RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE,

KARNATAKA

COMPLETED PROFORMA FOR REGISTRATION OF SUBJECT

FOR DISSERTATION

“EFFICACY OF LEKHANEEYA MAHAKASHAYA GHANAVATI

IN DYSLIPIDEMIA: A RANDOMIZED CONTROLLED TRIAL”

BY

DR. DEEPAK BSR 1ST YEAR M.D. (AYU) SCHOLAR

DEPT OF P.G STUDIES IN KAYACHIKITSA

S.D.M COLLEGE OF AYURVEDA

HASSAN.

GUIDE

DR. LAKSHMIPRASAD.L.JADHAV M.D (AYU),

ASSOCIATE PROFESSOR AND HEAD

DEPT OF P.G STUDIES IN KAYACHIKITSA

S.D.M COLLEGE OF AYURVEDA

HASSAN.

2012-2013

S.D.M COLLEGE OF AYURVEDA

HASSAN-573201

From ,

Dr.Deepak.B.S.R

Preliminary MD Ayurveda,

Department of Post Graduate Studies in Kayachikitsa,

S.D.M. College of Ayurveda and Hospital, Hassan- 573201.

To,

The Registrar,

Rajiv Gandhi University of Health Sciences,

BANGALORE, Karnataka.

Through:

The Principal and H.O.D Dept. of PG Studies in Kayachikitsa,

S.D.M. College of Ayurveda & Hospital, Hassan-573201

Subject: Submission of completed proforma for Registration of Synopsis for Dissertation.

Respected Sir,

I request you to kindly register the below mentioned subject against my name for the sub-

mission of the dissertation to the Rajiv Gandhi University of Health Sciences, Bangalore for par-

tial fulfillment of M.D. (Ayurveda) in Kayachikitsa.

The Title of Dissertation :

“EFFICACY OF LEKHANEEYA MAHAKASHAYA GHANAVATI

IN DYSLIPIDEMIA: A RANDOMIZED CONTROLLED TRIAL”

Herewith I am enclosing completed proforma for Registration of Subject of dissertation.

Thanking You,

Date : Yours faithfully

Place : Hassan ( DEEPAK BSR )

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES, BANGALORE, KAR-

NATAKA.

ANNEXURE-II

COMPLETED PROFORMA FOR REGISTRATION OF SUBJECT OF DISSERTA-TION.

1. NAME OF THE CANDIDATE : DR. DEEPAK BSRAND ADDRESS PRELIMINARY MD AYURVEDA,

(IN BLOCK LETTERS) DEPARTMENT OF PG STUDIES IN KAYACHIK-ITSA, S.D.M.COLLEGE OF AYURVEDA & HOS-PITAL, HASSAN - 573201.

PERMANENT ADDRESS : S/O.SURESH KV,

‘SOUPARNIKA’, 3rd MAIN, 3rd CROSS, BASAVESHWARANAGAR, SHIMOGA-577204

2. NAME OF THE INSTITUTION : SDM COLLEGE OF AYURVEDA & HOSPITAL,

HASSAN - 573201.

3. COURSE OF STUDY : M.D. (AYURVEDA), KAYACHIKITSA. & SUBJECT

4. DATE OF ADMISSION : 16.11.2012

TO THE COURSE

5. TITLE OF THE TOPIC: “EFFICACY OF LEKHANEEYA MAHAKASHAYA

GHANAVATI IN DYSLIPIDEMIA: A RANDOMIZED CONTROLLED TRIAL”

6. BRIEF RESUME OF THE INTENDED WORK:

6.1 Need for the study:

Dyslipidemia is one of the most important contributing factors to the atherosclerosis of large and

medium sized arteries, leading to Coronary Heart Disease(CHD).1 Cardiovascular

diseases(CVDs) are the most prevalent cause of death in both developed as well as developing

countries. Rapid urbanization and its accompanying adverse lifestyle changes are likely to be the

risk factors of CVDs.2According to National Commission on Macroeconomics and Health

(NCMH), a Government of India undertaking, there would be around 62 million patients with

coronary artery disease (CAD) by 2015 in India and of these, 23 million would be patients

younger than 40 years of age.3 Abnormal cholesterol levels are estimated to cause 18% of the

global CVDs and 56% of the global Ischaemic Heart Diseases(IHD).4 For every 1% reduction in

lipid level, the risk of heart diseases reduces by 2.5%.4

These statistics increase the responsibility of physicians to a great extent in identifying the cause

and treating dyslipidemia. Dyslipidemia, being a chronic disorder, needs to be managed with safe

and effective medicines. Ayurveda has a wide range of herbal drugs which have been proved

effective in the management of dyslipidemia5. This ancient science must be further thoroughly

explored to evolve better drugs to manage this disorder.

An earlier study on hyperlipidemia came to the conclusion that it can be treated on the principles

of Apatarpana and by following the line of treatment of Sthaulya or Prameha, since these

conditions arise due to Medo Dushti.6 The drugs with Lekhana Karma are said to cause

Karshana.7 Earlier experimental and clinical studies have demonstrated the hypolipidemic

potential of the constituent drugs of Lekhaneeya Mahakashaya.15-23 Earlier studies have also

shown significant hypolipidemic action of Shuddha Guggulu.8 Based on the above facts, the

present study on efficacy of Lekhaneeya Mahakashaya in comparison with that of Shuddha

Guggulu in the management of dyslipidemia has been planned.

6.2 Review of literature:

Dyslipidemia is a disorder of lipoprotein metabolism, which can manifest as an elevation of

plasma cholesterol, triglycerides, or both, or a low high density lipoprotein level or all three

together that contributes to the development of atherosclerosis.9 Atherosclerosis (also known

as arteriosclerotic vascular disease or ASVD) is a condition in which an artery wall thickens as a

result of the accumulation of fatty materials such as cholesterol and triglyceride.10 Physical

inactivity and atherogenic diet, among others, are considered as risk factors for dyslipidemia and

Coronary Heart Disease.11

Nidana for Santarpanottha Vikara have been mentioned as Ati Snigdha, Madhura, Guru and

Pichila Ahara; Chesta Dwesha, Shayya Asana Sukha(sedentary life style) and Divaswapna. 12

Srotolepa is one of the Santarpanottha Vikara.12 Due to Avarana of Marga by the Medas,

Poshana of subsequent Dhatu in the body is hampered and there is Upachaya of Medodhatu.13

These are the references from classical literature bearing similarity to the aetiology, features and

complications of dyslipidemia.

The action which causes the Shoshana and Ullekhana of Dhatu and Mala of the body is termed

as Lekhana.7 Hence, it can be interpreted that Lekhana Dravyas possess Medohara and Sroto-

shodhaka properties. Lekhaneeya Mahakashaya comprises of Musta, Kushta, Haridra,

Daruharidra, Vacha, Ativisha, Katurohini, Chitraka, Chirabilwa and Haimavati.14

Earlier experimental studies(on animal models) and clinical trials on Cyperus rotundus

Linn.15(musta), Saussurea lappa C.B. Clarke16 (kushta), Curcuma longa Linn.17(haridra),

Berberis aristata DC.18 (daruharidra), Acorus calamus Linn.19(vacha), Aconitum heterophyllum

Wall.ex.Royle.20(ativisha), Picrorhiza kurroa Royle ex Benth.21(katurohini), Plumbago zeylanica

Linn.22 (chitraka) and Pongamia pinnata (Linn.) Merr.23 (chirabilwa), which are constituents of

Lekhaneeya Mahakashaya, have shown significant hypolipidemic activity.

Guggulu consists of exudate of Commiphora wightii (Arn.) Bhand, Syn. Balsamodendron mukul

Hook. ex Stocks Commiphora mukul Engl., {Fam. Burseraceae}.24 In an earlier study, 24

patients of dyslipidemia were treated with Gomutra Shodhita Guggulu(GSG) in the dose of

3gm/day in three divided doses for 30 days with lukewarm water. Results showed that

S.Cholesterol was reduced by 4.90%, S.Triglyceride was reduced by 16.40%, S.HDL was

reduced by 1.61%, S.LDL was increased by 6.17% and S.VLDL was reduced by 16.40%. Most

of the results were statistically highly significant and significant.8

PREVIOUS RESEARCH WORKS-

1. Shastri VV. Effect of certain indigenous drugs on intra -arterial thrombosis associated

with Hyperlipidemia. BHU, Varanasi. (1967).

2. Nigam RP. Clinical trial of Arogyavardhini - herbal in the cases of raised Raktagata -

Sneha (Hyperlipidemia). Lucknow. (1981).

3. Dattu Virkar. Mustadi Mahakashaya (Lekhaneeya Gana) ka Hyperlipidemia (Rasagata -

Sneha - Vrudhi) mein prayog aur Chikitsatmaka adhyayana. Mumbai. (1997).

4. Seemaja G. A clinical study to assess the efficacy of Ayurvedic Compound in the

management of Hyperlipidemia. Trivandrum. (2003).

5. Tripathi UC. Concept of Medoroga viz.-a- viz. hyperlipidemia and its management with

Navaka guggulu. Puri. (1985).

6. Shashirekha CK. A comparative study to evaluate the effect of Shuddha Guggulu and

Shodananga snehapana in Hyperlipidemia w.s.r. to Medoroga. Dept of Kayachikitsa,

GAMC, Mysore. ( 2006).

7. Umesh Sapra. Clinical Study Of Hyperlipidaemia And the Effect Of Panchatikta Ghana

In Its Management-A Double Blind Study. IPGT&RA, Jamnagar.(2007).

8. Tripathi SN. Studies on the use of Oleo-Gum-Resin Guggulu, an indigenous drug in the

disorders of lipid. BHU, Varanasi. (1973).

9. Upadhyaya BN. Clinical and experimental study on hypocholesterolemic and

Hypolipidaemic action of Gum Guggulu (C. Mukul). BHU, Varanasi. (1975).

10. Gupta Mithilesh. Effect of C. mukul on endocrinal and biochemical changes in

hyperlipidaemia. BHU, Varanasi. (1977).

6.3 Objective of the study:

1. To evaluate the efficacy of Lekhaneeya Mahakashaya Ghanavati in the management of

dyslipidemia.

2. To evaluate the efficacy of Shudda Guggulu in the management of dyslipidemia.

3. To compare the efficacy of Lekhaneeya Mahakashaya Ghanavati with that of Shudda

Guggulu in the management of dyslipidemia.

7. Material and methods7.1. Source of data

Sample source: Subjects from OPD and IPD of S.D.M College of Ayurveda and hospital,

Hassan.

7.2. Method of collection of data (including sampling procedure, if any)

A. Diagnostic Criteria:

The diagnosis will be based on serological investigation i.e. serum lipid profile as per

ATP III Guidelines.25

Total cholesterol: >200 mg/dL [>5.18 mmol/L]

LDL-cholesterol: >100 mg/dL [>2.59 mmol/L]

Triglycerides : >150 mg/dL [>3.88 mmol/L]

HDL-cholesterol: <40 mg/dL [<1.04 mmol/L]

B. Inclusion Criteria:

Patients having one or more of the diagnostic criteria of dyslipidemia

Patients in the age group of 18-60 years, belonging to either sex, irrespective of caste, reli-

gion & socio-economic status

Subject currently on a statin or other lipid-lowering therapy, willing to withdraw the medi-

cation

Subjects willing to sign informed consent

C. Exclusion Criteria:

Patients with poorly controlled diabetes mellitus (random blood sugar to 250mg/dl) and

uncontrolled hypertension

Cardiovascular conditions or cardiac surgery within the prior 6 months

Other systemic disorders viz., thyroid disorders, renal disorders, cerebro-vascular accident,

PCOS

Pregnant and lactating women

Use of lipid-altering drugs which cannot be stopped

D. Laboratory Investigations:

1] Serum lipid profile.

2] Blood investigations – Random blood sugar, haemoglobin%, total count, differential count,

erythrocyte sedimentation rate.

3] Urine investigations - urine routine and albumin.

E. Study Design:

Randomized, standard controlled trial on OPD basis in a tertiary Ayurveda teaching

hospital located in district headquarters.

The subjects fulfilling the inclusion- exclusion criteria will be randomly divided into two

groups.

Study Group: 15 patients will be treated with Lekhaneeya Mahakashaya Ghanavati with

following specifications:

Dose 2g per day ( two divided doses)Anupana Lukewarm waterAushadhasevana Kala Adhobhakta (after food)Route of administration Oral routeDuration 4 weeks

DRUG : Lekhaneeya Mahakashaya Ghanavati.

Constituents:

Sl.No

Sanskrit Name Botanical Name Part Used Proportion

1 Musta Cyperus rotundus Linn. Rhizome 1 part2 Kushta Saussurea lappa C.B. Clarke Root 1 part3 Haridra Curcuma longa Linn. Rhizome 1 part4 Daruharidra Berberis aristata DC. Stem 1 part5 Vacha Acorus calamus Linn. Rhizome 1 part6 Ativisha Aconitum heterophyllum Wall.ex.Royle. Root 1 part7 Katurohini Picrorhiza kurroa Royle ex Benth. Rhizome 1 part8 Chitraka Plumbago zeylanica Linn. Root 1 part9 Chirabilva Pongamia pinnata (Linn.) Merr. Stem Bark 1 part

Source and authentication of Drugs: The drugs will be procured and authenticated from

reliable sources.

Method of Preparation: Kwatha (decoction) of above drugs (coarse powder) will be pre-

pared by adding 1 part of drug to 8 parts of water and reducing to 1/4 th. This Kwatha is

further heated until Ghana is formed.26 Then it will be rolled into pills of 500mg each and

dried.

Packaging: 56 pills (each 500 mg) in a plastic container.

Shelf Life: 1 year.

Control Group: 15 patients will be treated with Shuddha Guggulu Vati with following

specifications :

Dose 3g per day ( Three divided doses)Anupana Luke Warm WaterAushadhasevana Kala Adhobhakta (after food)Route of administration OralDuration 4 weeks

DRUG: Shuddha Guggulu Vati

Constituents:

Sanskrit

NameBotanical Name/Scientific Name Part Used Proportion

Guggulu Commiphora wightii (Arn.) Bhand Exudate 1 part

Source and authentication of Drugs: The drugs will be procured and authenticated from

reliable sources.

Method of Preparation (27): Ashodhita Guggulu is broken into small pieces and bundled in

a piece of the cloth and boiled in Dola Yantra containing Gomutra. The boiling is contin-

ued till the Guggulu becomes a soft mass. It is then taken out of the cloth and spread over

a smooth wooden board smeared with ghee or oil. By pressing with fingers,

the sand and other remaining foreign impurities are removed. It is taken out and again

fried with ghee and ground in a stone mortar (khalva). This is Shodhita Guggulu. Then it

will be rolled into pills of 500mg each and dried.

Packaging: 84 pills (each 500mg) in a plastic container.

Shelf Life: 2 years.

E. Assessment criteria:

Serological investigations: Total cholesterol, Low density lipoprotein, Triglycerides,

High density lipoprotein.

F. Data Analysis:

The findings before and after treatment will be recorded and evaluated statistically by applying

suitable statistical tests and p<0.05 will be considered statistically significant.

7.3 Does the study require any investigations or interventions to be done on patients or

other humans or animals? If so please describe briefly.

No

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

Yes.

8 List of references

1. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in

Adults; Executive Summary of the Third Report of the National Cholesterol Education

Program(NCEP) Expert Panel on Detection, Evaluation and Treatment of High Blood

Cholesterol in Adults(Adult Treatment Panel III). JAMA 2001;285:2486-97.

2. Chaturvedi V, Bhargava B. Health care delivery for coronary heart disease in India-where

are we headed? Am Heart Hosp J 2007;5:32-7.

3. Indrayan A. Forecasting vascular disease cases and associated mortality in India. Reports

of the National Commission on Macroeconomics and Health. Ministry of Health and Fam-

ily Welfare, India, 2005. Available from: http://www.whoindia.org/EN/Section102/ Sec-

tion201_888.htm. [Last accessed on 2012 Mar 26]

4. Lichtenstien AH, Appel J, branda M, et al. Diet and lifestyle recommendations revision

2006. A scientific statement from the American Heart Association Nutrition Committee.

Circulation 2006;114:82-96.

5. Phadke AS. A review on lipid lowering activities of Ayurvedic and other herbs. Natural

Product Radiance 2007;6(1):81-9.

6. Nadkarni MA. Clinico Experimental Study Of Hyperlipidaemia And Its Management By

Mustadi Ghana Vati. IPGT&RA, Jamnagar.(2009)

7. Sharangadhara. Vidyasagar P. Sharangadhara Samhita with Dipika commentary of Ad-

hamalla and Gudarthadipika commentary of Kashiramvaidya. 2000. Varanasi(India): Kr-

ishnadas Academy; 2000.p.37.

8. Umesh Sapra. Clinical Study Of Hyperlipidaemia And the Effect Of Panchatikta Ghana

In Its Management-A Double Blind Study. IPGT&RA, Jamnagar.(2007)

9. Soneil Guptha. Lipids and Lipoprotien metabolism. Munjal YP. API Textbook Of Medi-

cine. 9th edi. Mumbai: The Association of Physicians of India; 2012. Vol 2.p.1235.

10. Maton, Anthea; Roshan L. Jean Hopkins, Charles William McLaughlin, Susan Johnson,

Maryanna Quon Warner, David LaHart, Jill D. Wright (1993). Human Biology and

Health. Englewood Cliffs, NJ: Prentice Hall. ISBN 0-13-981176-1. OCLC 32308337

11. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and

Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report

of the National Cholesterol Education Program (NCEP)Expert Panel on Detection, Evalu-

ation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).

Bethesda: National Institutes of Health;2002.

12. Acharya JT. Charaka Samhita with Ayurvedadeepika commentary of Chakrapani.4th edi.

Varanasi(India): Chaukhambha Sanskrit Sansthan; 1994.p.122.

13. Bhavamishra. MedoAdhikaraha. Mishra K. Bhavaprakasha with Hindi Teeka of Lalashali-

grama vaishya. Dec 2004. Mumbai(India): Khemraj Shrikrishnadas Publication;

2004.p.1027.

14. Acharya JT. Charaka Samhita with Ayurvedadeepika commentary of Chakrapani.2005.

Varanasi(India): Chaukhambha Surbharati Prakashan; 2005.p.32.

15. Dominic A A, Parkavi C, Murugaiah K, Dhanaraj TS. Hypolipidemic Activity of Cyper-

ous rotundus on CCl4 Induced Dyslipidemia in Rats. Asian J Pharm Tech 2012;2:51-53.

16. Mohamed saleem et al. A review on phytochemical and pharmacological aspects of Saus-

surea lappa. Int.J.Rev Life Sci.2012;2:24-31.

17. Pashine L et al. Effect of turmeric(Curcuma longa) on overweight hyperlipidemic sub-

jects: Double blind study. Indian Journal Of Community Health 2012;24:113-17.

18. Razzaq FA, Khan RA, Feroz Z, Afroz S. Effect of Berberis aristata on lipid profile and

coagulation parameters. African Journal of Pharmacy and Pharmacology 2011;5(7):943-7.

Available online http://www.academicjournals.org/ajpp.

19. D'Souza T, Mengi SA, Hassarajani S, Chattopadhayay S. Efficacy study of the bioactive

fraction (F-3) of Acorus calamus in hyperlipidemia.Indian J Pharmacol 2007;39:196-

200.Available from: http://www.ijp-online.com/text.asp?2007/39/4/196/36539

20. Augustine A, Subash AK. Hypolipidemic effect of methanol fraction of Aconitum hetero-

phyllum wall exRoyle and the mechanism of action in diet-induced obese rats. J Adv

Pharm Technol Res 2012; 3(4): 224–8.

21. Singh V, Chaudhary A , Gunjan. Anti-Hyper Lipidemic activity of Picrorhiza kurroa

Royle ex Benth Roots. Int J Drug Dev & Res 2012;4 (3): 88-91

22. Kanchana N, Sadiq AM. Hepatoprotective Effect Of Plumbago Zeylanica On Paracetamol

Induced Livertoxicity In Rats. Int J Pharm Pharm Sci 2011;3(1): 151-4

23. Kumar P, Semalty A, Mir SR, Ali M, Amin S. Hypoglycemic And Hypolipidemic Activ-

ity Of Pongamia pinnata(Linn.) Pierre In Streptozotocin-Induced Diabetic Rats. Int J

Pharmacology 2010;6(5):738-43.

24. Anonymous. The Ayurvedic Pharmacopoeia Of India Part- I. New Delhi: Ministry Of

Health And Family Welfare, Department Of Ayush, Government Of India; Volume

1.p.57.

25. National Cholesterol Education Program Expert Panel on Detection, Evaluation, and

Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report

of the National Cholesterol Education Program (NCEP)Expert Panel on Detection, Evalu-

ation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).

Bethesda: National Institutes of Health;2002.

26. Acharya YT. Siddha Yoga Sangraha. 11th edi. Nagpur: Baidyanath Ayurveda Bhavana;

2000. p. 4.

27. Anonymous. The Ayurvedic Formulary Of India-e-book-Part 1. 2nd edi. New Delhi: The

Controller of Publications, Ministry Of Health And Family Welfare, Department Of In-

dian Systems of Medicine and Homeopathy, Government Of India; 2003.

9. SIGNATURE OF THE CANDIDATE:

10. REMARKS OF GUIDE :

11. NAMES AND DESIGNATION OF,

11.1. GUIDE : DR.LAKSHMIPRASAD.L.JADHAV, M.D.(Ayu)

Associate Professor,

Dept. of PG Studies in Kayachikitsa,

S.D.M. College of Ayurveda & Hospital

Hassan (Karnataka)

11.2. SIGNATURE :

11.3. H.O.D. : DR.LAKSHMIPRASAD.L.JADHAV, M.D.(Ayu)

Associate Professor,

Dept. of PG Studies in Kayachikitsa,

S.D.M. College of Ayurveda & Hospital

Hassan (Karnataka)

12. SIGNATURE :

12.1. REMARK OF

CHAIRMAN & PRINCIPAL :

12.2. PRINCIPAL : Dr. PRASANNA. N. RAO M. S. (AYU), Ph.D.

S.D.M. COLLEGE OF AYURVEDA AND

HOSPITAL HASSAN - 573 201

12.3. SIGNATURE :