跳至主要内容

Evaluation of Acute and Repeated Dose Toxicity of the Polyherbal Formulation Linkus Syrup in Experimental Animals

Read full paper at:
http://www.scirp.org/journal/PaperInformation.aspx?PaperID=52208#.VIj6DsnQrzE

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.
Cite this paper
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. 
 

[1] Irwin, R.S. and Madison, J.M. (2000) The Diagnosis and Treatment of Cough. New England Journal of Medicine, 343, 1715-1721.
http://dx.doi.org/10.1056/NEJM200012073432308
[2] French, C.L., Irwin, R.S., Curley, F.J. and Krikorian, C.J. (1998) Impact of Chronic Cough on Quality of Life. Archives of Internal Medicine, 158, 1657-1661.
http://dx.doi.org/10.1001/archinte.158.15.1657
[3] Irwin, R.S., Boulet, L.P. and Cloutier, M.M. (1998) Managing Cough as a Defense Mechanism and as a Symptom. Chest, 114, 133S-181S.
http://dx.doi.org/10.1378/chest.114.2_Supplement.133S
[4] Salawu, O.A., Chindo, B.A., Tijani, A.Y., Obidike, I.C., Salawu, T.A. and Akingbasote, A.J. (2009) Acute and Sub-Acute Toxicological Evaluations of the Methanolic Stem Bark Extract of Crossopteryx febrifuga in Rats. African Journal of Pharmacy and Pharmacology, 3, 621-626.
[5] Angell, M. and Kassierr, J.P. (1998) Alternative Medicine—The Risk of Untested and Unregulated Remedies. New England Journal of Medicine, 339, 839-841.
http://dx.doi.org/10.1056/NEJM199809173391210
[6] Nadig, P.D. and Laxmi, S. (2005) Study of Anti-Tussive Activity of Ocimum Sanctum Linn in Guinea Pigs. Indian Journal of Physiology and Pharmacology, 49, 243-245.
[7] Dhawan, K. and Sharma, A. (2002) Antitussive Activity of the Methanol Extract of Passiflora incarnate Leaves. Fitoterapia, 73, 397-399.
http://dx.doi.org/10.1016/S0367-326X(02)00116-8
[8] Dhule, J.N. (1999) Antitussive Effect of Adhatoda Vasica Extract on Mechanical or Chemical Stimulation-Induced Coughing in Animals. Journal of Ethnopharmacology, 67, 361-365.
http://dx.doi.org/10.1016/S0378-8741(99)00074-4
[9] Chang, H.M. and Butt, P.P.H. (1986) Pharmacology and Applications of Chinese Materia Medica. Vol. 1, World Scientific, Singapore, 304.
http://dx.doi.org/10.1142/0284
[10] Suekawa, M., Ishige, A., Yuasa, K., Sudo, K., Aburada, M. and Hosoya, E. (1984) Pharmacological Studies on Ginger. I. Pharmacological Actions of Pungent Constitutents, (6)-Gingerol and (6)-Shogaol. Journal of Pharmacobio-Dynamics, 7, 836-848.
http://dx.doi.org/10.1248/bpb1978.7.836
[11] Mandal, S.C., Kumar, C.K.A., Mohana Lakshmi, S., Sinha, S., Murugesan, T., Saha, B.P. and Pal, M. (2000) Antitussive Effect of Asparagus racemosus Root against Sulfur Dioxide-Induced Cough in Mice. Fitoterapia, 71, 686-689.
[12] Srinath, K., Murugesan, T., Kumar, C.A., Suba, V., Das, A.K., Sinha, S., Arunachalam, G. and Manikandan, L. (2002) Effect of Trichodesma indicum Extract on Cough Reflex Induced by Sulphur Dioxide in Mice. Phytomedicine, 9, 75-77.
http://dx.doi.org/10.1078/0944-7113-00086
[13] Mandal, S.C., Ashok-Kumar, C.K., Lakshmi, S.M., Sanghamitra, S., Murugesan, T., Saha, B.P. and Pal, M. (2000) Antitussive Effect of Asparagus racemosus Root against Sulfur Dioxide-Induced Cough in Mice. Fitoterapia, 71, 686689.
http://dx.doi.org/10.1016/S0367-326X(00)00151-9
[14] Nosál’ová, G., Mokry, J. and Hassan, K.M. (2003) Antitussive Activity of the Fruit Extract of Emblica officinalis Gaertn. (Euphorbiaceae). Phytomedicine, 10, 583-589.
http://dx.doi.org/10.1078/094471103322331872
[15] Keter, L.K., Mwikwabe, N.M., Mbaabu, M.P., Sudhee, H.M., Tolo, F.M., Dhanani, P. and Orwa, J.A. (2013) Validation of Safety and Efficacy of Antitussive Herbal Formulations. African Journal of Pharmacology and Therapeutics, 2, 26-31.
[16] Gupta, Y.K., Kaytyal, J., Kumar, G., Mehla, G., Katiyar, C.K., Sharma, N. and Yav, S. (2009) Evaluation of Antitussive Activity of Formulations with Herbal Extracts in Sulphur Dioxide (SO2) Induced Cough Model in Mice. Indian Journal of Physiology and Pharmacology, 53, 61-66.
[17] Calixto, J.B. (2000) Efficacy, Safety, Quality Control, Marketing and Regulatory Guidelines for Herbal Medicines (Phytotherapeutic Agents). Brazilian Journal of Medical and Biological Research, 33, 179-189.
http://dx.doi.org/10.1590/S0100-879X2000000200004
[18] Firenzuoli, F. and Gori, L. (2007) Herbal Medicine Today: Clinical and Research Issues. Evidence-Based Complementary and Alternative Medicine, 4, 37-40.
http://dx.doi.org/10.1093/ecam/nem096
[19] Greenblatt, D.J. and Shader, R.I. (1971) Uses and Toxicity of Belladonna Alkaloids and Synthetic Anticholinergics. Seminars in Psychiatry, 3, 449-476.
[20] Red Book (2007) Guidance for Industry and Other Stakeholders Toxicological Principles for the Safety Assessment of Food Ingredients. Revised Edition, Chapter IV, 000045.
http://www.cfan.fda.gov/guidance.html
[21] ICH Harmonized Tripartite Guideline (2002) Guidance for Good Clinical Practice. E6 (R1); PMP/ICH/135/95. European Agency, London.
[22] Yasmeen, I. and Siddiqui, H. (2012) Study of the Antitussive Potential of Glycyrrhiza glabra and Adhatoda vasica Using a Cough Model Induced by Sulphur Dioxide Gas in Mice. International Journal of Pharmaceutical Sciences and Research, 3, 1668-1674.
[23] Nosal’ova, G., Saab, B.R., Pashayan, N. and El, C.S. (1992) Antitussive Efficacy of the Complex Extract and the Polysaccharide of Marshmallow (Althaea officinalis L. var. Robusta). Pharmazie, 47, 224-226.
[24] Al-Snafi, A.I. (2013) The Pharmaceutical Importance of Altahea officinalis and Althaea rosea. International Journal of PharmTech Research, 5, 1378-1385.
[25] Sutovska, M., Capek, P., Franova, S., Joskova, M., Sutovsky, J., Marcinek, J. and Kalman, M. (2011) Antitussive Activity of Althaea officinalis L. Polysaccharide Rhamnogalacturonan and Its Changes in Guinea Pigs with OvalbumineInduced Airways Inflammation. Bratislavské lekárske listy, 112, 670-675.
[26] Clarke, M.L. and Clarke, E.G.C. (1967) Veterinary Toxicology. Bailliere Tindall, London.
[27] Zbinden, G. and Roversi, F. (1981) Significance of the LD50 Test for the Toxicological Evaluation of Chemical Substances. Archives of Toxicology, 47, 77-99.
http://dx.doi.org/10.1007/BF00332351
[28] Daswani, G.P., Brijesh, S. and Birdi, J.T. (2006) Preclinical Testing of Medicinal Plants: Advantages and Approaches. Workshop Proceedings on Approaches towards Evaluation of Medicinal Plants Prior to Clinical Trial, Foundation for Medical Research at Yashwantrao Chavan Academy of Development Administration (YASHADA), 60-77.
[29] Ogbonnia, S.O., Mbaka, G.O., Anyika, E.N., Osegbo, O.M. and Igbokwe, N.H. (2010) Evaluation of Acute Toxicity in Mice and Subchronic Toxicity of Hydro-Ethanolic Extract of Chromolaena odorata (L.) King and Robinson (Fam. Asteraceae) in Rats. Agriculture and Biology Journal of North America, 1, 859-865.
http://dx.doi.org/10.5251/abjna.2010.1.5.859.865
[30] Stewart, M.J., Moar, J.J., Steenkamp, P. and Kokot, M. (1999) Findings in Fatal Cases of Poisoning Attributed to Traditional Remedies in South Africa. Forensic Science International, 101, 177-183.
http://dx.doi.org/10.1016/S0379-0738(99)00025-0
[31] Saad, B., Azaizeh, H., Abu-Hijleh, G. and Said, O. (2006) Safety of Traditional Arab Herbal Medicine. EvidenceBased Complementary and Alternative Medicine, 3, 433-439.
http://dx.doi.org/10.1093/ecam/nel058
[32] Colson, C.R. and De Broe, M.E. (2005) Kidney Injury from Alternative Medicines. Advances in Chronic Kidney Disease, 12, 261-275.
http://dx.doi.org/10.1016/j.ackd.2005.03.006
[33] Cheng, C.W., Bian, Z.X. and Wu, T.X. (2009) Systematic Review of Chinese Herbal Medicine for Functional Constipation. World Journal of Gastroenterology, 15, 4886-4895. 
http://dx.doi.org/10.3748/wjg.15.4886                      eww141211lx
标签：

评论

发表评论

此博客中的热门博文

Does Immigration Promote the Investment of the Monopolistic Firm?

In the present paper, we examine the effect of increasing uncertainty of immigrants’ growth on the optimal timing of investment of a firm that has a monopolistic power over the labor market. It is revealed that when the uncertainty of immigrants’ growth is more than a threshold level, increasing uncertainty of immigrants’ growth accelerates the optimal timing of firms’ investment and enhances the economic growth, even if the uncertainty of immigrants’ growth is formulated by the geometric Brownian motion, which is in sharp contrast to the standard result that an increase in the uncertainty postpones the optimal timing. With an increase in the immigrants over the past ten years, workforces in the host countries have been growing significantly to the extent that the immigrants represent 70% of the increase in the workforce in Europe, and 47% in the United States as OECD indicates. In the present paper, we attempted to investigate the effect of increased uncertainty caused by the growi...
发表评论
阅读全文

Education Policy Implementation: A Mechanism for Enhancing Primary Education Development in Zanzibar

Education is one of the fundamental rights of individuals; therefore, the government of a country needs to develop and strengthen educational policy and quality as well as to ensure that everyone has equal access to basic education. The improvement of access and quality of education in the world is becoming as an essential factor in development, whereas the basic education (primary school), is acknowledged as a foundation of the higher educational development for every country. To fulfill this goal, governments introduce several policies and procedures; however, it requires some reforms and participation from the politician, policymakers, and other stakeholders to re-examine educational policy so that it can lead to multiplication and betterment of the reforms. Educational reforms actually focus on accountability. A positive educational development and reform is very challenging and needs more effort and strategy on how to use and utilize the resources effectively as such it can achie...
发表评论
阅读全文