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.
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.
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.
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.
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.
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