Rajiv Gandhi University of Health Sciences s55

“PRECLINICAL EVALUATION OF POLYHERBAL FORMULATION NR/CAL/6 FOR ITS CALCIUM ENHANCING ANB CALCIUM ABSORBING ACTIVITY IN OSTEOPOROSIS”

SYNOPSIS FOR M. PHARM DISSERTATION

SUBMITTED TO RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BENGALOORU, KARNATAKA

SUBMITTED BY

PRAVEEN.S I M. PHARM DEPARTMENT OF PHARMACOLOGY P.E.S COLLEGE OF PHARMACY BENGALOORU – 560050 (2008-2009) RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BENGALOORU, KARNATAKA. ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1.0 NAME AND ADDRESS OF THE PRAVEEN.S CANDIDATE. P.E.S.COLLEGE OF PHARMACY HANUMANTHANAGAR, 50 FT. ROAD, BENGALOORU-560 050.

PERMANENT ADDRESS

#62/A,PIPELINE,MANUVANA,VIJAYANAGAR, BANGALOORU-560040.

2.0 NAME OF THE INSTITUTION. P.E.S. COLLEGE OF PHARMACY

HANUMANTHANAGAR, 50 FEET ROAD, BENGALOORU – 560050.

3.0 COURSE OF STUDY AND M.PHARM. SUBJECT. PHARMACOLOGY.

4.0 DATE OF ADMISSION TO 16th JUNE, 2008 COURSE.

5.0 TITLE OF THE TOPIC:

“ PRECLINICAL EVALUATION OF POLYHERBAL FORMULATION NR/CAL/6 FOR ITS CALCIUM ENHANCING ANB CALCIUM ABSORBING ACTIVITY IN OSTEOPOROSIS ” 6.0 6.1 . NEED FOR THE STUDY:

Osteoporosis is the most frequent metabolic condition experienced by elderly individuals. It is a systemic skeletal disease characterized by low bone mass and micro architectural deterioration of bone tissue with a consequent increase in bone fragility and susceptibility to fracture(1). Osteoporosis constitutes a major public health problem, leading to a decrease in the quality of life, to disability and even to death through its major symptomatic manifestation, the fracture particularly of the hip.

Using the WHO definition of osteoporosis, it has been estimated that 54% of all postmenopausal white woman have osteopenia, and another 30% have osteoporosis. About 70% of women older than 80 years have osteoporosis.(2)

Clinical interest in osteoporosis related to fractures and associated disability. The lifetime risk of a hip, wrist, or clinically diagnosed vertebral fracture is about 40% for white woman and 13% for white men.(3)

In ancient system of medicine, a several number of herbal plants have been used for osteoporosis, bone calcification and fracture. NR/CAL/6 is a polyherbal formulation with Hibiscus rosa sinensis, Cestrum diurnum, and Glycyrrhiza glabra.

The present study was undertaken to evaluate the beneficial effects of extracts of this formulation using suitable animal models of osteoporosis and also to study the various parameters that are predictive of either bone resorption or bone formation.

6.2 OBJECTIVE OF THE STUDY

 To determine acute oral toxicity study of methanolic extract of NR/CAL/6 as per OECD guidelines.  To investigate anti-osteoporosis activity of methanolic extract of NR/CAL/6 in bilateral overectamized female rats.  To investigate anti-osteoporosis activity of methanolic extract of NR/CAL/6 in methyl prednisolone induced female rats. 8.0 REFERENCES :

1. Peak WA, Burckhardt P, Christiansen C. Consensus development conference: Diagnosis, prophylaxis and treatment of osteoporosis. Am J Med. 1993;94(6):646-50. 2. MELTON LJ, CHRISCHILLES EA, COOPER C, LANE AW, RIGGS BL. Perspective: how many women have osteoporosis? Journal of bone and mineral research. 1992;7:1005-10. 3. Chrischilles E, Shireman T, Wallace R. Costs and health effects of osteoporotic fractures. Bone. 1994;15(4):377-86. 4. Prajapati, Putohit, Sharma, Kumar. A handbook of Medicinal Plants; 2003. 5. Begum AS, Madhur G. Research and Medicinal Potential of the genus Cestrum(Solanaceae) – A Review. PHCOG REV. 2007 JUL-DEC;1(2):320-32. 6. Ghosh A, Chowdhury N, Chandra G. Laboratory evaluation of a phytosteroid compound of mature leaves of Day Jasmine (Solanaceae: Solanales) against larvae of Culex quinquefasciatus (Diptera: Culicidae) and nontarget organisms. Parasitol Res. 2008 Jul;103(2):271-7. 7. Chennaiah S, Qadri SS, Reddy CV, Rama SV, Shyamsunder G, Raghuramulu N. Incorporation of Cestrum diurnum leaf improves intestinal Ca transport in broilers. J Steroid Biochem Mol Biol. 2007 Mar;103(3-5):645-50. 8. Chennaiah S, Qadri SS, Rao SV, Shyamsunder G, Raghuramulu N. Cestrum diurnum leaf as a source of 1,25(OH)2 Vitamin D3 improves egg shell thickness. J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):589-94. 9. Sarkar K, Narbaitz R, Pokrupa R, Uhthoff HK. The ultrastructure of nephrocalcinosis induced in chicks by Cestrum diurnum leaves. Vet Pathol. 1981 Jan;18(1):62-70. 10. Vasudeva N, Sharma SK. Post-Coital Antifertility Activity of Hibiscus rosa-sinensis Linn. roots. . Evid Based Complement Alternat Med. 2008 Mar;5(1):91-4. 11. Shivananda NB, Sivachandra RS, Orette FA, Chalapathi AV. Effects of Hibiscus rosa sinensis L (Malvaceae) on wound healing activity: a preclinical study in a Sprague Dawley rat. Int J Low Extrem Wounds. 2007 Jun;6(2):76-81. 12. Gauthaman KK, Saleem MT, Thanislas PT, Prabhu VV, Krishnamoorthy KK, Devaraj NS, et al. Cardioprotective effect of the Hibiscus rosa sinensis flowers in an oxidative stress model of myocardial ischemic reperfusion injury in rat. BMC Complement Altern Med 2006 Sep 20;6:32. 13. Nivsarkar M, Patel M, Padh H, Bapu C, Shrivastava N. Blastocyst implantation failure in mice due to "nonreceptive endometrium": endometrial alterations by Hibiscus rosa-sinensis leaf extract. Contraception. 2005 Mar;71(3):227-30. 14. Menegazzi M, Di PR, Mazzon E, Genovese T, Crisafulli C, Dal BM, et al. Glycyrrhizin attenuates the development of carrageenan-induced lung injury in mice. Pharmacol Res. 2008 Jul;58(1):22-31. 15. Cui YM, Ao MZ, Li W, Yu LJ. Effect of glabridin from Glycyrrhiza glabra on learning and memory in mice. Planta Med. 2008 Mar;74(4):377-80. 16. Sharifzadeh M, Shamsa F, Shiran S, Karimfar MH, Miri AH, Jalalizadeh H, et al. A time course analysis of systemic administration of aqueous licorice extract on spatial memory retention in rats. Planta Med. 2008 Apr;74(5):485-90. 17. Gupta VK, Fatima A, Faridi U, Negi AS, Shanker K, Kumar JK, et al. Antimicrobial potential of Glycyrrhiza glabra roots. J Ethnopharmacol. 2008 Mar 5;116(2):377-80. 18. Krishnamurthy DR, Reddy CM, Saraswati BP. Effect of Benzene Extract of Hibiscus Rosa Sinensis on the Estrous Cycle and Ovarian Activity in Albino Mice. Biol Pharm Bull. 1997;20 (7):756-8. 19. Liu J, Burdette JE, Xu H, Gu C, van Breemen RB, Bhat KP, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem. 2001 May;49(5):2472-9. 20. Albert PM. Fennel and anise as estrogenic agents. J Ethnopharmacol. 1980 Dec;2(4):337-44. 21. Kamboja VP, Dhawana BN. Research on plants for fertility regulation in India. Journal of Ethnopharmacology. 1982;6(2):191-226. 22. Pandey SK, Sahay A, Pandey RS, Tripathi YB. Effect of Asparagus racemosus rhizome (Shatavari) on mammary gland and genital organs of pregnant rat. Phytother Res. 2005 Aug;19(8):721-4. 23. Ju YH, Carlson KE, Sun J, Pathak D, Katzenellenbogen BS, Katzenellenbogen JA, et al. Estrogenic effects of extracts from cabbage, fermented cabbage, and acidified brussels sprouts on growth and gene expression of estrogen-dependent human breast cancer (MCF-7) cells. J Agric Food Chem 2000 Oct;48(10):4628-34. 24. Okamoto JM, Yoko OH, Hideyuki Y, Hiroyuki Y. Pomegranate extract improves a depressive state and bone properties in menopausal syndrome model ovariectomized mice. J of Ethnopharm. May 2004;92(1):93-101. 25. Boué SM, Wiese TE, Nehls S, Burow ME, Elliott S, Carter CH, et al. Evaluation of the estrogenic effects of legume extracts containing phytoestrogens. J Agric Food Chem. 2003 Apr 9;51(8):2193-9. 26. Gnudi S, Giardino R, Mongiorgi R, Fini M, Zati A, Figus E, et al. Evaluation of an experimental model of osteoporosis induced in the female rat through ovariectomy. Boll Soc Ital Biol Sper. 1993 Jul-Aug;69(7-8):461-8.

08. NAME OF THE CANDIDATE PRAVEEN.S

09. SIGNATURE OF THE CANDIDATE (PRAVEEN.S )

10. REMARKS OF THE GUIDE

MR.MUKUND HANDRAL 11.1 NAME AND DESIGNATION OF THE GUIDE ASST. PROFESSOR, DEPT. OF PHARMACOLOGY P.E.S. COLLEGE OF PHARMACY BENGALOORU-560 050.

11.2 SIGNATURE

11.3 HEAD OF THE DEPARTMENT Dr.NANDA KUMAR

HOD DEPT. OF PHARMACOLOGY P.E.S. COLLEGE OF PHARMACY BENGALOORU-560 050.

11.4 SIGNATURE

12.1 REMARKS OF THE PRINCIPAL

12.2 SIGNATURE Prof. Dr. S.Mohan

PRINCIPAL AND DIRECTOR P.E.S. COLLEGE OF PHARMACY BENGALOORU -560 050