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International Journal of Ayurveda and Pharma Research ISSN: 2322-0902 (P) ISSN: 2322-0910 (O) Research Article TO STUDY THE EFFECT OF KUTAJA GHANA IN ATISAR VEGAVASTHA (ACUTE DIARRHEA) Shisode Nileema Raju Reader, Department of Swasthvritta, Tilak Aayurved Mahavidyalaya, Pune, Maharashtra, India. ABSTRACT Diarrhea is a major disease in India. To avoid heavy economic burden for its treatment it is necessary to introduce a drug which is easily available, also cost effective and having quick result. So Kutaja Ghana is made as drug prepared by method given in Rasoddhar tantra. We found that percentage of total alkaloids increased after preparation of Kutaja Ghana. Connesine is active ingredient of Kutaja, its confirmation done by NMR and mass index study. Chromatograph of chloroform soluble extract of Kutaja powder shows 55.32% of connesine and that of Kutaja Ghana shows 99.10% of connesine. Also clinical trial of 60 patients confirmed its efficacy to treat diarrhea. Random selection of 60 patients from IPD or OPD of Ayurveda seva sangha hospital Nashik had done. 250 mg three times a day was the dose of group A patients treated with Kutaja ghana. Duration of treatment was three days. Group B was treated with Sanjivani vati 250mg three times a day. Thus probability of occurrence of value obtained by chance is much less than 0.05, the critical of 5%level of significance. The difference is real in 98% experiments hence highly significant. Statistical Analysis of the Data to Verify Difference Between the Effect of Drugs Kutaja Ghana and Sanjivani vati. KEYWORDS: Diarrhoea, Atisar, Alkaloid, Connesine, Kutaja Ghana, Hollharhena antidysentrica. INTRODUCTION Diarrhoea disease causes heavy economic burden on health services, as the disease occupy 1/3 rd of hospital beds. UK, USA proved that many of the patients in outpatient clinics belong to gastroenterology section. Diarrhea diseases are major cause of illness and death in most of the developing countries. In some countries up to 40% of deaths among children under age of 5 years are diarrhea related, more than 2 million under 5 years in the world s poorest countries still die needlessly every year of diarrhea related dehydration. There is definite relation between food habits, nutrition, and poor sanitation practice. Poor nutrition may lead to certain diseases as kwashiorkor, sprue, celiac disease, and pellagra which are associated with diarrhea. Diarrhea starts with frequent occurrence of watery stool in large quantity. If it is not treated in this stage, because of loss of water and minerals through stool, patient gets dehydrated. Primarily dryness of mouth, dyspnoea on exertion, and latter on condition worsens to cause more and more dehydration skin turgor lost, body temperature get minimizes, thready pulse, low B.P. etc, this may leads to acute renal failure. At this stage if patient is not treated properly then he may have hypovolumic shock and latter on because of dis-electrolitemia patient dies. Materials and methods MATERIALS Kutaja Family-Apocynaceae Name-Hollarhena antidycentrica White kuda Bark of white Kuda is used for this study. It is bitter, pungent and astringent by taste. It s Vipak (post digestion taste) is Katu and Veerya (potency} is hot. It is Pitta and Kapha pacifying drug. It is Agnidipan, Grahi and Pachan (it ignites digestive fire helps in digestion and solidifies stool). Standardization of white Kutaja bark was done by microscopic examination, in which it is that found stone cells in groups rectangular to elongated, also thin walled cork cells and calcium oxalate crystals, few starch grains are seen as identification characteristics. Chromatograph of chloroform soluble extract of Kutaja powder shows 55% of connessine. Confirmation of connesine was done by NMR study and mass index study. Total alkaline percentage was 3.5 % Total ash was 5.82%. Collection of Kutaja bark was done soon after rainy season from old white Kutaja plant, it was dried in shadow to preserve its active principle. After drying fine powder is prepared in grinder of Aushadhi bhavan Nashik. Method to prepare Kutaja Ghana With this standardized white Kutaja powder with standardized text method Kutaja extract was prepared as described in Rasoddhaar tantra. Take 2 Prastha (1280 gms) Kutaja powder add 24 Prastha (15380 liters) of water in it boil it on dim fire to preserve essential ingredients still it remains 3 Prastha (1920 liters) filter it with muslin cloth, After this boil the decoction by indirect heat in water bath, so that water gets evaporated. To get totally water free powder, keep it in oven at 100 degree Fahrenheit for 4 hours. Make fine even powder by grinding it in a mixer, thus we get small granules of Kutja Ghana. From 4 kg of Kutaja powder we get 500gms of Kutja Ghana powder. Then 250mg powder filled gelatin capsules are prepared. Disintegration time of Kutaja Ghana capsules is approx 20 minutes and dissolution time is 30 minutes. Almost all Ghana gets dissolved to attain it s maximum concentration. IJAPR March 2016 Vol 4 Issue 3 36

Chromatograph of chloroform soluble extract of Kutaja Ghana shows 99.10% of connesine. Total alkaloid percentage is 10.7%. Total ash 8.25%. NMR and mass index study identified connesine percentage. I found that all the classics repeatedly mentioned that use of Kutaja in Atisar is effective remedy. Charak told that it is a drug of choice whenever we expect immediate treatment to stop watery stools. It is a single drug therapy so we can easily find its efficacy in acute diarrhea patients. Also I had tried to find out active ingredient percentage of Kutaja powder and Ghana formed, on the basis of modern parameters. METHODS Random selection of 60 patients from IPD or OPD of Ayurveda seva sangha hospital Nashik had done. 250 mg three times a day was the dose of group A patients treated with Kutaja ghana. Duration of treatment was three days. Group B was treated with Sanjivani vati 250mg three times a day. Patients in age group 6 yrs to 60yrs with more than three times watery stools were selected. Patient were examined for frequency and interval between two subsequent motions. Faecal material was examined for quantity, odour, colour, and Samata of stool. Also some associated symptoms like Aruchi (tastelessness), loss of appetite, pain in abdomen, nausea, flatulence, headache and also patients were examined for symptoms related to signs of dehydration. Tongue examination, B.P., pulse, Int. J. Ayur. Pharma Research, 2016;4(3):36-41 weight, and abdominal examination was done. Lab investigations done for haemogram, microscopic and Ayurvedic stool examination were done. Separate case proforma was prepared and a criterion for cure of each symptoms its grade was decided. OBSERVATIONS Maximum incidence of Atisar found in patients belonging to age group 50-60 yrs, more of them i.e. 83% were married. Housewives and workers 38% were commonly affected. It is irrespective of Prakruti but Vata dosha plays prominent role in Samprapti of Atisar. 43% Vataja Atisar is more common Katu (pungent) spicy food was major cause found to cause Atisar (20 patients), after that heavy food is important cause (12 patients). In primitive symptoms (Purvarupa) Udar tod (slight pain in abdomen) and Avipak (undigested food) were common Most common symptom of Atisar is definitely frequency of watery stools with the pain in abdomen, dryness of mouth, thirst, loss of appetite are also some of the common symptoms. 46% of patients reduced number of motions on first day itself. Complete cure found within 1 day after using Kutaja Ghana, while in group B mild to moderate cure possible on first day. Majority of patient get cured within 2 days of treatment. Table 1: Symptoms wise improvement in the treatment of Group A and Group B Symptoms Complete cure Moderate cure Mild cure Uncured Gr A Gr B Gr A Gr B Gr A Gr B Gr A Gr B Reduced no of motions 1 st day 12 3 14 11 3 12 1 4 Reduced no of motions 2 nd day 20 7 2 6 7 16 1 1 Increased interval between 2 motions 12 3 7 13 4 9 2 5 Increased interval of motions 2 nd day 22 9 7 8 6 13 0 0 Consistency 1 st day 29 10 0 0 0 0 1 20 Cons 2 nd d 30 25 0 0 0 0 0 9 Micturation and defecation same time reduced 1 st day Micturation and defecation reduced 2 nd day 13 11 0 0 0 0 7 12 20 16 0 0 0 0 0 7 Loss of appetite reduced 9 6 2 12 15 8 0 4 Pain in abdomen reduced 16 10 4 12 6 3 3 4 Headache 19 13 0 9 2 1 1 4 Skin turgor regain 5 8 0 0 1 0 3 3 Shabdasahishnuta (reduced capacity to hear sound) 20 16 1 0 4 7 1 5 Samata of stool 3 6 0 0 0 0 10 6 Samata of tongue 9 3 2 0 0 0 5 IJAPR March 2016 Vol 4 Issue 3 37

Shisode Nileema Raju. To Study the Effect of Kutaja Ghana in Atisar Vegavastha (Acute Diarrhea) Statistical Analysis of the Data Table 2: Data to judge effectiveness of Kutaja Ghana S.No Name of Varient N1 SD Mean SE T Value Table value conclusion 1 1 st day motion 30 2.975 5.1 0.441209 11.55915 1.699 significant 2 2 nd day motion 30 3.8 5.8 0.499194 11.6161873 1.699 significant 3 Interval increased day 1 30 7.468 7.51 0.641566 11.7057 1.699 significant 4 Interval increased day 2 30 12.55 14.63 1.228304 11.9162 1.699 significant Thus probability of occurrence of value obtained by chance is much less than 0.05, the critical of 5%level of significance. The difference is real in 98% experiments hence highly significant. Statistical Analysis of the Data to Verify Difference Between the Effect of Drugs Kutaja Ghana and Sanjivani vati Total population divided into two groups Group 1-treated with Kutaja Ghana Group B treated with Sanjivani vati H0- it is assumed that there is no real difference between the effect of both drugs H1-Kutaja ghana is better to cure symptoms than Sanjivani vati Table 3: Unpaired t-test is applied for quantitative symptoms Symptoms SD SE DF Mean A Mean B Calculated D Table Value Conclusion Value 1 st day motion 4.9758 1.28 58 5.1 2.766 1.8167 1.672 Real difference 2 nd day motion 6.1223 1.58 58 5.8 4.2 1.0122 1.672 No difference Increased interval 1 st day 8.1103 2.09 58-7.51-2.216-2.5281 1.672 No difference Increased interval 2nd day 15.19 3.92 58-14.63-5.983-2.2047 1.672 No difference There is no difference between the effect of Kutaja Ghana and Sanjivani vati in all symptoms except number of motions after one day treatment, Kutaja Ghana is more useful to reduce number of motions within one day. Chi square test is for independence of attributes for qualitative symptoms Table 4: Showing improvement in Aruchi Kutaja ghana 10 13 3 1 27 Sanjivani vati 5 7 12 3 27 Total 15 20 15 4 54 V1 10.117 Kutaj is more effective to cure Aruchi than Sanjivani vati Table 5: Showing improvement in Jivha samats Cure grade Complete Moderate Uncured total Kutaja ghana 9 9 12 30 Sanjivani vati 3 11 16 30 Total 12 20 28 60 V1 3.7713 V2 5.99 Both drugs are equally effective to cure Jivha samata Table 6: Showing improvement in Cure micturation and defecation at the same time Kutaja ghana 20 0 20 Sanjivani vati 13 7 20 Total 33 7 40 V1 8.6277 Available online at: http://ijapr.in 38

Int. J. Ayur. Pharma Research, 2016;4(3):36-41 Kutaja Ghana is more effective than Sanjivani vati to cure this symptom Table 7: Showing improvement in Stool consistency 1 st day Kutaja ghana 29 1 30 Sanjivani vati 20 10 30 Total 49 11 60 V1 9.0167 Thus stool consistency is effectively treated by Kutaja ghana within one day than Sanjivani vati Table 8: Showing improvement in Stool consistency cured on 2 nd day Kutaja ghana 30 0 30 Sanjivani vati 25 5 30 Total 55 5 60 V1 5.6545 Thus Kutaja Ghana is more effective to improve stool consistency on 2 nd day. Table 9: Showing improvement in Samata of stool Kutaja ghna 3 10 13 Sanjivani vati 6 6 12 Total 9 16 25 V1 0.3963 Both drugs are equally effective to cure Samata stool Table 10: Showing improvement in Cured grade of cyst of EH Kutaja ghana 2 9 11 Sanjivani vati 1 5 6 Total 3 14 17 V1 0.3963 Both drugs are equally effective to cure cyst of EH in stool Table 11: Showing improvement in Cure grade of Kshudhamandya (loss of appetite) Kutaja ghana 9 15 2 0 26 Sanjivani vati 6 8 12 4 30 Total 15 23 14 4 56 V1 14.042 Kutaj ghana is more effective to cure loss of appetite IJAPR March 2016 Vol 4 Issue 3 39

Shisode Nileema Raju. To Study the Effect of Kutaja Ghana in Atisar Vegavastha (Acute Diarrhea) Table 12: Showing improvement in Cure grade of udarshula Kutaja ghana 16 6 4 3 29 Sanjivani vati 10 3 12 4 29 Total 26 9 16 16 58 V1 6.7814 Both drugs are equally effective to cure pain in abdomen (Udarshul) Table 13: Showing improvement in Cure grade of headache Kutaja ghana 19 2 0 1 22 Sanjivani vati 13 1 9 4 27 Total 32 3 9 5 49 V1 12.721 Kutaja Ghana is more effective to cure headache. Table 14: Showing improvement in Cure grade of Annadwesh food hatred- Kutaja ghana 16 1 0 4 21 Sanjivani vati 12 0 7 5 24 Total 28 1 7 9 45 V1 9,7681 Kutaja Ghana is more effective to cure Annadvesh Table 15: Showing improvement in Cure grade of Utklesh (nausea) Kutaja ghana 12 1 1 1 15 Sanjivani vati 10 0 0 4 14 Total 22 1 1 5 29 V1 6.2442 Both drugs are equally effective to cure Utklesh Table 16: Showing improvement in Cure grade of skin turgor Kutaja ghana 5 0 1 3 9 Sanjivani vati 8 0 0 3 11 Total 13 0 1 6 20 V1 2.4434 Both drugs are equally effective to cure skin turgor Table 17: Showing improvement in Cure grade of Bhrama Kutaja ghana 5 0 1 3 9 Sanjivani vati 8 0 0 3 11 Total 13 0 1 6 20 V1 2.4434 Both drugs are equally effective to cure Bhrama (giddiness) Available online at: http://ijapr.in 40

Calculated T Value in this experiment is higher than the higher value obtained by chance hence probability of occurrence (p) of value obtained by chance is much less than 0.05 the critical or 5% of significance. The difference is real in 98% experiments, hence highly significant. For quantitative symptoms compared to t test is applied. Kutaja is more effective to cure number of motions after one day treatment. Chi square test is applied to attributes for qualitative symptoms. In qualitative symptoms both drugs are equally effective to cure Samata of tongue, stool and EH cyst in stool, pain in abdomen etc. All other symptoms are better cured with Kutaja Ghana, this is statistically proven. CONCLUSION Kutaja is cost effective and easily available drug throughout India. Kutaja contains alkaloids which are responsible for its action on Atisar. Connesine is important alkaloid among them. Kutaja powder collected soon after rainy season from 8-10 yrs old plant is good for its medicinal value, it contains 3.5% of total alkaloids and Kutaja Ghana prepared from it by Ayurvedic authentic method contains 10.7 % of total alkaloids and also in analysis it was found with less impurities in Ghana preparation. Chromatograph of chloroform soluble extract of Kutaja powder shows 55.32% of connesine and that of Ghana is 99% connesine. In market preparations we found very less percentage of connesine as they may not follow proper collection and preparation method so this method we can use for standardization of Kutaja Ghana. Connesine can be identified or confirmed by NMR and mass index study. Kutaja is drug of choice for Pittaja atisar. Some OPD patients who are suffering from Atisar since many days or months and have tried lots of medicine are also relieved from the symptoms within 2 days with Kutaja Ghana. ACKNOWLEDGEMENT I am very thankful to my guide Dr. Mrs D.S. Pandit Department of Pathology, Ayurved hospital, Nashik and Dr. V.K. Maurya, college of pharmacy Nashik. Int. J. Ayur. Pharma Research, 2016;4(3):36-41 REFERENCES 1. Charak samhita Chakrapanidatta tika Author Yadavji trikamji Aacharya Publisher Chaukhamba prakashan Varanasi 1992. 2. Sushruta Samhita Dalhana tika Author Yadavji Trikamji Acharya Publisher Chaukhamba prakashan Varanasi 1992. 3. Ashtang sangraha Induvakhya Authors-Vd. Ananta Damodar Aathavle Vd. Mahendra Aathvle Publisher Srimad atreya prakashan pune. 4. Ashtang Sangraha Arundatta tika Edited by- Bhishagcharya Harishstrin paradkar Publisher Chaukhamba Prakashan Varanasi 1998. 5. Kashyapa Samhita Author Pandita Hemraja Sharma Publisher Chaukhamba Prakashan Varanasi Part 18 th part 2 (page no 346-349) 4 th edition 1999. 6. Bhavprakash Vidyotini tika Author Brahmashastri and Rupalalji vaishya Publisher Chaukhamba prakashan Varanasi Part 1 and part 2 page no 346-349 3 rd edition 1999. 7. Sargandhar Samhita Tikakar Aacharya Radhakrishna Parashar Publisher Baidyanath Aayurved bhavan Nagpur 9 1984 page no 32-66, 132, 306-307. 8. Clinical methods in Aayurveda Author- Prof.K.R. Shrikant Murti L.A.M.S. H.B.A. (Banglore) Publisher Chaukhamba Prakashan, Varanasi (page no 152-231) 1 st edition 1983. 9. Research in Ayurveda A classified directory of all India P.G. and PH.D. thesis of Ayurveda 197 Author Dr. M.S. Baghel Publisher Mrudu Ayurved Publisher and cell Jamnagar. 10. Aadarsha Nighantu Vol 1 Bapla G. Vaidya Publisher Chaukhmbha Surbharti prakashan P.O.B ox no 1065 Varanasi 221001 India 1 st edition 1968 page no 847-854. 11. Studiies in the pharmacognosy of the ayurveda drug Author A.N. Namjoshi Publisher Board of research in Aayurveda Bombay 1960 page no 22-26. 12. Aushadhi nirman part 1 author- S.A. Mndake Tilak Ayurved college Pune 1 st edition 1967 page no 142-146. Cite this article as: Shisode Nileema Raju. To Study the Effect of Kutaja Ghana in Atisar Vegavastha (Acute Diarrhea). International Journal of Ayurveda and Pharma Research. 2016;4(3):36-41. Source of support: Nil, Conflict of interest: None Declared *Address for correspondence Dr Shisode Nileema Raju Reader Department of Swasthvritta Tilak Aayurved Mahavidyalaya, Pune, Maharashtra, India. Mobile: 09422058413 Email: nileema.shisode7@gmail.com IJAPR March 2016 Vol 4 Issue 3 41