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TITLE
CERTIFICATE
DECLARATION
ACKNOWLEDGEMENT
CONTENTS
ABBREVIATIONS
I Introduction and Review of Literature
INTRODUCTION
REVIEW OF LITERATURE
Fig.1: Schematic representation of pathogenesis of atherosclerosis
Fig.2: Schematic representation of the relationship between the production of free radicals, Lipid peroxidation and antioxidant systems
Lifestyles and CVD
Diet and habits
Cigarette Smoking
Alcohol consumption
Biochemical / Physiological characteristics and CVD
Hypertension
Dyslipidaemia
Glucose intolerance and Diabetes
Obesity
Other Cardiovascular Risk Factors
Left ventricular hypertrophy (LVH)
Hyperhomocysteinaemia
Lipoprotein (a) [Lp (a) ]
Hypertriglyceridaemia
Increased fibrinogen level and other thrombogenic factors
Oxidative Stress
Infectious agents
Inflammation
Therapeutic strategies in CVD
Drugs
Drugs lowering plasma lipoproteins - Statins
Bile acid binding resins
Gemfibrozil
Nicotinic acid derivatives
Probucol
Omega-3 fatty acids
Animal model
II Materials and Methods
MATERIALS
2: 1. Plant materials
2: 2. Chemicals
Fig. Captions
2: 3. Instruments
2: 4. Animals
2: 5. Maintenance of Animals
2: 6. Test compounds preparation
METHODS
2: 7. Antioxidant activity study
2: 7a. Superoxide radical scavenging activity
2: 7b. Hydroxyl radical scavenging activity
2: 7c. Inhibition of lipid peroxidation
2: 8. Anticoagulant activity
2: 9. Platelet aggregation inhibition activity
2: 10. Lipoprotein lipase releasing activity
2: 11. Anti inflammatory activity
2: 11a. Carrageenan induced pedal oedema in rats 2z0
2: 11b. Formalin induced paw oedema 221
2: 12. Toxicity Study
2: 12a. Acute toxicity study
2: 12b. Sub acute toxicity study
2: 12c. Glutamate.pyruvate transarninase (GPT) 223
2: 12d. Glutamate oxaloacetate trarwarninase (GOT) 223
2: 12e. Alkaline phosphatase (ALP) 224
2:12f. Lactate dehydrogenase (LDH)
2: 12g. Gamma Glutamyl Transferase (GGT) 2 ~ 6
2: 12h. Estimation of Creatinine 227
2: 12. Estimation of urea228
2: 13. Hypolipidaemic study
2: 13a. Estimation of t& cholesterol 229
2: 13b. Estimation of HDLCholesterol230
2: 13c. Estimation of triglycerides 231
2: 13d. Estimation of LDL cholesterol~
2: 13e. Estimation of phospholipids 233
2: 14. Antioxidant enzyme study
2: 14a. Superoxide dismutase (SOD) 213
2: 14b. Catalase 234
2: 14c. Glutathione peroxidase 2 3
2: 15. Senun lipid peroxidation
2: 16. Enzymes of lipid metabolism
2: 16a. Lipoprotein lipase
2: 16b. 3-Hydroxy 3-Methyl Glutaryl- CoA reductase
2: 17. Extraction and estimation of tissue lipids
2: 18. Aortal staining for fat deposition
2: 19. Statistical evaluations
III Studies on the therapeutic potential of the formulation
1. STUDIES ON ANTIOXIDANT ACTTVITY
Introduction
Materials and methods
Animals
Antioxidant activity
Superoxide radical scavenging activity
Hydroxyl radical scavenging activity
Inhibition of lipid peroxidation
Results
DISCUSSION
2. STUDIES ON ANTIPLATELET AGGREGATIONACTIVITY
Introduction
Methods
Platelet aggregation inhibition activity
Results
DISCUSSION
Fig. 3: 1 - Effect of the formulation on ADP induced plateletaggregation inhibition
3. STUDIES ON ANTICOAGULANT ACTIVITY
Introduction
Materials and methods
Animals
Anticoagulant activity by plasma recalcification method
Result
Effect on plasma recalcification time
DISCUSSION
4. STUDIES ON LIPOPROTEIN LIPASE ENZYMEACTIVITY
Introduction
Materials and methods
Animals
Lipoprotein lipase enzyme releasing activity.
Results
DISCUSSION
5. STUDIES ON ANTI-INFLAMMATORYACTIVITY
Introduction
Materials and methods
Animal
Anti-inflammatory activity
Results
DISCUSSION
Fig. 3: 2 - Effect of the formulation on Carrageenan induced pedaloedema in rats
Fig 3: 3 - Effect of the formulation on formalin inducedpedal oedema in rats
6. STUDIES ON HYPOLIPIDAEMIC ACTIVITY
Introduction
Materials and methods
Animals
Hypolipidaernic activity
Results
Fig.3.4- Percentage change in body weight of rats treated with HFD and the formulation for a period of 30 days
DISCUSSION
Fig. 3: 5 - Percentage change in the serum lipid profile of ratstreated with HFD and formulation compared to normal ratsfor a period of 30 days
Fig. 3: 6 - Percentage change in the lipid profile of rats treated withHFD and formulation compared with HFD fed for a period of 30 days
Fig. 3: 7 - Atherogenic index of rats treated with HFD and theformulation for a period of 30 days
IV Toxicity studies of the formulation biochemical parameters
Introduction
Materials and methods
Animals
Acute toxicity study
Sub acute toxicity study
Results
Effect on heart function
Effect on liver function
Effect on kidney function
DISCUSSION
V Antiatherogenic efficacy of the formulation in rabbits
Introduction
Materials and Methods
Results
Fig. 5: 1 - Effect of the formuIation on serum total cholesterol in rabbitsfed HFD for a period of 90 days compared to HFD fed group.
Fig 5: 2 - Effect of the formulation on serum higlycerides in rabbits fed HFD for a period of 90 days compared to HFD alone fed group
Fig 5: 3 - Effect of the formulation on serum phospholipids in rabbits fed HFD for a period of 90 days compared to HFD alone fed group.
Fig 5: 4 - Effect of the formulation on serum LDL cholesterol in rabbitsfed HFD for a period of 90 days compared to FWD alone fed group
Fig 5: 5 - Effect of the formulation on serum HDL cholesterol in rabbitsfed HFD for a period of 90 days compared to HFD alone fed group
Fig 5: 6 - Effect of the formulation on lipid peroxidation of rabbitsfed HFD for a period of 90 days
Fig 5: 7 - Effect of the formulation on atherogenic index inrabbits fed HFD for a period of 90 days
Fig. 5: 8 - Effect of the formulation on tissue cholesterol of rabbitsfed HFD for a period of 90 days
Fig. 5: 9 - Effect of the formulation on tissue triglycerides ofrabbits fed HFD for a period of 90 days
Fig. 5: 10 - Effect of the formulation on tissue phospholipids ofrabbits fed HFD for a period of 90 days
Fig. Caption
DISCUSSION
VI Antioxidant and hypolipidaemic effect of a herbal formulation - Liposem
Introduction
Materials and methods
Animals
Antioxidant effect
Superoxide radical scavenging activity
Hydroxyl radical scavenging activity
Inhibition of lipid peroxidation
Hypolipidaemic effect
Results
The Antioxidant activity
Hypolipidaernic activity
Fig 6: 1 - Percentage weight increase of rats treated with Liposem for aperiod of 30 days
Fig 6: 2 - Percentage increase in the serum lipid profile of rats treatedwith HFD and Liposem for a period of 30 days compared to normal rats.
DISCUSSION
Fig 6: 3 - Percentage change in the serum lipid profile of rats treated with3FD and Liposem for a period of 30 days compared to HFD alone fed group
Fig 6: 4 - Atherogenic index of rats treated with Liposem for a period of 30 days
VII Summary and Conclusion
References