Evaluation of Anti-Tussive Effect of Ardraka Paka and its Modified Syrup in Sulphur Dioxide Induced Cough Model

Introduction

Pharmacological evaluation of traditional medicinal plants has recently drawn attention and witnessed growing interest among researchers globally. The advancement of science and technology in modern pharmaceuticals has rendered the evolution of new concepts, including new dosage forms and administration techniques. Conversion of formulations into various dosage forms to achieve added benefits, keeping intact the therapeutic properties, has gained momentum in the recent past, which has great importance in the market.¹

Ardraka Paka (ADP) is a classical formulation mentioned in Bharatha Bhaishajya Rathnakara, Yogachintamani and Ayurveda Sara Sangraha, having Ardraka as the main ingredient with other Prakshepa dravyas and Jaggery as the sweetening agent.^2-4 It is indicated in Shwasa, Kasa, Smritibhramsha, Swarabhanga, Arochaka, Hridroga, Grahani, Gulma, Shoola and Shopha.

Polyherbal combinations with various bioactive principles have been used for centuries to treat a wide range of diseases. Modification of a semisolid formulation into a polyherbal syrup offers advantages such as improved palatability, greater acceptance, and ease of administration. Syrups are among the most popular recommended dosage forms for alleviating cough and other respiratory symptoms. Among all syrup formulations, polyherbal cough syrups have gained greater popularity compared to the conventional cough syrups, which often contain synthetic agents that may cause undesirable side effects.

Considering these facts, the present study was undertaken to evaluate the anti-tussive effects of the polyherbal formulation ‘Ardraka Paka’ and its modified syrup form, ‘Ardraka Paka syrup’ (ADS), using a sulphur dioxide induced cough model.

Materials and Methods

Test drugs

The test drugs ‘Ardraka Paka’ and ‘Ardraka Paka syrup’ were prepared in the RSBK Department lab of Alva’s Ayurveda Medical College, Moodubidire, following the standard operating procedure (SOP).

Standard drug: Codeine phosphate (10 mg/kg)

Chemicals used: Sulphur dioxide (SO₂ )

The details of test drugs 1 and 2 are as follows.

Sample

i) Wistar albino rats of both sexes, weighing between 140 and 200 g, were used for experimentation.

ii) The experimental protocols were approved by the Institutional Animal Ethics Committee (IAEC Approval No. MC/UCMS/IAEC AAMC/CPCSEA/ IAEC/2018-2019-AL-08), in accordance with the guidelines formulated by the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA), India.

iii.) The experiments were conducted in the animal house attached to Alva’s Ayurveda Medical College, Moodubidire, Karnataka.

Dose fixation

The dose selection was based on the body surface area ratio, using the table of Paget and Barnes (1969).⁵ The rat dose of Ardraka Paka was determined to be 0.54 g/ kg, and the corresponding Ardraka Paka syrup dose was 0.9 mL/kg body weight.

The stock solution was freshly prepared just before administration to the animals, using distilled water and unidirectional grinding with a mortar and pestle.

Route of drug administration: Oral

Methodology

The selected animals were divided into four groups, each consisting of six animals. All the drugs were administered orally. Group 1 served as the normal control and received the vehicle, distilled water, at a dose of 10 mL/kg. Group 2 was treated with Codeine phosphate (10 mg/kg) and served as the standard group. Groups 3 and 4 were drugtreated groups, receiving ADP and ADS, respectively. The test drugs and vehicle control were administered one hour prior to SO₂ exposure. The rats were exposed to SO₂ for one minute in the desiccators. After exposure, they were removed and placed in an upturned filter funnel. The free end of the funnel was attached to a stethoscope which was used to monitor the cough reflex and the number of cough episodes in five minutes was recorded. The mean of cough bouts recorded by the two observers was taken, and the percent inhibition in number of cough bouts was calculated.

Statistical analysis

All the values were expressed as the Mean ± SEM (Standard Error of Mean). The results obtained from the present study were analyzed using One way ANOVA, followed by Dunnett’s Multiple ‘t’ as post hoc test. The obtained data were computed for statistical analysis using Graph Pad 3.1 software. Differences between the data were considered statistically significant at *P <0.05 and **P <0.01. The level of significance was noted and interpreted accordingly.

Results

The data related to the effect of ADP and ADS on antitussive activity has been depicted in Table 3. The data shows a decrease in the number of bouts in the standard, ADP, and ADS groups, when compared to the normal control group. The observed  reduction was found to be statistically highly significant in the standard and ADS groups.

Both the test drugs, ADP and ADS, showed a reduction in the number of cough bouts. The standard group showed a 49.25% reduction, while the ADP and ADS groups showed 7.57% and 31.44% reductions, respec tively. Upon comparing the two test groups, Group ADS showed a statistically significant decrease in the number of cough bouts and was found to be more effective com pared to Group ADP, which exhibited an insignificant effect.

Discussion

The cough suppressant activity elicited by the test formulations ADP and ADS may be attributed to the herbal components present in the blend of polyherbs, including ginger, Trikatu, Chaturjata and other spices. The percentage inhibition of cough bouts observed in the standard and ADP and ADS groups was 49.25%, 7.57% and 31.44%, respectively. On comparing both the test groups, Group ADS was found to be more effective in reducing the frequency of cough bouts than Group ADP.

The main ingredient in both test formulations is ginger, which is known to possess anti-tussive activity due to the presence of compounds such as 6-gingerol and 6- shogaol. Among these, 6-shogaol is generally more potent than 6-gingerol and has been shown to exhibit antitussive effects.⁶ Ginger contains 1-4% volatile oils, including cineole, zingiberene, borneol, and resins such as gingerol and shogaol. Cineole exhibits antitussive effect by suppressing the cough reflex through direct action on the cough centre in medulla.⁷ Ginger contains diverse bioactive compounds such as gingerols, shogaols, and paradols, and possesses multiple bioactivities, such as antioxidant, anti-inflammatory, and antimicrobial properties.^8,9,10

Trikatu is an effective bioavailability enhancer, commonly used in the treatment of cough and asthma.¹¹ The main ingredient Jaggery is found to have beneficial effects in treating throat and lung infections.¹² Cumin is an anti-congestive agent and is a good expectorant due to its rich essential oils and thus used for cough, cold and bronchitis.¹³ Cumin seeds - the relaxant effects of the macerated and aqueous extracts exhibit bronchodilator activity, and the crude extract of Cardamom is found to contain alkaloids, flavonoids, saponins, sterols and tannins. The flavonoids are well known for their bronchodilator activity. The presence of such a class of compounds in Cardamom is likely to contribute to its airway relaxing action.¹⁴ Vidanaga contains Embelin - a bioactive component found to exhibit anti-inflammatory activity.¹⁵ All the above findings support the traditional claims related to the cough suppressant activity by virtue of the pharmacological actions of the bioactive components present in each of the ingredients.

Based on the present study findings, it can be inferred that ADS demonstrated significantly greater anti-tussive activity compared to ADP. In general, liquid dosage forms are more suitable and effective for cough relief as they are absorbed at a much faster rate compared to solid dosage forms. Liquid formulations are generally preferred for paediatric and geriatric patients. Additionally, liquid preparations offer a soothing effect on the inflamed mucosa of the upper respiratory tract, thereby effectively helping to reduce cough. Regarding efficacy, it has been proven that liquids are faster-acting than solids due to their rapid absorption.¹⁶ This may be the probable reason for the superior anti-tussive effect exhibited by ADS compared to ADP.

Conclusion

The study findings indicate that both the test formulations, Ardraka Paka and Ardraka Paka syrup, exhibit anti-tussive effects, as evidenced by a reduction in the number of cough bouts. On comparing both the test groups, Group Ardraka Paka syrup showed a statistically significant (P <0.01) decrease in the frequency of cough bouts and was found to be more effective compared to Ardraka Paka, proving the potential anti-tussive activity of Ardraka Paka syrup.

Acknowledgements

The authors are grateful to Principal, Dr. Sajith M, Alva’s Ayurveda Medical College and Hospital, Vidyagiri, Moodubidire, and Dr. Subramanya Padyana, Director, ATMA Research Centre, Alva’s Ayurveda Medical College, Moodubidire, for providing constant support and cooperation for the research work.

Conflicts of Interest

Nil

Source of Support:

Nil