PHYTOCHEMICAL AND BIOLOGICAL EVALUATION OF LEAF OF Lantana camara Linn.

SYNOPSIS FOR M.PHARM DISSERTATION SUBMITTED TO

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES BY ARCHANA V.R

Department of Pharmacognosy

THE OXFORD COLLEGE OF PHARMACY

BANGALORE-560078 RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, KARNATAKA, BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. Name of the candidate and Archana V.R address The Oxford college of pharmacy, J.P. Nagar, 1st Phase, Bangalore-560078.

PERMANENT ADDRESS: Sri Skandha Nilayam, c/o Thyagaraj No:69, 1st Main, 8th Cross, Kakatheeya Nagar, Ittamadu, Bangalore – 560 085

2. Name of the Institution The Oxford college of Pharmacy, J.P. Nagar, 1st Phase, Bangalore-560078.

3. Course of study and Subject M.Pharma, Pharmacognosy

4. Date of Admission 19 June 2009.

5. Title of the Topic PHYTOCHEMICAL AND BIOLOGICAL EVALUATION OF LEAF OF Lantana camara Linn. 6. Brief resume of the intended work: 6.1- Need for the study:

Lantana camara also known as Lantana aculeate and Lantana, belonging to the family verbenaceae, is a native of tropical America, but more naturalized in many parts of India1. The leaves contain oxidase, catalase, amylase, invertase, lipase, tannins, glycosidase, sugars, resins, lipase and volatile constituents like sesquiterpenes – caryophyllene, l-alpha- phelladrene and small amounts of aldehydes and alcohol.The bark of stems and roots contain a quinine like alkaloid – lantanine and seeds contain fixed oil. The flowers contain volatile oil, anthocyanins, a yellow flavone, pink pigment and a carotene2. The leaves of Lantana camara is also reported to contain triterpenes – lantoic acid3, oleanonic acid, lantadene A, lantadene B, lantanilic acid, icterogenin, camaroside4 and a new triterpenoid – lantadene D. The roots are reported to contain new carbohydrates i.e. lantanose A and B and a new triterpenoid – lantaiursolic acid5. The whole plant was reported for various activities such as nematicidal, antifungal, pesticidal6. In folklore medicine it is known to be used as rheumantism, malaria, tetanus, ataxy of abdominal viscera, cuts, ulcers, swellings7. So far various studies have been carried out for different phytochemical and pharmacological activity, but not much scientific data available with respect to leaf part of Lantana camara. Therefore the aim of present study is to carry out isolation of the phytoconstituents from the leaves of Lantana camara, antioxidant and antimicrobial activity of the extracts and/or isolated compounds. 6.2 – REVIEW OF LITERATURE :

1. 3β, 19α dihydroxy ursan-28-oic acid and 21, 22β-epoxy-3β-hydroxy olean-12-en-28 oic acid, the two novel triterpenoids were isolated from the roots of Lantana camara. Oleanolic acid a hepatoprotective compound, was isolated from the roots of the Lantana camara and is converted into it’s 28 → 13β-lactone by a facile photo-oxidation reaction8.

2. A new triterpenoid i.e. ursane was isolated from the leaves of Lantana camara and by means of spectral analysis it’s structure was elucidated as 3, 24-dioxo-urs-12-en-28-oic acid9.

3. A new triterpene lantanilic acid was isolated from the leaves of Lantana camara and it’s structure was determined as the β, β-dimethylacryloyl ester of lantaninilic acid10.

4. A novel flavonol glycoside {camaroside} and a new phenylpropanoid glycoside {lantanoside} were isolated from the leaves of Lantana camara, which are potential antitumor agents and by spectroscopic methods and chemical transformations they are named as 3,5-dihydroxy-4,6-dimethoxyflavonol-7-o-glucopyranoside and 3,4-dihydroxy- β-phenylethyl-o-alpha-L-rhamnopyranosyl ( 1→ 3 )-4-0-cis-caffeoyl-β-D-glucopyranoside respectively11.

5. The aqueous leaf extract of Lantana camara is effective in wound healing activity in the experimental animals ( rats ).Wound healing efficacy was measured by morphological and biochemical parameters and the treatment showed good results and are evaluated as a therapeutic agent in tissue repair processes associated with skin injuries12. 6. Two flavonoids linaroside (1) and lantanoside (2) were isolated from the Lantana camara and their common acetyl derivatives (3) were examined against Mycobacterium tuberculosis, strain H ( 37 ) Rv for the antimycobacterial activity and the acetylated type of flavonoid compound was found to be the most active13.

7. Five new derivatives of the pentacyclic triterpenoid lantadene A, isolated from the leaves of Lantana camara, were synthesized, characterized and screened for their cytotoxicities against four human cancer cell lines. Further the three most potent compounds were studied for their in vivo tumor inhibitory potential upon oral administration in two-stage squamous cell carcinogenesis using induced by 7,12- dimethylbenz[a]anthracene (DMBA), and promoted by TPA. The results are discussed in terms of SAR14. 6.3 – Objective of the study :

1. Collection of the leaf of Lantana camara from Bangalore (Karnataka) and the leaf was authenticated by RRI, Bangalore.

2. Preparation of the extract by soxhlet extraction/ maceration.

3. Isolation of the phytoconstituents from the extract, based on phytochemical screening, by column chromatography / other methods.

4. Characterization of isolated phytoconstituents by UV, IR and NMR spectroscopy.

5. The different extracts and/or isolated compound would be studied for antioxidant activity and antimicrobial activity.

7. Materials and methods : 7.1 – a) Source of Data: Search on Medline and other Journals from The Oxford College of Pharmacy, RGUHS – Digital library.

b) Place of work : The Oxford College of Pharmacy, Bangalore. 7.2 – Method of Collection of Data :

Collection - The leaf was collected from Bangalore (Karnataka) and the leaf was authenticated by RRI, Bangalore. Extraction - Extracts of the leaf will be prepared by soxhlet extraction/ maceration. Isolation - Isolation of phytoconstituents from the selected extract will be done using column chromatography and other separation techniques. Identification and Characterization - The isolated compounds will be identified and characterized using analytical methods like UV, IR and NMR spectroscopy. Antioxidant activity - The extract/isolated compounds will be studied for in-vitro free radical scavenging activity by 2, 2-diphenyl-1-picrylhydrazyl ( DPPH )15. Antimicrobial activity - The antimicrobial activity of the extract/isolated compound in comparison with the standard would be carried by Disc Diffusion Method for gram positive and gram negative organism16.

7.3 – Does the study require any investigation or inventions to be conducted on Patients or other humans or animals? If so, please describe briefly.

-Not applicable -

7.4 – Has ethical clearance been obtained from your institution in case of 7.3?

- Not applicable - 8. BIBLIOGRAPY : 8.

1. Indian Medicinal Plants a compendium of 500 species. Orient Longman private limited, Chennai. 2004;3:300. 2. The wealth of India a dictionary of Indian raw materials and industrial products. Council of scientific and industrial research, New Delhi. 2003;6:31-34. 3. Ram Rastogi P, Mehrotra BN. Compendium of Indian medicinal plants. Central drug research institute, Lucknow and national institute of science communication,New Delhi.1989;4:423-424. 4. Pan WD, Mai LT, Li YJ, Xu XL, Yu DQ. Studies on the chemical constituents of the leaves of Lantana camara. Yao Xue Xue Bao 1993;28(1):35-9. 5. Ram Rastogi P, Mehrotra BN. Compendium of Indian medicinal plants. Central drug research institute, Lucknow and national institute of science communication, New Delhi.1994;5:478. 6. The wealth of India a dictionary of Indian raw materials and industrial products. Council of scientific and industrial research, New Delhi. 2002;4:22-23. 7. Khare CP. Indian medicinal plants. An illustrated dictionary. Springer (India) private limited, New Delhi. 2007:362. 8. Laxminarain Misra, Hartmut Laatsch. Triterpenoids, essential oil and photo- oxidative 28→13-lactonization of oleanolic acid from Lantana camara. Phytochemistry 2000;54(8):969-974. 9. Yadav SB, Vyasji Tripathi. A new triterpenoid from Lantana camara. Fitoterpia 2003;74(3):320-321. 10. Barua AK, Chakrabarti P, Chowdhury MK, Basak A, Basu K. The structure and stereochemistry of lantanilic acid, the β,β-dimethylacryloyl ester of lantaninilic acid isolated from Lantana camara. Phytochemistry 1976;15(6):987-989. 11. Shashi Mahato B, Niranjan Sahu P, Subodh Roy K, Om Sharma P. Potential antitumor agents from Lantana camara: structures of flavonoid and phenylpropanoid glycosides. Tetrahedron 1994;50(31):9439-9446. 12. Nayak BS, Raju SS, Eversley M, Ramsubhag A. Evaluation of wound healing activity of Lantana camara L.- a preclinical study. Phytother Res. 2009;23(2):241- 245. 13. Begum S, Wahab A, Siddiqui BS. Antimycobacterial activity of flavonoids from Lantana camara linn. Nat prod Res. 2008;22(6)467-470. 14. Sharma M, Sharma PD, Bansal MP, Singh J. Synthesis, cytotoxicity and antitumor activity of lantadene A congeners. Chem Biodivers. 2007;4(5):932-939. 15. Vani T, Rajani M, Sarkar S, Shishoo C. Antioxidant properties of the ayurvedic formulation Triphala and it’s constituents. Int.J.Pharmacognosy 1997;35(5):313-317. 16. Indian Pharmacopoeia. Government of India ministry of health and family welfare. 1996;(2):A105-106. 9. Signature of Candidate

10. Remarks of the Guide Recommended

Mrs.Usha Gavani 11. 11.1 Name and Designation of Guide Asst.Professor Department of Pharmacognosy

11.2 Signature

11.3 Co-Guide -

11.4 Signature -

11.5 Head of the department Dr.Padma M. Paarakh Professor and Head Department of Pharmacognosy

11.6 Signature

12. 12.1 Remarks of Chairman and Forwarded to the University for scrutiny Principal

13. Signature Dr.Padma M. Paarakh Principal The Oxford College of Pharmacy, J.P.Nagar, 1st Phase, Bangalore-560078.