Evaluation of Acute and Repeated Dose Toxicity of the Polyherbal Formulation Linkus Syrup in Experimental Animals
Allah Nawaz1,2, Saira Bano1, Zeeshan Ahmed Sheikh1, Khan Usmanghani1,3*, Iqbal Ahmad4, Syed Faisal Zaidi5, Aqib Zahoor1, Irshad Ahmad6,7
1Research and Development Department, Herbion Pakistan (Pvt.) Limited, Karachi, Pakistan.
2First Department of Internal Medicine, Faculty of Medicine, Graduate School of Medical & Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
3Jinnah University for Women, Karachi, Pakisntan.
4Baqai Institute of Pharmaceutical Sciences, Baqai Medical University, Karachi, Pakistan.
5Department of Basic Medical Sciences, College of Medicine, King Saud bin Abdulaziz University of Health Sciences, Jeddah, KSA.
6Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan.
7Clinical Pharmacy and Health Care, Jinnah University for Women, Karachi, Pakistan.
DOI: 10.4236/cm.2014.54022   PDF   HTML   XML   4,190 Downloads   5,065 Views   Citations


The objective of the present study was to evaluate the pre-clinical efficacy and toxicity of polyherbal cough syrup Linkus. Method: Animals (healthy Wistar albino rats; (150 - 250 g) of either sex) were housed under standard environmental conditions; i.e. 25°C ± 1°C and 12 h dark/light cycle. Food and water were available at libitum. The rats were treated orally with the recommended doses of the test drug (Linkus). After 15 minutes, they were individually placed in a closed Plexiglas chamber (20 × 10 × 10 cm) and exposed to citric acid (0.1 g/ml) inhalation for 7 minutes. The cough reflexes were produced and counted for the last 5 minutes and compared with those of the control animals. The following studies were conducted to evaluate the toxicity of the test drug in healthy Wistar albino rats: lethal dose50 (LD50); rats of either sex (n = 10/sex) were treated orally with doses (1 or 5 g/kg) of the test drug. Mortality and behavioral changes were observed for 1 week. Repeated dose toxicity on the healthy Wistar albino rats of both sexes (n = 5/dose/sex) was treated orally with doses of 20 mg/kg (adult human dose = ~1400 mg), 500 mg/kg (adult human dose = ~35,000 mg) and 1000 mg/kg (adult human dose = ~70,000 mg) of test drug (Linkus) for 14 days. Additionally, the control animals were treated orally with water for 14 days. Results: In female rats, the test drug (Linkus) at the dose of 300 mg/kg caused significant (p < 0.01) reduction in the cough reflexes as compared to the control. However, in male rats, a significant reduction was observed at the tested dose of 200 mg/kg (p < 0.05) and 300 mg/kg (p < 0.01). The test product did not cause mortality in rats at the given doses of 1 or 5 g/kg. Other signs of toxicity like hair loss and weight reduction were not observed. In female and male rats, the test drug (Linkus) at different doses did not show any abnormal effects on complete blood count profile of rats. Serum enzyme markers, i.e. alanine aminotransferase (ALT), alakaline phosphatase, gamma glutamyle transferase (GGT), direct bilirubin, creatinine, and proteins were also observed and found that the test drug at a higher dose did not cause any of the abnormality and had shown significant p value as compared to the control. Conclusion: The test drug (Linkus) could be an effective and safe cough syrup because it did not show any of the side effects or toxicity on experimental animals.

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Nawaz, A. , Bano, S. , Sheikh, Z. , Usmanghani, K. , Ahmad, I. , Zaidi, S. , Zahoor, A. and Ahmad, I. (2014) Evaluation of Acute and Repeated Dose Toxicity of the Polyherbal Formulation Linkus Syrup in Experimental Animals. Chinese Medicine, 5, 179-189. doi: 10.4236/cm.2014.54022.

Conflicts of Interest

The authors declare no conflicts of interest.


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