. AC significantly reduced the number of cough reflexes by 40.18%, while AM reduced it by 34.97%. In both groups, the result is statistically highly significant (P < 0.001) in comparison to control group. Furthermore, the results of standard drug were more than the observations of control group. Hence, AC-treated group produced pronounced effect followed by AM in comparison to control group [Table 3].
Table 3: Effects of test drugs on sulfur dioxide-induced cough reflex

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  Discussion Top


The bronchi and trachea are so sensitive to light touch that very slight amount of foreign matter or other causes of irritation initiate the cough reflex. The cause of cough is obviously diverse, but the common link between them all is the activation of subsets of airway sensory nerves. Diseases of the respiratory system can lead to activation of sensory nerves at the level of the airway lumen following the release of inflammatory mediators, increased mucus secretion, or damage to the airway epithelium. Disorders of other organs that have neurons carried in the vagus probably interact with airway neurons in higher neuronal centers to elicit the cough reflex.[10] Anti-tussives are cough suppressants. There are two ways to inhibit coughing, namely centrally and peripherally. Centrally acting agents work by inhibiting the cough center in brain, elevating the threshold for coughing. Peripherally acting agents work either by anesthetizing the local nerve endings or acting as demulcents.[11]

Statistically highly significant reduction in the number of cough reflex was observed in the test samples, AC and AM, and the observed effect is nearer to the central cough suppressant – Recodex – with more pronounced effect in AC. The central cough suppressants are among the powerful anti-tussives. They produce this effect by suppressing central cough center by stimulating opioid receptors in this center. The mechanism involved may be sialogogue and demulcent effect. They may be increasing the flow of saliva acting as protective and soothing agent, increasing the production of respiratory tract fluid, thus covering and protecting the mucosa. Another possible mechanism involved to relieve cough may be anti-inflammatory effect of the trial drugs. Considering this, it can be suggested that the test formulations may be acting by any one or more of the above mechanisms. Although both the formulations were equally effective as the standard control drug used for suppressing cough reflexes in highly significant manner and provided significant relief in cough, further studies can determine the underlying anti-tussive mechanisms.

Drugs with Vatakaphahara and Vatanulomna (pacifies Vata and Kapha) are beneficial in case of Tamaka Shwasa (bronchial asthma).[12]Shunthi and Pippali possess these qualities and rest of all the ingredients are Vatakaphahara and may be beneficial in this condition. Pushkaramoola is one of the components of Ashtangavaleha and is well-known drug for Hikka (Hiccup), Shwasa (bronchial asthma), Kasa (cough), and Parshavashoola (pain in flanks).[13] Its anti-histaminic[14] and mast cell-stabilizing activities[15] have also been reported. Other ingredients such as Pippali and Karkatashringi possess Kasahara (cough relieving),[16]Hikka nigrahana (hiccup relieving)[17] properties. Recent studies reported mast cell-stabilizing activity, antihistaminic, bronchial smooth muscle relaxation mechanism at molecular level and thus anti asthmatic activity.[18]Pippali also possess anti-allergic[19] and anti-tubercular[20] properties. The anti-inflammatory activity of Shunthi is also reported.[21]Katphala is used in treating asthma.[22] Its anti-allergic activity[23] is also reported. Collectively, these activities will be beneficial in pacifying the symptomatology of Tamaka Shwasa (bronchial asthma). Pharmacological activities of the ingredients of Ashtangavaleha have shown their use as anti-inflammatory drugs and in asthmatic conditions. Its ingredients also show anti-allergic, mast cell-stabilizing, antihistaminic, and antioxidant properties. Looking into the properties of ingredients of test drugs, overall combination of ingredients of Ashtangavaleha may be perfect blend to relieve cough.


  Conclusion Top


Results in the present study for anti-tussive activity may be taken as standard. Ingredients of formulation such as Pippali and Shunthi have been reported individually for anti-tussive activity. Further other components of this compound formulation also reported for the same activities, making the whole formulation perfect blend to have antitussive activity.

In standard control group, remarkable suppression of SO2-induced cough episodes were observed. The observations of the current study signify that Asthangavaleha prepared by classical method, i.e., powder form and Ashtangavaleha prepared by modified method, i.e., Avaleha (linctus) form have highly significant anti-tussive effect against SO2-induced cough reflex comparable to the standard drug. Thus, both test drugs can be safely administered to alleviate cough.

Acknowledgment

Authors are thankful to the management of Department of Pharmacology and Animal house attached to the institute, IPGT and RA, Gujarat Ayurved University, Jamnagar for providing facilities to carry out this work.

Financial support and sponsorship

Institute for Postgraduate Teaching and Research in Ayurveda, Gujarat Ayurved University.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Reynolds SM, Mackenzie AJ, Spina D, Page CP. The pharmacology of cough. Trends Pharmacol Sci 2004;25:569-76.  Back to cited text no. 1
    
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Paneliya A, Nariya M, Patgiri BJ, Prajapati PK. Pharmaceutical Standardization of Vasavaleha and Granules and their Effect on Tamaka Shwasa (Bronchial asthma). MD Ayu dissertation. Institute for Post Graduate Teaching and Research in Ayurveda, Jamnagar: Gujarat Ayurved University; 2014.  Back to cited text no. 3
    
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Singh YS, Galib R, Ashok BK, Prajapati PK, Ravishankar B. Evaluation of anti tussive activity of Shirishavaleha – An ayurvedic compound formulation in sulphur dioxide induced cough in mice. Indian Drugs 2010;47:38-41.  Back to cited text no. 4
    
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Sharma PV, editor. Chakradatta of Cakrapanidatta with the Commentary Ratnaprabha by Mahamahopadhyaya Sri Nischala Kara; Hikka Shwasa Chikitsa. 1st ed., Ch. 12. Verse 24-29. Jaipur: Swami Jayaramdas Ramprakash Trust; 1993. p. 291.  Back to cited text no. 7
    
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Mazzone SB, Canning BJ. Central nervous system control of the airways: Pharmacological implications. Curr Opin Pharmacol 2002;2:220-8.  Back to cited text no. 10
    
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Acharya YT. Charaka Samhita, Charaka Chikitsa 17/147. 1st ed. Varanasi: Chaukhamba Surbharti Prakashan; 2008. p. 539.  Back to cited text no. 12
    
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Singh N, Nath R, Gupta MC, Kohli RP. An experimental evaluation of anti-asthmatic potentialities of Inula racemosa, Quarternary. J Crude Drug Res 1980;18:89-96.  Back to cited text no. 14
    
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Nadkarni's KM. Indian Materia Medica. 3rd Revised ed. Vol. 1. Bombay: Popular Prakashan Pvt. Ltd; 2002. p. 871.  Back to cited text no. 22
    
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Patel K, Rao Nj, Gajera V, Bhatt P, Patel K, Gandhi T, et al. Anti-allergic activity of stem bark of myrica esculenta buch – Ham. (Myricaceae). J Young Pharm 2010;2:74-8.  Back to cited text no. 23
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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