Preclinical study of Siddha Drug Chandra Prabava Chendooram for its Ovulation inducing, Hypolipidemic and Anti-Oxidant Activities

In this dissertation work, I have selected “Chandra Prabhava Chendooram” from the classic Siddha Literature “Anuboga Vaithiya Navaneetham Paham -4” authored by Mohammed Abdulla Shahib for the evaluation of safety, efficacy and therapeutic potency in “Soothaga Vaayu” for its Ovulation inducing, Hypolipidemic and Anti – oxidant activities. Chandra Prabhava Chendooram is a mineral preparation. It is very effective and traditionally used in the treatment of Soothaga Vaayu (PCOS). Collection of literature reviews regarding the ingredients of trial medicine carried out in Siddha aspect, geological aspect, botanical aspect and Pharmaceutical review. Various collection of Siddha and modern literatures about the ingredients of the drug supports the fact of Ovulation inducing activity. All the ingredients of the trial drug CPC were collected from the Rajendra raw drug shop at Nagarkovil district, Tamilnadu. Each ingredient verified and authenticated by the Gunapadam experts from the department of PG Gunapadam of Government Siddha Medical College, Palayamkottai. The trial drug was prepared as per the procedure given in the literature of “ANUBOGA VAITHIYA NAVANEETHAM PAHAM -4” The Siddha standardization of the trial drug Chandra Prabhava Chendooram indicates the drug is orange in colour. Organoleptic characters are orange in colour, pleasant, salt taste, coarse powder in appearance and smooth to touch. Physicochemical analysis of “Chandra Prabhava Chendooram” shows, a. The percentage of loss on drying at 105◦C is 1.20%. The low moisture content of the drug reveals the stability and its shelf-life. The water soluble ash value of CPC was 8.50%. The water soluble ash value is higher than acid insoluble ash. It represent the good quality of the drug CPC. Acidinsoluble ash value of the prepared formulation CPC (0.87%) shows that a very small amount of the inorganic component is insoluble in acid. b. water-soluble extractive values of CPC is 8.70% c. Chandra Prabhava Chendooram shows acidic pH (6.80). The pH level plays a role in enzyme activity by maintaining the internal environment thus regulating the homeostasis. It also an important factor for drug absorption. Because of the acidic nature, the drug is more readily absorbed in an acid medium like stomach which enhance the bio availability of the drug. Microbial limit test shows viable aerobic and fungal counts within normal level and specific pathogens Escherichia coli, Salmonella Sp, Pseudomonas aeruginosa and staphylococcus aureus are nil. Therefore, the test drug is free from any microbial contamination and it has standard quality. The information obtained from microbial screening tests will be use full in finding out the quality of the drug. The biochemical analysis of my drug shows Calcium, Sulphate, Chloride, arbonate, ferric iron, ferrous iron, Unsaturated compound, Amino acid. From that Calcium and Phosphorous and Iron plays a vital role. Low level of calcium and phosphorous develope a risk of PCOS, Since my drug contains Calcium and Phosphorous, it reduces the risk of PCOS to occur.Calcium is ffective in the treatment of Anovulation, Oligomenorrhoea with possible consequence for pregnancy rates in PCOS patients. Calcium is also important in follicle maturation and egg development, since my drug has calcium and phosphorous the follicle maturation is held correctly and the egg was developed well in PCOS. Iron metabolism is the major metabolism in our body. In PCOS, serum ferritin levels are increased, with patients who have glucose intolerance. Even in iron overload it is mainted by iron sparing effect. The iron present in my drug prevents the Iron deficiency anaemia, and the menstrual disorders which occurs due to anaemia. The Phyto chemical analysis of my drug shows as alkaloids, carbohydrates ang glycosides, tannins fixed oils and fats. SEM analysis of the CPC shows most of the particles present in the sample are micro size, nano size particles with atomic weight of elements. FTIR- Analysis related the Sulfoxinitro compounds, Alkenes, Conjugated Aldehyde, Acid halide, Alcohols. ICP- OES Result shows the trial drug has below detection level of calcium, pottasium, magnesium, sodium, phosporus, zinc, sulphur, iron, copper. It is evident that the drug “chabdra prabava chendooram” is devoid of heavy and toxic metals. This reveals the safety of the drug. From the XRD results, this sample is known to exhibit crystalline and amorphous nature. Sharp and Narrow peaks represent crystalline nature. This is about 67.4% of the sample. This ensures the stability of the drug remaining 32.6% represent amorphus nature. Crystalline state is 10 time more stability than that of amorphus state. So increase the stability of the drug the difference peak shows that the presence of minerals in the sample. The XRD fingerprint shows both the similarities and different of the sample successfully. From the Acute oral toxicity study, the rats were treated with different concentration of Chandra Prabhava Chendooram from the range of 5mg/kg to 2000mg/kg. This dose level did not produce the signs of toxicity, functional and behavioral changes, and mortality in the test groups as compared to the controls when observed during 14 days of the acute oral toxicity experimental period. So No- Observed-Adverse-Effect- Level (NOAEL) of Chandra Prabhava Chendooram in 2000 mg/kg. These results showed that a single oral dose of the CPC showed no mortality of these rats even under higher dosage levels indicating the high margin of safety of this drug. The drug CPC has be considered safe. As it did not cause either any lethality or adverse changes with general behavior of rats and also there were no observable detrimental effects (200 to 400mg/kg) over a period of 28 days. Hence the drug CPC can be considered to be safe drug for prolonged use as revealed by toxicological studies. From the pharmacological studies, The results of ovulation effect of Chandra Prabhava Chendooram revealed the significant influence at the dose level of 200mg/kg and this marked effect was ensured with the histological evaluation of ovary of experimental rats also. Hence it may be concluded that the Chandra Prabhava Chendooram is an excellent traditional medicine in the treatment for anovulatory conditions like PCOS and the effect may be attributed to the elevation of the ovulation stimulatory hormones in animal models. The drug CPC at high dose (400mg/kg) and low dose (200mg/kg) exhibited significant hyperlipidemic activity in atherogenic diet induced rats. This drug showed improvement in the parameter like body weight, serum and atherogenic index, SGOT, SGPT, urea, protein and blood glucose level as well as normalization of liver parenchyma and so might be of value in hypolipidemic activity. The Antioxidant activity of the drug CPC was tested by DPPH assay. The results showed that there was a concentration dependent Antioxidant activity of of CPC at the concentration increased from scavenging activity 77.42 % at conc 300 and the lowest percentage of inhibition(19.16 %) at conc 20 . Ascorbicacid (Standard)showed highest percentage of inhibition(162.30%)at 300 and the lowest percentage of inhibition 88.29 at conc 20.It shows that CPC having significant anti oxidant activity Both Gram positive and Gram negative bacteria E.coli, Klebsiella pneumoniae and Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi were found to be resistence when compared to the standard drug . The mineral drug Chandra Prabhava Chendooram exhibited no anti microbial activity . As per Siddha literature, diseases are caused due to change in mukkutram. In my disease, vaadha humor is affected. To treat vaadha, the drug must be in suitable taste that lower the effect of vaadha. So according to kannusamyiam, "வாத மேலிட்டால் மதுரம் புலியுப்பு" Hence the drug “Chandra Prabhava Chendooram” is having salt taste, it act as antagonist for the taste which increase vaadha humor in the disease “SoothagaVaayu”. Thus the medicine “Chandra Prabhava Chendooram” proves its potency to cure the disease “Soothaga Vaayu” (PCOS). CONCLUSION: From the literature review and the results of Siddha standardization and Physicochemical, Bio-chemical and Phytochemical analysis, Instrumental analysis, Microbial limit test, Instrumental analysis, Toxicological, Pharmacological studies and Anti-microbial studies it has been concluded that the trial drug is a Chandra Prabhava Chendooram in selected from the text book of “Anuboga Vaithiya Navaneetham Pakam - 4” authored by Mohameed Abdulla Shakib got a significant Ovulation inducing, Hypolipidemic and Anti-oxidant activities. So it can be safely used for Soothaga Vaayu as an effective drug