STUDY ON PHARMACOLOGY AND TOXICOLOGY OF CARISSA CARANDAS (AUCT.) AND HERBAL PRODUCTS USED IN CARDIOVASCULAR DISEASES

Abstract

BACKGROUND OF RESEARCH: Herbal medicines have been used for thousands of years. The practice continues today because of its biomedical benefits and place in cultural believes in many parts of the world. The economic reality of the inaccessibility of modern medications for many societies has also played a major role in the broad use of herbal medicines. The World Health Organization has recognized the contribution and value of the herbal medicines used by a large segment of world’s population. A growing interest in usage has created the need for greater precision in preparation and evaluation and has stimulated research into herbal medicines’ various uses and applications. AIMS OF RESEARCH: This study was carried out on the pharmacological and toxicological screening of ethanol: water (1:1) extract of leaves of Carissa carandas (Auct.) and a Poly Herbal Product Mufarreh Yaqooti Motadil (Hamdard Laboratories (Waqf.) Pakistan), and comparative study of these with allopathic medicines. This Herbal product also contains extracts from animal and mineral origin. It has been used traditionally for the treatment of different cardiovascular disorders particularly it has cardio tonic property. But the use was not having any scientific evidences or data for the mechanism of action to prove its efficacy and safety. RESEARCH METHADOLOGY: In this effort we planned to evaluate the In vivo and In vitro the pharmacodynamic study of this drug on different cardiovascular parameters. Another Aquous:Ethanol (1:1) extract of Carissa Carandas leaves was also used for screening and following parameters were studied in different doses by precise methods: i. Effect of tested samples on Blood pressure using invasive method of I.V. cannulation on Sprague Dawley Rats, using four channel Recorder. ii. Comparative study with the synthetic drugs for hypotensive effect. iii. Determination of mechanism of action for Hypotensive activity. XIII iv. Diuretic activity of the tested materials on healthy male and female Sprague Dawley rats. v. Comparison of the diuretic effect with the conventionally used allopathic medicine, Furosemide. vi. Effect of the tested samples on different Cardiac parameters using Intact Heart, model of Frogs (Rana cyanophlictis). vii. Determination of mechanism of action for cardiac activity. viii. Comparison of these cardiac parameters with Digoxin using Intact Heart model of Frog. ix. Cardiac activity of tested samples by invasive method of Langendorf’s Assembly of Isolated Heart, using heart models of Rabbits (Oryctolagus cunniculus). x. Antihyperlipidaemic Activity of the tested samples on rats by the method of histopathological study of organs like Heart, Liver, Kidney and Spleen for structural changes xi. Biochemical screening of serum for different chemicals like Cholesterol, HDL, LDL, Total Protein, Creatinine Uric acid etc., and enzymes like ALAT, ASAT, Alkaline Phosphatase, etc., for functional changes of the organs in these models. xii. Toxicological studies of the tested samples for the Safety Evaluation of these herbal products after Acute (for determination of LD50), Sub acute and Chronic use of drugs in NMRI Mice and Sprague Dawley Rats. xiii. Histopathological and Biochemical Screening for structural and functional changes respectively, in Rat models for safety evaluation. FINDINGS AND CONCLUSION: The Drug and extract has shown very significant results for pharmacological activity on cardio vascular system.The toxicological studies of the extract and drug on treated animals showed that, they are very safe in acute treatment even with a very high dose i.e., 5000mg/kg which did not show any mortality. The high dose was also used for Sub acute and chronic toxicity testing and was found to have no toxic effects except some adverse effects on liver, spleen and kidneys, only by Chronic administration of Carisssa carandas leaves extract in very high dose, as demonstrated by Biochemical and Histopathological evaluations. Other Poly Herbal Drug Product did not show any toxic effects. It is suggested that further studies for the Pharmaceutical preparation of a product form this extract should be performed in doses less than 5000mg/kg. That will help to introduce a potent, safe and cost effective drug for our people suffering from cardiovascular disorders