Preclinical Safety Evaluation of Aagasagarudan Kizhangu Chooranam

Aagasagarudan Kizhangu Chooranam was taken as dissertation drug for the evaluation of its toxicity profile. This is a single drug formulation which was prepared by purification of Aagasagarudan Kizhangu through Pittaviyal process and administered with Naattu sarkkarai as adjuvant. The drug was chosen from the Siddha text Gunapadam mooligai vaguppu. The above drug is indicated for virulent poison, Anemia, Pruritus, Thyroidism, Leprosy and Herpes zoster. The raw drugs were procured from Rajan Herbals shop; Broadway, Chennai and the drugs were identified and authenticated by Asst. Professor of Botany, National Institute of Siddha. The drug was underwent physicochemical, biochemical analysis, heavy metal analysis using ICP-OES, Phytocompound analysis using GC-MS and organic functional group analysis using FT-IR techniques. Acute and long term toxicity studies were conducted as per WHO guideline. The weak acidic pH of AGC enhances the bioavailability of the drug. Decreased Water soluble ash value indicates easy facilitation of diffusion and osmosis mechanisms. The Ash value of the test drug shows the purity, ICP-OES results shows the heavy metals such as lead, mercury, nickel, copper, arsenic and cadmium were found in below detection level. The Biochemical analysis of the drug contains Silicate, Phosphate, Zinc, Iron, Calcium, Magnesium, Ammonium, Potassium, Starch and Alkaloids. Through GCMS analysis, the identified compounds like 9,12-Octadecadienoic acid, (2-phenyl-1,3-dioxolan-4-yl) methyl ester, having so many medicinal values such as Hypocholesterolemic 5-Alpha reductase inhibitor, Antihistaminic, Anticoronary, Insectifuge, Hypocholesterolemic, Antieczemic, antioxidant and anti microbial activities. The FT-IR Spectra analysis indicates the presence of some organic functional groups such as alcohols, phenols,1`,2`amines, amides, Alkynes, Alkenes, Alkyl halides, Nitro compound, Alcohols, carboxylic acids, esters, ethers, Aliphatic amines, alkenes, Carboxylic acids, Aromatics. Amines and Carboxylic acids possess which enhances the drug effect against the disease. The Acute toxicity study results revealed that no mortality in dose level 2000mg/kg body weight group animals. It concludes that LD 50 cut-off of Aagasagarudan kizhangu chooranam may be above 2000mg//kg body weight as per WHO guideline. Long term toxicity study was conducted for about 90 days as per the WHO guideline. The different dose levels of Aagasagarudan kizhangu chooranam selected were Low dose (360mg/kg b.wt), Mid dose (720mg/kg b.wt) and High dose (1440mg/kg b.wt) respectively. The control animals were administered normal saline only. The haematology and biochemical parameters were subjected to one way ANOVA analysis which shows no significant changes in CBC, Lipid profile, RFT and LFT in all test groups compared to control group in blood. The histopathology report of organs reveals that all organs such as Brain, Heart, Lung, Stomach, Liver, spleen, kidney, testes, uterus and ovary were normal in low, mid and high dose groups when compared to control group. CONCLUSION: From the results of this study, the qualitative analysis of (AGC) reveals the Purity and Bioavailability of the drug. As heavy metals were found in Aagasagarudan Kizhangu Chooranam are within the permissible limit, the drug is safe enough for oral consumption. Toxicity studies states that there was no mortality and signs of toxicity observed for acute oral administration of AGC with the therapeutic dose (2000 mg/kg b.wt) in the prescribed manner. In long term toxicity study there was no significant changes in haematological, biochemical parameter in AGC treated groups when compared to control group. The histopathology report also confirms that there are no remarkable cellular changes at all the dose levels. It clearly demonstrates that there was No Observed Adverse Effect Level (NOAEL) upto the high dose level (1440 mg/kg b.wt). Based on these results it can be conclude that, the dose level of Aagasagarudan kizhangu chooranam 2 to 4gm (Arai Muthal Oru Varaagan Alavu) mentioned in the Siddha literature Gunapadam mooligai vaguppu is safe dosage for human consumption. In upcoming days it should be carried out to study the pharmacological activity and clinical trial to prove the efficacy of the drug