Abstract
Objectives
Madhulai Manappagu – a well-known sastric and widely prescribed Siddha herbal syrup formulation indicated for treating Veluppu Noi (Anaemia especially Iron deficiency Anaemia) has been in day today practice in Tamil Nadu for a quite longer decades. The syrup is a herbal preparation which has a sweet pleasant odour and a palatable taste, contain the juice of pomegranate (Punica granatum L.) as the main ingredient. Though the formulation is a fruit juice, the safety profile of the syrup is not established and is being marketed without toxicological evaluation. The study is aimed at ascertaining the acute and sub-acute toxicity assessment of Madhulai Manappagu in Wistar Albino rats.
Methods
The acute and sub-acute (28day repeated oral) toxicity studies were performed as per the guidelines mentioned in the Organization for Economic Cooperation and Development (OECD) 423 (adopted on December 2001) and TG 407 (adopted on October 2008) with slight modifications respectively. For acute toxicity study, three female rats were randomly selected as control; three female rats were randomly selected and were administered a single dose of 5,000 mg/kg body weight per oral route. For sub-acute (28day repeated oral) toxicity studies, three doses of test drug MM of 500 mg/kg/day (low dose), 750 mg/kg/day (intermittent dose) and 1,000 mg/kg/day (high dose) were selected for administration. Both sexes of Wistar Albino rats were randomized into four groups of 10 animals each (five males, five females). Group I was kept as control group. Group II, III and IV served as low, intermittent and high doses of MM respectively. Animals were observed for mortality, morbidity, body weight changes, feed and water intake. Haematology, clinical biochemistry, electrolytes, gross pathology, relative organ weight and histopathological examination were performed.
Results
In the acute toxicity study, rats showed no toxicological signs on behavior, gross pathology and body weight of rats when treated with a single dose of 5,000 mg/kg body weight per oral route. In the subacute (28 days repeated oral) toxicity study, rats have showed no significant changes on behavior, gross pathology, body weight, and hematological and biochemical parameters when treated with Madhulai Manappagu in three different doses.
Conclusions
The toxicity studies which include both acute and 28 days repeated (subacute) oral toxicity studies, revealed no observed adverse effect level (NOAEL) of Madhulai Manappagu in animals. Thus the safety of the drug in human usage was ensured.
Acknowledgments
The authors express their gratitude to the Tamilnadu Dr. M.G.R Medical University, Chennai for granting registration of this study as PhD thesis of the corresponding author. The authors also thank Assistant Professor, Department of Pharmacology, National Institute of Siddha, staffs of animal house of NIS and PG scholars of the Department of Kuzhandhai Maruthuvam for their relentless help in carrying out the study in a well-designed protocol.
-
Research funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
-
Author contributions: MMS conceptualized the study and ML and RM reviewed the study proposal. MMS conducted the animal study and GN supervised the animal experiments assisted in data collection. MMS drafted the manuscript. All the authors gave feedback on the manuscript and approved.
-
Competing interests: None. The authors declare that there is no conflict of interests regarding the publication of this paper.
-
Ethical approval: The study received approval from Institutional Animal Ethical Committee of National Institute of Siddha, Chennai (1248/Go/Re/S/2009/CPCSEA 21.05.2015) vide IAEC Protocol number NIS/IAEC-11/2016/04.
References
1. Development of Standard Siddha Terminologies, National Institute of Siddha, WHO-GOI, 2010-11; 102p.Search in Google Scholar
2. Meenakshi Sundaram, M, Logamanian, M, Banumathi, V. Physicochemical standardization of Siddha syrup preparation Madhulai manappagu”. IOSR-JDMS 2018;17:17–28.Search in Google Scholar
3. Kuppusamy, KN. Siddha Maruthuvam – Pothu, 7th ed. Chennai: Department of Indian Medicine and Homoeopathy; 2007. p. 324–31.Search in Google Scholar
4. Kandasamy, N. History of Siddha medicine, 2nd ed. Chennai: Directorate of Indian Medicine and Homoeopathy; 1998.Search in Google Scholar
5. Shanmugavelu, M. Noi Naadal Noimudhal Naadal, Part 1, 3rd ed. Chennai: Department of Indian medicine and Homoeopathy; 2003.Search in Google Scholar
6. Kuppusamy Mudaliar, KN, Uthamarayan, CS. Siddha Vaidya Thirattu, I ed. Chennai: Department of Indian Medicine and Homoeopathy; 2009.Search in Google Scholar
7. India Pharmacopeia I, Government of India, Ministry of Health and Family Welfare, vol. I. Indian Pharmacopeia Commission; 2014.Search in Google Scholar
8. Lavekar, GS, Padhi, MM, Rao, MM, Srikanth, N, Prameela Devi, K, Dr. Gurucharan, B, et al.. Ayurveda and Siddha for Anaemia (Pandu/Veluppu noi) control, Anaemia control through Ayurveda and Siddha (background papers) for National Campaign on Anaemia Control through Ayurveda and Siddha. New Delhi: Department of AYUSH, Ministry of Health and Family Welfare, Govt. of India; 2009:4 p.Search in Google Scholar
9. Meenakshi Sundaram, M, Logamanian, M, Banumathi, V. Evidence based Siddha therapeutics in treating female infertility. Int J Curr Res 2017;9:59703–5.Search in Google Scholar
10. Sriram, S. GC-MS study and phytochemical profiling of Mimosa pudica linn. J Pharm Res 2011;4:741–2.Search in Google Scholar
11. Malayappan, MS, A Vanitha, Mockaiyathevar, L, Ramasamy, M. Pharmacological evaluation of anti-anaemic activity of Madhulai Manappagu. IOSR J Den Med S 2020;19:30–5.10.1515/jcim-2020-0327Search in Google Scholar
12. Stafilov, T, Karadjova, I. Atomic absorption spectrometry in wine analysis – a review. Macedonian J Chem Chem Eng 2009;28:17–31. https://doi.org/10.20450/mjcce.2009.218.Search in Google Scholar
13. Rahimi, HR, Arastoo, M, Ostad, SN. A comprehensive review of punicagranatum (pomegranate) properties in toxicological, pharmacological, cellular and molecular biology researches. IJPR 2012;11:385–400.Search in Google Scholar
14. Ghai, OP. Essential pediatrics, 4th ed. New Delhi: CBS Publisher; 1996:63p.10.1007/BF02730811Search in Google Scholar
15. Santhanam, I. Illustrated text book of pediatrics, I ed. The Health Sciences Publishers; 2018:877p.Search in Google Scholar
16. Achar. Textbook of pediatrics. Orient Longman, 3rd ed. reprint; 1995:571p.Search in Google Scholar
17. Meenakshi Sundaram, M, Logamanian, M, Banumathi, V. Paediatric management in Siddha system of medicine, cloud. IJAAYUSH 2017;6:282. https://doi.org/10.23953/cloud.ijaayush.282.Search in Google Scholar
18. Meenakshi Sundaram, M, Bhavani, P, Logamanian, M, Banumathi, V. Medicinal values of pomegranate (Madhulai) – Siddha view. IOSR J PHR 2018;8:34–8.Search in Google Scholar
19. Vijibala, M, Karolin Daisy Rani, R, Velpandian, V, Pitchiah Kumar, M. Pre-clinical toxicological profiling of Siddha formulation sambirani poo Kuligai by acute and sub-acute toxicity studies in accordance with OECD guidelines. Int J Curr Res Med Sci 2018;4:1–10.10.22192/ijarbs.2017.04.12.027Search in Google Scholar
20. Nadkarni, KM. Indian materia medica, 3rd ed., vol. 1. Bombay: Popular Prakashan; 2005:1631–5pp.Search in Google Scholar
21. Ajibola, A, Chamunorwa, JP, Erlwanger, KH. Nutraceutical values of natural honey and its contribution to human health and wealth. Nutr Metabol 2012;9:61. https://doi.org/10.1186/1743-7075-9-61.Search in Google Scholar PubMed PubMed Central
22. Agarwal, SG, Gupta, A, Kapahi, BK, Baleshwar, Thappa, RK, Suri, OP. Chemical composition of rose water volatiles. J Essent Oil Res 2005;17:265–7. https://doi.org/10.1080/10412905.2005.9698897.Search in Google Scholar
23. Mohammed Iqbal, PA. Pharmacy and pharmaceutics of Siddha medicine, 1st ed. Chennai: National Institute of Siddha; 2016:92p.Search in Google Scholar
24. Sambasivam, TV. Siddha Tamil dictionary, Part I, 2nd ed., vol. II. Chennai: Department of Indian Medicine and Homoeopathy; 2006:558p.Search in Google Scholar
25. Sundaram, MM, Logamanian, M, Meenakumari, R. Anti-oxidant property of Madhulai Manappagu – a Siddha herbal syrup for iron deficiency anaemia in children. Int J Pharm Sci Invent IJPSI 2020;09:01–7.Search in Google Scholar
26. Pharmacopoeial Laboratory for Indian Medicine (PLIM). Guideline for standardization and evaluation of Indian medicine which include drugs of Ayurveda, Unani and Siddha systems. Govt. of India: Department AYUSH, Ministry of Health & Family Welfare.Search in Google Scholar
27. OECD. OECD guideline for testing of chemicals, repeated dose 28-day oral toxicity study in rodents: TG 407-adopted. Paris, France: OECD; 1995.Search in Google Scholar
28. Mohammed Iqbal, PA. Pharmacy and pharmaceutics of Siddha medicine, 1st ed. Chennai: National Institute of Siddha; 2016:92p.Search in Google Scholar
29. Suvarna, SK, Layton, C, Bancroft, JD. Bancroft’s theory and practice of histological techniques, 7th ed. London: Churchill Livingstone; 2013.Search in Google Scholar
30. Wonder, HKM, George, KA, Gyasi, EB. Acute and sub-acute toxicity studies of the ethanolic extract of the aerial parts of Hilleria latifolia (Lam.) H. Walt. (Phytolaccaceae) in rodents. West Afr J Pharm 2011;22(1):27–35.Search in Google Scholar
31. Sathish, R, Anbu, J, Murgesan, M, Anjana, A, Kumar, A. Toxicity study on Siddha formulation mega Sanjeevi Mathirai in albino rats. Int J Pharma Bio Sci 2012;3:P121–30.Search in Google Scholar
32. Olson, H, Betton, G, Robinson, D, Thomas, K, Monro, A, Kolaja, G, et al.. Concordance of the toxicity of pharmaceuticals in humans and in animals. Reg Toxi Pharma 2000;32:56–67.10.1006/rtph.2000.1399Search in Google Scholar PubMed
33. Adeneye, AA, Ajagbonna, OP, Adeleke, TI, Bello, SO. Preliminary toxicity and phytochemical studies of the stem bark aqueous extract of Musanga cecropioides in rats. J Ethnopharmacol 2006;105:374–9.10.1016/j.jep.2005.11.027Search in Google Scholar PubMed
34. Shatoor, AS. Acute and sub-acute toxicity of Crataegus aronia syn. Azarolus (L.) whole plant aqueous extract in Wistar rats. Am J Pharmacol Toxicol 2011;6:37–45.10.3844/ajptsp.2011.37.45Search in Google Scholar
35. Mayne, P, Mayne, PD. Cli Chem in Diag and Treat, 6th ed. London, UK: A Hodder Arnold Publication; 1994.Search in Google Scholar
36. Greaves, P. Histopathology of preclinical toxicity studies: interpretation and relevance in drug safety evaluation, 3rd ed. New York, NY, USA: Academic Press; 2007.Search in Google Scholar
© 2021 Walter de Gruyter GmbH, Berlin/Boston
